UNITED STATES OF AMERICA

FOOD AND DRUG ADMINISTRATION

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CIRCULATORY SYSTEM DEVICES PANEL

OF THE MEDICAL DEVICES ADVISORY COMMITTEE

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510(k) DISCUSSION AND RECOMMENDATIONS

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THURSDAY

JULY 29, 2004

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            The Advisory Panel meeting convened in the Grand Ballroom of the Holiday Inn, Two Montgomery Village Avenue, Gaithersburg, Maryland at 9:00 a.m., Warren K. Laskey, M.D., Acting Chairperson, presiding.

 

PANEL MEMBERS PRESENT:

WARREN K. LASKEY, M.D., Acting Chairperson, Uniformed Services University of the Health Sciences

MITCHELL KRUCOFF, M.D., Voting Member, Duke University Medical Center

PANEL MEMBERS PRESENT (Continued):

WILLIAM H. MAISEL, M.D., M.P.H., Voting Member, Brigham & Women's Hospital

SHARON-LISE NORMAND, Ph.D., Voting Member, Harvard School of Public Health

NORMAN S. KATO, M.D., Consultant, Cardiac Care Medical Group

JOSEPH P.ORNATO, M.D., Consultant, Medical College of Virginia Hospitals

RICHARD E. RINGEL, M.D., Consultant, Johns Hopkins Hospital

JOHN C. SOMBERG, M.D., Consultant, American Institute of Therapeutics

GEORGE W. VETROVEC, M.D., Consultant, Medical College of Virginia

MICHAEL MORTON, Industry Representative, Cardiac Surgery, North America Sorin Group

CHRISTINE MOORE, Consumer Representative

GERETTA WOOD, Executive Secretary

 

 

 

PRESENTERS:

Office of Surveillance and Biometrics Presentation:

BEVERLY GALLAURESI, RN, MPH, Food and Drug Administration

OSCAR TOVAR, M.D., Food and Drug Administration

Morning Public Session:

MICKEY EISENBERG, M.D., Ph.D., Professor of Medicine, University of Washington

KELLY HARRIS, Lake Oswego, California

RICHARD A. LAZAR, ESQ.,      CEO, Early Defibrillation

Law & Policy Center

MATT McKEE, Cardiac Science, Inc.

ROBERT E. O'CONNOR, M.D., MPH, Professor of Emergency Medicine, Thomas Jefferson University

FRANK POLL                       

Sponsor Presentation:

DR. LANCE BECKER, Director, Emergency Resuscitation Center, University of Chicago

CARL MORGAN, Co-founder, Philips

DR. JEREMY RUSKIN, Founder and Director, Cardiac Arrhythmia Service and Clinical Electrophysiology Laboratory, Massachusetts General Hospital

DAVID SNYDER, Director of Research, Philips

U.S. Food and Drug Administration Presentation:

OSCAR TOVAR, M.D., Lead Reviewer, FDA

Afternoon Public Session:

JOHN GREGOIRE, Plano, Texas

MARY NEWMAN, National Center for Early Defibrillation

GRAHAM NICHOL, M.D., Chair, American Heart Association AED Task Force                

MICHAEL D. WILLINGHAM, Vice President, Regulatory Affairs Medtronic Emergency Response Systems

 


                  C O N T E N T S

                                              PAGE

Conflict of Interest Statement ................. 7

Introductions ................................. 10

Automatic External Defibrillators, Dr. Oscar

      Tovar and Beverly Gallauresi ............ 13

Open Public Hearing Comments:

      Dr. Mickey Eisenberg .................... 37

      Kelly Harris ............................ 41

      Dr. Robert O'Connor ..................... 45

      Matt McKean ............................. 48

      Richard Lazar ........................... 50

      American Red Cross Statement ............ 56

      Frank Polleothico ....................... 58

 

Philips Medical HeartStart Home, K040904:

 

      Carl Morgan ............................. 61

      David Snyder ....................... 64, 108

      Dr. Lance Becker ........................ 94

      Dr. Jeremy Ruskin ...................... 121

 

FDA Presentation:

 

      Dr. Oscar Tovar ........................ 157

 

Committee Lead Reviewer, William H. Maisel,

      M.D. ................................... 172

 

Panel Discussion ............................. 203

 

Questions to the Panel ....................... 276

 

Open Public Hearing Comments:

 

      John Gregoire .......................... 352

      Dr. Graham Nichol ...................... 355

            C O N T E N T S (Continued)

 

                                              PAGE

 

Open Public Hearing Comments (Continued):

 

      Michael Willingham ..................... 360

      Mary Newman ............................ 367

      Safe a Life Foundation Letter........... 373

      Mark Grogan Letter, dated 7/13/04 ...... 374

      Dr. Arthur L. Kellerman Letter, 7/12/04 386

      Richard Brown .......................... 383

      Jim Baum ............................... 388

      Bill McNellis .......................... 394

 

 

 


               P R O C E E D I N G S

                                       (9:04 a.m.)

      ACTING CHAIR LASKEY:  Well, good morning.  The Circulatory Systems  Devices Panel is meeting today to discuss the pre-market notification for the Philips Medical HeartStart Home, K040904.

            Ms. Wood, if you can read the conflict of interest statement, please.

            MS. WOOD:  Before I read the conflict of interest, I'd just like to clarify something on the agenda.  There will not be a vote today since this is a 510(k) device.  The vote was inadvertently left at the bottom of the agenda.  So please disregard that.

            The following announcement addresses conflict of interest issues associated with this meeting and is made a part of the record to preclude even the appearance of an impropriety.  To determine if any conflict existed, the agency reviewed the submitted agenda and all financial interests reported by the committee participants. 

            The conflict of interest statutes prohibit special government employees from  participating in matters that could affect their or their employer's financial interest.  However, the agency has determined that participation of certain members and consultants the need for whose services outweighs the potential conflict of interest involved is in the best interest of the government.

            Therefore, waivers have been granted for Drs. Mitchell Krucoff and Joseph Ornato for their interest in firms that could potentially be affected by the panel's recommendations.

            Dr. Krucoff's waiver involves consulting with a competitor on an unrelated matter for which he receives an annual fee of less than $10,001.

            Dr. Ornato's waiver involves consulting with a competitor on an unrelated matter for which he receives an annual fee of less than $10,001.

            The waivers allow these individuals to participate fully in today's deliberations.  Copies of these waivers may be obtained from the agency's Freedom of Information Office, Room 12A-15 of the Parklawn Building.

            We would like to note for the record that the agency took into consideration other matters regarding Drs. Mitchell Krucoff, William Maisel, Joseph Ornato, Richard Ringel and John Somberg.  These panelists reported past or current interests involving firms at issue, but in matters that are unrelated to today's agenda.

            The agency has determined, therefore, that these individuals may participate fully in the panel's deliberations.

            The agency also would like to note that Dr. Warren Laskey has consented to serve as Chair for the duration of this meeting.

            In the event that the discussions involve any other products or firms not already on the agenda for which an FDA participant has a financial interest.  The participant should excuse him or herself from such involvement, and the exclusion will be noted for the record.

            With respect to all other participants, we ask in the interest of fairness that all persons making statements or presentations disclose any current or previous financial involvement with any firm whose products they may wish to comment upon.

            ACTING CHAIR LASKEY:  Thanks, Geretta.

            If I can have the panel members introduce themselves beginning with Dr. Zuckerman.

            DR. ZUCKERMAN:  Bram Zuckerman, Director, FDA Division of Cardiovascular Devices.

            DR. KATO:  Norman Kato, cardiovascular surgery, private practice, Encino, California.

            DR. ORNATO:  Joe Ornato, cardiologist and emergency physician, Chairman of Emergency Medicine, Virginia Commonwealth University Medical Center, Richmond, Virginia.

            DR. RINGEL:  Richard Ringel, Division of Pediatric Cardiology, the Johns Hopkins School of Medicine.

            ACTING CHAIR LASKEY:  Warren Laskey, interventional cardiologist at Uniform Services University here in Bethesda.

            MS. WOOD:  Geretta Wood, Executive Secretary.

            DR. NORMAND:  Sharon-Lise Normand, Professor of Health Care Policy and Biostatistics, Harvard Medical School and Harvard School of Public Health.

            DR. SOMBERG:  John Somberg, Rush University, Chicago.

            DR. KRUCOFF:  Mitch Krucoff, cardiology, Duke University Medical Center and Director of the Cardiovascular Devices Unit at the Duke Clinical Research Institute, North Carolina.

            DR. MAISEL:  William Maisel, electrophysiologist at Brigham & Women's Hospital in Boston.

            MS. MOORE:  Christine Moore, consumer member.

            MR. MORTON:  Michael Morton.  I'm the industry representative and an employee of Sorin Group.

            ACTING CHAIR LASKEY:  Geretta, if you could please read the voting status statement.

            MS. WOOD:  Pursuant to the authority granted under the Medical Devices Advisory Committee charter, dated October 27, 1990 and as amended August 18th, 1999, I appoint the following individuals as voting members of the Circulatory System Devices Panel for this meeting on July 29th, 2004: 

            Warren Laskey, M.D.

            Norman S. Kato, M.D.

            John C. Somberg, M.D.

            George W.  Vetrovec, M.D.

            Joseph P. Ornato, M.D.

            Richard E. Ringel, M.D.

            For the record, these individuals are special government employees and are consultants to this panel under the Medical Devices Advisory Committee.  They have undergone the customary conflict of interest review and have reviewed the material to be considered at this meeting.

            This is signed by Daniel G. Schultz, M.D., Director, Center for Devices and Radiological Health, and dated July 23rd, 2004.

            ACTING CHAIR LASKEY:  Thanks, Geretta.

            Before we proceed with the open public session portion today, I just wanted to introduce Dr. Oscar Tovar who will give us a short presentation on adverse event reports on the AED.

            Dr. Tovar.

            DR. TOVAR:  Hi.  I would like to apologize because Ms. Beverly Gallauresi who worked with me wasn't included in the agenda, but she is the first presenter.

            MS. GALLAURESI:  Good morning.  I'll overlook that little oversight.  I won't take it personally.

            Good morning.  My name is Beverly Gallauresi.  I'm a nurse analyst in the Division of Post Market Surveillance, Office of Surveillance and Biometrics in the Center for Devices and Radiological Health.

            I'll present a brief overview of the medical device reporting system and an abbreviated summary of adverse event and product problem reports associated with automatic external defibrillators.

            The medical devices reporting, or MDR, system is a nationwide passive surveillance system which includes both mandatory and voluntary reporting.  Since 1984, manufacturers and importers have been required to submit reports to the FDA of device related deaths or serious injuries, as well as events involving device malfunction, that may cause or contribute to a death or serious injury.

            The Safe Medical Devices Act of 1990 introduced mandatory reporting or device related deaths and serious injuries by user facilities, most notably hospitals and nursing homes.  Voluntary medical device adverse event in product problem reports are most often submitted by health care practitioners, consumers, patients or family members and are received through FDA's MedWatch program.

            In general, approximately 95 percent of medical device reports received by FDA are from manufacturers, one percent from importers, and the remainder equally split between voluntary and user facility reports.

            Under the medical device reporting regulation, an adverse event is an event whereby a medical device has or may have caused or contributed to a death or serious injury.  This includes events associated with device problems or failures, as well as those events involving use error.

            The manufacturer and user device experience, or MOD, is a database that includes all voluntary AED adverse event reports received from December 1993 to the present and mandatory adverse event reports from August of 1996 to the present.

            Now we'll describe the search methodology we used to obtain the data set of automatic external defibrillator device reports. 

            All medical devices approved or cleared for marketing have a unique three-letter identified called a product code.  We searched the MOD adverse event database by product code for AED.  As I previously stated, the MOD database includes voluntary AED adverse event reports from December 1993 to the present, and mandatory adverse event reports from August 1996 to the present.

            However, for this analysis we included only mandatory manufacture reports from August 1996 through December 2003.

            Medical device adverse event reports contain information about adverse event or product problems, including where and how the event occurred, who was involved, and consequences associated with the reported event.  Reports submitted by manufacturers contain their evaluations of the adverse event, including coded conclusions drawn from  investigations.

            These numbers represent adverse event reports associated with AEDs submitted by all manufacturers for the eight-year period from August 1996 to December 2003.  As you can see, the FDA has received 7,644 manufacturer adverse event and produce problem reports associated with AEDs.  The number of death reports, 590; injury, ten; and malfunction, 7,044.

            These reports are reviewed in detail to assess signals of actual or potential device related problems.

            The MDR system, while providing signals of actual and potential device related problems, has some limitations.  Under reporting of adverse events to hospitals, manufacturers, and the FDA by health care practitioners is a well known and recognized phenomenon.  Thus, events reported to the FDA represent a subset of the total occurrence of events.

            In addition, manufacturers are not required to submit denominator information, such as the number of devices manufactured, distributed, and implanted.  Thus, due to under reporting and lack of denominator data, accurate incidence rates are unable to be determined based on these data.

            Furthermore, reports received may not be representative and reflect a variety of reporting biases.  Thus, for example, reporting may vary by manufacturer and by the presence or absence of publicity.  Because adverse event reports vary in completeness and details, causality often remains uncertain.

            Dr. Tovar will now discuss in more detail reported problems associated with AEDs based on review of mandatory manufacturer adverse event reports that have been submitted to the FDA.

            DR. TOVAR:  Thank you, Beverly, and again, please accept my apologies.

            I am Oscar Tovar.  I am a medical officer in the Office of Device Evaluation and in the Office of Surveillance and Biometrics.

            This morning I am going to present a descriptive analysis from adverse event reports on automatic external defibrillators from 1996 to 2003.  The benefits of early defibrillation in public places have been shown in numerous studies as the PAT trial (phonetic), the Chicago area airport, and the Las Vegas casinos.

            Along with this, there is a steady increase in the deployment of automatic external defibrillators.  The estimated AED growth rate for the United States was 8.2 percent for 2000 and 2001; 11.5 percent for 2002; and 22 percent for 2003.  It is estimated to be about 20 percent per year in the next five years.  This data was obtained from Cross and Sullivan.

            These are the AEDs shipped in the United States for years since 1999 to 2003 and the forecast for the next six years.  The plot shows a progressive increase in the number of AEDs shipped.

            The success of early defibrillation implies that the AED works in the first attempt and consistently in the following attempts, if necessary.  The AEDs, as any other device, are subject to failure, but an AED failure to deliver a defibrillation shock decreases significantly the probability of survival of a patient in ventricular defibrillation.  This association of device failure and survival highlights the importance of the awareness of these failures for wherever.  There is scarce information about adverse events associated with AED use.

            The goals of this study were, one, to assess adverse event reports, particularly death, associated with AED failure from 1996 to 2003; and to determine AED component failure or factors that resulted in failed defibrillation associated with death.

            For this purpose, Beverly and I review medical device reports submitted by AED manufacturers to the FDA for AED related adverse events.  The MDRs were received from August 19, 1996 to December 31st, 2003.  We analyzed the MDRs using the manufacturer and user facility device experience or MOD database from the FDA.

            Ms. Gallauresi mentioned before that the conclusions and the determination of the component failure reported by the manufacturers were grouped in categories and were used to assess the association of device and component failure with the patient death.

            I have arbitrarily separated data from 1996 to 2003 in two groups of four years each.  The early years, that's the way I call it, the first four years, from 1996 to 1999, and the recent years, from 2000 to 2003 because AED availability and technology was somehow different.

            From 1996 to 1999, we have 191 deaths associated to an AED failure.  Of course, these are the deaths that were reported.

            We have also 1,579 malfunctions and only six injuries and the category that classify things that could have fit into these previous categories as other.

            From 2000 to 2003, 399 deaths were reported related to an AED failure; 5,465 malfunctions; and four injuries.

            This view is intended to show the difference between the early years of AEDs, of AED deployment, and the four more recent years of AED deployment.  The malfunctions have increased almost three and a half times and death more than doubled.

            But we have to have an account, increasing numbers of AEDs.  The ratio of death to malfunction is about 12 percent for 1996 to 1999 and seven percent for 2000 to 2003.

            Now I am going to present the different categories per year.  The report of malfunctions increased from 105 in 1996 to 1,917 in 2003.  It is easy to associate this increase with increase of AED deployed.  Maybe better device self-agnostic.  With this I was to say that with self-diagnostic, want to imply the device detects the malfunction before use by a patient.  You're in daily, weekly or monthly self-diagnostics.  That means that it's not during the use of the patient -- on the patient, but during the self-diagnostic.

            There were very few injuries per year.  The maximums were three injuries per each year, and as you can see, there are very few per every single year during this period.

            From 1996 to 2000, there were below 70 deaths per year, but in 2001, there was an increase over 100 deaths per year and have remained about 100 deaths per year associated with the increase probably in the AED numbers of probability reporting.  There are several possibilities.

            Twenty-six manufacturers reported during this period.  The results are reported as percentages because in some instances there were multiple conclusions per report.  This is a retrospective and ‑- I'll say it again -- descriptive analysis because the absence of an accurate denominator, even if we know the number of AEDs that have been employed, it is extremely difficult to determine the number of devices used during this period. 

            That's why it is important that we take this data with caution, and I'm going to mention this again later in the presentation.

            The following slides will show the report of results of the failure analysis in the two periods of time.  These were the most frequent conclusions.

            No conclusion with 32.3 percent.  No device failure with 26.7 percent.  Device failure cause or was related to event in 22.4 percent.  Unknown if the device contributed to event in 12.2 percent.  And user error caused or contributed to event with only 4.4 percent, and device maintenance contributed to event in two percent.

            There is a little confusion, what is every single category.  For this I thought that the best way to explain it was with real examples.  I had edited the reports in an effort to remove any identifiers or note that it is not literal, and what I am going to read are event descriptions.

            For example, an example of no conclusion can be drawn and also device failure occur and was related to event.  This was the report.  Reporter alleged that while attending to the defibrillator, a patient who had been in a car accident and was in full cardiac arrest, the device delivered two shocks but then did not deliver more shocks.  The patient subsequently expired.  The report indicated the patient outcome was not a result of the reported malfunction.

            An example of device failure, this one.  Device failure directly caused event.  The reporter alleged that when attempting to defibrillate the patient believed to be in ventricular defibrillation, the defibrillator did not deliver a shock.  The defibrillator displayed an error message, and the defibrillator could not be switched on.

            An example of device failure occurred and was related to event.  The reporter alleged that medics were attempting to defibrillate a patient, but the device would not discharge.  The medics attempted to shock the patient a total of four to five times, but the device continued to not discharge.  The medics then obtained another device and defibrillated the patient.  The patient subsequently expired.

            And the last example is an example of user error caused event and device perform according to specifications and order.  The Complainant alleged that while attempting to defibrillate a patient with paddles, the user charged the device with the paddles and the paddle container and the device appropriately displayed an error message and failed to discharge.

            Second, third, fourth and fifth devices were used in an attempt to continue treating the patient with the same result.  Each device had a set of paddles previously attached.  The user did not remove the paddles from the container on any of the devices prior to charging the energy.  That's the way you read this report.

            Now I'm going to show the results from manufacturers' conclusions from 2000-2003.  The no conclusion has increased to 60 percent.  The no device failure here is 12.1 percent.  The device failure caused or was related to event in 9.6 percent, and the remaining categories add to three percent.

            This is just for final comparison between the two periods.  The major difference is where in our conclusion and in none if device contributed to event; the non-conclusion slice, as I said before, has increased from 32.3 percent to almost 60 percent.  On none if device contributed to event decreased from 27 to 15 percent.

            As I said before, what I presented were the conclusions about the events, and now I am going to present what were the components of the device that failed during those attempts.  These are the results of the failure analysis in terms of the component or the factor that failed in the case of an AED failure.

            Electrical component was the most frequent result reporting with 42 percent.  The electrical component included, for example, diodes, relays, circuit boards, switchers, capacitors, et cetera.  There are something like 21 components reported in the category of electrical component.

            Device performed according to specifications was reporting 32 percent.  Device operating outside of specifications in 4.4 percent, and mechanical problems in almost two percent.

            From 2000 to 2003, electrical component was 36.5 percent.  Other was 30 percent.  Device performed according to specifications, 21 percent.  The defibrillator subassembly is a new category here and includes, for example, pads, cables, et cetera, and the remaining categories add to five percent altogether.

            Electrical component decreased from 42 to 36 percent.  Device performed according to specification decreased from 32 to 21.1 percent.

            We have to keep in mind again that there is an increase in AED's availability.

            The AED recalls for this period are shown here per year, and as you can see, the recalls per year were between zero in 1998 to six in 2000 and 2003.

            These results suggest that the number of reported deaths associated with AED failure is actually more frequent than injuries.  The number of reported AED failure is increasing along with increase in AED reporting or deployment.

            There is a relative decrease in reported electrical component failure.  There is a relative decrease in reported device operating outside the specification, which includes use area, and increasing number of reported deaths over time associated with AEDs may have several contributing factors, including increased device availability.

            Thank you for your attention.

            ACTING CHAIR LASKEY:  Thank you very much, folks.

            Are there any questions for the presenters from the panel, questions, comments?  Several.  Good.

            Dr. Maisel.

            DR. MAISEL:  Oscar, just so I want to make sure I understand what you presented, it looked like there were about 7,600 events and about at least in the early portion of your data 25 percent or so were identified as being caused by the device.  Does that mean the total number of device related events was 7,600 divided by four or around 1,800 or 1,900 that we can conclude were due to the device?

            DR. TOVAR:  No.  It's not that you can divide it by four because that's why I presented per year.  There is a progressive increase per year.  So the devices or the malfunctions reported, including death, are increasing per year.  So injuries, malfunctions, injuries not too much, but malfunctions and death were increasing per year.

            DR. MAISEL:  Right.  What I'm trying to get at is you have reported 7,600 events, and I am trying to understand.  I understand that many of those events might be reported, but not due to device malfunction.

            DR. TOVAR:  That's correct.

            DR. MAISEL:  And it appeared that about 25 percent were due to device malfunction or that was the manufacturer's conclusion.

            DR. TOVAR:  Yeah, if I understand your question well, I said during the presentation that some of the report or some of the malfunctions were caught during the device diagnostics.  For example, it was not during the use, not during the use on a patient.  It was, as I say, during a daily diagnostics, weekly diagnostics, yearly/monthly diagnostics.  But it was not all the malfunctions were -- actually there are not too many during an actual use.

            ACTING CHAIR LASKEY:  Mitch.

            DR. KRUCOFF:  Thank you both for just sort of giving us the perspective.  I wonder if you could help me understand, given the level of illness that patients have in order to deploy this device in all the other vicissitudes of putting an MDR type of data set together, can you help us understand how you would decide or try and understand whether a patient who is fibrillating would or would not have survived if the device had functioned well, i.e., how do you conclude that the device's malfunction is associated with a death event when essentially the sudden death is the presentation?

            How the device causes a problem versus how it just fails to turn around a problem?

            DR. TOVAR:  Right.  I think we both can answer this question, but Beverly is always ready to jump.

            MS. GALLAURESI:  That's kind of the unknown.  Sometimes it's very obvious when the device completely fails and doesn't work.  I mean obviously the patient is in fibrillation and so then you don't know if the patient could have been resuscitated or not.

            I mean, is it answering your question or am I misunderstanding your question?

            DR. KRUCOFF:  Well, somewhere in there you're coming at least in some events it looks like to a conclusion that the device malfunction was somehow ‑-

            MS. GALLAURESI:  May have caused or contributed.

            DR. KRUCOFF:  Right.

            MS. GALLAURESI:  And then it's the manufacturer that evaluates the device and they report their conclusion codes, and then we have to take that information as the manufacturer reports it.  We can't really assess. 

            With these reports you can't really have cause and effect.  We can tell when a device fails, and then a patient wasn't resuscitated.  That's the information that we have.  So it's the great unknown.

            I don't know if perhaps a patient never would have been saved.

            DR. KRUCOFF:  Right.  Even if it had worked ‑-

            MS. GALLAURESI:  Even if it had worked.

            DR. KRUCOFF:  -- would they have been successfully defibrillated.

            MS. GALLAURESI:  Yes.

            DR. KRUCOFF:  That's what I find would be very -- so there are no criteria per se to understand that because I can't imagine what it would be.

            MS. GALLAURESI:  Have to look above.

            DR. TOVAR:  I would like to add to this that, yes, the manufacturer reported a death that was associated with the use of the device.  It doesn't matter the situation.  However, sometimes it's not related.  That's why I brought up an example in the car crash.  It looks like the victim was really injured, and it could have  had several, multiple causes to lead to the cardiac arrest of this patient.  The AED was used, but the patient died.  The manufacturer reported this event, but probably the cause of the death was not the ventricular defibrillation or cardiac arrest.

            DR. KRUCOFF:  Oscar, all I was trying to understand in your two pie charts over seven years, as the device failure caused or was related to event drops from 22.4 percent to 9.6 percent.  I guess what I was trying to understand is is that a difference in reporting, a difference in interpretation.  Are the devices doing better or just what?  How do you interpret that change in percentage over seven years?

            DR. TOVAR:  Right, right.  Probably we'll leave it at that unless you have a --

            DR. KRUCOFF:  No, no.  Thank you.

            DR. TOVAR:  Okay.

            DR. SOMBERG:  In the device caused the death outcome, do you have any direct data where the device fired and caused fibrillation or is most of the data the example you gave, that the device being placed on the patient did not successfully work by having a save?

            DR. TOVAR:  Yeah, that's a very good question, and that's what I was trying to remember, that I was going to comment on the previous question.

            These devices when they say directly cause is when they did not fire, when they did not shock.  At least I have seen many of these individual reports; in any single occasion I saw something that the device caused by the shock.  It caused death because it didn't fire.

            DR. SOMBERG:  I see, and is it also correct to state that from my understanding the engineering behind these is that there's a default mode and that the device has question of the arrhythmia due to motion, due to other intervening confounders?  It goes to default and does not fire as a safety component?

            DR. TOVAR:  Yes.  If the device diagnoses a non-shockable rhythm, it won't fire even if the patient has been in cardiac arrest, and if the patient has been during a long time in ventricular defibrillation, for example, it has a great or high probability to grow into a system with --

            DR. SOMBERG:  We're not finding for asystole.  We're not -- but if there's motion or other artifact --

            DR. TOVAR:  For those things, that will depend, yes.

            DR. SOMBERG:  And there's a question.  It doesn't fire to say given the benefit of the doubt the algorithm is not to fire.  So the device may have actually worked and the vicissitudes were that there was artifact and it could not identify the proper rhythm.

            DR. TOVAR:  Yeah, that's correct.

            ACTING CHAIR LASKEY:  Well, thank you both for this exhaustive effort, and I guess just to quickly sum up, you're doing the best you can with extremely limited data set.  I wouldn't say that there's a lack of a reliable denominator.  There is no denominator.  It's not that it's unreliable.

            And I think if we wanted to fill in the other three cells in a two-by-two table, we can.  You're just giving us one cell. 

            So what can we do with this?  I think it's a blip and it's something important to note, but it just underscores the importance of getting accurate statistics if we're going to make use of them.

            But we certainly appreciate and applaud your effort, and I guess on behalf of the panel we would just ask the agency to continue to seek out ways to improve the data collection so that we can get more accurate handles on these things.

            DR. TOVAR:  Thank you.

            ACTING CHAIR LASKEY:  Thank you much.

            We have a busy, busy morning, and I'd like to commence with the open public hearing, and before we proceed with the roster of speakers, I have one brief statement to read, which is that both the Food and Drug Administration and the public believe in a transparent process for information gathering and decision making. 

            To insure such transparency at the open public hearing session of the Advisory Committee meeting, FDA believes that it is important to understand the context of an individual's presentation.

            Are you timing me on this?  Is that the ‑-

            (Laughter.)

            ACTING CHAIR LASKEY:  For this reason, FDA encourages you, the open public hearing speaker, at the beginning of your written or oral statement to advise the committee of any financial relationship that you may have with the sponsor, its product and, if know, its direct competitors.

            For example, this financial information may include the sponsor's payment of your travel, lodging, or other expenses in connection with  your attendance at the meeting.

            Likewise, FDA encourages you at the beginning of your statement  to advise the committee if you do not have any such financial relationships.  If you choose not to address this issue of financial relationships at the beginning of your statement, it will not preclude you from speaking.

            With that, I would like to being the open public hearing session this morning.  Speakers, as previously forewarned, will be limited to we're now at five minutes for their presentations, and we have the little electronic  timer up here just to keep everybody honest.  As I say, we have a lengthy schedule.

            The first speaker of the morning is Dr. Mickey Eisenberg.  Dr. Eisenberg.

            DR. EISENBERG:  Thank you.

            My name is Mickey Eisenberg.  I have studied out of hospital cardiac arrest for almost 30 years as a clinician and researcher at the University of Washington.  I'm also the Medical Director of the EMS Program for King County, Washington.

            MS. WOOD:  Pull the mic up just a bit, sir.  Thank you.

            DR. EISENBERG:  As to financial disclosure, I am here on my own coin.  I have receive no salary support or honoraria from defibrillator manufacturers.  Two defibrillator companies have contributed to a University of Washington research fund which I have used in the past to support the salary of a research assistant to study out of hospital cardiac arrest.

            Let me start with a few facts.  Eighty percent of cardiac arrests occur in the home.  Defibrillation is the only effective therapy for ventricular fibrillation, or VF.  VF usually occurs with little or no warning.  Defibrillation, if delivered quickly enough, leads to a very high survival rate.  When delivered in two or three minutes from collapse, 75 percent of patients survive.  When delivered in ten minutes, survival rate falls to ten percent or less.

            And I might point out that that's the situation in most communities throughout America.

            AEDs are effective, safe.  Their operation can be readily mastered by lay persons.  We've trained several hundred seniors in the use of AEDs using only a ten-minute video.

            Patients resuscitated from VF generally make good recoveries, and the shorter the time from collapse to defibrillation, the better the neurologics outcome.

            You will undoubtedly hear in the coming few hours about the efficacy, safety, and labeling of AEDs, and rather than talk about these issues, I would prefer instead to address the issue of dissemination.

            I believe widespread dissemination of AEDs, especially in the homes of higher risk patients, offers the means to improve the current grim mortality statistics.  The question is how best to achieve this.  Do we use the current medical approach or do we use a consumer approach?

            In the medical approach, which is what we have now, physicians control dissemination.  The device is deemed potentially dangerous.  Thus, prescriptions are required.  Reimbursement by insurance companies may or may not occur.  Cost effectiveness studies demanded by insurance companies and HCFA are near impossible to do because of the ever shifting nature of indications for ICDs. 

            Manufacturer costs, sale priced to the patients remain high because of modest distribution and lack of competition.  The net effect is limited dissemination in people's homes. 

            Contrast this approach, the medical approach, to the consumer approach.  Because the device is considered safe and training is simple, it's my hope that this committee will recommend over-the-counter status.  Economies of scale will lower the cost.  Competition will increase, and the net effect will be a lower price.

            Like any consumer choice, the consumer decides whether there is adequate value for his or her money.  I suspect many older adults will consider $700 for a home AED as good an investment as optional side airbags, carbon monoxide monitors in their home, home security systems, and any other personal safety device.

            Clearly, this argument is a simplification of a very complex subject.  Nevertheless, the existing prescription based medical approach is leading to only a trickle of AEDs in the homes.  A consumer approach with over-the-counter status is, I believe, the best means to achieve widespread dissemination in people's homes, and that can only result in more lives saved.

            Thanks very much.

            ACTING CHAIR LASKEY:  Thank you, sir.

            The next speaker on our roster is Kelly Harris.  Ms. Harris.  Is there a Harris in the group?  Yes.

            MS. HARRIS:  Good morning.  I'm Kelly Harris.  I'm a sudden cardiac arrest survivor. 

            I was flown here by Philips who made the defibrillator that saved me a year a half ago.

            I don't really have anything prepared, but what I want to do is just put another face to a survivor because I  know a lot of people think that -- excuse me.  I'm very nervous, too -- I know a lot of people think that sudden cardiac arrest only happens to maybe senior people or someone who is unfit or overweight, and as you can see, I'm quite the opposite of that.

            This happened to me when I was only 27 years old.  When I went to Philips about six or seven months ago to meet their team up in Seattle, they offered me my own home defibrillator for free, which I thought was great.  It was an amazing offer.

            And as I got to talk to them I said, "Well, I'm going to be living alone soon.  I have my own implantable defibrillator.  So I don't really need it for myself, but I want it to go to my family because, you know, whatever condition I may have might be hereditary, and I would feel much safer to have it around them."

            And immediately I was told that that might not be possible, and that even for myself to get it, I would need a prescription from my cardiologist, and so that was surprising because I thought, well, I have already had my cardiac arrest.  What more proof do you need that I need one?

            So anyway, we went ahead and contacted my cardiologist, and he said that, first of all, it wasn't his top priority.  So right there that was a lag in time for me to get one, but he said, again, he was happy to do it.  He would just want to do more research first.

            So from the time I contacted him to the time my sister and her family got the defibrillator I would say it was about six or seven weeks.  And so that's a long time since sudden cardiac arrest is sudden, and it can happen at any time.  And in that seven weeks, someone could have died in that time. 

            So anyway, it ended up happening, and they have it.  It's around my family, which is all that I wanted, and I don't know.  Basically I'm just here to say that I believe it's like having maybe a fire extinguisher in your house.  You don't need one after your house burns down.  You pretty much need one before that.

            The same with this.  It's going to be too late when someone has a cardiac arrest.  That's not the time to go ahead and prescribe them or their family a defibrillator.  It should be three in one who wants one.  It can't hurt anybody because it only allows a shock if there's a shockable rhythm.  So it reads the heart rhythm.

            I couldn't put it on anyone conscious or unconscious that doesn't have a chaotic heart rhythm.  So regardless if you push the button, it's not going to do anything.  It can't hurt anybody.  So if that's the concern with liability, that doesn't exist.

            It also is helpful because it will walk you through the steps of CPR as well, and so it just speaks very clear English.  As long as you understand English and can push a button, you'll be fine.

            And last year I was flown to New York to do a video news release with Brandy Chastain, who is their spokesperson, and once that was complete, we actually attended a Girls Talker Camp, and Brandy was there to show all of the girls how to use the AED.  She went through it one time and then had a young lady do it who was probably about, I'd say, 13 years old run through it, and she did it correctly the first time on the dummy.

            So it's very easy.  It's not just for adults to use or for medical personnel.  Children can use it as well.

            So I guess that's all I have to say, and I just wanted you to know that this can happen to anybody.  It could be your child, your sister, niece, nephew, grandchild.

            So all right.  That's it.  Thank you.

            ACTING CHAIR LASKEY:  Kelly, thanks for your time.  You're becoming an excellent public speaker.  It's nice to know our soccer team has great maturity as well.

            All right.  The next speaker is Dr. O'Connor.

            DR. O'CONNOR:  Good morning.  Thank you for permitting us  this opportunity to speak.

            My name is Robert O'Connor.  I'm the President-elect of the National Association of EMS Physicians.

            The association is an organization of EMS medical directors, as well as other pre-hospital care professionals who are committed to excellence in pre-hospital care.

            Regarding financial disclosures, I'm here on my own funding.  In the past I've received indirect research support from AED manufacturers to support the salary of a research assistant.

            Sudden cardiac death is one of the major public health problems.  It has claimed as many as 350,000 lives per year.  Many sufferers of cardiac arrest can be successfully resuscitated.  This requires integration of 911 access, bystander CPR, prompt defibrillation, and pre-hospital advanced life support.  It must be integrated.  It must be accomplished in a very timely fashion.

            Since AEDs have been developed, it has made early defibrillation feasible, first, by EMS responders, fire personnel, then by nontraditional police, security guards, et cetera, and finally by the lay public, as has been recently demonstrated.

            Access to AEDs must not result in prolonged delays in activation.  So we encourage the integration of a 911 response with the use of an AED.

            Making AEDs available to non-traditional responders or minimally trained bystanders is an effective strategy for achieving early defibrillation in many communities.  Regardless of the deployment strategy, we must insure that these AED programs are integrated into the local EMS system and included in their quality assurance programs.

            Integration of AED programs into these systems is essential to insure the minimal delays take place during resuscitation.

            So in summary, we would like to speak in favor of the removal of the prescription requirement for AEDs, with the understanding that either through labeling or intrinsic properties of the device itself, that it specify training and CPR as well as AED operation to anyone who is potentially going to use the device; that the device be located in an immediately recognizable and accessible location, recognizing that if this is in the home, the occupant of the home may be the person who suffers cardiac arrest and there may be a bystander not familiar with where they keep things in the house.

            And then finally, that the requirement for integration with existing 911 systems, namely, through first and foremost 911 activation, be contained within the device as well.

            Thank you.

            ACTING CHAIR LASKEY:  Thanks much.

            I understand there's a different speaker this morning from Cardiac Science other than Kenneth Olson.  So can the representative from Cardiac Science -- thank you.

            MR. McKEAN:  Good morning.  My name is Matt McKean (phonetic), and I am the Director of Regulatory Affairs for Cardiac Science, speaking on behalf of Cardiac Science and Ken Olson.

            Of course, as an employee of Cardiac Science, they paid for my travel and my salary.

            My comments here today are I didn't know if I was going to be before or after.  So I'll adopt this accordingly.

            Based on the results of the PAD study and the clinical evidence that is now in place to support expanding the deployment of AEDs into the public domain, and since the majority of the SCA events occur in the home, granting easier access to AEDs will put more AEDs in homes and improve the survival rate of SCA victims, as has been discussed thus far.

            Should the panel recommend over-the-counter for AEDs and FDA adopts this decision, Cardiac Science is calling for FDA to implement a least burdensome approach for all AED manufacturers to use to obtain rapid 510(k) clearance of qualified devices.  This least burdensome approach could come in two forms or perhaps others, but two that come to mind are issuing a guidance document within 30 days to stakeholders including industry and FDA reviewers that allows simple modification of labeling to remove the on the order of physician or prescription requirement language from the IFU as a simple notification submission to FDA.

            An alternative approach would be for the use of a 30-day special 510(k) vehicle currently in place to modify the labeling and present that to FDA.

            Also, regarding classification of the device, currently classified as a Class III, FDA should consider down classifying the AED to a Class 2 for the following reasons.  AEDs are cleared under the 510(k0 regulatory framework and do not require PMA application.  Clinical studies have been conducted and published to support the safety and efficacy of AEDs when used within labeling.

            And, second, in the event of AEDs become over-the-counter approved, the integrity of the regulatory classification scheme for Class 3 devices would be compromises or, i.e., contraindicated.

            So those are my two comments that I'd like to present both to the panel and to FDA.

            ACTING CHAIR LASKEY:  Thank you.

            Next up is Richard Lazar.

            MR. LAZAR:  Good morning.  My name is Richard Lazar.  I'm the CEO of the early defibrillation Law and Policy Center, which should tell you I'm a recovering lawyer. 

            I am here on my own dime and on behalf of EDLPC.  I am not here at the request of or on the dime of any of the manufacturers.  In the interest of disclosure, I have in the past done consulting work for two of the major manufacturers and occasionally I'm invited to speak at conferences sponsored by manufacturers.

            I have provided the panel with written submission which goes into some detail in terms of my views of the current prescription model and how it operates in the real world of public access defibrillation, and I won't reiterate those comments here.  It does go into the whole issue of supervision under the direction of a practitioner and adequate indications for use.

            My comments this morning are directed really and admittedly at a high level on the issue of public health policy, and here's what I think we know in that regard.

            We know that SCA strikes somewhere between 250,000 and 450,000 people annually in the United States.  We know that most of those events occur in public places or the home.  We know that the frequency of sudden cardiac arrest in particular venues is unpredictable and perhaps unknowable.  We know that most SCA events are caused by ventricular fibrillation. 

            We know that currently the survival rates for sudden cardiac arrest are somewhere on the order of five percent on an annualized basis -- I'm sorry -- on a nationalized basis, and what that means in real terms is somewhere between 240,000 and 430,000 people die from this condition, and only about 12,500 to 22,500 survive.

            We know that rapid defibrillation with AEDs is a safe and effective therapy capable of successfully treating VF induced SCA.  We know that based on the current design and usability  characteristics of AEDs that the devices are being promptly and properly used by both trained and untrained users in a variety of venues.  We know those things.

            The conclusion that I draw from those facts is that widespread deployment of AEDs us a public health solution that will, indeed save thousands of lives because AED coverage areas in terms of geography is limited, that is, how long it takes someone to retrieve and use the device.

            We know that really the solution is to have AEDs deployed throughout places of daily life.  We know those things to be true.  At least I believe them to be true.

            With regard to the prescription model, which is really the issue before the panel this morning, the prescription requirement currently in place today adds an unnecessary layer to the purchasing process for those that want to buy and deploy AEDs, and it creates a perception that AEDs are difficult to use and are not designed for use by lay people, when in fact the data suggests otherwise.

            The perceived benefits of the prescription model which we derive from sort of the drug prescription relationship between a physician and a patient doesn't transfer well to the public access defibrillation environment, and reasons are described in my written submission, but basically a drug  prescription model is a one on one relationship whereas an AED prescription model really involves the doctor and three potential persons, the buyer, the user, and the patient with regard to the AED.

            So the notion of a consultative or instructive interaction between a physician and a patient doesn't occur in the public access model nor, frankly, could it based on how the system works, and the notion of shared information between a physician and a patient about risks and benefits in those sorts of things can't take place.

            So, again, my judgment the prescription model simply doesn't transfer well to public access  defibrillation.

            Finally, from a public health perspective, the question I pose to myself is what would change if over-the-counter status were granted for AEDs?  It would be easier for people and organizations and corporations to buy and deploy AEDs.  It would create a perception in the mind of potential purchasers that AEDs are, in fact, easy to use and intended for use by lay people

            From a risk standpoint, which is certainly an FDA mandate, would more people die from sudden cardiac arrest?  The answer, of course is no.  Most people are dying already.

            Would more people survive who suffer sudden cardiac arrest?  And I think the answer from the data we have today is absolutely yes.

            So unlike drug interactions and issues relating to the taking of drugs, the issue with sudden cardiac arrest is very binary from a public health perspective.  People either live or people die, and the only variable that we can impact here  is the promptness with which defibrillation occurs, and that means to continue this effort we have already undertaken over the last decade, for the first time in the health care system industry, continuing to put these therapeutic medical devices in the hands of lay people.

            And by the way, just a final note not related to anything else, this is a policy change that wouldn't cost the government any money.  People who buy and deploy AEDs pay for them themselves.  Whether the insurance industry ultimately does will remain to be seen, but by and large this is not a government funded effort.

            So that's the conclusion of my comments.  I'm happy to take any questions the panel might have.

            ACTING CHAIR LASKEY:  Thank you.

            MR. LAZAR:  Thank you.

            ACTING CHAIR LASKEY:  And our last scheduled speaker is Dr. Gordon from the Red Cross.

            MS. WOOD:  Actually Dr. Gordon submitted a statement to be read into the record.

            This is the American Red Cross position statement regarding over-the-counter automated external defibrillators.

            "Sudden cardiac arrest can happen any time and anywhere, and it claims the lives of more than 680 Americans each day.  The American Red Cross believes that this is a tragedy that can and should be prevented.  We believe the introduction of an over-the-counter AED would be a positive step toward insuring that properly trained citizens are better able to respond to an unexpected cardiac emergency event.

            "The Red Cross continues to champion community access to defibrillation as part of an ongoing commitment to save more lives.  As a supporter of public access to defibrillation since 1998, the organizations vision is to have at least one person in every household trained in life saving first aid, CPR, and AED use.

            "Because the Red Cross reaches over five million people annually with our first aid, CPR, and AED programs, we know that the availability of a properly trained person and an AED is key to providing the best care to a cardiac arrest victim until emergency medical personnel arrive.

            "The Red Cross currently provides defibrillation information in all CPR courses and encourages the public to make defibrillation a part of their emergency preparedness plans at home, at school, at work, and at other public places.  The inclusion of defibrillation in preparedness plans and greater access to AEDs can enhance preparedness efforts, help reduce the public's vulnerability and enable citizens to respond to cardiac emergencies.

            "The American Red Cross mission is to help people prevent, prepare for, and respond to emergencies.  We believe that removing barriers to public access to AEDs and training more people could result in more of the American public responding to an unexpected cardiac event.  If the removal of this barrier results in even a five percent decrease in the number of lives lost each year, this positive step would result in approximately 25,000 lives saved annually. 

            "Please join the American Red Cross in helping citizens save more lives."

            ACTING CHAIR LASKEY:  Thanks Geretta.

            Is there anyone else who wishes to address the panel today on the topic?

            If not, then -- yes, sir.

            MR. POLLEOTHICO:  Good morning.  My name is Frank Polleothico (phonetic).  I'm a registered nurse.  I'm the executive director of the AED Instructor Foundation.  We are a 501(c)(3) nonprofit corporation funded manufactured AEDs and also funded by programs that we conduct.

            I'm here to speak on behalf of the recommendation to remove prescription, and we fully support that.  However, I want to emphasize the fact that AEDs, despite all of the wonderful things we've heard this morning, and I fully believe, do not save lives.  AED programs save lives, and AEDs that are not instituted, AED programs that are not implemented and are not part of an on-site emergency preparedness plan, that involve training and leadership and guidance and some oversight, not needlessly bureaucratic, but within the context of an on-site program, be it in a home or a small business, are not going to work.

            There were 15 million people trained in CPR in this country.  Yet paramedics and EMTs report that less than five percent of the time that they respond to a cardiac arrest emergency is somebody doing CPR.  We must not just give people AEDs.  We must do it in the context of them being prepared to use them.

            The growing number of horror stories of AEDs being on site and not utilized scares me.  I just heard of another one last night.  I probably hear about two a week.

            So clearly AEDs are marvelous.  I have personally used them.  I've used them successfully, and I've used them where the patient didn't survive, and I know the benefit they provide.  In my experience as an emergency nurse and as a paramedic, as the former Director of EMS for the City of New York, I can only speak to the missing link that AEDs help to fill in the wonderful system of emergency medical services that has been developed in this country in the last 30 years.

            But AEDs must be operated in context, and while I think the prescription does nothing to help that, and as I agree with all of the speakers so far, I won't even reiterate that; the prescription does nothing to help the AED program issue.

            However, guidance and control, involvement directly from the EMS system is essential or AEDs will not fulfill the promise of reducing the tens of thousands of needless premature deaths that occur in this country every year.

            I thank you.

            ACTING CHAIR LASKEY:  Thank you.

            All right.  Last call.  Does anybody else wish to come forth this morning?

            If not, then I will close the open public hearing portion and would like to proceed with the sponsor's presentation, and if I could just have Geretta.

            MS. WOOD:  I would just like to remind the speakers to introduce yourself and state your relationship to the company and any other conflict of interest you might have.

            MR. MORGAN:  Can we have about 60 seconds to set up a demonstration?

            MS. WOOD:  Sure.

            MR. MORGAN:  All right.  Good morning.  I'm Carl Morgan, one of the founders of HeartScreen, which is now a part of Philips Medical Systems.  I'm an employee of that organization.

            As you've heard, we are here today because we propose to remove the prescription requirement for the Philips HeartStart home defibrillator.  The prescription requirement reads as follows on our device:  "caution.  Federal law restricts this device to sale by or on the order of a physician."

            Our organization was formed 12 years ago to prevent hundreds of thousands of unnecessary deaths due to sudden cardiac arrest.  We believe that our focus during that entire 12 years has been towards providing small, easy to use, automatic external defibrillators specifically designed for people that do not have defibrillation in their job description, that is, AEDs that can be used by virtually anyone to help save a life in a moment of need.

            A lot has gone on in this 12 years, but I think of note this morning is that for the last five years our organization has been in discussion with FDA on removing the prescription requirement from defibrillators.

            In November 2002, we launched the HeartStart Home Defibrillator, which we believe is an idea design for prescription removal.  We filed our 510(k) in 2004, and we're here today to present.

            During our discussions with FDA, we found that the law requires that medical device labeling must bear adequate directions for use.  FDA regulations further define that to mean directions under which the layman can use a device safely and for the purposes for which it's intended.

            In addition, certain devices, including historic defibrillators, must bear this prescription caution, and this comes under the conditions if a device is not safe, except under the supervision of a practitioner licensed by law to direct the use of such a device, and because of that perceived lack of safety, adequate directions for use cannot be prepared.

            This description suggests a basis for removing the prescription requirement for the HeartStart Home Defibrillator.  That is, today we hope to demonstrate for you that the technology has an established history of safe use.

            Further, we hope to demonstrate for you that the Heart Start Home Defibrillator can be used safely and for its intended purpose based upon its labeling alone.

            Your presenters today include David Snyder, our Director of Research at Philips Medical Systems in Seattle; Dr. Lance Becker, a noted resuscitation researcher, Professor of Medicine and Director of the Emergency Resuscitation Center at the University of Chicago.

            Dr. Becker will present the results of some of our studies and provide some perspective on the need for early defibrillation.

            Dr. Jeremy Ruskin, a noted researcher in the management of cardiac arrhythmias.  Dr. Ruskin is the founder and Director of the Cardiac Arrhythmia Service and Clinical Electrophysiology Laboratory at Massachusetts General Hospital.  Dr. Ruskin will provide today some clinical perspective on the management of sudden death by providing early defibrillation capability.

            I'd now like to introduce David Snyder, our Director of Research at Philips Medical Systems in Seattle.

            DR. SNYDER:  Thank you, Mr. Morgan.

            Good morning, members of the panel, Food and Drug Administration, the public.  It is, indeed, a pleasure to be speaking to you today. 

            I will be speaking to you twice.  First I'll be introducing you to the product, and then later I'll be standing before the podium to present some study results to you.

            With that I'd like to proceed to an introduction to the product.  As you've seen a picture, this is the Philips HeartStart Home Defibrillator.  It did receive clearance from the Food and Drug Administration in November of 2002 specifically for use in the home by lay responders.

            The indications for use of this product are for application to an unresponsive or not breathing victim or not breathing normally victim, and I want to draw particular attention to the second indication, which is "if in doubt, apply pads."  These indications were designed to prevent the necessity for adequate assessment skills on the part of the responder in case of a sudden cardiac arrest.  It is not essential for proper use of this product for a person to be able to properly assess whether a patient is in cardiac arrest.  Again, if in doubt, apply the device.

            The safety and effectiveness of the technologies employed in this product have been established over a long history of AED products, and I'll give you some more background on that in a few minutes.

            But at this point, I would like to do a demonstration for you.  The operation of the device is very simple.  Activate it by pulling the handle.  Place the pads per voice instructions, and press the shock button.

            I do want to say you just got an inadvertent demonstration of one of the product's features.  The beeping was because we have practice pads installed in this device.  After a certain amount of time with practice pads, which cannot deliver therapy, the device will start alerting you telling you that it's not ready for use.  So it was not happy being not ready for use.

            Okay.  This is the HeartStart Home Defibrillator in its case.  The first thing I want to draw your attention to is it does have a first aid reminder to activate EMS.  We recognize that rapid defibrillation is only one element in the important chain of survival in order to assure survival from sudden cardiac arrest.  So "call 911" is right on the front.

            We also recommend placement in a visible place adjacent to a telephone so that can be done properly.

            There's also a place as you put the device in service to add your own address information.  One of the comments that was made this morning is correct.  If you have an arrest in your home, it may not be one of the family members that is called upon to respond to the emergency and use the device.  It may be a visitor to your home, and they not even know your address.  So that information is right on the front with the EMS reminder card.

            When you open the device, you're presented with a pair of scissors for cutting away clothing, a quick reference card that can be used, and the device itself.  What I'm going to do now is walk through a mock cardiac arrest scenario with our manikin here so that you can understand and see how the voice prompts interact with the user.

            So you begin, and again, these are practice pads.  It's a safe device.  It can't deliver therapy.  You begin by activating the device.

            (The following is a transcript of the recording played by the defibrillator while being demonstrated.)

            DEFIBRILLATOR:  Begin by removing all clothing from the patient's chest.  Cut clothing if needed.  When patient's chest is there, remove protective cover and take out white adhesive pads.  Look carefully at the pictures on the white adhesive pads.  Peel one pad from the yellow plastic liner.  Place pad exactly as shown in the picture.  Press firmly to patient's bare skin.

            When the first pad is in place, look carefully at the picture on the second pad.  Peel the second pad from the yellow plastic line.  Place pad exactly as shown in the picture.  Press firmly to -- no one should touch the patient.

            Analyzing.

            No one should touch the patient.

            Analyzing.

            Shock advised.  Stay clear of patient.  Press the flashing orange button now.  Shock delivered.  No one should touch the patient. 

            Analyzing.

            Shock not advised.   Be sure emergency medical services have been called.  It is safe to touch the patient.  Check airway.  Check breathing.  Check circulation.  If needed, begin CPR.  For help with CPR, press the flashing blue button.

            Pinch nose, tilt head, and give two full breaths.  Breathe.  Breathe.  Place the heel of one hand in the center of the check between the nipples.  Place your other hand on top of the first.  Push the chest down firmly two inches.  Keep time with the beat.

            Pinch nose, tilt head, and give to full breaths.  Breathe.  Breathe.  Continue with compressions.

            Pinch nose, tilt head --

            (End of defibrillator audio demonstration.)

            DR. SNYDER:  And that's really all there is to it.

            I would like to draw your attention to a few aspects of the scenario you just saw.  First is that there was as second level of EMS reminder.  The first level again is labeling right on the exterior of the device to activate EMS.  Should for any reason that not happen, there is a second vocal reminder after first shocks are delivered.  Make sure emergency medical services have been activated.

            The second thing I want to mention is that once you complete your initial sequence of CPR, you are instructed to stop CPR, at which time a reanalysis of the heart is performed.  If shocks are indicated, you're given the same guidance on delivering shocks.  If not, you proceed directly to the opportunity to get CPR coaching again.  If you're firm in your CPR skills, you can elect not to get the voice prompts and just proceed without the prompts.

            These CPR prompts are intended to reinforce.  They're not intended to teach CPR.  We found that was impractical to do, but we also found that even people who have had regular CPR training don't remember the protocols well.  They don't remember placement of hands.  They don't remember depth of compression.  They don't remember how many compressions, how many ventilations.  So the voice coaching is really designed to reinforce those skills.

            Another thing you may have noticed was the pacing of the prompts was very methodical.  It was not rapid.  We also found in user testing, which we'll be talking a little bit later about, that if you got ahead of certain responders, not everybody responds at the same rate, but if you got ahead of people and issued instruction before they had completed the previous task, they tended to completely fail.  That is, if we went too fast, we could get a little bit faster for shock, but a certain percentage of people couldn't do it at all.  So the pacing is very methodical to insure that the vast majority of people are able to complete these tasks successfully.

            Now, should you be secure in your skills, you know what you're doing.  You move quickly.  The prompts will actually catch up with you.  The device will detect where you are and the stage of applying these pads and delivering a shock and jump forward to catch up with you.

            And I want to give you another demonstration right now so that you can see how that works.  What I'd like you to pay attention to this time, you heard a lot of very detailed prompts.  Now, this time we're going to go much more quickly, and you'll see that all of those detailed prompts do not appear in this scenario because I'm completing tasks.

            I'm also going to apply the device to myself.  This is now a live defibrillator, and if it detects V up (phonetic), it will deliver a shock.  I'm doing this to demonstrate my confidence in the specificity of this product, and I'm going to apply it, lead two.  It's not a good defibrillation vector, but it is a representative vector for the ECG that's observed by a defibrillator

            DEFIBRILLATOR:  Begin by removing all clothing from the patient's chest.  Cut the -- place pad exactly as shown in the picture.  Press pads firmly to patient's bare skin.  No one should touch the patient.

            DR. SNYDER:  Okay.  I can press this button as many times --

            DEFIBRILLATOR:  Analyzing.

            DR. SNYDER:  -- as I want.  It's not going to deliver a shock.

            DEFIBRILLATOR:  No one should touch the patient

            Shock not advised.

            DR. SNYDER:  I'll press the button again.  No shocks.

            DEFIBRILLATOR:  -- emergency medical services --

            DR. SNYDER:  It simply will not do it.

            DEFIBRILLATOR: -- have been called.  It is safe to touch the patient.

            DR. SNYDER:  So that's a quick run-through of how the product works.  You can see that for people not secure in their skills it gives them very detailed instructions.  I'll talk about how we derived those instructions a little bit later in the presentation.

            If you're secure in your skills from your AED training, you can proceed very rapidly.

            So with that introduction, I'd like to now mention a concept which one of the introductory speakers this morning actually talked about, and that is the notion of a defibrillator as a piece of safety equipment as opposed to a piece of medical equipment prescribed for a particular patient at risk.  And this product was specifically designed as a piece of safety equipment. 

            In fact, the labeling in our pre-sales materials on the outside of the retail box and in the owner's manual contains the statement in the first bullet, which is:  "if you have concerns about your health or an existing medical condition, talk to your doctor.  A defibrillator is not a replacement for seeking medical care."

            Again, this device is designed as safety equipment.  It's to address this problem of the large cohort of patients for whom symptoms have simply not presented, and they are not a part of the medical system at elevated risk for sudden cardiac arrest.

            This is a product designed because we don't know who might need it or when.  It's equipment that's intended to be used perhaps once in a lifetime.  Best case is it will never be used, but perhaps once or twice in a lifetime, and because of this use model, we have identified some characteristics that are important to this kind of product.

            First of all, it must be safe for any user.  The second is it absolutely has to be ready to use when needed.  Mostly it's going to sit on a shelf and gather dust, but the device has to be able to assure its readiness when the emergency occurs.

            And finally, it has to be very easy to use in the moment.  We're not talking about EMTs that do this several times a year.  These are people, again, who may do this once in a lifetime.

            Now, we're going to be presenting you some data on the reliability and safety history of these products, a point I need to establish right at the beginning, is that the HeartStart Home Defibrillator, which is shown in the upper right of this slide, has core technologies that are actually common to all of the defibrillators that Philips Medical Systems has produced.

            The ForeRunner defibrillator was introduced in 1996.  That was followed by the FR-2 in 2000,  and the HeartStart Home Defibrillator in 2002.

            The ECG analysis system you just saw demonstrated is common to all of these.  There has been no change in what we call the life threatening arrythmia detector across this base.  So any results derived from uses of the earlier devices are also applicable to the HeartStart Home.

            You also heard mention in Dr. Tovar's presentation -- I think it was actually the Q&A -- about ECG validity measures, the ability to detect artifact within the ECG.  That is, signals that are introduced mechanically or electrically that are not of cardiac origin, and this is a key aspect of safety in these products.  It's essential that the device understand whether it's truly analyzing cardiac signal or artifacts, and we do have an ECG validity system that, again, is common across all three of these products and has been very effective, and with the advent of the HeartStart Home, we have actually reinforced this capability with a second way to determine whether artifact is present.

            Now, this is not a feature that's common to all defibrillators.  Some have similar capabilities and some have no capability in this regard.

            The therapy that's delivered by this device is a 150 Joule impedance compensating biphasic waveform.  Again, it's common across the entire product line.

            For the FR-2, we introduced pediatric attenuation capability or pediatric treatment capability, the ability to deliver 50 Joules for a pediatric patient, and this technology has also been taken forward to the HeartStart Home Defibrillator.

            And finally, key pieces of the user interface, the core interface, that is, pieces that measure things like pad connection, adequacy of pad connection, various pieces of safety prompting and the general protocol management technologies are common across all three of these products.

            Now, there is a distinct difference between the earlier products and the HeartStart Home in that the earlier products in the bottom left hand of the slide had ECG displays as well as manual override capability should a trained medical professional have a disagreement with the advisory system.

            These were deemed inappropriate for a lay market because of no training in ECG interpretation, and they were removed specifically because of the lay use model, and that feature has actually been replaced by enhanced prompting on proper pads placement which I also demonstrated for you.  This was an area that we found that lay responders had a great deal of difficulty with.

            And we have also added the CPR coaching, again, to reinforce skills that have already been obtained.

            So the sensitivity and specificity of the ECG analysis system is due to a fairly sophisticated design.  We actually take multiple looks at the ECG.  the first is rapidity of the signal conduction.  It's really a mathematical measure of the electrical health of the myocardium.  We also look at the amplitude of the ECG; a measure that we call stability, which is the repeatability of the morphology of the ECG complexes.

            Normal sinus rhythms and organized rhythms are highly repeatable.  VF is very unrepeatable, and it's a strong predictor.  We also look at heart rate.  Now, the important point of this slide is that no single one of these indicators is capable of making the machine advise a shock.  It actually takes the concurrence of all four of these measures before the machine will advise a shock.

            I'd like to demonstrate the sensitivity and specificity of this algorithm by presenting a few studies that have been published.  The first bullet was the post market study that Philips undertook with the introduction of the biphasic wave form into the marketplace.  This was done with our first generation, AED, the ForeRunner, and we reported on the first 100 consecutive applications to VF patients.  This involved a total cohort of 286 out of hospital patients.  That is, 186 were in nontreatable rhythms.

            And in this study, the authors reported 100 percent sensitivity to treatable rhythms and 100 percent specificity to rhythms that should not receive a shock.

            The second study I would like to draw your attention to was published by American Airlines in the New England Journal of Medicine.  They reported on, again, our first generation AED, the ForeRunner, which they had equipped their airplane fleet with and flight attendants to use.  They reported on the first 200 consecutive uses of this product, 15 VF patients in all.  These were applications both in flight and in terminal.  In some cases the device was retrieved from the airplane to treat a sudden cardiac arrest in terminal.

            In particular, I want to draw your attention to the specificity number here.  Again, it's 100 percent specificity to these 185 applications in untreatable rhythms, 100 percent sensitivity to the VF patients.

            This device was often used as a cardiac monitor in flight.  If there was a physician in attendance that wanted to look at the cardiac rhythm, the airline did apply the device as a monitor so that the physician could watch the ECG screen.

            Now, the authors didn't specifically report on the amount of time spent in doing cardiac monitoring, but our shock advisory system, our arrythmia detector, is active throughout monitoring.  That is, we are continuously looking.  So by a very conservative estimate we're guessing that at least tens of thousands of analyses were performed on these patients in nonlethal arrhythmias without a single false positive advisory.

            Now, I do want to tell you that we know of one inappropriate shock that has been delivered by these devices.  It was a case of successful defibrillation.  The patient presented in a course VF.  It was recognized.  The device was charged.  VF was terminated, and the resulting rhythm following shock was actually low amplitude atrial fibrillation with no ventricular activity.  It was truly indistinguishable from ECG alone from a very fine VF.  The device did analyze that, recommend and deliver a shock based on this atrial fibrillation with no ventricular activity, but there was no negative outcome.  The patient survived neurologically intact.

            Now, I want to present you with some use estimates, and I'm going to put a big caveat on this.  In fact, I'm going to jump to the bottom bullet first.  These projections are based on a non-random sampling based on ForeRunner and some FR-2 AEDs.  As devices are returned to us for service, they have an internal memory that we're able to examine to see how many times the device has been used, how many shocks have been delivered, and so forth, and from these we have been able to extrapolate out to our installed base of over 150,000 AEDs since 1996, and actually this is over 170,000 today.

            And what the data tells us is that probably greater than one million total applications to patients have been performed with this line of defibrillators, and of those, approximately 200,000 patients required shocks, and approximately 800,000 patients did not require shocks.

            So when you consider that one inappropriate known shock, it has to be considered in the context of approximately a million patient applications.

            I also want to report that we have seen six confirmed AED emergency use failures across this installed basis and over a million applications.  Four of those had no patient impact.  One, the patient impact was indeterminate, and in one case there was possible patient impact.  This was actually an event that occurred subsequent to our filing in the 510(k) for this product, and it has been filed as an MDR.

            During all of this experience since 1996, we have had no complaints about the effectiveness of the biphasic therapy.

            Now, you heard a lot about MDRs, medical device reports, this morning.  So we have summarized the top three causes of MDRs from this line of products, and I want to reinforce the fact that in spite of the large number, 7,000 MDRs, over 7,000 MDRs, over the time period that these products have been on the market, Forst & Sullivan 2003 estimated that Philips Medical Systems has about in excess of 40 percent of the U.S. AED market, and in spite of that 40 percent market share, we are responsible for fewer than one percent of the filed MDRs during that period.

            This is a summary of our first top three causes of MDRs.  The first is a failure of the voice prompting system due to a speaker failure.  Basically one of the wires to the speaker can break, in which the device does not present voice prompts.

            There was no patient involvement in any of these cases, and we filed 35 MDRs on this particular failure.

            The next most frequent cause has been poor patient pads connection.  We have filed 11 MDRs on this subject.  Patient impact in these cases has been indeterminate, and we suspect pads damaged as the root cause of this problem, although we've been unable to confirm because pads are one of the first things that's discarded after execution of a code, and we have been unsuccessful by and large at retrieving these pads following failure.

            But, again, you must put the  11 failures in the context of an estimated one million patient applications.

            And the third most frequent cause of MDRs has to do with algorithm sensitivity.  Patient impact in this case was indeterminate.  These were basically very long down time, low amplitude, low rate VF, right on the borderline of being classified as an asystole.  So patient impact is truly indeterminate in this case.  The ECGs simply did not meet the rate criteria of our algorithm.  It was not a product malfunction

            Now, this slide illustrates steps we have taken in the HeartStart Home Defibrillator, which you are considering today.  We use our MDRs as a learning experience, ways to improve our products and to address issues that we see through the MDR reporting system.

            So I've taken these same three top issues from the ForeRunner in FR-2 experience and show you the actions that we have taken in the design of the HeartStart Home Defibrillator.

            The first problem is no voice prompts.  Now, that's mitigated in the ForeRunner  and the FR-2 because there are instructions written on a screen.  Because there is no screen here, we have been able to develop a speaker self-test.  So as part of the self-test, which you heard a little bit about this morning; you'll hear more in the remainder of the presentation, once a week we turn the device on, and it's able to determine whether the speaker is functional or not.

            With regard to the second issue, the poor patient pads connection, sometimes this is due to skin condition of the patient, but it may also be attributable to pads.  So in the HeartStart Home Defibrillator, we've enclosed the pads in a rigid plastic container, but more importantly, we now have a pad self-test.  Every 24 hours the device powers on.  It checks for electrical continuity and presence of the pads, but it is also able to do an electrical determination of the condition of the electrogel, the adhesive aspect of the pads, to determine if any drying has happened.

            And if the pads get to a state, before they get to a state actually, where they wouldn't be usable for defibrillation, we can alert the owner of the product that the pads are drying out.  They need to be replaced.  They call customer service and get information on how to replace the cartridge.

            I want to move on now to reliability.  We have made a great effort to improve the reliability of these products because basic design and fundamental product reliability is really essential to safe use and lack of failures, and for context, we've presented data on first year, all causes failure rates for three different products.

            The first is code master manual defibrillator, which those of you in EMS and hospitals may be familiar with.  It was introduced in 1991, and during the first year of service of that product we experienced a seven percent all causes failure rate.

            Now, these aren't emergency use failures.  These are failures from all causes.

            With the introduction of the ForeRunner AED in 1996, we were able to improve that first year all causes failure rate by nearly an order of magnitude to 1.3 percent of devices shipped, and with the advent of the HS-1 -- and I want to mention what the HS-1 is for just a moment -- we're considering the HeartStart Home Defibrillator. 

            It also has a sister product which is identical.  AED is the same product, but the labeling and accessories provided with it are really adapted to a commercial market to a corporate market.

            So from a standpoint of the use of the product, reliability of the product, the functioning of the product, they're identical.  So for some of this data, we've put statistics from both of these products together and they're identified as the HS-1.

            So over that entire installed base, the first year annualized failure rate of the HS-1 class of products was again reduced by an order of magnitude to .04 percent all causes failure.  That's one failure out of 2,500 devices shipped in the first year.

            I want to go into some more detail now about the self-test.  This is a diagram that shows you the testing that we do.  It's done on daily, weekly, and monthly basis.

            On a daily basis we power up the device.  It checks for the readiness and condition of the pads to make sure the electrogel is suitable for use.  It also checks the functioning of the two computers that are included in the device.  It checks all of the circuitry, references.  You no longer have to calibrate this device.  It has internal references, and it checks for functionality of the therapy circuitry.

            On a weekly basis we do all of those tests.  Plus we add a full calibration of the ECG front end and a test of the audio system to make sure that the speaker is functional.

            On a monthly basis, again, we do all of those.  Plus we add a full high voltage charge of the defibrillator capacitor and discharge of 150 Joules into an internal load that's contained in the device.  You do not have to attach an external load.

            So on a monthly basis, absolutely everything in this box is tested, and we have a very comprehensive test that's performed on a daily basis.

            Now, I mentioned our design process of learning from simulated use, and up here I've identified some problems.  The way we do this is we take our best cut at what's a good product.  What's going to interact well with the user?

            And then we go out and we seek volunteers, and we have primarily sought untrained volunteers in environments such as shopping malls and senior citizens centers.  And we'll provide them with this product and a manikin and ask them if they could try to save the manikin, and we watch how they interact with the device.  We see where people succeed well.  We see where they have difficulties, and where they have difficulties, we take the device design back.  We come up with new ideas.  We implement them.  Then we go back out and we do it over again, and we continue with this iterative process until we've satisfied ourselves that all of the common issues are addressed.

            Five of them are listed here.  I'm only going to discuss two of them because they're of key importance.  The first is that lay responders don't understand electricity or defibrillation, and a lot of the examples they see on television are not very appropriate for actual use.  And we found that if people aren't given explicit instructions, they will do things that are really nonsensical from a defibrillation standpoint.

            A common mistake is to put pads on top of clothing.  As you saw in the demonstration, what we've done is two things.  We've added emergency scissors, and we've added an explicit voice instruction to begin by removing all clothing from the patient's chest, cut clothing if needed.

            Now, the scissors and the cut clothing as needed is another cue that time is of the essence here.  You don't have to unbutton the shirt.  Destroying clothing is fine.  We give you permission to do it, and we give you the tool to do it with.

            The second problem we identified that I want to highlight is poor pad positioning.  There's a lot of research being published even today.  There were two more just this month published.

            On the problem of properly positioning the defibrillation pads not only among lay users, but among medical professionals, it's a very challenging things for people that don't understand what needs to be done.

            Because of that, we've added explicit graphics on the pad.  You saw those when I was holding the pads up.  They show proper placement.  But we also found beyond that, to get people to pay attention to the graphics, we had to add a voice prompt that said look carefully at the picture and place it exactly as shown.

            By taking these kind of steps, we've been able to achieve a very high success rate in the ability of lay responders to apply this product to a patient and successfully deliver defibrillation shock, and you'll see some study data on that in just a few minutes.

            Just a little bit more about the product that's being considered.  Most of what you're going to see and hear about today is the device itself, what you saw on the table, what you saw me holding and demonstrating.  There's actually much more to the total product than just that box.

            In particular, I want to draw attention to the purchase aspect of the ownership life cycle for this product.  We have specific information on the problem of sudden cardiac arrest, what a defibrillator does, et cetera, et cetera.  It's contained in the product packaging itself.  It's also available in pre-sales materials.

            We maintain a product Web site that also has resources and links to resuscitation organizations and frequently asked questions. 

            We also have the customer service available that can provide product information, training resources, and in particular, if you purchase the product we offer grief counseling following use, and we also offer throughout this life cycle access to physicians should you have a question you would like to address to a physician.

            Another aspect of the product that may not be obvious has to do with set-up and maintenance, and that is there are voice prompts in this device that were not demonstrated that help you actually set the device up.  When you install the battery, it tells you it's not ready for use.  Install the pads cartridge.  If you remove the cartridge, it will tell you to reinsert it.  It wants to be ready for use, and it's very unhappy if it's not ready for use, and it will start giving you instructions and warnings to make sure that it is ready for use.

            This also is important in case of any failure that may be detected by the self-test.  Again, the device will start chirping, and that blue information button that I used for CPR information will start flashing.  If you press the button, it will give you information on what needs to be corrected.  You can contact Philips customer service and get help in correcting the issue.

            So that wraps up my introduction to the HeartStart Home Defibrillator.  Again, it was designed specifically as safety equipment, really a paradigm shift in the way we're using these products.

            The technology is using the device that has a history of safety and readiness, and it was specifically designed for ease of use in the hands of the lay responder.

            With that I'd like to introduce Dr. Lance Becker, Professor of Medicine, University of Chicago.

            DR. BECKER:  Thank you very much.

            My name is Lance Becker.  I'd like to thank the panel and the public for coming.  This is quite a honor to be here.

            I'd like to disclose that I'm a paid consultant to Philips this morning.  In addition, I have no equity or stock in that company nor any of the other manufacturers.

            I have been a consultant to several of the other defibrillator manufacturers over the years.  I have intellectual property, some patents in resuscitation that involve cooling induction, and I compete for grants for the University of Chicago.

            In my real life, I'm an emergency medicine doctor on the South Side of Chicago, and I have studied cardiac resuscitation for many years.  It's my pleasure to do a clinical overview of the problem of cardiac arrest and our therapies, although had I known that Dr. Eisenberg was going to be here beforehand, since he's the world's expert on that, he could have probably done it for me.

            I will then go over some of our safety and usability data in our simulated study.

            In the United States, we have about two million people a year that die.  Those are the number of deaths each year in our country, and most experts estimate that about half of those deaths, about a million deaths a year occur from some form of cardiovascular disease.

            You've heard a lot of different numbers on how many sudden cardiac arrests there are, and most experts agree that it's somewhere in the vicinity of a quarter of a million deaths per year from cardiac arrest.

            Now, while there's some dispute on what the actual numbers are, no one disputes that this is not a major public health concern, and I think none of us in the room would have to go too far before we could think of an individual who we know who has died from sudden cardiac arrest.

            Now, I want to make two points about the epidemiology of this disease.  The first is that because 80 percent of these occur in the home and 50 percent of these are witnessed in the home, the point I want to make is we do not right now have a national idea, a strategy for how to deal with home cardiac arrest, other than call for the EMS system, and we know that the survival rate in the home is far worse than the survival rate in public places.

            So lacking a home strategy, I just want to suggest how important the potential of a home device may actually be.

            The second point that I want to make is that according to the American Heart Association and many other investigators, the majority of victims of sudden cardiac arrest have no prior symptoms.  That is to say they are not high risk patients who have been identified as having had a mild cardioinfarction or anything.

            They are individuals who are first getting their wake-up call to cardiac disease when they sudden collapse and die.  And it's for this reason and for that segment of our population that the notion of moving from a prescription to a public access to public availability is so important.

            Now, a few words about how we treat cardiac arrest.  This is from the American Heart Association, and it says that the way that we try to save victims of cardiac arrest is that we want them to receive early access, early CPR, early defibrillation, and then early advanced care.

            And note that the American Heart Association suggests a goal of receiving defibrillation in less than five minutes, and I'd like to spend just a few more minutes on why time is so very critical during cardiac arrest.

            You can see here in the shaded area the mortality curve that we see with each passing minute of cardiac arrest, and you can see on this axis is the probability of survival.  Minutes go across the bottom, and with each passing moment somewhere between seven, ten percent of the potential individuals who could be rescued are lost.

            If we just start to think, well, how long does it take to defibrillate someone, we learn some very important information.  We know that in most arrests, it takes somewhere around four minutes before the collapse is recognized and EMS is called and an ambulance is dispatched.

            Well, time unfortunately does not stop for that.  It then takes a certain amount of time for the ambulance to get to the address.  In very good systems, six minutes is considered a very good response for the EMS system.

            Time continues to pass.  It takes a certain amount of time to get to the patient, to apply the pads, and so in very good locations, significant numbers of our current survivors are defibrillated at approximately 12 minutes after their collapse, and what we know is that that is a very prolonged time, and it's not surprising that most studies have survival rates in the vicinity of five percent or less.

            Now, the notion has been for many years that we want to move victims of cardiac arrest up that curve so that defibrillation can be done at a much earlier point, and you can see that in theory as you move up that curve, you'll have much higher rates of survival.

            And what I want to do now is share with you some of the data that lets us know that that is, indeed, true, that one can, indeed, move up that curve.

            These are three studies all published in the New England Journal of Medicine that I'd like to just talk about for a minute.  The first is the American Airlines program.  In that study, you'll note that they had 15 patients up in the air with ventricular fibrillation, a survivor rate of 40 percent, and no adverse outcomes.

            In our own study in Chicago O'Hare and Midway Airports, we basically placed AEDs about a minute walking through the terminals of O'Hare and many airports have followed suit.  The result that we had was a nearly 61 percent survival rate, 11 of 18.  I might add that ten of those individuals were alive a year later.

            Many of these defibrillations were done by lay people.  Half were done by people simply walking through the terminal.  There were no adverse events.  In the Las Vegas study, in the casinos, you'll see again a 60 percent survival to discharge, and again, no adverse events.

            Now, I want to point out that the airline study and the casino study are sort of individuals using the AED who have a duty to use the  AED.  It's part of their job.  In the O'Hare experience, ours was more mixed, particularly with people simply walking through the terminal, but the study that I think has really given us a great deal of information is the recent public access defibrillation trial. 

            I have to highlight that the principal leader of that study, Dr. Joe Ornato, is here on the panel and can probably speak to it in more detail than I will, but the basic question here was would AEDs plus CPR improve survival compared to CPR alone, and this was a large NHLBI sponsored study, 20,000 lay responders trained, 23 cities, 1,000 sites, and the results were that in the arm that had the AED, survival was doubled compared to CPR alone.

            Importantly, there were no serious adverse events associated with AED use, and there were no recorded instances of EMS not being called or a failure, a failure of EMS to be notified. 

            Individuals retained their skills during this study, and that was measured, and the conclusions really were -- and I think it's very important for this panel -- that layperson can use AED safely to provide early defibrillation.

            So if we try to summarize those, it's clear that rapid response is what saves lives, that the time is critical, and that early defibrillation is highly effective and we want to do it as early as possible, and so a primary question for this panel is:  can the HeartStart Home Defibrillator be used safely by lay people.

            And I'd now like to share the simulated data that we generated in Chicago in an attempt to provide some information on that question.

            Our study had two primary hypotheses.  The first was that the HeartStart Home Defibrillator and the FR-2 are safe and safe even in the absence of training.  We were designing essentially a worse case scenario, someone who had never seen the device and who did no training whatsoever.

            Our second hypothesis was the HeartStart Home and the  FR-2 would have high usability when used with primary labeling components, including the voice prompts that you've heard David demonstrate and watching the trainee video.

            The methodology that we used is a mock cardiac arrest scenario with a fully clothed manikin and an AED, and the details of this are in your packet.  It's much like the demonstration actually that David performed up here earlier.

            I'd like to share with you the enrollment.  You can see that for the two devices, there were both naive and video trained individuals.  Of note, for the FR-2 here, that videotape was an eight minute videotape that those individuals watched, and then all volunteers went to a simulated use.

            For the HeartStart Home, a three minute videotape was watched by the volunteers, and they then went to the simulated test. 

            Our primary endpoints, first they were safety and successful use, and I want to define those.  Safety meant that there was no touching of a patient in a manner that it could result in a shock across the rescuer's chest. 

            Successful use meant that they had to complete a whole series of adequate deliverables, and those including power the unit on, attaching the pads with the appropriate placement, allowing the device to analyze, if necessary plugging in the pads, and then defibrillating within five minutes.

            Our secondary endpoints that I'll be sharing include the time that it took from when the volunteers stepped into the room, from when pads were placed successfully, and how long it took for them to then deliver the shock.

            Results of the study, for the FR-2 are on this slide, and I first want to highlight that you'll note that in terms of safety, both the naive users and the video trained users were completely safe, and as you'd expect, when we look at successful use, you can see here that about 50 percent of the naive users were able to actually operate the FR-2 without any instructions or any training by listening to voice prompts.

            After watching the videotape, you'll notice that this improves to 86 percent, and this was not at all surprising to me.

            If we look at the data on pad attachment, we can see that, again, there's a beneficial effect to watching the videotape with the pads being attached faster and the shock delivered in a more timely fashion.

            Now, as we look at the HS-1, the Home Start, we see that again the safety was complete for both devices, rather, for both naive users and video trained users, and what I want to highlight in this successful use is that we see what to me appear a difference in the naive users.  Eighty-seven percent of the naive users, that is, individuals who had never seen the device before, were able to successfully use this device in the five-minute period.  When they watched the videotape it only increased to 89 percent, which is not statistically different.

            And I just want to add that it was this observation that made me first aware that not all of the devices would function the same in terms of human use, and it was for this reason that it is the HeartStart Home that is being brought forward today as an acceptable over-the-counter device.

            When we look at the effect of the video on improving pad placement and the time to shock, again we see that while there was no difference in successful use, there indeed was some improvement in the amount of time that it takes, and of course, it is everyone's intention and suggestion that we hope that individuals who use these devices will be totally trained and fully trained with a formal course.

            We, indeed, got these results under what we would consider to be fairly adverse conditions.

            Now, like all studies, there are limitations to this, and I want to be forthright about those.  The simulated use cannot simulate everything in a real use.  The chaos and noise and uncontrolled setting of someone falling down and dying in front of you, and I might add that you can't take volunteers and subject them to that.  It is not ethical.

            So the ability to do a simulated test where you would actually have a real person with a naive -- you know, it would just be totally unethical.  So there are limitations to simulations.

            Our demographics were those that were due to convenience.  We picked to very different places, an urban emergency department and then a parochial school after school program, and those were the people who we studied.  And of course, another limitation was that real human anatomy is far more varied than one will find on a manikin, and that's another limitation.

            But what I want to tell you all is that despite these limitations, this was and is the state of the art of doing simulation studies, and I think there are some important things that we can learn from this.

            The first is that in terms of safety we can see that both devices were used safely in all cases.  We note the significant improvement that took place with the FR-2 when individuals watched that videotape.  They improve significantly in their ability to successfully use the device.

            But importantly, the HeartStart Home Defibrillator was successfully used by both naive and video trained volunteers at a rate of 87 and 89 percent, very high.  And I want to try to draw one conclusion from this, which is that most of our data right now on the effectiveness of defibrillators is based on the FR-2 device, and as we see, the superior human characteristics, the use characteristics in the HeartStart Home, it seems to me that we have very good data to suggest that the experience with the HeartStart Home will be certainly as good and very likely better than our experience has been to date with the FR-2, which has been highly successful in previous studies.

            I thank you, and would now like to have David continue with the labeling evaluation and the other surveys.

            DR. SNYDER:  Thank you, Dr. Becker.

            There are three studies that I would like to present to you, actually two studies and a continuation of an existing study.  The first is a labeling evaluation and simulated use.

            We did undertake some validation studies to gauge the ability of people to read and comprehend additional labeling components that were developed for the product, and then we continued on to simulated use very much like Dr. Becker just described.

            We also have conducted a survey of likely lay users of our earlier products, the ForeRunner and the FR-2.  Now, it's important to understand that these products from the very beginning have been sold to lay operators and even into homes.  There's been no prohibition on that, and physicians have certainly prescribed them for that application.

            So we made an attempt to contact as many of those people as possible and find out what issues they may or may not have had with the use of their product.

            And finally I want to describe  a post market study which was already underway.  It was launched with the FDA clearance of the HeartStart Home Defibrillator for home use to look for specific issues that may come up in home use.

            To begin with the labeling evaluation, the purpose of the study was to test the comprehension ability of the public basically to read these additional labeling materials, comprehend them.  We gave them a written examination to see how well they understood the materials.

            These materials specifically are the owner's manual, the quick reference card which you saw in the case of the device when I demonstrated it, a training video which ships with the product and the quick start poster which is a guide to assembling the device and putting it into service.

            In addition, for two of those pieces we proceeded on to a simulated  use in order to demonstrate safe and successful use after reviewing only one aspect of this additional labeling, and these are the pieces of labeling that are actually included in the defibrillation case and would be accessible in the event of an emergency use.

            I want to show you what these look like.  the owner's manual is right here.  It has the same form factor as the quick reference card that you saw in the demonstration, and it's inserted in a pocket behind the quick reference card and is actually not visible when you first open the case.

            This is the training video, standard VHS, and the quick start guide, and as you can see in some of the graphics, it demonstrates how to open the battery in the pads' cartridge and assemble them into the device.

            A methodology involved recruitment of volunteers in three geographically diverse shopping malls.  We sought people with no medical or defibrillator training and having received no CPR training within the prior two years.

            This was a precaution against, again, accidentally enrolling people that had been exposed to AEDs because so many CPR courses within the last two years had begun teaching AED skills as well.

            We saw a broad age range in this enrollment and were successful in recruiting volunteers over the range of 21 years to 74 years of age.  Forty percent of our volunteers were in the 45 to 65 age group, and 20 percent approximately were in the 66 to 74 percent age group -- excuse me -- 66 to 74 year age group.

            The hypothesis for the comprehension test -- this was a little tricky.  So I want to be careful with it -- was that the labeling materials were well understood, and what we sought to show was that 90 percent of these people could achieve a passing grade.        If you refer back to your grade school experience, a passing grade was 70 percent of questions answered correctly, or a C, and you'll see that in the slides.  So we wanted 90 percent of these people to be able to get a passing grade on the written exam, and we powered the study to establish a lower confidence limit on those results of 80 percent, given the presumption of a 90 percent passing grade.

            The hypothesis for simulated use was that the HeartStart Home Defibrillator is safe and that the HeartStart Home Defibrillator can be successfully used by lay persons to deliver defibrillation shock, and this was powered for a noninferiority test against a presumed success rate of 90 percent, with a ten percent detection margin.

            I want to say that this is an arbitrary goal.  There are no gold standards for either of these tests, either the reading comprehension or performance and simulated use.  We tried to set a high bar, and I'll point to the public access defibrillation trial.  They recorded in abstract that three months following initial training approximately 89 percent of the people still had adequate AED skills.

            So we used that as kind of our benchmark for what we wanted people to be able to achieve in the simulated use.

            This diagrams the enrollment randomization for the study.  the study was first stratified according to how much time the volunteer had to spend with us.  If they had 15 minutes available, they were randomized into the reading comprehension only arms and either viewed the training video or reviewed the quick start poster and then took a written comprehension exam.

            If they had 30 minutes to spend with us, they were stratified into a randomization between either owner's manual or quick reference.  Again, the materials that are in the case, should you use the device in an emergency, they took the written comprehension test and then proceeded to a simulated use test.

            Primary endpoints were essentially the same as those reported by Dr. Becker:  safe, meaning no touching of the patient in a manner that could result in a shock delivered across the rescuer's chest; and successful, meaning shock delivered with pads positioned in a manner likely to defibrillate, and the activities necessary to do that were turning the device on, deploying the pads in proper position, allowing the device to analyze without interruption, and delivering the defibrillation shock.

            Secondary endpoints as for the Chicago study were time to pads on and time to shock.

            The written comprehension test, first of all, the labeling materials themselves are written to a sixth grade reading level or lower according to a Flesch-Kincaid score.  Topics for the test included what is the definition of a sudden cardiac arrest.  Is it different from a myocardial infarction, stroke, so forth?

            Questions regarding set-up of the device, the importance of training, how is the device properly stored; rescue steps; post shock care and so forth.

            These are the results of the reading comprehension test.  A C grade is shown here.  This was our goal.  We wanted 90 percent of people to get a C grade or better, and what you'll see is the median scores on all four of these pieces of material were actually in the 90 percents.

            Now, this slide does contain some information which has been provided to the FDA, but not reviewed, and I want to draw attention to that.  We have shown interquartile ranges, the 25 and 75 percentiles.  That was not originally submitted to the FDA in our 510(k), and we've also shown the 90 percentiles which are these -- excuse me -- ten percentiles, which are these dots.

            And you can see that in all cases 90 percent of the people achieved a C grade or better, and in fact, the medians were in the A grade range.

            These are the results of the simulated use test.  Our lower confidence limit goal is shown here, the 80 percent. And in the case of the owner's manual we did not meet our predefined goal.  You can see that the lower confidence limit actually extends somewhat below the 80 percent lower confidence limit goal.

            In the case of the quick reference card, however, we actually achieved an observed successful use rate of 97 percent among these volunteers with a lower confidence limit that easily exceeded and a highly significant non-inferiority result.

            Median time to show is similar as that reported in the Chicago study as 104 seconds following owner's manual, 89 seconds following quick reference.  This is from entry to room now.  This is not once you've turned the device on.  This is entry to room to deliver of shock.

            Limitations to the study are clearly the same as associated with the simulated use study performed at the university of Chicago.  Given those limitations we conclude from the study that all of the labeling was well understood.  At least 90 percent received a passing grade, 70 percent correct or better, and the lower confidence limit on passing grades was actually greater than or equal to 88 percent in all cases.

            The defibrillator was used safely in all cases.  That was 178 mock arrests, and successful use was achieved by 97 percent of the individuals with a lower confidence limit of 92, following review of the quick reference card, which is the recommended labeling for emergency use.

            Now, we did take some follow-up actions as a result of this study.  I want to show them to you here.  First of all, we added information to the training video and the quick start poster regarding the intended use of the various labeling materials, and in particular, we modified the cover of the owner's manual to clarify its purpose as a guide to set up maintenance and accessories as opposed to an emergency use piece of labeling.

            I'd now like to briefly describe the results of the lay user survey I mentioned.  The purpose of this study was to determine if lay use of Philips AEDs resulted in any previously unreported or not understood problems.

            The method was to establish a contact list of all people who had owned an AED at least a year and in an environment in which a lay use may have occurred.  We specifically excluded all medical professionals.

            We were able to identify 145 homes and almost 2,700 businesses and public facilities where a lay use may have occurred.  We then attempted contact via a phone center and seven attempts were made for each person or installation that had been identified.

            A brief interview was conducted, and in particular, we asked if the defibrillator had been used by a layperson.  If the answer to that question was yes, we requested a detailed interview between a medical professional and the lay user of that device.

            The results of that survey were that we were able to contact 78 homes and 1,645 businesses.  No problems were reported.  Two hundred and nine of the businesses or 13 percent had used their AED at least once to respond to a suspected cardiac arrest.  This doesn't mean that the paths were necessarily attached to the patient or that shocks were delivered, but a patient collapsed.  It was suspected to be cardiac arrest and a person responded.

            We also identified nine uses in home or home offices.  We were able to conduct 11 detailed interviews regarding incidents in which paths had been applied to unresponsive patients by lay responders.  EMS was called in every case.  Three patients appropriately received no shocks.  They were not in VF.  Eight patients did receive shocks, of which six survived a hospital admission and four received shocks solely by lay responders, and all four of those survived to hospital admission.

            Now, these are anecdotal data.  I don't want to draw too much attention.  The real purpose of the study was the first sub-bullet up here, which was that no problems with use of the product were reported.

            In conclusion, a limitation to the study are obviously that it was a survey interview.  Participation is voluntary and bias is, therefore, possible, but we conclude from what we observe that no harm or injury to users by standards or patients was reported.  No malfunctions or problems were reported.  All users expressed willingness to use a defibrillator again should they suspect a sudden cardiac arrest, and finally no safety or effectiveness issues were reported.

            To wrap up, I'd like to talk a little bit about the post market study that's currently underway for the HeartStart Home Defibrillator, and we do propose an extension to that study should over-the-counter clearance be granted for this product. 

            The purpose of the study is to evaluate lay uses of the HeartStart Home Defibrillator for safe and appropriate application.  The methodology is similar to the phone survey you just heard about.  Philips is generating contact lists following one year of ownership for using the one year in order to allow some opportunity for an event to have occurred.  There's not point in calling people one month after they purchased their defibrillator because it's very unlikely it will have been used.

            We're also enrolling people in the study should they contact Philips for accessory replacement.  Certainly if a customer calls us for a new set of pads there's a possibility that those pads had been used in a rescue.  Through both of these avenues, we then asked was the AED used.  If the answer is yes, similar to the other survey, we request a detailed interview with a medical professional.

            We propose to extend the study by an additional four years should we be granted OTC clearance for the HeartStart Home Defibrillator, that is, we will continue this process for four years following receipt of the clearance or terminate it should we record 200 home uses of the HeartStart Home Defibrillator, results to be reviewed by a data safety and monitoring board and reported annually to the Food and Drug Administration.

            I'd now like to introduce Dr. Jeremy Ruskin, Director of Cardiac Arrythmia Service, Massachusetts General Hospital.

            DR. RUSKIN:  Thank you.

            Good morning.  It's a privilege to participate in this important discussion.  I'm Jeremy Ruskin.  I'm here as a paid consultant to Philips Medical.  I own no equity.

            I also consult for Medtronic on implantable arrhythmia control devices, and I've been asked to make a few comments about the HeartStart AED and the problem of sudden cardiac arrest from a clinical perspective.

            Just by way of introduction, I want to underscore what you heard from Dr. Becker, but from a slightly different perspective.  When I began my academic career in the 1970s, my colleagues and I focused on evaluating the electrophysiologic and anatomic substrate of survivors of out of hospital cardiac arrest.

            And we understood from risk stratification schema that patients who were at highest risk for cardiac arrest were those with prior myocardial infarction, left ventricular dysfunction, heart failure, and spontaneous ventricular arrhythmias.

            What we learned from our own observations and also from those of Drs. Eisenberg and Cobb and his colleagues in Seattle, that in fact the profile of survivors was somewhat different from that of the high risk subset that we just described, and that is that prior infarction was present in only about 50 percent of survivors.  More than a third had normal or near normal left ventricular function.  Fifty percent had no clinical or prior historical evidence of congestive heart failure, and about half had no spontaneous arrhythmias.

            And the question then is what explains this seeming paradox, and it is explained by what you've heard from Dr. Becker, and that is that many cardiac arrest survivors, in fact, are drawn from an undetected high risk patient pool whoa re not definable prior to the event.  These are patients in whom sudden cardiac arrest is the first manifestation of their underlying heart disease, and this represents a failure of our risk stratification schema.

            This subset is now at least beginning to be addressed from a primary prevention standpoint with implantable cardioverter defibrillators.  But from an epidemiologic and preventive medicine standpoint, we have no approach to this subset at the present time, and it is this group that is targeted by more widespread availability of AEDs.

            This slide depicts for you the dissemination of defibrillator technology from physician delivered, hospital based defibrillation in the 1960s to emergency medical systems in the 1970s and '80s, to public access defibrillation in the 1990s, and most recently to the concept of defibrillation as a lay procedure in the early 2000s.

            With the evolution of this technology and thinking, it is perhaps reasonable to think about the device under discussion today as a piece of time critical safety equipment, much in the way that we think of air bags fire extinguishers, smoke alarms, and seat belts.

            All safety equipment has benefits and limitations.  We know that smoke alarms reduce the risk of dying in a fire by as much as 40 percent, but that, in fact, alarms may be deactivated because of nuisance factors.

            Seatbelts save approximately 11,000 lives per year and reduce the risk of death in car accidents by as much as 45 percent, but we also know that they are not used as much as a third of the time.

            Air bags reduce the risk of a fatal event in a head-on collision by as much as 30 percent and have saved large numbers of individuals since their widespread implementation.

            But we also know that they may cause injury or even death in children and small adults.

            This slide depicts for you the absolute numbers of deaths attributable to motor vehicle injuries in the green line and sudden cardiac arrest in the red line for the year 1999 as a function of age group.  And as you can see, even in the mid-'40s, the risk or the numbers that toll from sudden cardiac arrest begin to exceed those from accidents, and in fact, you see the curve rise very steeply into the mid-'60s.  Still a relatively young group of individuals, many of them not known to be at risk, and experiencing cardiac arrest as the first manifestation of their underlying heart disease.

            This slide depicts the ten-year probability of experiencing any number of emergency events, including reportable fires, air bag deployment, sudden cardiac arrest in all households, and sudden cardiac arrest in households over the age of 45, and you can see that the ten-year probability of a household over the age of 45, experiencing a sudden cardiac arrest is three times that of a reportable fire, and substantially higher than that of air bag deployment in a motor vehicle.

            The benefits of removing the prescription requirement would include broader access to a safe and effective technology that constitutes the only definitive treatment for a sudden cardiac arrest and thereby provide an opportunity to save some of the lives that would otherwise be lost to this public health problem.

            The question that arises in proposing this kind of a change in thinking and change in practice is whether or not the AED can, in fact, cause harm.  In addressing this question, it's important to underscore that the HeartStart AED is intended for the same user and patient population as the currently cleared prescription device.

            And as you've also heard, this device is designed with safety first and foremost in mind, and some of the critical safety features include an extremely sensitive and specific ECG analysis algorithm, an extremely robust artifact detection algorithm, and the absence of a manual override to preclude the delivery of inappropriate or incorrect shocks.

            The safety of this device of the Philips AED line is supported by the use experience.  These are estimates of use.  You've heard of these from David Snyder, including an estimated more than one million patient applications, with an estimated approximately 200,000 individuals requiring shocks, with only one known inappropriate shock in this vast experience and no complaints about shock effectiveness.

            This overriding commitment to safety is verified by an established history of safe use and the demonstrated fact that the HeartStart AED can be used safely for its intended purpose based upon its labeling alone by lay responders.

            A number of theoretical risks have also been raised with regard to the OTC AED  concept.  One is whether or not an OTC AED would interfere with appropriate medical care.

            Clearly, an OTD AED is not a substitute for any kind of medical care.  Risk factors continue to need to be addressed.  Care and prescribed therapies for preexisting conditions need to continue.  Physicians will retain the option to prescribe AEDs in cases of medical necessity.  And finally, the target populations, particularly those in comparison with those who require ICDs, are entirely different, as Dr. Becker emphasized and I did earlier.

            Another issue that's been raised is whether or not the OTC defibrillator will interfere with the EMS response.  We know that the sudden cardiac arrest survival rate is abysmally low, less than five percent, precisely because defibrillators logistically cannot be delivered in time to victims in a vast majority of instances.

            Philips supports calling EMS in its labeling, as you've heard, and in verbal prompts and recognizes that early defibrillation is only one part, but a critical part of the emergency response.

            Finally there's no evidence that a prescription requirement would in any way enhance an EMS response. 

            In approaching an issue of an OTC home defibrillator, it's important to consider this with realistic expectations.  Sudden cardiac arrest is an epidemic and major public health problem of enormous proportion.  It is the most common cause of death in adults.

            We know also, as you've heard innumerable times this morning, that current survival rates are unacceptably low, in the range of five percent.

            It's also important to recognize that an AED is not considered by anyone to be a cure for the problem of sudden cardiac arrest.  As many as 40 percent of arrests are likely to be unwitnessed.  Devices will in some instances be used incorrectly, and there will be some device failures.

            There will also be human and logistical factors that will interfere with effective use.

            Those limitations notwithstanding, OTC defibrillators represent a paradigm shift and a step towards wider access that will provide the potential to save some lives that will otherwise be lost.  It's important to consider that long term with widespread dissemination, even a small impact, perhaps salvage of as few as five in 100 cardiac arrests would double current survival rates.

            Ultimately the prevention of sudden cardiac arrest lies in the prevention of coronary artery disease, but until this goal is achieved, current strategies for addressing this public health scourge include risk factor modification by life style changes and appropriate medications, revascularization and implantable defibrillators in the highest risk patient subsets, and widespread availability of on site rapid defibrillation.

            Defibrillation is one of the most important therapeutic advances in the history of medicine.  Over the last five decades we've come to take this therapy for granted in a medical environment.  We now have a technology that is designed specifically and cleared for use by lay responders.

            Removal of the prescription requirement will provide broader access to a safe and usable technology and thereby provide the opportunity to salvage some lives that in the absence of prompt defibrillation will otherwise be lost.

            Thank you.

            DR. SNYDER:  And that is the completion of our presentation.

            ACTING CHAIR LASKEY:  Great.  Thank you.

            I would just ask the panel members if there are any queries at this point.

            Dr. Kato.

            DR. KATO:  One other reason that the sponsor is going to eliminate the or desire to eliminate the prescription requirement is to broaden the availability of these devices to the public.  Do you have an estimate for what you think the annual growth would be in terms of AED deployment sine you're already seeing a 20 percent growth per year?  At least that's what you presented.

            You know, on a cursory review last night, it seems that you can get these things over the Internet now.

            DR. SNYDER:  It's a good question, and we don't have specific data on any anticipations of growth rate, given removal of the prescription requirement.

            We have, however, in conversations with people who have attempted to purchase home defibrillators via our phone contact system, we've discussed with them the problems that they've had in obtaining prescriptions, and we do have data on that, and it has not been submitted as part of our 510(k).

            If you would like to view some of that, I could show you the data. 

            I would like to also mention that the internet sites that you're referring to are actually doing it under prescription.  It's not a methodology that we really endorse because no benefit is being provided by that prescription.  If an individual contacts Philips to purchase a home defibrillator, we actually walk them through the process of learning about the product, and we do ask them to visit their own physician, set up an appointment, and we perform follow-up after that appointment to see if they were able to get a prescription or not, and again, we do have the data for those that were refused prescriptions to tell you the reasons that they were refused.

            And I'd be happy to share that with the permission of the Executive Secretary if the panel would like to see it.

            DR. KATO:  So currently you're involved in a fairly elaborate system of education of these patients as they obtain these AEDs from your company, right?

            DR. SNYDER:  Correct.

            DR. KATO:  So what is the advantage of just being able to purchase one of these at Save-on (phonetic) without that educational benefit?

            DR. SNYDER:  Well, first of all, over the counter doesn't necessarily imply Save-on, but we would continue to sell the product through the channels we're using now.  It's certainly an eventuality, but the educational materials provided with the product do educate the purchaser about the problem and the possibilities.

            In addition, if someone is to purchase a HeartStart over-the-counter defibrillator, they do have a 30-day, fully money back, no questions asked guarantee.

            So even if they purchase it without studying, after reviewing the materials if they decide it wasn't a purchase they desire to make, they can get a full refund on that.

            But the issue we're really attempting to address is the fact that there is very significant fallout in people how have made committed decisions to purchase a defibrillator when they contact their physician  and attempt to get a description, a large number are denied those prescriptions.

            DR. KATO:  So you have data that physicians are actually denying these prescriptions now?

            DR. SNYDER:  That's correct, yes.

            DR. KATO:  What happens if this device is used at a pool or at the beach?

            DR. SNYDER:  It's an excellent question, and it's a problem we have had concerns about.  We actually performed a study on this, which was published last year.  What we found was that even defibrillation and wet environments on wet surfaces was entirely safe to the responder.  We actually instrumented a surrogate.  It was actually a turkey, and we attached defibrillation pads and set out a grid so that we could do electrical measurements and only very small voltages were present.

            And I can tell you that I personally have defibrillated a patient in the pouring rain with no adverse consequences.  It's actually a very safe thing to do.

            DR. KATO:  Was the turkey alive or dead?  Is there a difference with --

            (Laughter.)

            DR. KATO:  Well, I mean, is there a difference in resistances?

            DR. SNYDER:  No.  The turkey was dead, but it was selected to present a reasonable approximation of a human impedance.

            ACTING CHAIR LASKEY:  It was fresh killed, Norm.

            DR. SNYDER:  It was one of the more embarrassing studies we've ever published.

            DR. RINGEL:  I have a number of questions regarding the pediatric usage.

            DR. SNYDER:  Yes.

            DR. RINGEL:  I would like to point out that even though you have suggested that this will be labeled for pediatric usage, none of the speakers talked at all about any of the pediatric issues, the algorithms, the pads or anything like that.  So you'll have to bear with me because there are a lot of questions to follow.

            We can start off with the question as to why you are suggesting the system with two sets of pads.  I think it has potential for a great confusion, and you don't explain how these pads would interact.  For instance, I don't think your tests tested removing an adult cassette, put it in a pediatric cassette and then using the pediatric cassette.  I'm not sure you give guidelines to tell people how to figure out if someone is 55 pounds or less.

            I'm confused by one of the statements in your brochure when you say, "Note.  If you're not sure about the child's exact age or weight or if infant child pads are not available, do not delay treatment.  Use the adult pads, but place them on the child's chest and back  as shown in using the HeartStart."

            So if that's the case and you can use the adult pad effectively, why not just have one set of pads and avoid the confusion?

            I also have concerns about the fact that most small child and infant arrests are  respiratory arrests.  They are not fibrillation  or cardiac arrests, and there's no mention about or study about how  this delay in fiddling or fumbling with the AED might delay appropriate respiratory care.

            There are more, but you can start at any time.

            DR. SNYDER:  All right.  I'll attempt to answer all of them in order.  If I miss one, please let me know at the end.

            DR. RINGEL:  Sure.

            DR. SNYDER:  First of all, with regard to cartridge exchange, we did perform a design validation on people's ability to do this.

            Slide up, please.

            We performed a design validation with ten volunteers, and I want to admit right up front that clearly this aspect of the product has not been validated to the same standards as the primary use of the product, which is adult defibrillation.

            But we have performed validations.  We sought ten volunteers.  These were people who had previous adult AED training, but no training on this particular product.  So they had never seen this product before.  Nor had they received any prior training in pediatrics.

            The sample size was based on an FDA guidance document called "Do It by Design" from '96.

            All volunteer viewed a training video, which included a pediatric chapter on pediatric application of the device prior to the test.  The scenario was that upon entering the room they were presented with a toddler manikin, and an AED with an adult cartridge installed.  A pediatric cartridge was available in the AED case.

            Next slide, please.

            The results of the validation are tha t all ten of the volunteers were able to recognize the need for exchanging the cartridge.  Ten out of ten Retreat the pads cartridge or knew where it was located in the case and seven out of ten of those were able to exchange the cartridge, remove the adult cartridge and insert the pediatric cartridge with an average time to do so of 40 seconds.

            And of the seven that successfully exchanged the cartridge, all seven were able to deliver defibrillation shock with adequate pads placement.

            Now, I want to emphasize that these people had never had an opportunity to operate the release latch of the cartridge.  So, again, they had never seen the product.  They had never inserted or removed a cartridge, yet 70 percent were able to succeed.  That's an admittedly small sample size, and it's obviously a limitation  that the panel needs to take into consideration.

            With regard to the next question, guidance on 55 pounds or less, I'll show you the labeling we have in the quick reference guide.  Slide up, please.

            The statement is zero to eight years, less than 55 pounds use the pediatric pads, and it chose adult pad placement adjacent.

            Now, the guidance we give in the owner's manual is if uncertain about whether they're 55 pounds or greater, to go ahead and use the adult cartridge.  We believe this to be an entirely safe does, and it's consistent with current AHA recommendations on pediatric defibrillation if pediatric defibrillation is unavailable, go ahead and use an adult does with the biphasic therapies.

            We have selected the anterior posterior positioning because we also did a validation on pad placement.  I don't have specific data with me, but we found that in very small children, ability to place anterior-anterior pads was quite poor because people go the pads adjacent, not providing a good defibrillation vector.  But we found very high success rates in placing anterior-posterior pads.  So that is the recommended placement, and for simplicity, we wanted to keep the pad placement consistent for all infant child application even if you were using the adult pads.

            The next question was with regard to respiratory arrest.  Your statement is correct that there is no discussion of respiratory arrest, and I think that this is an issue of some controversy in the resuscitation community today as to what the proper sequence of rescue is, given perhaps lack of information about the nature of arrest.

            So for that we really have to defer to our policy and recommendation body, such as the American Heart Association.  What we're trying to do here is to provide the opportunity to defibrillate, but I think it would be out of place for a manufacturer to make some specific recommendations in that regard.

            Did I address all of your questions?

            DR. RINGEL:  Many of them.  I think that some of the others we can discuss this afternoon.

            DR. SNYDER:  Okay.

            DR. RINGEL:  That will be fine.  Thanks.

            ACTING CHAIR LASKEY:  Dr. Somberg.

            DR. SOMBERG:  Is there a population the manufacturer has identified that would not be appropriate for this device?  For instance, and I'm not suggesting it is an inappropriate population, but I'm just using it as an example patients diagnose and with current epilepsy, for instance, who are prone to seizure disorder.

            is there any population that has come to the fore from your consumer queries, et cetera, that suggest caution should be identified in that group?

            DR. SNYDER:  If you'll give me a moment, I'll consult with my team and give you an answer on that.

            DR. SOMBERG:  Or maybe for the sake of time you might want to come back at a later point.  Is that what our chairman would like?

            ACTING CHAIR LASKEY:  He may have the answer.

            DR. SNYDER:  I have the answer.  The only group that we've really identified as inappropriate is that for people with certain medical conditions, this is out of our owner's manual, who are likely to suffer SCA, an implantable cardioverter defibrillator may be advised.  The HeartStart is not intended as a substitute for an ICD.

            Now, the other group I would say that could not really derive benefit from a homodefibrillator or would have minimal benefit, it's not necessarily an inappropriate market, would be people in single persons households.  Obviously if they live alone, the only time another responder would be available in the event of sudden cardiac arrest is if they were a guest in the home.

            DR. SOMBERG:  Where is the concern about having an ICD in place?  Located that's in the manual you said?

            DR. SNYDER:  That's correct.  It's page 2 of the owner's manual.

            DR. SOMBERG:  So that's just probable the only instance where a physician's place in the chain might be a benefit to discern whether someone has an ICD or not?

            DR. SNYDER:  Well, remember there's specific labeling on the outside of the carton, as well as in the owner manual and the pre-sales material saying if you have concerns about your health or a medical problem, that this is not a substitute for medical care and that you need to contact your physician.

            On the specific language, if you have concerns about your health or an existing medical condition, talk to your doctor.  A defibrillator is not a replacement for seeking medical care.  This message is repeated throughout our labeling materials.

            ACTING CHAIR LASKEY:  Dr. Krucoff.

            DR. KRUCOFF:  I'd just like to follow the quick question on not so much the indication for an ICD, but in patients who collapse in public settings, is there any instruction to the responder in how to identify that the patient who is on the floor has an ICD, or do you have any experience with if you defibrillate both externally and internally simultaneously how the two devices are likely to interact?

            DR. SNYDER:  We do not have specific instructions, and I would like to defer to  Dr. Becker to address the question of interaction between internal and external.

            DR. BECKER:  We don't have a lot of data on that.  I mean, not quantitative data that's really going to answer the question.  What we do know is that numerous individuals have had the device applied to them who have internal devices, and the device is operated normally.

            The specific scenario that you're suggesting, the possibility that the internal device is about to shock and a shock is delivered is one that I have yet to see report as any kind of adversity.

            DR. KRUCOFF:  I guess as Jeremy pointed out, on the one hand, you know, a third of the folks who are sudden death survivors don't have low EFs and indications, but I think we have to recognize that there is a skyrocketing number of individuals who are now candidates for permanently implantable defibrillators.  So that population is going to be more and more a part of our population.

            We can talk a little bit more about that this afternoon.

            MR. MORGAN:  I had one other just quick question as to whether --

            DR. SNYDER:  Can I add just one comment on that?  I think it's important to point out that in the presence of an AED or ICD by the time you could

retrieve an AED and get it applied and get to the point of a shock, there's multiple opportunities for internal defibrillation shocks and the possibility certainly exists that the ICD has failed or is not defibrillating.  In that case shock by an AED would be an appropriate activity.

            DR. KRUCOFF:  Yeah, I guess it's a crossover.  If while you're running to get the AED the patient on the floor has their internal defibrillator fire but they don't convert, I mean, a lot of the safety margin of your device is based on its not shocking rhythms that are inappropriate to shock.

            DR. SNYDER:  That's correct.

            DR. KRUCOFF:  The population I'm thinking of are patients who actually would potentially have a shockable rhythm, and without a layperson's appreciation, we now have the potential for two devices, each appropriately going after that same rhythm.

            So this is one of the places that I just think we can talk about more later this afternoon.

            I had one quick question just on your anticipation of what the removal of the prescription feature would do.  I guess if it's not so much Dr. Kato's answerable rate of growth, most of the data that we've seen today have by a power of ten or more public access type, you know, shopping malls, airports, airline systems.

            Do you all have a sense or have you examined the ramifications of without prescription how much more a private home presence is likely to eventuate or whether you think the proportion that we're seeing in the data currently reported would be maintained?

            DR. SNYDER:  The proportion of home deployment versus public deployment?

            DR. KRUCOFF:  Right.

            DR. SNYDER:  No, I'm afraid we don't have any projections.  Really what we're operating on is I'm going to fall back on the mission of our company, which is to make defibrillation available to as many people as possible as quickly as possible, and we have identified the home as a way to do this, and we have identified the prescription requirement as a barrier to the purchase of these products.

            We really are unable to extrapolate beyond that because we don't know how well accepted this will be accepted by the public, and it's certainly a sensitive --

            DR. KRUCOFF:  Well, that's the point, isn't it?  If you remove the barrier, what happens next?  If it's different from the basis of what we're thinking about as a good reason to remove the barrier, what happens next is different than how do we know what happens next.

            DR. SNYDER:  Well, it will only be different potentially in the extent of the deployment.  Is there a specific concern that you have that I might be able to address?

            DR. KRUCOFF:  Well, for instance, in a public access area, if there are 100 people standing around in the  middle of an airport and somebody collapses, there's likely to be an EMT or a nurse or somebody who steps forward in the use in addition to other laypeople or a calmer lay person as opposed to ten people who panic.  Because, as you say, simulating these events in the types of simulations any of us could do is simply not possible.

            In a home there may be a single individual.  It may be a teenager.  It may be a spouse, and I think some of the performance characteristics when you have people step forward in a lay environment out of a public may, in fact, be quite different than if you have one individual in the house, and at least the data that I'm looking at and aware of, that we have very little knowledge about a lot of home use.  Even though we keep calling this a home use, the vast majority is really public access use.

            DR. SNYDER:  Yes.  I do have a small amount of data I can share with you.  You're correct there's not very much.

            Slide G-11, please.

            MR. MORTON:  Dr. Laskey, Dr. Laskey.  Let me ask the sponsor.  Let us not lead you into economic and business results that you might present.  We've got some legitimate questions, but you need to protect that information for yourself.

            DR. SNYDER:  Yes, thank you.

            DR. KRUCOFF:  I'm sorry.  I had no intention of going there.  In fact, I'm not interested in the business.  To me the real ramification is the user.

            MR. MORTON:  It's just the penetration.

            DR. SNYDER:  Yes, I understand the question.

            If we can have the slide up, please.

            There are a limited number of studies that have looked at this.  I can draw your attention to these three.  They're all home use studies.  In 1987, Chadda and Cammerer reported on experience with AEDs in the home.  In the study they saw five arrests.  Two of five were converted to sinus rhythm.  One use was by a spouse, and there were no adverse events reports.

            They concluded that AED use was feasible by family members and lay persons.

            Another study by Swenson trained 48 families of sudden cardiac arrest survivors.  In their study they observed five arrests, four uses by spouses.  Three of the individuals were resuscitated.  These are very admirable survival rates, by the way.

            Again, no adverse events reported, and concluded that AED was far easier to learn and maintain than CPR.

            And finally, Dr. Eisenberg who spoke this morning has done a study in which they observed two VF arrests in home.  One patient was resuscitated and no adverse events were reported.

            I would also on this question like to defer to Dr. Jeremy Ruskin.

            DR. RUSKIN:  May I first offer a response to something that Dr. Krucoff raised earlier about ICDs?  Since I'm standing here, I'll take the opportunity.

            It's unusual for a patient with an ICD to lose consciousness these days.  The detection and charge times are so fast that for a patient to actually go down and stay down long enough for somebody to think about getting an AED would suggest that something is wrong.

            And in that circumstance, at least in an in hospital environment, we routinely recommend that standard external defibrillation be performed without any hesitation or question, and I'd be interested in Bill Maisel's thoughts about that since he's got plenty of experience as well.

            DR. MAISEL:  My only other comment is that we routinely defibrillate patients in the EP lab during ICD testing.  If they fail internal defibrillation, we routinely defibrillate patients for atrial fibrillation who have ICDs, and the general recommendation is simply not to put the pads directly over the device.

            I noted in the user manual that that's mentioned.  If that person has a known pacemaker or defibrillator, not to put it over the device.

            DR. KRUCOFF:  Actually, Bill, I'd like to come back to that this afternoon because, you know, that to me would be the key piece, is just to make people aware that if there's a lump, you know, under the skin somewhere, put the pad somewhere else.

            DR. RUSKIN:  That said, and that is absolutely in agreement, I think, with everybody's current procedure.  There's precious little evidence that you can actually do damage to these devices.  It's not impossible, but it's difficult to do.

            With regard to your second question, I'm going to interpret it in a very broad sense, and that is the issue of whether or not there is effectiveness data on home use of the type that we'd all like to see as academics and clinical investigators.

            And I think the answer is no.  We don't have clinical trial data to direct to the question that you've asked, and it's a critical question.  And I've struggled with this, and the conclusion that I've come to in trying to construct in my own mind some sort of benefit risk assessment is really to raise the question of what the stakes are and then what the risks are.

            And on the risk side, I think you've heard very solid data from a randomized control trial to three other uncontrolled trials, to field experience, to simulated use data, that with this device at least there are simply no safety issues that have been raised.  I mean there just is no evidence of harm to an individual victim or to a user, and there are no theoretical concerns right now for which there are signals in the experiential database with regard to safety.  That's my own personal interpretation.

            I think the safety is on very solid ground.  You look as if you disagree with that.

            DR. KRUCOFF:  Well, my only real concern because the issue we're here to discuss is if you pulled a physician prescription out of the loop, then the 40 to 60 patient type family cohorts that we have data on, these are all selected patients and presumably I would think a physician was probably in that loop of identifying them as good candidates for inclusion in these studies, for instance, as one.

            And what I'm literally sitting here and I think we're probably all going to have to balance is what is the burden of requiring the prescription and having the physician in the loop versus  what happens if relative to the 45 well selected homes, 45,000 families who can go to Target, you know, and buy one of these things go out and start buying these things.  What happens next?

            DR. RUSKIN:  Well, I think that's a critical question, and my own bias is that, one, no harm will come to anyone because I can't find in any of the data from all the trials and the field experience and the simulated use studies evidence of a safety concern, which for me is the most important question if you're going to expand access.

            then the next question is what can you expect on the benefit side, and the answer is we don't know with certainty, but if you take a fraction, just a tiny fraction of current survival rates and you extrapolate that to a broader application of this technology, there will be some lives saved, and the question is really what's the benefit or -- excuse me -- what's the risk.  What's the target, which is a 95 percent lethal condition and what is the experience to date outside the home?

            All of those, I think, add up to an overwhelming benefit risk assessment, but we can't put a number to it with regard to the home application for precisely the reason that you've raised.  We don't have that experience in the home.

            The question is:  is that achievable?  And personally I don't think it is.  I don't think you can do a study that's large enough with an event rate so low in the general population to answer the question.  It's not dissimilar to the QT issue that keeps coming up on the drug side.  It's not answerable in a clinical trial.

            So where are you left?  You're left with trying to construct the best benefit risk ratio that you can from the available data.  It's not a perfect situation, but my own bias is that with a situation in which we're losing 95 out of 100 victims and we know that defibrillation in every other scenario it has been tested works, even if the success rate is a tiny fraction of what it is at O'Hare Airport, close to 40 percent and 60 percent in other studies, take that down to five percent or take it down to one percent.  I think you're still going to save some lives.

            DR. KRUCOFF:  Yeah, I don't think there's going to be any argument about that from anybody, Jeremy.  I think the real question is what's the burden of the physician in the loop versus what's the concerns about taking the physician out of the loop.

            ACTING CHAIR LASKEY:  We're going to come back to this subject, this language, I'm sure.  I would suggest we take a break so we can at least hear the FDA presentations before lunch.

            But I have just about noon.  If we could take a ten minute break and resume at 12:10.

            Thank you.

            (Whereupon, the foregoing matter went off the record at 11:58 a.m. and went back on the record at 12:13 p.m.)

            ACTING CHAIR LASKEY:  The plan here is to have the FDA presentation followed by some short questioning, hopefully very short, and then we'll break for lunch.

            DR. TOVAR:  Well, during this presentation, I am going to show a brief summary of the regulatory history of the HeartStart Home Defibrillator.  Next I will present the regulatory context of a prescription device followed by a summary of the review.  The panel questions are going to be presented in the afternoon.

            At this time I would like to present the members of the review team.   Dr. Lesley Ewing was the primary clinical reviewer.  Michael Mendelson, peter Carstensen reviewed human factors.  Gay Kamer is statistics.  Dr. Victor Krauthamer, risk analysis, and Ms. Beverly Gallauresi, post market.

            And I will use some of the clinical aspects of this submission as well.  I was the lead reviewer.

            The purpose of this submission is to remove the prescription requirement from the Philips HeartStart Home Defibrillator prescription label.  This is a summary of the regulatory history for the HeartStart Home Defibrillator that the sponsor presented previously.  In September of 1996, the FDA cleared the ForeRunner AED.  In May 2001, the FDA cleared the FR-2 defibrillator with attenuated defibrillation paths for pediatric use with prescription caution.

            In November, 2002, the FDA cleared the HeartStart Home Defibrillator designed for home use.  All the three previous were always with the prescription caution.

            In April 2004, Philips submitted a 510(k) proposing removal of the prescription caution from the labeling.

            As I mentioned before, this device has had a prescription caution that reads, "Caution.  Federal law restricts this device to sale by or on the order of a physician."

            The Code of Federal Regulations defines a prescription device as a device which, because of any potentiality for harmful effect or the methods of its use or the collateral measures necessary to its use is not safe, except under the supervision of a practitioner licensed by law to direct the use of such device and hence for which adequate directions for use cannot be prepared. 

            The present regulations do not describe requirements for removing the prescription language.  However, the definition of prescription device suggests that two elements must be met to remove the prescription language.

            One, the device is safe to use without supervision of a licensed practitioner, and adequate directions for use can be created.

            Therefore, the FDA's review has focused primarily on the device labeling and human factors evaluation, and those are the summaries that I'm going to present.

            First, I would like to talk about the device itself, the automatic defibrillator.  Philips Medical Systems states that the HeartStart Home Defibrillator and its accessories, including this 510(k), are the same as the HeartStart Home prescription defibrillator.  The previous was the over the counter.

            And these similarities are in the way from therapy, the sign, functionality, technology, software, manufacturer processes, acceptance criteria, and packaging with some modification to the text of the written materials.  The target populations is going to be the same, adults and children.

            In summary, this device is the same device already used and comes with a prescription.

            These are the indications for use of the device.  The HeartStart Home Defibrillator  is intended to be used to treat someone who the rescuer thinks may be a victim of sudden cardiac arrest.  A person in sudden cardiac arrest does not respond when shaken and he's not breathing normally.  If in doubt, apply the pads.

            For children eight years or older or who weighed 55 ponds or more, use the defibrillator with the adult pads that come with it.  For younger children or those who weigh less than 55 pounds, the special infant child pads should be used if available.

            Next I'm going to present the summaries of our review.

            Around 80 percent of sudden cardiac arrest occur in homes.  However, the greater experience with 80 is in public places, like for example the PAD trial in the Chicago area airport, the casinos study, et cetera.

            Cardiac function, the ventricular fibrillation deteriorates rapidly with time.  This fibrillation in function is associated with rapid decrease of survival of sudden cardiac arrest produced by ventricular defibrillation.

            A victim of cardiac arrest loses approximately ten percent of the probability of survival, which means that state in VF has been previously presented.

            Therefore, rapid access to a defibrillator addresses this problem, and in some instances might be sufficient.  A recent report presented previously by Dr. Baker proposed that if the duration of ventricular defibrillation is less than four minutes, the electrical phase, a defibrillation shock could be sufficient to compare VF to a normal sinus (phonetic) rhythm.  Between four and ten minutes are the circulatory phase.  CPR should proceed or you might need it for defibrillation. 

            Beyond ten minutes of ventricular defibrillation of the metabolic phase, other additional measures like control reperfusion, cooling, et cetera are required.

            In an effort to increase survival from sudden cardiac arrest, the American Heart developed the chain of survival.  If a person is un responsive  to links and the chain of survival are early access or call 911 or the EMS because other conditions can cause unresponse in victim, for example, stroke, choking, et cetera.

            We have a question for the panel on this issue.  Early CPR is the next link, pump and blow, and the defibrillation.  Use the AED followed by early advanced care or care provided by EMS personnel.

            The timing of CPR relative to defibrillation is one concern for this type of device.  CPR should precede defibrillation in the chain of survival according to the American Heart, according to the guidelines from 2000.

            However, we are aware of the dynamics of this sequence.  When the chain of survival was established, the arrival of the defibrillator to the victim would take some time, and research suggests that even changes can be done to CPR.  That means the weight of CPR is done.  We are aware of all these changes, and we want to recognize that.

            But so far this is the sequence.  However, the design of the device allows that if the victim collapse is witnessed, there is a reasonable probability of a prone application of the AED and shock delivery within four minutes and probably no need for CPR.

            If the victim collapses, is a witness, there is a high probability of longer duration of defibrillation and pressing of non-shockable rhythm, and in this situation the device should not deliver a shock and even call CPR.

            Of course, with this examples, I am not trying to cover every single situation during a rescue attempt.  I am trying to put the extremes of the spectrum, and we have also a question for the panel on this issue.

            The next studies were presented by Philips previously, and I'm not going to repeat all of the results, and the next studies that I'm going to just mention were simulated tests with the manikin or comprehension tests to study appropriate and timely use, speed of application of the elctropads of the AED, as well as safety and effectiveness of the defibrillator, and this were the three studies, the safety and the civility study, the Liberty label (phonetic) user survey and the signed validation.

            The Sarapo Infant/Child Cartridge was a study to show the ten users who had viewed the training video could recognize the need to change from adult pads to infant/child pads and successfully change the cartridges.  This was one of our concerns and is one question for the panel.

            The labeling, label evaluation was a written test.  The purpose was to assess the participants' comprehension of one of four labeling items.  There was a simulation part with 190 subjects were tested on how to set up and place pads based on their understanding of the labeling.  We have, again, another question for the panel.  And there was a marketing survey.

            The comments or concerns that we have are -- actually our main concern on the previous test was that testing was preceded by a script read to the subject informing them that the manikin was a simulated victim of sudden cardiac arrest; that the victim required immediate help, and then that an AED might be used to help the victim, and also the EMS has been already called.

            Survival rates and adverse events with home use of AEDs have not been directly evaluated.

            The full performance summary, Philips reported 150,000 units distributed with approximately 200,000 uses and reported 59 devices among functions that are represented here, and at the time of our review there were four AEDs, and specifically the FR-2s that fail in a use related event.  That means that you compromise delivery of therapy.

            The sponsor dates are different from ours because they are including the reports up to date.  That's why they presented six.  One case was a case that it was believed it was a simulated case, and it turns out to be that a patient was involved.

            Human factors.  Human factors examines all aspects of assistance interface that are necessary for safe and effective use.  The definition of use includes the installation, calibration, operation, maintenance, repair and ultimately the disposal of the system or its components.

            Training and labeling are part of the use interface of a device.  In this context, delivery of medical care is only one part of a device's use.  In devices for emergency use, as this one, concerned with preparing a device at maintained readiness are extremely important.  For the HeartStart Defibrillator, it appears that the user must accomplish the following basic activities:  set up training, operation, storage, and maintenance of the device.

            The actions needed for the operation of this device includes determine that a patient is unresponsive.  Notify 911.  Turn on the device.  Expose the patient's chest.  Place electrodes.  Respond to the device's instructions, possibly pressing a shock button and possibly perform CPR.  And attend to the patient until arrival of emergency personnel.

            Philips' testing covers some aspects of device wrap (phonetic) and device operation.  However, Philips' testing did not cover training, storage, or maintenance.

            And we have two questions for the panel on this issue.  FDA considered this a track device requiring the sponsor to have processes in place to promptly identify users in the event of a recall.  The sponsor proposes the use of a registration card to build a database of shipment records.

            However, in the case of a recall, multiple methods of identification will be used, like Web sites, collaboration with consumer organizations, public warnings.  We have a question for the panel regarding this issue.

            For the post market surveillance, Philips is planning to continue with the NDR reporting as for the prescription device and also has a follow-up survey of post market study that consists of a follow-up survey of U.S. customer after one year of after-years of the device, whichever come first.  Purpose:  assess safety and effectiveness following use of the nonprescription device and also a strategy that ties the direct reordering of pads.

            Our final comments are uncertainty remains regarding the public's ability to safely use AEDs given the increased access, and we have conveyed this concern in some of the questions.  The sponsor has presented data that characterizes the human factors attributed to the device and labeling. 

            However, survival rates and adverse events with home use of AEDs have not been directly evaluated.

            Thank you.

            ACTING CHAIR LASKEY:  Let's see.  Is there anybody else from the agency who's presenting?  Is that it?

            Okay.  Anybody have a comment?  Yes, John.

            DR. SOMBERG:  I'm going to ask the same question to the FDA group here as I did to the sponsor, and that is in your review have you identified a population, a subpopulation that you think would be placed in some degree of jeopardy by the use of this device?

            And if you have identified that population, would the physician link in the prescribing obviate that problem?

            DR. TOVAR:  No, we didn't identify that population

            ACTING CHAIR LASKEY:  Yes, Dr. Vetrovec.

            DR. VETROVEC:  A somewhat different question, but in the experience of the agency with other devices, I recall that there has been approval of the Heart Card for monitoring heart rhythm that patients can elect to do.  That does require at least not a prescription but physician input, but is there any other model that the agency has dealt with in which prescriptive authority has been removed from a medical device?  And what has been the experience with that?

            DR. TOVAR:  As far as my knowledge, I don't recall anything on that, but probably Megan could help me with this.

            MS. MOYNAHAN:  Megan Moynahan, FDA.

            Our primary experience with over-the-counter products has been with over-the-counter diagnostics, blood tests, urine tests for pregnancy, ovulation, glucose monitoring, and that.  I think there is something called a liquid bandage, which is considered a therapeutic device, but besides that, our primary experience has been with over-the-counter diagnostics.

            ACTING CHAIR LASKEY:  I thought I saw your hand up earlier, Mitch.

            DR. KRUCOFF:  No.

            ACTING CHAIR LASKEY:  No?  Okay.

            Well, then I apologize for our premature break.  I didn't realize we'd be so brief. 

            That brings us to the lunch hour, which we've been smelling for the last hour.

            (Laughter.)

            ACTING CHAIR LASKEY:  We've been trying to do something about that with management, but I have 12:30.  If we can adjourn and break for lunch and meet back here at 1:30, I think we'll still stay to schedule.

            Thank you much.

            (Whereupon, at 12:34 p.m., the meeting was recessed for lunch, to reconvene at 1:30 p.m.)

 

 

 

 


         A-F-T-E-R-N-O-O-N  S-E-S-S-I-O-N

                                       (1:37 p.m.)

            ACTING CHAIR LASKEY:  Okay.  Welcome back again.  Thank you for your promptness.  Hopefully this will get us through the remainder of the day on schedule.  And I'd like to resume this afternoon and open by having our lead reviewer, Dr. Maisel, give his review and/or query the sponsor.

            So Bill.

            DR. MAISEL:  Good afternoon.  I don't think there's any debate that AEDs effectively defibrillate the heart and can restore the rhythm back to normal, and there have been some very impressive results that have been cited and discussed this morning regarding public access defibrillation:  American Airlines, Chicago Airport, casinos, the public access defibrillation trial.  I think public access defibrillation is a good thing, but I don't think that's what we're debating today.

            I think you could make the argument that with prescriptions public access defibrillation could go on as it is now with AEDs wherever they needed to be. 

            So what I'd like to try to focus my remarks on are the specific implications of removing the prescription from this device and the first topic I'd like to try to cover is the intended patient population, and it has been stated by both the sponsor and the FDA that there is no change in the intended patient population.  I'm not sure that I completely agree with that statement.

            Something is happening when a patient goes in to see a physician and because not every one of those patients walks out with an AED, and so I'd like to ask the sponsor if they could be a little bit more specific in both their presentation and in the packet they presented some anecdotal comments that physicians made or that patients made stating what their physicians said regarding the reasons for refusing to give them a prescription or dissuading them from getting a prescription.

            So I wonder if you have any data from physicians or from patients reporting about their physicians, about the reasons why physicians turn down patients for an AED.

            DR. SNYDER:  We do have some data, if I can have Slide G-33 up, please.

            This is information gleaned from our telephone fulfillment center.  Now, this is the point of contact for a customer who has either gained information from a Web site, a print advertisement, seen a spot that we've run on television, has interest in a home defibrillator.  This is the number they call to get information from Philips.

            First, I want to draw to your attention the fact that in this three-month period or -- excuse me -- four-month period we had contacts from a little over 5,850 people interested in a home defibrillator.

            Now, of those, based on the information and materials provided by Philips through the phone contact, 90 percent of those did decide that this was not the purchase for them and declined to pursue the purchase further.

            So the first point I want to make is this has not been a hard sell, and in fact, Philips has successfully dissuaded 90 percent of our potential customers.

            But of those that have decided to proceed, the 9.6 percent -- that's 619 individuals -- these are people who have researched the issue, made the decision that they are willing to put down a credit card in order to secure a purchase.  We then instruct them in the need to get a prescription from their physician and assist them in making that appointment so that they can talk to their physician about a prescription.

            Next slide, please.

            Of those people that go to their physician to get a prescription, 71 percent were refused a prescription.  Twenty-nine percent did receive a prescription from their physicians.

            Now, we've done a further breakdown of this data.  It has not been submitted to the FDA.  We did categorize the reasons given for refusal of prescription.  With the permission of the Secretary, I'd be happy to share that data.

            MS. WOOD:  That would be fine.

            DR. SNYDER:  Next slide, plesae.

            This is a breakdown of all the reasons for refusal cited by the physicians when these people who had made a purchase commitment decided to attempt to get a prescription.  Now, you'll notice that there are more reasons cited than there were refusals.  This is because sometimes multiple reasons were given.  So this is categorized as a percentage of all reasons given.

            The most common reason for not prescribing a defibrillator, 48 percent, was that it doesn't meet or doesn't treat your condition or you don't need it, and I think this is really the point that we're trying to make in our presentations here today, is that what we're trying to address is the population that doesn't have an identified medical issue.

            The second most common reason for refusal is simply that the physician was not comfortable with prescripting the device or no reason at all is given.

            The remainders fall in the four percent or less reasons for refusal, and they include things like some physicians offered to implant an ICD instead.  The cost was cited, suggesting to use EMS instead, and so forth.

            Slide down, please.

            ACTING CHAIR LASKEY:  I'm sorry.  These are per patient report or you went to the physicians and got their --

            DR. SNYDER:  No, this is patient reported reason that they were given by their physician for refusing the prescription.

            DR. MAISEL:  Okay.  Thank you.

            I find that very interesting and useful information.

            Next, I just want to clarify a couple of things about the device description.  You did a very thorough job of explaining the device and what it does, and I understand that the device is already approved and, therefore, there's been no new arrythmia testing, but it would help me to understand a little bit more regarding the algorithm for detecting ventricular fibrillation, exactly what it's doing.  You put up that slide with a variety of generic statements, and my main issue is just trying to understand from a safety standpoint what sort of circumstances might make the device misinterpret a rhythm.

            DR. SNYDER:  Slide up, please.

            This is a graphic depiction of basically how the algorithm works.  I talked about the four different mathematical measures we take of the ECG, and what I've done in this graph is I've plotted three of those.  The first is the morphological stability of the complex.  Again, how repeatable is the complex, not the heart of our intervals, but the shape of the complex.  How repeatable is it from one to another.

            And as it's scored from the low end here, you can consider this to be a zero.  It's a high stability you can consider to be a one.

            Similarly, the conduction properties, the health of the myocardium, this is basically measured by rapidity of edges in the complexes, sharp transitions in the complexes and so forth, and that's plotted along this axis from lowest conduction, which would be a very sinusoidal in nature, ventricular tachycardia, for example, up to the very highest conduction values, which would be typical of a normal QRS complex or a rhythm of super ventricular origin.

            And then on the vertical axis we have the heart rate, which in this graph goes from zero complexes per second asystole up to 600 per minute -- excuse me -- not per second.  What I've plotted here are the results of analyzing three different rhythms, and this was our validation database and our original development exercise of this algorithm.

            The red dots represent rhythms for which our over reading physicians -- we sought consensus from three professionals, a cardiologist, an electrophysiologist, and emergency physician.  The red dots are the rhythms that they judged would benefit from a shock.

            The green rhythms that you see down in the lower corner are the rhythms for which no shock should be advised.  Those include super ventricular tachycardias, normal sinus rhythm, bradycardias.

            And what you'll see is characteristic, for example, of normal sinus rhythm, is it has very high stability, very high conduction, at a modestly low rate.  So it falls down in this corner.

            In order for us to advise a shock, when we plot those three numbers, it has to fall on the other side of the gray surface.  For a no shock or for a rhythm requiring shock, it has to be above the surface.  If it falls below, that results in a no shock advice.

            So that you see, ventricular fibrillation, for example, resides in this part of this graph.  It has low stability.  It has moderate conduction, and it has moderate to high rates.  So this is the cloud representing ventricular fibrillation.

            With tachycardias, you often get higher stability, higher conduction properties, and they reside in this part of the space.  Normal sinus rhythms, bradycardias, asystoles, they reside way down here.

            Now, of course, there are some indeterminate rhythms, rhythms for which for fusion status it's really uncertain from the ECG alone.  We have taken a conservative approach to these arrhythmias, and those are represented by the small number of red dots for which the majority of our over eaters would have preferred the shock, but our algorithm represents a no shock, and this reflects the conservative nature that's responsible for the truly high specificity we've achieved with this arrythmia system.

            DR. MAISEL:  Is that latter statement then consistent with what I read, that -- and I'm quoting the most common reported concern, I guess, from users -- was that the device did not recommend or deliver a shock for a rhythm that was considered shockable?  Can you comment on that statement?

            DR. SNYDER:  Yes.  That statement would be in the case of a very fine VF, either had a very low rate of complexes, typically below about 130, or it was a very low amplitude which actually was right on the edge of whether we considered it an asystole or actually a fine VF.

            So these are patients from which outcome from shock, certainly the arrythmia could be terminated, but it actually may be more appropriate and beneficial to do CPR and see if the nature of the arrythmia could be improved.

            DR. MAISEL:  Another question I had regarding the device description was there was a mention of the event review data management software.  In other words, I'm trying to understand if a patient does survive their experience, is there a rhythm strip that some medical personnel can review, and if so, how do they obtain that strip?

            DR. SNYDER:  Yes, there is.  I'm looking for the proper slide if you give me a moment.  There is a number of pieces of information we record within the device.  Here we go.  Slide up, please.

            Internal to the device is a memory, and we actually performed three types of data collection.  First of all, there's data which is useful in handoff to a second tier responder, and it's available audibly through the voice prompts of the device.  And this information is accessed by pressing the I button.  There are instructions in the owner's manual so that purchaser knows how to do this for EMS when they arrived.  Certainly EMS organizations will become aware of this as well.

            It will report the number of shocks that have been delivered to the patient and the minutes of use.  So that information is available immediately to second tier response.

            The device also records information for the purpose you referred to, review through our event review software.  It records event data for 15 minutes, including internal storage of the electrocardiogram  in events, all events.  That's shock advisories, shocks delivered, and so forth that occurred during those first 15 minutes of patient use.

            And then finally there is some more internal data that's recorded, including device manufacturing identification, records of self-test performance and so forth.  So we have a complete record of the devices, the diagnostics on a day-to-day basis.

            DR. MAISEL:  I was a little confused.  I believe I read that it said the event review data management software continued to require a prescription.  Is that --

            DR. SNYDER:  That's correct.  It does.  The event review software is really not appropriate for a lay user.  I can't envision why a lay user would have need to evaluate the ECG.  It's really appropriate for an EMS reviewer, physician review.  And it's the same software we use for all of our other defibrillator products.  So any system that has event review software has full access to the  ECG information that's contained in this device.

            DR. MAISEL:  So I'm a little bit confused.  Does the product that we would be giving OTC status to have -- it has the capability to store the ECGs --

            DR. SNYDER:  That's correct.

            DR. MAISEL:  -- but only an appropriate medical person can --

            DR. SNYDER:  Can actually gain access to that information.

            DR. MAISEL:  -- get it out of that device?

            DR. SNYDER:  Yes.

            DR. MAISEL:  Why is that?  Why can't -- I just see that potentially as a barrier to the patient getting appropriate care once they get taken off to the hospital.

            DR. SNYDER:  Can you explain in more detail your concern?

            DR. MAISEL:  A patient has a cardiac arrest.  They're resuscitated.  EMS comes and they would like to immediately take the patient to the hospital.

            DR. SNYDER:  Yes.

            DR. MAISEL:  There is a delay in trying to retrieve from the device the rhythm strips that will be helpful to the patient's subsequent care.

            DR. SNYDER:  That's certainly a limitation of the product.  Unless the hospital had the specific event review software, they would not be able to gain access to that.  The information they would have is the length of time the product was attached and how many shocks had been delivered.

            DR. MAISEL:  I see that as a little bit of a limitation.  It's, you know, going back to ICDs in the early 1990s when people got shocked and we didn't know why.  Certainly you've demonstrated relatively convincing sensitivity and specificity of the device, but that concerns me a little bit.

            DR. SNYDER:  I will add that this capability is similar to all other AEDs that I'm aware of in that some additional facility is required to extract the data from them.  I'm unaware of any AEDs for even public access or EMS response that have built in printers.  With that kind of functionality you typically go up to a manual defibrillator.

            DR. MAISEL:  All of those AEDs require a prescription.

            DR. SNYDER:  That's correct.

            DR. MAISEL:  Two main safety issues that I wanted to discuss and mainly trying to get at the point of whether the AED is truly helpful in all cases or whether there are circumstances under which it could actually be harmful.

            The first is I'd like to discuss the potential delay in notifying EMS, and I'm a little bit concerned that the only initial notification warning on your device is simply a sticker on the outside of the device, and maybe you can discuss why you chose not to have the very first thing that the device says when you turn it on be, "Notify EMS," or, "Call 911."

            That seems like a very simple thing to do.  Why was that not done.

            DR. SNYDER:  Certainly.  I'll address that question first, and then I'd like to ask Lance Becker to come up to add a little more perspective on the history of notification of EMS.

            But the reason we didn't make the initial voice prompt, "Call EMS," because imagine the scenario.  The device is placed in the home according to recommendations adjacent to a phone.  The arrest occurs in a remote part of the house.  The event is witnessed.  You go to retrieve the AED.  You then walk back to the patient.  You open the device, and then you get the instruction to activate EMS at which point you have to go back to the telephone, dial EMS, discuss the problem with EMS, then go back to the defibrillator and actually deploy.

            If we get past the initial labeling, and I want to emphasize that our experience with lay people using AEDs is that they don't fail to activate EMS, and in fact, the studies you heard about this morning were using products that had no labeling about calling EMS.

            So we've taken that successful EMS notification history and we've now added two more layers of labeling to remind people to call EMS.  So we're quite confident in that regard.

            DR. MAISEL:  So are you suggesting that if a user does not immediately notify EMS and they bring the AED to the side of the patient they should not go back and notify EMS?  I mean what you just said suggests that you're suggesting something other than the chain of survival.

            DR. SNYDER:  the protocol that has been implemented is if you fail to activate EMS per protocol, take the device to the site of the patient in VF.  The protocol that's implemented is to deliver shocks and then issue a reminder.

            DR. MAISEL:  Okay.  I guess I also have an issue with that, I think, for a number of reasons.  You've cited many examples of when the device is used or put on a patient and it does not do anything for the patient.  There are times when the shocks are delivered, but EMS subsequently comes and delivers additional shocks.

            I think notification of EMS before use of the device remains a critical component, and the scenario you describe worries me a little bit, and I am concerned that the label alone is not adequate.

            DR. SNYDER:  Yes.  I think Dr. Becker has some information he might like to add to my comments.

            DR. BECKER:  The concern that you raised is one that has been sort of peer reviewed, expert reviewed by a number of very large panels, and it is with some difficulty that everyone agrees that you may not be able to come up with something that is perfect in every case.

            What the American Heart Association determined as they thought about this subject is what do you do -- it's sort of facetiously called the loan rescuer issue, and the issue is if you are the lone rescuer, do you apply a defibrillator or do you call EMS first.

            And in fact, the decision was that in the adult, you should apply the defibrillator first and see if that was a shockable rhythm and then go to the telephone, and that is the American Heart Association standard, and that's an international standard as well.

            So one can imagine why that could be problematic in a very few cases.  I think the thing to remember with this device is in approximately 60 seconds you will then be prompted to call EMS.

            So those are the current ways that we do it.

            DR. MAISEL:  The other potential safety issue I wanted to discuss was the timing of CPR, and certainly there is some data, and we can debate the merits of the data that in patients who have been down for longer than four or five minutes, that CPR first rather than immediate defibrillation might be of some benefit.  And I certainly recognize the trouble in making things more complicated than they need to be.

            Are there instances in your mind when CPR should be administered prior to placing the AED on the patient?  For example, in a patient who is found down and either the time is known to be down for longer than four or five minutes or it's not known how long the patient has been down?

            DR. SNYDER:  I'd like to first review what I believe is the study you referred to, and just review the data quickly so that we can consider it, and then again, I'm going to ask Dr. Becker to answer the more general question.

            Slide up, please.

            I believe you're referring to the study that was done in Oslo, Norway conducted by Lars Wik, and this study examined 200 VF sudden cardiac arrests over a period of 36 months.  Patients were randomized to either immediate defibrillation.  There was 96 in this arm or three minutes of CPR prior to defibrillation, and there were 104 patients in this arm.

            Now, in the system during the duration of this study, the mean collapse to arrival time -- so that's collapse of patient estimated until ambulance arrives at curbside -- was 12 minutes.

            Next slide, please.

            Now, the general hypothesis was that three minutes of CPR performed prior to shocks would result in survival benefit for the overall population, and this hypothesis was not sustained in this study.  There was a trend towards that result.

            If you look, return of spontaneous circulation had a trend towards better results with the CPR first arm, the same for survival to admission and survival to one year or survival for one year following arrest, though none of these differences were significant.

            Next slide, please.

            Now, what was interesting in this study was they examined the subset of patients for whom not the down time, but the ambulance response time was greater than five minutes, and in this cohort of patients they discovered that there were significant improvements in return of spontaneous circulation, survival to hospital admission, and one year survival.

            But if we add up the numbers that Dr. Becker provided to us this morning, that is, approximately four minutes typically from collapse to activation of EMS, in this case five minutes is the cutoff for ambulance response.  That's nine; another two to deploy and deliver defibrillation.  We're really talking about a ten or 11 minute down time population in this study.

            And if we go to the next slide,  which represents ambulance response times of less than five minutes, we see that the trend is actually reversed.  Again, none of these differences are statistically significant, but observed rates  of ROSC was actually higher in shocks where survival was higher and one year survival was also higher, again, not statistically significant, but the trend was in favor of shocks first for, and when we're speaking of down time, approximately ten minutes or less.

            And certainly with this device we're hoping to achieve response times much less than that.  This is the response that's appropriate to EMS arrival.

            Dr. Becker, would you like to add further comments?

            DR. BECKER:  This is an issue that a lot of us are very interested in, and I think the point that I would like to make is that what we have to go on today is exactly what the device, in fact, advises.

            And if I could have the slide up, please.

            This is the AED treatment algorithm that is currently circulated all over the world, and what it essentially says is that as soon as you have an AED available to you, you attach the AED and you defibrillate if that rhythm is ventricular fibrillation.

            So I just want to highlight -- slide down -- that our current state of international and national recommendations is when you see ventricular fibrillation, to defibrillate that rhythm.

            Now, there is a body of data that is emerging to suggest that there may be a time where it would be better to receive CPR first, and I personally believe that that's probably going to be true, but as of yet, there is not a national organization that has made such a recommendation.  There's not an international organization, and there are really fine training organizations that will be examining this, and that may be something that will change in the future.

            DR. MAISEL:  What would be the recourse for -- "recourse" is probably the wrong word -- but a person purchases the device and there are significant changes in the recommendations regarding defibrillation or CPR over the course of the next two or three or five or ten years, and you know, there are hundreds of thousands of devices out there that are not doing the recommended algorithm.   How would we respond to that situation?

            DR. SNYDER:  Well, to begin with the device is actually configurable.  Again, you use the event review software so that it's not configurable by the lay responder.  But the protocol can be changed.  It supports one, two, or three shocks after every interval of CPR, should they be indicated.

            It also has various CPR compression intervals that can be programmed, anything from a half minute to three minutes at a time.  So there is a good deal of flexibility built into the device.

            Beyond that, if protocols are adopted that the product is not currently capable of supporting, the software can be upgraded in the device, and this would most likely be handled by a male end upgrade for the product.

            DR. MAISEL:  Finally, I wanted to touch on some of the safety issues that have been discussed this morning both by the FDA and Philips.  From your submission it appears that there's about 167,000 devices that are in service and close to 450,000 device service years, and so I think the relatively small number of adverse events that have been reported in the context of that is not that concerning to me.

            What is of more concern is that there do continue to be a number of recalls related to these products.  I know Philips themselves had a recall related to their AED, and I'd like to have you walk through how a patient notification system would work if a patient needed to be notified or a buyer needed to be notified that their device was under advisory or recall.

            DR. SNYDER:  Certainly.  First, I'd like to bring up Slide S-77, please.

            I would like to review our recall history for the panel's benefit because certainly there have been many recalls of defibrillators. 

            Slide up.

            The recall history, this product line of defibrillators, the ForeRunner, the FR-2, and the On-Site, is we have had one Philips AED recalled.  That's not one recall.  It is one recall, but it's one device.

            The FR-2 has been built with components that might cause -- excuse me?  Oh, this was in a device -- excuse me -- that had been built with a component that could lead to an early self-test failure.  It was not a device that we understood to be disabled.  It was actually a functional defibrillator, but we did recall the device.  The customer was contacted the next day, and the device was retrieved.

            So our recall history is very solid, partly because of the comprehensiveness of the self-test.  We call it our recall prohibitor.  Because of the fact that we do a full functional test every day, we're able to identify random component failures and products before they occur in an emergency use and we're able to address that.

            Now, to answer the rest of your question regarding our actual recall strategy, I'd like to introduce our regulatory Affairs Manager Theresa Scarr (phonetic).

            MS. SCARR:  Thank you.

            I would like to start with our commitment to performing post market surveillance on this product, both now and in the future if we obtain OTC clearance.  We have a number of ways -- slide up, please -- number of ways that we currently and will in the future contact customers in the event of a recall.

            Our current procedures require us to examine the shipments and the locations that we have shipped products to and there are three types of customers that we ship products to now, and these will not be changing.  We ship products directly to customers ourselves.  We drop ship products.  That means we send them to customers of some of our distributors, and we also send to stocking distributors, such as retail stores, and so those are already currently on our list of customers.

            And I want to point out that our current databases extend further than just the product registration database that Dr. Tovar mentioned this morning.  We also maintain a shipping database of all of these locations where we have shipped to, and we have multiple ways of keeping track of where our customers are, including with our post market study and pads reorders.

            And so in the event of a recall, our procedure requires consideration of the locations -- next slide, please -- and we work with our customers, stocking distributors, as needed to contact their customers, and if that doesn't appear to be effective in the procedure, we require effectiveness checks of all recalls.  If that doesn't appear to be effective, then we will move to consideration of public communications through press releases, news media, Web sites, Consumer Safety Product Commission, and we continue to work with our distributors as needed to insure the effectiveness of recalls.

            DR. MAISEL:  Okay.  That sounds great.  I think the product registration card with the device is going to be an extremely important thing for buyers to understand that they should be sending that in.  I hope they don't get the idea that they'll be contacted or tried to be sold other products, and obviously I don't think it should be used for that purpose.

            DR. SNYDER:  I think it is worth noting that we do provide an incentive for registering your product, and in fact, if you contact Philips to purchase a defibrillator, the customer service actually fills out the registration card on line to make sure we have that information.

            DR. MAISEL:  Great, and finally could you just talk a little bit about the expected lifetime of the device?  I saw shelf life mentioned.  I saw battery duration mentioned, but what is your feeling about the total lifetime of the device with multiple batteries, et cetera?

            DR. SNYDER:  If I may, I'd like to call our Chief Engineer, Mr. Dan Powers, to address that question.

            MR. POWERS:  Dan Powers, Chief Engineer, Philips AEDs.

            Our specified design life for the defibrillator is seven years, and we base our use estimates and our qualification test planning on that lifetime in addition to what we estimate the use per year to be for defibrillators such as this.

            Obviously this product will be a very low use device, and we expect that the lifetime will be well in excess of what we specify internally for the lifetime.

            As far as batteries go, there's a four year standby life for the batteries and a ten year shelf life, and pads are 28 months or 30 months of shelf life with a two year installed life.

            Does that answer your question?

            DR. MAISEL:  It does.  I guess I have a little bit of -- now, my recollection is the labeling has an expiration date on the device.  Is that true or am I making that up?

            MR. POWERS:  No.

            DR. MAISEL:  So there's no way for a buyer to know when their device, quote, expires?

            MR. POWERS:  There's nothing in the device to expire.  The whole purpose of self-test is to -- well, the major purpose of self-test is to detect those types of issues.  So the device itself expires when self-test says it expires.

            DR. MAISEL:  Okay.  So you said two different things then.  You said the device is expected to last seven years or that it will last at least seven years.  So if I'm a buyer and I have a device and it's ten years old and the self-test still says it's okay, can I be comfortable that that device is going to work?

            MR. POWERS:  Yes.

            DR. MAISEL:  And so are the instructions keep your device until your self-test says it's not working?  That could be 20 years, 25.  I mean, is that your position?

            MR. POWERS:  Yes.

            DR. MAISEL:  Okay, great.  I don't have any other questions.  I guess my general position is that I think the sponsor has done a superb job in demonstrating both the effectiveness and the safety of the device.  I don't know that we have all of the information we'd like to see in the population for which it's intended, which is the home use population.  Nevertheless I think the benefits of having the device available over the counter strongly outweigh the small perceived or potential risks, which really are hypothetical at this point and not really well demonstrated.

            We have heard multiple presentations that there are very few issues of actually harming patients, although devices certainly can malfunction.  I still feel strongly that having them is better than not having them.

            I will turn it back to you, Warren.

            ACTING CHAIR LASKEY:  Thanks, Bill.

            Okay.  Time for the panel.  Norm, did you want to start today or should I start on the other?

            DR. KATO:  Start on this side.

            ACTING CHAIR LASKEY:  Okay. 

            PARTICIPANT:  I don't get a vote?

            (Laughter.)

            DR. KRUCOFF:  Okay.  Well, let me just follow.  A lot of Bill's comments were things that I was interested in.  So I'll try and be brief.

            And, again, I think we all start on the same platform that this is not a discussion or an argument certainly about the utility or the value of AEDs.  I think the real question is what role does the physician prescription requirement play in sort of the whole picture.

            And some of the things that have been discussed -- and I will also say that I appreciate very much the array of expertise and information that's been brought forth both from the sponsors and their experts and from FDA.  There are some things that I think probably don't bridge in my mind.  The drug prescription model, for instance, really doesn't translate to me where a drug gets purchased for an individual, whereas this is a device that can be in public access in a lot of different configurations, even in a home with a visitor or trained or untrained people.

            And the real question in my mind is, again, not the utility that the prescription process or the physician role implies, but with the rapidly changing landscape, where does the physician's discretion or awareness of other issues that either currently or in the very near future may eventuate that makes this more complex or that actually creates safety related issues through a kind of back door that's not anticipated today?

            And how much does it matter if we pull that discretion out of the picture?

            And I guess what I've been listening for, on the one hand, is how much of an obstruction is the physician's role today with the prescription to getting the product out there, but the back door side that I guess I'd like to come back to a little bit is with a growing population who have more and more complex AICDs implanted, AICDs that go through phases of defibrillation, rhythm reevaluation, packing, rhythm reevaluation; what are the growing possibilities that the device that's so safe at discriminating defib. and not defib. rhythms -- I'm convinced of that.  You guys have done a great job making a convincing show there, but that actually with rhythms that you would want to defibrillate but you're now completing with an implanted device that's actually also doing multiple things over time, where we have an ongoing growing population with these devices, is that a back door to safety issues that we don't see so much today, but that with more access and more implants might eventuate tomorrow that if a physician's prescription was required, there would be a level of awareness of what's changing over time in the patient populations who fly on airplanes or walk through shopping malls and those kinds of decisions.

            And that's honestly where I'm stuck because that's not a failure of the device.  The device is going to be seeing defib., but the device is not tooled to understand that it may be seeing defib. while something else is also getting ready to defib. or trying to pace or do other things at a point along the way, and I'm sort of stuck on that.

            And what goes with that is a concern, and again I'm not sure that the physician prescription is the right answer, but if we recognize that a lot of the data that we've seen about the value of AEDs are in patients who currently -- actually the highest occupations would be identified as candidates for ICDs. 

            So as we think about a growing access, if we make this OTC and we get into more public access where the highest risk patients have ICDs, we're getting out into a population where, in fact, they're are lower risk population.

            I recognized you showed data.  Some of these are not predictable.  Some of these are not going to be identified ahead of time, but if we look at what is the shifting terrain over the net five years, more and more high risk patients who are really vulnerable to VT/VF, sudden death events are going to have ICDs.  That means fewer and fewer of them occupy the random, undetected population that would benefit from AEDs on a wider basis.

            And I haven't seen the numbers, and I'm not sure how we get the numbers, but it really concerns me that we have a changing terrain with more and more complex devices that would actually be involved when this device is correctly charging itself and getting ready to defibrillate, where the expected results or concerns if a physician prescription is in the loop might have more wisdom over time than if we pulled that plug completely.

            And then the flip side is how much of an obstructionist is the physician prescription piece as it is, which I get the flavor from everybody who's more involved.  I'm a plumber.  So you know, this is not my front line, but we do work a lot with ECG devices in a lot of venues, including pre-hospital.

            So I guess can any of the sponsors help me with understanding a little bit better just how obstructive the physician is?

            You know, the numbers that you shared, which were very helpful, still don't say to me it looks like the vast majority of people are the 5,000 hits you got on your Web site or whatever.  Most of those are people who just weren't interested.  It wasn't that the physician turned them away.

            And then of the actual physician comments you show, how many really were telling their patients, you know, something that's accurate.  You don't need one of these things.

            And, again, I know you don't know.  None of us can know.  So is there some way you can help me understand how obstructionist is the physician's prescription requirement today relative to how different would the access to these devices really be if that was OTC?

            DR. RUSKIN:  I can't give you a databased answer to that.  I think that the best data is what you heard from David Snyder, but I think from that data it's clear that with the limited experience Phillips has at least with this, even patients who knew what they wanted and understood how the defibrillator worked, a large majority were advised by the physician that they saw not to get a device and were not given a prescription.

            I don't think the physician can actually make that decision in the context of what we're talking about here, which is a piece of time critical safety equipment that an individual or a family may choose to have in their home or in any environment.  Because it's precisely that group in whom the event is unpredictable, and therefore, I don't think a physician or anybody else provided the individuals who wished to purchase it understand what they're getting can really make an accurate prediction.

            And I think that probably gets to the heart of the matter, and what I'm going to say now is pure speculation and opinion, and that is I think most of us as physicians are used to prescribing for diseases, for individuals who have diseases that we can evaluate, quantify, and then make some sort of a risk benefit assessment and prescribe therapy for that perceived risk or that illness.

            We're not used to prescribing for an environment, which is really what we're talking about here, and I think it gets back to the issue that you raised with implantable devices.  Yes, it's true that the numbers of people with devices is growing very rapidly, but that is not the target population here, and we follow more than 1,000 patients with ICDs at my institution, and there may be one or two who had AEDs, but none of us know about it because clearly these are people who are on the radar screen.  They're followed.  We talk to them four times a year.

            The issue has occasionally been raised by a family and someone with an ICD, but that's a clear-cut situation in which the individuals are in the medical system and they're being followed, and that's not the target population.

            Is there a potential for some interaction?  I think one can't possibly exclude that with certainty, but that's what post marketing surveillance is about.  That's what experiential observation is about, and I don't see a way to actually make a dent in the problem without expanding access because this group is not identifiable by you or me or anybody in this room, and it is not within the realm of what we do on a daily basis to be thinking about prescribing devices for these patients.

            Most of them will never call a doctor I don't think, certainly not in my experience.  I have never had a call, a cold call from an asymptomatic 55 year old saying, "You don't know me, but I wonder if you'd be willing to write a prescription for a defibrillator.  I want to have one in my home."

            The real question to me is what value does that add, and I can't see any.  I can't see any from a safety perspective, and I can't see any from an effectiveness perspective, provided they know what they're actually getting, and I don't think it's the physician's role there.  I think that's the role of the manufacturer and the rest of society to educate ourselves about, you know, what is a defibrillator.  What does it do?

            I don't think that a physician writing prescriptions is going to fill that need.

            DR. KRUCOFF:  Okay.  I guess to me the question is is the physician writing prescriptions obstructing that, but I understand your comments.

            All right.  Let me shift gears a little bit.  Has any thought been given as more and more of these get out and we have another population that actually doesn't want these used on them in end of life settings as to how or when or why increased access to these devices, assuming that if this goes OTC that the one unequivocal reality will be that more of these devices will be more available, more widely, under a wider range of untestable circumstances.

            Have you all considered at all the ethical aspects of defibrillators applies to people who don't want them?, but can't speak for themselves in these kinds of public settings?

            DR. BECKER:  Well, again, it's not an easy question to really answer.  If you think jus the design, this is in the phone.  You would think that most people in the home would not put a device there that they don't want used on themselves, but it is possible that that situation could change and a device could be there.  The real issue is not about the AED though.  It's about the resuscitation, and so what you're really raising is is it appropriate to resuscitate someone who doesn't wish to be resuscitated?

            And, again, that has been reviewed extensively with chapters written about it, and what most, i think, thoughtful people suggest is that until such time as you have sort of a verifiable DNR order, do not resuscitate order, until such time as someone can express the wishes of that individual, most of us feel that the right thing to do is to attempt a resuscitation.

            And of course, there are a very few times when that may be inappropriate, and at that point the therapy can be withheld.  Additional therapy can be withdrawn at that point, and that has not, though it has been discussed a great deal, that has not turned out to be one of the major controversies or real problems that has emerged in our large scale studies.

            DR. KRUCOFF:  Okay.  I take your point, but I guess what I'm anticipating is we're going to talk about a real life experience that starts to go potentially in a population exposure by a power of ten, and at that level -- and this is an issue, again, that to me is less than the individual home than in a business place, than in an IBM tower that has 4,000 employees in it that currently would have to at least consult a physician to write a prescription before they could put an AED on every floor in the tower, and a physician might actually be smart enough to say, you know, if we're employing people who have a terminal disease, we can have a way of identifying them or if we're employing people who have AICDs, we might have a way of identifying them as opposed to an MBA making the decision because they can now do that as an OTC product that we're less likely to get sued for being an inadequate work place if we have these things on every floor.

            It's the shift of that kind of decision making and the real population who we're talking about being treated now not by hundreds of thousands, but by millions that to me is the least visible reality and least testable certainly in a simulation environment in this kind of potential shift.

            DR. BECKER:  Again, I don't think we have a very precise answer for you, but I think what we know is that in broad strokes this has not been a problem even though we already have many devices in public settings.

            DR. KRUCOFF:  But those have all been placed with a prescription, right.

            DR. BECKER:  Indeed, they have, and as it goes up, I guess my thought would be we should be so lucky as to have that problem because it would really indicate that we have saved many, many other lives in the process.

            I'm just saying if you just compare the cost benefit, we know we're saving lives.  It may be that we occasionally resuscitate an individual for whom resuscitation is not indicated.  That is not anything unique to the AED.  I do that in the emergency department all the time, and we know how to take care of that.

            So I would only say that we should be so lucky that that is our problem.

            DR. KRUCOFF:  Well, I wish I could go there.  Okay.  I just have two other quick, just technical questions thinking back about the individual at home.

            Understanding that you guys now are checking your speaker, that you building in a check for loss of speaker function, if Mom collapses out on the sidewalk and I grab my AED as a teenager and in running out the door bang it into the door and break the speaker, is there a back-up function?  Is there any LCD output?  Is there anything instruction or am I just out of luck?

            DR. SNYDER:  Excuse me.  The back-up is actually the quick reference card which has a detailed depiction of the graphics in the process, and we have performed a validation study, a very small one to evaluate individuals' ability to use this product in the absence of the voice prompts.

            Speaker up, please.

            This slide shows our results of our testing under condition of speaker failure with the HeartStart Home device.  We recruited 990 volunteers.  Again, these are people never exposed to this device.  We disabled the HeartStart speaker and all other functionality on the device remain the same.

            The quick reference card was present in the AED case, and we presented the same scenario, entry to the room with a manikin, the naive untrained user was asked to attempt to save this person, and AED was available if they chose to use it.

            The results were that we were successful in delivering shocks in eight out of nine of those volunteers.  The average time to shock was just over 90 seconds.  There was one failure due to individual placing pads over the clothing.  As I mentioned earlier, this is an issue.

            Now, the pictures and the quick reference card do show baring the chest, but we're certainly handicapped when we don't have the voice prompts, but nonetheless, we did have an eight out of nine success rate at delivering shocks in the absence of the voice prompts.

            DR. KRUCOFF:  Okay, and presumably that would be the same thing if you're just in such a noisy area.  There's traffic or whatever that you can't hear the volume.

            DR. SNYDER:  That's correct.  That's actually one of the purposes of the quick reference card, is exactly for that eventuality.

            DR. KRUCOFF:  Or if you're just excited and it says something, but you missed it.  So you go to the card, and it's the same back-up.

            DR. SNYDER:  You could,b ut now missing a prompt is covered because you remember the device can detect the stage you're at, and if you haven't completed a task, it will repeat the prompt again and again.

            DR. KRUCOFF:  Okay.

            DR. SNYDER:  And if you're  still failing, it will actually change the way it describes the activity you need to make in case there's a miscommunication or misunderstanding the prompt.  We say it a different way.

            DR. KRUCOFF:  Thank you.

            DR. SOMBERG:  Well, I've been very impressed by the sponsor's presentations and the concept of this device and the benefit it could do, but with that said, I have a concern that 50 percent of the people who did come and request the -- when through the requesting of the prescription were told that it's probably not appropriate by the physician.

            That is a bit troubling, and I empathize  in what your statement is, that it's not really knowable what the reasons were, but is it knowable what type of physician turned this down?  Was it a cardiologist versus a generalist?  Is there any other data that was queried during that interaction with the patient?

            You don't look like you're smiling.

            DR. SNYDER:  No, the answer is easy.  No, we don't have that information.

            DR. SOMBERG:  Okay.  Because that would have addressed some of the speculation that we heard that it may have been a lack of physician education, et cetera.

            But with that said, and I was going to ask this, which is what one of the recommendations is later, and I think it's important to say that both the sponsor and the FDA could not come up with an indication or a subpopulation that a physician would clearly identify that would be harmed by this device, and I think that's very important since half of the people may have been told by a physician out there that it was not appropriate, but we really don't really know what that group would be.

            And, therefore, I'm suspect on that decision. 

            Now, this doesn't relate to taking away the physician approach or prescription because it could be said for the device in general, but I'm just going to say it very quickly, that I think there needs to be -- and it was said by the FDA in their review.  So I think our doing it is still appropriate -- that repackaging storage and essentially getting it ready for the next use is a potential weakness here, and I think the sponsor could do just a little bit more on certain guides for that, how to get it ready, put it back together, get the equipment.

            I know when batteries go dead on things, I said I'm going to reorder them, et cetera, and all sort of things.  Clearly it's an emotional experience that will shock people, if you will, into thinking about this, but I think there could be some sort of card that's provided that gives you a checklist on what you have to do that's usually good in that regard.

            Also, I think the sponsor should consider that there may be subgroups that are especially likely to buy this who could benefit from some recommendations, and there might be a device patient circulars, if you will, or something like that, and I'm thinking specifically a pediatric one and even a subpediatric in terms of the SIDS population because, I mean, that is a group of potentially at risk individuals.  They're parents of people who might be worried about this, might buy that.  There may be special training to be used for that, and there may be special information  out there.

            I always need to be reinforced that respiratory is more important than rhythm in children, and I'm not even sure.  When they get to be this small I get very concerned myself in what knowledge do I have, and I have a lot more than I think people who use it.

            So these are some things that could be.  Another thing is congestive heart failure, and we talk about pump failure versus rhythm, and You know, I can see we just discussed this extensively yesterday, but there is certainly almost half of people seccumb electrically, and we've pumped this.  This is going to be a target population.  It may be appropriate for everybody who has a loved one who's at risk because of low ejection  fraction may want to be trained in CPR, the use of an AED, et cetera, but there are certainly different situations.

            And since there may be a higher frequency of use in this population, but there may be also pump dysfunction, asystole and all of that, there could be a little description of this that a layman could deal with as well.

            So I've just been thinking about this for a bit, and it seemed the sponsor really has a very thorough approach to this.  So they may think of the subpopulations in developing a little series of cards like we give out for different diets, you know, for different, you know, gout population with CAD and some other groups.

            You might have a different series of cards that could be given out that could be very helpful.

            Also, there was one thing that did disturb me, and that was the patient or probably the person who used the device was invited to contact the company after its use.  Invited?  I mean, I think it should say very clearly and maybe when you -- it could probably be put in as a prompt, as well -- when you rehook up the device and all of that, have you contacted the company and reported the use of a device?

            I think that would be very helpful.  It's a contribution to humanity in general, to the company, to the validation of the product, and it helps in that regard.

            You know, people need to be sometimes very strongly guided, and when you use something, I mean, clearly when my air bag discharges, you know, I know it's laying around there.  When this thing discharges, it's the same sort of thing.  It really should be noted and action done.

            With that said, I do think that this will make a contribution to the public health, and I congratulated the sponsor for pursuing this.

            DR. NORMAND:  Hi.  I only have a few questions, given that there really wasn't much data presented.  I'm going to begin with some practical questions because you could think of me as the naive lay person on the panel.

            And I was sort of excited seeing the manikin and all of the action going on, and one of the things that I noticed was the color codes.  You have yellow and orange, and I was wondering were there any problems differentiating yellow and orange because I don't know.  My husband would say that was yellow, and I might say that's orange.

            So did you have any problems in your various tests about the color of the buttons?  I realize sometimes they flash, but I'm wondering if you're alone and looking back and forth.

            DR. SNYDER:  With respect to the buttons, actually there's only one, and it's the flashing shock button.  The yellow was the color of the pad's liner.

            We have not noticed any difficulties in the color sequencing.

            DR. NORMAND:  In the colors.

            DR. SNYDER:  Because of the fact that the items are marched through sequentially and they're illuminated.  Plus the voice prompting reinforces the proper activity at that time.  So, no, we haven't seen any difficulty with recognition of those.

            DR. NORMAND:  And then the other sort of practical thing, I think, there's an obvious answer to this, but we heard it in English.  There's Spanish versions and other language versions for this device?

            DR. SNYDER:  That's an excellent question.  At this point we're only asking for consideration of the English version of this product.  The on-site product under prescription is available in multiple languages, and should the marketplace express a desire for other languages, that's certainly possible.

            But the device under consideration today is English only.  It's labeled as English only, and for any household considering a purchase, that's obviously something they need to consider.

            DR. NORMAND:  Yeah, given the audit, that's a nice feature of the whole product, is to be automated in terms of telling you what to do, and clearly if you got something and couldn't understand it, that would be a problem.

            DR. SNYDER:  But I would like to remind of the results of the testing with the speaker disabled, which would be similar to the situation a person speaking a different language would have, and we did have a success rate of eight out of nine naive volunteers never having seen the device being able to deliver shock with effective vector.

            DR. NORMAND:  Okay.  That brings me to another set of questions regarding your simulation test.  I noticed in Tab 5.2 there are there are data here.  So I will comment on the data.

            DR. SNYDER:  Yes.

            DR. NORMAND:  In Tab 5.2, one of the tables, I was noticing that the education level of the participants, which seemed pretty high -- I think it was 47 percent -- have a college graduate.  Now, I don't know.  I'm pretty sure that's not really representative of the general population, but again, I'm not sure of the target population here, but that seems like a well educated testing population.  Could you comment on the numbers and the successes in a less educated population?

            DR. SNYDER:  Yes.  I need to ask you for reference on Tab 5 because I don't know the study by them.  Was it the labeling evaluation?

            DR. NORMAND:  It's 5.2, Table 1.2, and I have so much information in front of me.  It's the safety and usability characteristics, blah, blah, blah.  I can give you the page number.

            DR. SNYDER:  I think the best way to answer the question is we have collected that data in the case of the labeling evaluation study, and we have analyzed it by both education and age effects, although again, this was data that was not submitted to the FDA because it was not the primary hypothesis, but I'd be happy to share those results again with the Secretary's permission.

            MS. WOOD:  That's fine.

            DR. SNYDER:  Okay.  Let me bring up the slide, please.

            This shows the distribution of ages that we were successful in recruiting in the labeling evaluation study.  Now, recall that this was a study where the volunteers first reviewed a piece of the supplementary labeling material that came with the project, performed a written exam, and then proceeded to a simulated use.

            You can see the age distribution from 21 years of age up to 740.  It's not perfectly uniformly distributed, but it's reasonably good, and what you see is the success in the blue, the failures in the gray, and the failures are certainly fairly uniformly distributed.

            This study was not powered to detect these kinds of effects, but we don't see any reason to suspect that success by age is affected.

            Next slide, please.

            Owner's manual.  This is by education -- oh, excuse me.  Never mind.

            Quick reference again by age.  We weren't quite as successful in getting a uniformed distribution, but we had failures at both the high end and the low end of the age range.

            Next slide, please.

            And your primary question was regarding education.  These are the results by education.  For the owner's manual where we had the most failures, we had about equivalent percentages, slightly better in the advanced education, but again, we had in both groups failures.

            And with the quick reference guide -- next slide -- the only failures were actually in the advanced education group.  Slide down, please.

            (Laughter.)

            DR. NORMAND:  Didn't I tell you?  We overinterpret, I think.

            The next question I have relates to your survey of households.  You had some statistics regarding 145 households that you attempted to contact.

            DR. SNYDER:  Yes.

            DR. NORMAND:  And I noticed that you only had a response -- only 78 of the 145 responded to your telephone survey, and I was hoping you could characterize those that did not respond to this household, like where they were.  Were they rural households, et cetera, et cetera?

            DR. SNYDER:  I don't think we have that data.  Let me confer and I can find out if we do.

            MS. SCARR:  I'm Theresa Scarr, the Regulatory Affairs Manager again.

            This survey was a survey.  We contracted with the Telephone Center to attempt at least seven, if not more, times to contact individuals in homes and businesses,m and through that process there were some that just never responded and never picked up the phone.

            DR. NORMAND:  That's pretty standard though, but typically such an agency would then provide you with information about the people who didn't respond.

            MS. SCARR:  We had the list, yeah.

            DR. NORMAND:  I'm sorry.  I just didn't hear you.

            MS. SCARR:  We were the ones that provided them with our list.

            DR. NORMAND:  Okay.

            MS. SCARR:  From our database, the ones that I've mentioned before.  We have provided the contract telephone agency with a list of our home and business consumers of the ForeRunner and FR-2 devices for that survey, and they proceeded to contact them.

            DR. NORMAND:  Okay.  So you had no information that you can provide us regarding who didn't respond.

            MS. SCARR:  Just their names.

            DR. NORMAND:  Certainly don't want that.  Okay.

            I guess my next question is one that is probably, I think, a practical question, and I was wondering with the manikins, why don't you have little child manikins.  Why is it always an adult?  Was that always the case?  It's an adult-like manikin that's used?

            DR. SNYDER:  No.  That's not always the case.  In the pediatric validations, we performed or were done with a toddler manikin.  So there are different manikins available, but we've used the manikin that's been appropriate for the primary use, and in this case, the product is really intended primarily, and in fact, the way it ships is for adult applications.  So we evaluate it on adult manikins.

            DR. NORMAND:  Okay.  So you don't have any information about the success rate with the pediatric?

            DR. SNYDER:  Actually we do have data.  That was in some of the slides I showed earlier about the ability to both exchange the cartridges and deliver therapy, as well as the pad placement accuracy, and that was performed on pediatric manikins.

            DR. NORMAND:  Okay.  That leads me to the next question, and I may have misunderstood a response that was stated earlier, but there was a question raised about 911, the order of when you dial 911 and when you proceed with the shock, and I think the answer started out with an adult, that you could go to the shock.

            Should I infer by that that if it was a child, you should dial 911 first?  I may have overinterpreted the answer that was given.

            DR. SNYDER:  Were you asking specifically about what's implemented in the product or the comments of Dr. Becker about what's --

            DR. NORMAND:  The comments by Dr. Becker.

            DR. SNYDER:  Okay.  Dr. Becker?

            DR. NORMAND:  Were you meaning to say that there's a different rule or algorithm for children versus adults in terms of the order of dialing 911 or administering the shock?

            DR. BECKER:  Again, a topic that has received great attention by experts, and a difficulty one.

            The AHA in their guidelines would suggest that for a child, unlike an adult, one should first being CPR prior to calling 911 if you are the lone rescuer, and it's for exactly the comment that was raised.  The concern over respiratory distress is hypoxia being a leading cause of death in children.

            Does that answer your question?

            DR. NORMAND:  Yes, it answered the questions, but I just then want to make sure.  Are those instructions clear that there's a different protocol, so to speak, when you have a child versus an adult?

            DR. SNYDER:  The answer is, no, we do not have different instructions for this particular aspect of pediatric resuscitation.

            DR. NORMAND:  So I'll leave it to the clinicians on the panel to comment more for the pediatric sides of things.

            I just have one final question.  This has got to do with the post market information.  You indicated a product registration card that should be filled out.  Can you tell me what percent of products actually have a card filled out and sent in?

            DR. SNYDER:  We do have that information, and let me check.

            DR. NORMAND:  I don't think that's violating anything, is it?

            DR. SNYDER:  I need to check with my support team to get the exact number.

            We have approximately a 44 percent completion rate with owner's registration cards at the current time.

            DR. NORMAND:  I'm sorry.  Forty-four percent?

            DR. SNYDER:  Forty-four percent, yes.

            DR. NORMAND:  Okay, and so that's saying that -- is that across -- that's, of course, stratified, and clearly that must differ depending obviously if they register with you directly.  You're more likely probably to get the card than if it's bought -- I don't know -- somewhere else.

            DR. SNYDER:  I don't have specific information on that.

            DR. NORMAND:  Okay.  You don't have the stratified.  Okay.  No problem.

            That's all I actually have to ask.

            ACTING CHAIR LASKEY:  Well, in the interest of keeping us on time, I'll defer to the remainder of the panel, but I do have one area that's still bothering me.  I'm not clear about your system for getting back to the individual should Philips need to contact the individual for any reason whatsoever, be it upgrades, modifications, newly discovered hazards.

            I don't understand your system for this life saving device whereby this doesn't seem air tight.  There's no one-to-one connection between your company and the individual that purchased this.  The information that you're getting is relating to the wholesale buyer, to the distributors, occasionally to the individual that purchased this.

            Can you describe a mechanism whereby you can tighten this up?

            MS. SCARR:  Theresa Scarr, again, Regulatory Affairs Manager for Philips.

            I did go very quickly over the steps involved.  So I apologize for that earlier.

            For the different types of customers that we ship to, there are different methods utilized.  We will always try to directly contact either by phone or by letter whenever we discover an issue that requires a recall.

            And for direct sales, we go directly to the customer, with a combination of our databases that I mentioned before.  For our non-stocking distributors, we also ship directly to the customers, and so we have shipment records where we can contact those customers directly ourselves.

            And for stocking distributors, such as stores and other types of distributors that hold their own inventory, we work directly with them to coordinate recalls as needed.

            So the same methods before.  We use our shipment records by serial number.  Every shipment record is tied to a unique serial number so that we can identify which customers we ship to with those serial numbers, and we contact them directly, and if the product is no longer with the stocking distributor, for instance, we will work with them, with their own methods for customer communications, including their own databases for direct communications, opt-in E-mail, Web sites, in-store signage, et cetera.

            And if that doesn't appear to be effective, then our current process that will remain the same after OTC availability would be to evaluate the need for public communication.  In the case that we are not able to contact some customers with an important safety issue that we need to notify them about through these different methods I mentioned before, Web sites, press releases, et cetera.

            ACTING CHAIR LASKEY:  And did I understand you correctly?  I had heard that there were no ID numbers on these units.

            MS. SCARR:  Oh, oh, there are serial numbers on every --

            ACTING CHAIR LASKEY:  There are.

            MS. SCARR: -- device shipped, and the device itself does not have an expiration date.

            ACTING CHAIR LASKEY:  I see.  Thank you.

            George.

            DR. VETROVEC:  Well, I would just begin by seconding what some of the other panel members have said regarding congratulating the sponsor for really trying to, I think, do a very good job of presenting the material and being responsive.

            For my own perspective, the issue of a doctor prescription seems to be probably more of a barrier than a help.  One can always think of how a physician could make a good decision or learn something else about the patient that might change it, but there's probably more disinterested physicians who see this as a question that they're not really familiar with and may not give the best answer.

            The thing that worries me the most about this is the issue of once the patient is down and someone is trying to manage this, the thing that will make the biggest difference, it seems to me, is their obtaining expert help, which is EMS, and this issue about do you call first or shock first in the setting of being scared, confused, I think this is somewhat of an issue, and I don't know how well to define this for the individuals using it.  But I think that seems to me to be a crucial issue.

            And not to design your equipment for you, but in this era of technology, I kind of am surprised that it doesn't automatically call 911 with a GPS system.  That's a no charge phone call, and I find that amazing.

            That would seem to me to solve the problem, but this is an issue in my mind as to how you get the help that you need to make sure and the pediatricians -- I'm not a pediatrician -- have brought up these issues about, well, if it's breathlessness in a child, it's really why they're down, and this may not be the right device and calling may be the important first thing.

            That's the piece that I think needs to be well defined.

            DR. RINGEL:  First, I'd like to say that I've been persuaded by the information that was provided both here and in our packets as to the importance of making AEDs widely available, the lives that can be saved.

            I also agree with the other members that have said this.  I've been very impressed by product development by the company and the information provided by the company, the care taken to assure safety and efficacy.

            I'm well aware that you can't make an entirely idiot-proof device.  There are people that are going to mess it up, but it seems as if the company has tried very hard to address some of these issues.

            Having said that, I remain concerned over some of the pediatric issues, and this is a difficult position for me because, on the one hand, we in the pediatric word don't want to be seen as being so difficult that corporations will try to avoid us like the plague. 

            I was happy to see that you've taken this step to include pediatrics in your product so that if I come along and make all of these protestations, I am afraid that the next time you'll say, "Ah, forget about it.  They just cause us too much trouble."

            But now that I've said that, I'm going to launch into some of my concerns.  The two paddle design troubles me only because I have trouble understanding how this would work in practice.

            Say there's an elementary school that wants the device.  So they buy the device, and they say to themselves, "Well, we should have the pediatric paddles in the device."

            And then of course, it's much more likely that one of the parents or one of the teachers goes down than one of the kids because it's just way more likely even though there are fewer adults in the school.

            So then you have a situation where you have the pediatric paddles in.  It's recognized as pediatrics.  People come to the device.  They either then have to go find the adult paddles and put them in and be, you know, unemotional enough to realize that they have to switch the paddles.  So then they go and maybe they even put the pediatric paddles on the adult patient.

            Or another scenario where you're in an elementary school and the kid is over 55 pounds.  It's a big kid.  We have elementary schools that go from kindergarten up through fifth grade, and some of those fifth graders are very large.  So they put the pediatric paddles on thinking that it's a kid.  It's a child, and your algorithm, unless I've missed it, gives 50 Joules.  It doesn't step up to 150 afterwards.

            It would seem like it would be very simple to protect people from making that mistake of trying to use pediatric paddles on a large child or an adult; that you could have easily built an algorithm that the first shock is 50 and the next shock is 150, especially since we agree that, and you've said it in your own, that the American Heart Association says that if somebody is down and they need to be shocked, just shock them.  It doesn't matter how much juice you give them.  It's an important thing to do.

            So that would mitigate against many of my concerns if you had that algorithm built in, that first is low voltage; second is high voltage.  So that was one issue about the pads.

            I have concerns also then about the issue that you say it can be used for kids.  It is a pediatric approved device, let's say, or you market it as such, and then you don't include the pediatric pads.  Well, then why bother making pediatric pads?  Why not just make a diagram on your adult pads that say if you're going to use this for a kid, put it on the front and the back?  And then just have one set of pads, and you have your pediatric front-back and you just shock them with 150 because, again -- and I'm referring to your response to one of the FDA questions saying that the American Heart Association says then it's fine.  Just use adult pads and just shock them that way.

            It would seem to simplify things.  Include the children and not run the risk of complicating the issue, having people fumble around.

            That brings me to the next issue, is the fumbling.  Most pediatric arrests -- and, again, it's problems when we talk about pediatrics because it encompasses the ages up to 18, and really it's only the toddlers and the infants that we're talking about primarily respiratory arrest.  Once we get to the school age child, if they go down on the soccer field, they have long QT, they have hypotrophic cardiomyopathy, they have, you know, anomalous coronary arteries or something like that.

            So we're really talking about the lower end of our pediatric range, the toddlers and the infants.  But the issue there is respiratory, and we could get to the point somewhere these were so widely available that people forget the order of things.  So that comment about the order of things, I think, should be carefully written in the brochure, in the manual again, that for infants and toddlers, respiration, you know, ABC, airway breathing circulation.

            I think you know, that's the mantra in the pediatric world, and I think that that has to be included at least in the documentation, that infants and toddlers, it's ABC.  It's not SABC, shock, airway, breathe and circulation.

            So I just thought I'd mention those issues.  I think those pretty much cover the pediatric concerns.

            I must admit in your answer to one of the FDA questions, Question 12, your last paragraph I didn't understand at all, but I think I have just answered it.  Because there are currently no established criteria for assessing the usability of defibrillators, Philips believes this is an important question for the panel to consider and that different usability for criteria for the intended pediatric versus adult use may be appropriate.

            I think that's what I just did.  I don't know, but I think that's what I was addressing.

            That's it.

            ACTING CHAIR LASKEY:  Are we responding?

            DR. RINGEL:  I think they're going to try.

            DR. BECKER:  We are going to try. It's like I couldn't keep the list quite.  So I'll try to answer some of those questions.

            The first thing is that for the school situation that you raise, which is a really good one, most people would say have the adult pads as the default position because, in fact, the most likely person in a school to go down is not going to be a child, and so we just know epidemiologically again that the most likely person to have cardiac arrest is going to be an adult, and that's why the adult pads are sort of the default position.

            So what is actually required is if it's a child, you have to do the switch, and that part is exactly right.

            The critical thing is that I think if you just look at a worst case scenario, the pads are not there.  You know, AHA -- and there's good data to back it up -- would suggest just use the adult pads, and we all acknowledge that.

            DR. RINGEL:  So why have pediatric pads?  Why confuse the situation?

            DR. BECKER:  Well, one answer would be because the pediatric community really asked for it, and there is good reason that at certain weights, particularly in the small children, you begin to deliver more current than is really required to the heart.  So there's a good reason to have the pediatric pad, and the optimal thing would be to use it in a very small person, but at the same time, most of us also recognize, as do the pediatric EP folks, that if you have nothing better, you use what you have.

            DR. RINGEL:  But will it step up from 50 to 150 on a subsequent shock?

            DR. SNYDER:  No, it will not.  It's a fixed 50 Joule.

            And I do want to add you actually put your finger on precisely why we have pediatric pads.  Lance, correct me if I'm wrong, but I believe the AHA recommendation is in the absence of a pediatric treatment option for patients one year and older use the adult dose.

            But as you mention, the two groups that we're really concerned about is the top of the pediatric age range and the infant, and for the infant, I really don't believe that 150 Joules is necessarily appropriate.

            DR. RINGEL:  Right.

            DR. SNYDER:  The other benefit you get by snapping the cartridge in, that's how it's identified to the device.  What is the appropriate device?  It also switches the CPR protocol so that the voice coaching you get when you're performing CPR switches to pediatric CPR, and we have to have some mechanism in the device to recognize the pediatric treatment is desired.

            Now, we did consider putting a switch on the device, adult versus pediatric, but what we found was that confused and compromised the primary use of this product, which is treatment of adults.

            DR. RINGEL:  I appreciate all of that, and believe me, I probably haven't spent as much time as you guys thinking about it because you, I'm sure have talked about this a lot, but I have thought about it a lot.  The chance that you need to shock an infant, like I say, you said under a year is small, but the chance that you might need to shock a child playing soccer or whatever goes up a bit, and my concern is that someone well meaning will think that that's a small child, put the small pads on, and get 50 Joules and that's it.

            So it seems to me that you're more likely, even though this is rare -- all of this is vanishingly unlikely -- but you're more likely to be erring on the side of under treating an older pediatric patient than over treating an infant or small toddler.

            If the panel, EP people here -- tell me what you think about that, but my concern is that you've got that big elementary school kid, and they put the pediatric pads on.  They miss the 55 pound or whatever, think it's a small child, and they're not delivering enough.

            DR. SNYDER:  I actually do have some data that I can share.  Again, I keep apologizing for going to unpublished data.

            DR. RINGEL:  Okay.

            DR. SNYDER:  But we do have a post market study of pediatric attenuating pads that the 50 Joule defibrillation capability that's ongoing, and we did present to the last scientific session's interim results.  I do have updated results.  Again, the FDA has not reviewed this data, but I would be happy to share it with the Commission.

            MS. WOOD:  That's fine.

            DR. SNYDER:  Okay.  Slide up, please.

            To date we have -- excuse me -- as of July 4, we have 22 reported uses of the 50 Joule attenuating pads for treatment of patients.  The age range was from five minutes of age to 23 years of age, which I hope is going to address your question.  This was a very small adult, and in the case of the 23 year old, it was actually a medical professional that made the judgment that a reduced therapy was appropriate for this particular patient.

            Five of these patients received shocks, four VF.  The ages were 18 months, three, seven, eight, and ten years.  Average number of shocks required delivered to each patient was two, and four of those patients survived to hospital discharge.  So that's four or five patients treated with this therapy did survive to discharge.

            It was judged the AED performed appropriately in all uses, and again, no safety problems were recorded with use of the product.

            Slide down, plesae.

            DR. RINGEL:  Well, that obviously is very interesting, and again, as I stated before, it's very nice to see how much work you have done on this.

            So a ten year old, a normal size ten year old responded fine to the 50 Joule shock.

            DR. SNYDER:  That's correct.

            DR. RINGEL:  So I should feel better about the risk of under treating by misplacement of pads on large children.

            DR. SNYDER:  It's certainly an issue that can't be dismissed.  I think it's a fairly minimal issue, however.

            DR. RINGEL:  Okay, and an algorithm of ramping up is not practical or was rejected because?

            DR. SNYDER:  Well, interestingly the energies that we're using compared to previous protocols were considered rather high.

            DR. RINGEL:  Okay.

            DR. SNYDER:  Compared to weigh based protocols used with MDS defibrillators, we're actually delivering a fair amount more energy to the smaller patients.  So we did go ahead and advance the energy to give us a large degree of margin for these in-betweeners where accurate age and weight determination could not be performed.

            DR. RINGEL:  Okay, and then the final questions, again.  If this is felt then to be the appropriate way of going, why are you not giving the pads in the kits?

            And then the other question is: if it's likely that the -- which is a corollary to this -- it's likely that the pediatric pads are not going to be used, they're likely and I would agree that the thing that makes most sense even in an elementary school situation, which as I said before it's going to be an adult so that the adult pads should be in the machine.

            The pad that's in the machine will be checked regularly.  The pad that sits in the foil pack will not be checked regularly.  So if someone goes and buys the pediatric pads, there's no way to know that that pad is still functional as opposed to the one that's in the machine.

            So, again, that would be another concern over the two-pad system, and then, again, the question:  why are you not including the pad if you think it's important for kids to have the small pads?

            DR. SNYDER:  I do want to acknowledge that you have some valid concerns regarding two pads and confusion.  I don't want to dismiss those, but I do want to try and address as best I can the concerns with respect to this product.

            A pad that has not been or cartridge that has not been installed into the device actually has another layer of packaging around it that performs another vapor seal, which greatly extends the life of the pad.  So the day-to-day pad testing which is really performed to insure that the packaging has not been accidentally compromised, for example, by poking a hole in it, is really mitigated by the fact that there is an additional layer of packaging on top of the pediatric pads when they're stored not in the device.

            I think you had another concern I wanted to address, but I have forgotten what it was.

            DR. RINGEL:  Why aren't you giving the pads?

            DR. SNYDER:  Why aren't we giving them away.

            DR. RINGEL:  Right.

            DR. SNYDER:  One of our interests certainly in doing this is achieving broad dissemination, and I think our real purpose was not to burden the cost of the basic product for its most common application, which is the application for adults, and there are certainly going to be households where no children are present.

            It is available as an accessory item for anyone that's interested in purchasing it.

            DR. RINGEL:  Thank you.

            DR. ORNATO:  I have just one question to begin and a number of comments.  And my question is perhaps going to seem a bit odd, but perhaps you can help me better understand your intent. The device is entitled HeartStart Home Defibrillator, and yet I don't see in the indications for use or contraindications, unless I've missed it, anything either restricting its use to the home or not restricting its use to the home.

            We're to pay attention to the labeling and where it's leading the user.  What am I to understand about the intent of this product and will there be any, in your minds at least, any issues with respect to restriction because of the label you've chosen?

            DR. SNYDER:  You are correct in observing that there are no particular restrictions in the labeling materials, and in fact, as I mentioned, this product is identical in the case and the defibrillator itself is the product we saw for corporate markets.

            Where it has been specialized for the home is actually in the additional materials that are provided with it, the training video.  The owner's manual is different from the corporate owner's manual, and so forth.

            So the labeling components have been optimized for understandability by a home purchaser in order to enhance their ability to use the device.

            DR. ORNATO:  If this device were to be granted over-the-counter status, and a corporate user was to purchase it -- and I don't know if this is a question for you or perhaps my colleagues from the FDA, but it would certainly be enlightening to me if it's a fair question in terms of process to understand what that would mean in terms of its ability to be sold.

            DR. SNYDER:  I think it's more a question actually for the agency.

            DR. ZUCKERMAN:  I don't think that's the primary concern we would have.  I think the primary concern is what we've dealt with all day, which is the risk-benefit of removing a prescription label, make available to the consumer the device, and do we still end up with a positive risk-benefit profile.

            DR. ORNATO:  Okay, wonderful.  Thank you for that clarification.

            Okay.  That said, I just have a couple of very brief comments that I'm hoping may help my colleagues on the panel and the FDA maybe understand a couple of additional things regarding some of the questions that have been posed that haven't, I think, been fully resolved.

            As you heard earlier, I've had some personal involvement in the PAD trial, and I think there are some lessons that we've learned that have relevance to this device question that we're being asked, and there are also some notable differences.

            And so briefly, the similarities are that we're really talking about lay persons.  The differences fundamentally are that the lay persons in the PAD trial were trained and in advance were identified, and so as I'm trying to process the question regarding this device, there are from the get-go some issues with respect to getting into an area that is really to some extent a bit of an extrapolation beyond the information we have from the PAD trial in that these are not rigorously trained rescuers.

            On the other hand, I think it very clear even in the PAD trial that were was remarkable safety to this family of devices, and in the PAD trial the specific devices that were used were an earlier generation without the kind of, if you will, protective features that this device appears to possess in terms of coaching and guiding the lay person, and actually keeping up with them in real time whether they require prompts very quickly or not so quickly at all.

            In the PAD trial, we really had virtually no issues of safety with respect to the devices harming patients.  We deployed thousands of defibrillators 20,000 lay persons over a couple of year period.  No one was shocked who didn't need a shock, and not a single person who required a shock failed to be shocked by this family of devices.

            So I guess my personal confidence is that even the predecessors to this device in the family have already achieved a fairly high degree of safety, and certainly from what I've learned today, it appears as though this device is, if anything, setting the bar higher.

            As far as ICDs, Dr. Krucoff's concern, I think you're right, Mitch that clearly more and more folks are going to have ICDs, and interactions are going to be, I think, an increasing concern as time goes on, but the number is still relatively small.

            I am aware of one case, not published, but I've seen the case, seen the strips of approximately ten years ago where there was an interaction between an AED, a much earlier generation, and an implantable device where both committed to fire roughly at the same time, and one fired first.  I think it was the ICD.  Then the AED fired.  The ICD got the patient out of defib.  The external put him back in, and the ICD immediately cycled and got them back out and the patient did okay.

            So the only instance that I'm aware of proved to be not a particularly important one, but I think, as Dr. Krucoff has pointed out, these isolated exceptional cases, I think, over time will have to be watched, and I like the fact that there's a surveillance that's being proposed to look at such things.

            As far as the issues of efficacy of this device, I think the PAD trial would give me a lot of confidence that lay persons likely can use this device safely, but I think the efficacy is likely, but yet to be proven, and that's just a personal opinion.

            But I wanted the panel to be aware if you're not aware already that there is an NIH sponsored trial called the HAT trial.  Dr. Gus Brady is the principal investigator from Seattle, and it is unrelated to the PAD trial in that it's a different group of investigators.

            However, it is somewhat related in that it is putting AEDs in the hands of lay persons, but that trial will be, I believe several years.  So I don't think there will be a  lot of data that will help the FDA or the panel anything materially beyond what we likely know already.

            And finally, the issue of what is the value of the prescription is one that I may be able to help shed some light on from a maybe personal point of view.  As a medical director for a city EMS agency, I'm the EMS director for Richmond, and I wind up writing most of the prescriptions for AEDs that are used in public places in the city, and typically I'll get called because -- and this is not for home use so much as for public use businesses, hotels and the like.  The typical call will be that an entity, a corporation, an office, a gum, a YMCA, et cetera will make contact with a physician and try to get a prescription, and the sense that I've gotten is that there's a discomfort on the part of many physicians with writing the prescription.

            I think some have expressed to me a concern about liability.  I know a number of our physicians in the committee have called me personally asking about what their personal liability would be if they wrote such a prescription.  I don't think this is a trivial issue, and I think the medical directors in communities, perhaps the colleagues that I have that shared their experiences are somewhat similar, and I think that may be in part why we're seeing some of the experience that until today I was unaware of in terms of what you've stumbled into.

            So finally, in my mind this question is really boiling down to, I think, a point that a number of our colleagues from the company and their advisors and their consultants have made repeatedly, and that is I'm becoming persuaded strongly that the fundamental paradigm, to use your term, that we physicians operate under, which is we write a prescription for a medication or a device for a specific patient or for a specific user of a device for a specific patient.  It's really not applicable here, and I think I'm beginning to see that more and more clearly.

            Even when we medical directors write prescriptions for public access defibrillators and we have a cadre of trained people in a public building, just as in  Chicago O'Hare's experience, we have no idea who the victim is going to be, who the patient is going to be, and to a great extent we have absolutely no idea who's actually going to use that device.

            And so I think that internally is perhaps driving maybe more than almost any other of the important issues that we've all struggled with today to have to conclude that the real intent of the prescription really is not being met here, and therefore it falls back, in my mind to the regulatory two issues that our colleague started the day with.

            You know, is the labeling sufficient for the layperson without a physician?  Is it sufficient for that layperson to be able to safely and successfully have reasonable probability using the device?

            And I think this specific device appears to have set a fairly high bar, at least in my mind, in meeting that requirement, and so I think I will stop there.  That's kind of how I feel about it at this point.

            DR. KATO:  I have a couple of comments and a couple of questions.  I look upon the issue of AEDs as we've been struggling today, and I have to agree with many of my panel members who stated that we don't really have the data to extrapolate from, you know, corporate or public access programs.

            It's important to understand that there is federal and state legislation that requires standardized and proper training, annual review processes, coordination with local EMS facilities, medical director coordinators and a public access defibrillator director.  Overall emergency response has to be working, as well as scheduled maintenance and quality assurance of the device, and ancillary medical equipment provided by an EMS team.

            And I think that many of these facets of what makes the AED work and the amazing results that we've heard today not only in testimony from members of the public, but also in our panel packets and certainly from the sponsor, attest to the fact that in many cases there's a very good system out there that supports people who have been shocked by and resuscitated by an AED.

            To some degree I think the AED is a little bit ahead of its time in that if it goes out in an OTC fashion to the general public without the public understanding that these are the inherent assumptions behind the support system of making this AED work, I think that there may be a lot of problems, you know, with the public in terms of accepting these things for the long run.

            I'm also a little concerned that we did not have data regarding the storage and maintenance of this device.  As the sponsor clearly stated, most of the time in the general public this device will be sitting on a shelf gathering dust, and how does it respond just sitting there for four or five years before it's ever used?

            And that to me are some of the still critical questions that I have to ask about the device per se.  I think that as far as the physician prescription issue, that is becoming one of a regulatory nature.  I think that to some degree we are dealing with laws that have been written years ago and we have technology that's changing, and maybe we need to change the laws that govern this.

            But in general, I guess I'm a little bit concerned that we are raising the expectations of the public in this matter by claiming the -- and rightly so -- pointing to many of the great successes of this device without the underlying assumptions of why this works.

            On the other hand, I must congratulate the sponsor for working through a tremendous number of issues, and it is very gratifying to see a company so devoted to making a product the best it can be, and having touched it and played with it a little bit before the afternoon session, I just have to tell you I think it really does work.

            It seems to -- you know, it's a nice weight.  It looks nice and all of those good things that go with a good product, but I think that there are still several issues that I have to be very concerned about, you know, regardless of whether this becomes a physician prescription issue or not.

            DR. SNYDER:  I want to make sure I address all of your questions to the best of my ability.

            The first was a discussion regarding the relationship with EMS.  One of the things that makes such a discussion so difficult here is that these are state regulations, and they actually vary from state to state, and they're very much in flux.

            What I can tell you is that Philips sells a lot of defibrillators.  We sell in all states.  We're very used to working with these various state regulations and requirements and support them, and in fact, we often use or work closely with the states themselves in drafting legislation.

            What we can do is maintain a database, for example, on the product Web site with information about contacting local state agencies to determine what those requirements are.  That can also be available through the telephone customer service.

            So the information can be made easily available to the consumer.

            I'm trying to remember the second question you had.  Can you remind me of your second point?  There was the EMS relationship.  Storage.

            DR. KATO:  Storage.

            DR. SNYDER:  I think the best answer I have for you there is that the technology, the self-test technology that's used in the HeartStart Home is similar to what's used in the ForeRunner and FR-2 products, and we simply have no history of difficulties related to storage of the device.  The self-test is actually very good at detecting any problems that exist and alerting the owner of those problems.

            We did, by the way, in the labeling evaluation -- part of the questionnaire, and the questions, I believe, were communicated to you in your panel pack.  If not, I know they were in the 510(k) submittal -- many of the questions had to do with maintenance and storage and putting the device into service.  So we did to that extent validate the ability of people after reviewing materials to put the device or at least their knowledge of how to put the device into service, how it should be stored, which is near a phone and a visible place, and what steps, how maintenance notification is given to the customer, and the steps that need to be taken when that happens.

            ACTING CHAIR LASKEY:  We are actually ahead of schedule.  So congratulations.

            My suggestion, even though we call for a break, is we were here late yesterday, and my suggestion is to move forward.  Is that supported?

            I have one question before we get to the questions.  You may have answered this in passing, but are you prepared to distribute this device at no cost to individuals who want it and can demonstrate sufficient need?

            MR. MORTON:  Dr. Laskey, it's me.  Isn't that moving into more of the business plan and business aspects of that particular sponsor?

            ACTING CHAIR LASKEY:  Well, that's for someone else to answer.  I've sat here for almost five years now and never been concerned about the inequities, the societal inequities of these deliberative processes.  This is the occasion where it actually comes to mind.  This is not a prescription.  This is out there for purchase over the counter.

            So you answer that.  To me it's more of a rhetorical question, but I will --

            MR. MORTON:  My personal answer is I absolutely understand your concern as a caregiver, and I understand how that might be of interest to each of the members of the panel, but I do not believe that this panel is the forum for that question to be asked.

            MS. WOOD:  As the Executive Secretary, I'm going to have to say that that's out of the purview of this panel.  We do not consider economic considerations for any of the products that we look at.  Otherwise it could bias the opinions of these panel members.

            DR. MAISEL:  Dr. Laskey, could I make a comment?

            A related issue, and maybe I'll try to rephrase your question because I have struggled with the same issue, and I think it is relevant because it relates to the prescription question that we are asked to deal with.  Maybe a more generic question would be maybe the sponsor could comment on the expectations of availability to lower income populations or just a generic question about the availability of the product by removing the prescription requirement and potentially removing insurance coverage.

            So for patients who a physician still feels the device should be prescribed, there will still be that availability.

            That wasn't very well stated, but hopefully you get the gist at the question.

            MS. WOOD:  I'm sorry, but that's still not the business to be conducted by this panel.

            Yes?  Yes.

            MS. MOORE:  I noticed on one of the slides presented by the sponsors that there was an indication that four percent of those persons who were offered the device refused because of cost.

            So when I saw that then I said since it was introduced by the sponsor, then maybe this would be a legitimate concern to express knowing that the panel could not deal with it because this is not what we're talking about today, but if, for instance, I were to make a comment now, I would let it be know that I really had concern about that large population out there who would fall in this category of the four percent who would not be able to afford the device.

            MS. WOOD:  Well, I would have to say that on the other over-the-counter devices I would imagine we have not been able to consider this.  We don't consider cost, and that's the purview of another governmental agency to look at the cost.

            DR. KRUCOFF:  Geretta or Warren, can I take a third crack at --

            ACTING CHAIR LASKEY:  This is not about cost.  This is --

            DR. KRUCOFF:  Let me see if I can ask it.

            ACTING CHAIR LASKEY:  Just let me finish, Mitch.  This is not about cost.  This is about what we've been referring to is the removal of a barrier.  I don't see the prescription and description in this case as a barrier to the acquisition or the allowing of poor, uneducated, lower social run patient, however you want to call this.  That actually facilitates the access to this sort of health care, removing this, quote, barrier, which is a facilitator in this case, will represent an impediment to the access to this technology for a significant portion of the patient population, which probably is at greater risk, the LVH patient, and so on and so on.  I needn't go into it, but I'm sure everyone on this panel is aware of those individuals in the general population who are at high risk for sudden cardiac death who have not been part of the system.

            DR. KRUCOFF:  So can I ask the agency?  If a product becomes an OTC designation, does that de facto prevent doctors from writing prescriptions for the device?

            DR. ZUCKERMAN:  I don't think there would be any need to write that prescription.

            DR. RINGEL:  Besides the insurance company wouldn't pay for it because it's available over the counter.  So it becomes a moot point whether the physician writes the prescription or not.

            DR. ZUCKERMAN:  Okay, but I do want to reiterate Ms. Wood's comments.  Certainly the agency appreciates some of the impact of a device like this on different socioeconomic strata, but that type of line of questioning isn't going to fortunately impact one way or the other on how the FDA makes a decision.

            We have to make our decision based on the charge that we defined this morning, which is we have a prescription label right now because at a certain point in time we thought that there was a certain device complexity that required a prescription label to adequately allow for a safe risk-benefit profile when this device is used.

            Through a careful development program the sponsor has tried to move forward and that's really what the agency is asking for this afternoon.  Has the sponsor moved forward to a different point now where that prescription label can be removed?

            I realize that that's a narrow focus, but it is the focus of this afternoon's discussion.

            DR. RUSKIN:  May I offer a comment?  I think this obviously is a critically important issue, but I think there are some misconceptions here.  Current approved indications in which an insurance company will pay for an AED are extremely narrow.  So for the vast majority, if I were to write prescriptions for 99 percent of people out there who are likely to want to buy them, they won't be covered.  Their insurance will not cover them unless they fit a very narrow spectrum.

            In addition, there's no reason to believe that lifting the prescription requirement will eliminate my ability as a physician to prescribe within those accepted guidelines.  For example, if I want to buy a walker, I can go into a pharmacy tomorrow and buy one without a prescription, but if I need one out of medical necessity, it's a piece of durable medical equipment that's covered by my insurance company.

            And I don't see anything about this that would differ.  I can't speak for insurance companies, but certainly there's no reason to think a priori that this will be treated like an antihistamine and suddenly not covered.

            In addition, what is covered at the moment is a minuscule set of indications.  It's a tiny, tiny portion of the population.

            ACTING CHAIR LASKEY:  I understand.

            MS. WOOD:  Okay.

            ACTING CHAIR LASKEY:  And lest Geretta has a fit, I think we should probably should abandon this line.

            MS. WOOD:  This needs to be tabled, yes.

            ACTING CHAIR LASKEY:  I appreciate your response though.  Thank you.

            Okay.  Do you want to go through the questions then?

            MS. WOOD:  Yes.

            DR. SOMBERG:  Are we going to have a break for a minute?

            ACTING CHAIR LASKEY:  We voted.

            (Laughter.)

            PARTICIPANT:  He's voting with his feet.

            ACTING CHAIR LASKEY:  Okay.

            MS. WOOD:  Let's take a moment to bring the slides up.

            The first question regards usability testing and product labeling.  In terms of how a lay user would interact with the device, Philips usability testing focused on the ability of untrained users to set up the device to place pads promptly, to deliver shocks safely, and to know when to choose adult or pediatric pads.

            Philips' usability testing did not cover other tasks, such as self-training, storage, and maintenance.

            Please comment on the adequacy of the testing that was performed to support the notion that lay users can safely and effectively use the product.

            ACTING CHAIR LASKEY:  All right.  Well, the tradition here is I take the lead and you just tell me where I'm wrong or right, but I guess I'm getting a warm and fuzzy feeling that we all seem to agree that Philips has certainly done a commendable job to support the notion that users can safely and effectively use the product.

            But there are a number of exceptions.  Certainly Norm has just spoken articulately to the maintenance aspect of things, for example, and I guess one thing that still concerns me, and I'd like to hear if this is echoed in the rest of the panel.  It is just the patient, the subject population in which this was evaluated.  I'm not sure that this is a representative sample of the kind of people who will be looking to buy this.

            I didn't want to get down to the nitty-gritty and ask where these three shopping malls were, but I could just see from your bar graphs of the level of education.  That's generally above where we set our own bar, which is somewhat lower in terms of reading ability, comprehension ability. 

            So just join in, panel.  Am I out in left field here?  Do I --

            DR. RINGEL:  Well, I don't see how a physician prescription helps further the goal of educating people in using the device correctly because we might like to think it's all Marcus Welby out there, but it's unlikely that physicians will sit with their patients and then instruct them in its use.

            So I don't see the physician prescription protecting people from not understanding the device.

            ACTING CHAIR LASKEY:  That's not the question we're being asked.  The question is to assess the adequacy of the testing that was performed.

            DR. RINGEL:  Right.

            ACTING CHAIR LASKEY:  Not compare it to Marcus Welby.

            DR. RINGEL:  So my point being -- I'm sorry.  I didn't mean to be facetious -- is that I think it is adequate to show that the device would be used as effectively as an over-the-counter product as it is by a prescription product.  That's what I meant to say.

            DR. NORMAND:  Can I comment that I did indicate in my earlier comments that, indeed,  I felt that the sample for the simulation studies were not representative of the general population, that the education level was much higher in the numbers that I had seen.

            I also commented about the language issue as well, which is also not representative of the population.

            ACTING CHAIR LASKEY:  Bill and Mitch.

            DR. MAISEL:  I think there are obvious shortcomings in the testing that was done.  I think that the most impressive thing to me was the success rate of this newer device after testing in patients who had no instruction and were able to take it out of the box and use it properly was extremely impressive, I think, due to the diligence of the sponsor.

            I think things could be better, but I'm comfortable with where we are.  I guess the only caveat I want to put in is my feeling of personal incompetence to address some of the science of user interface testing.  You know, you can look at the numbers.  Does it sound rational?  Does it make sense?

            As a plumber I can give a comment, but I also don't want to over represent the limit which at least I feel competent to comment on how reflective.  I think we're all clear that you can't simulate the real event with the stress and that sort of stuff, but there is a whole other science of user interface testing and compatibility that I have to admit is not a personal area of expertise other than a very broad, gestalt answer to some of these questions..

            DR. ORNATO:  You know, there's another side of this.  I'm sort of viewing making a device like this over the counter sort of like consumer electronics in a way.  I know I struggle sometimes, and I'm pretty electronically literate, in trying to figure out, you know, the metaphor, how to program the VCR.

            And I'm a little bit concerned that although I understand your perspective and I think it's a fair one, what I'm struggling with is what really is the fair bar to put here.  You know, if the fair bar is that 90 percent or 98 percent of the population should be able to use something that's technologically, you know, got some challenges for some individuals, then I think we'll never make progress in this area.

            You know, I've been impressed with the steps that have been taken that have gone beyond any of the medical devices that I've personally had any involvement in using as a physician or even as a lay person, you know, if it's outside of my area. 

            So I think the issues are correct.  You know, it certainly would be great to have much bigger samples and much more diverse samples, but I've been really quite impressed that even in the lower, least educational groups it doesn't seem to be a major impediment to using this device.

            DR. KATO:  You know, in the heart surgery valve area, valves are tested for durability and there are engineering methods used to simulate, you know, years of use.  So one of my concerns here is -- and I agree with the sponsor -- these things, I believe, are going to be sitting on, unlike, let's say, the PAD trial or any other trial that's using patients who are at risk; so they're going to have events of sudden death at their house.  I think most of the time these devices will be sitting around for years, and I don't believe that we've had enough data to support whether they can effectively survive that long without being shocked, tested every week, rechecked every month to say what's going to happen five years down the road.

            ACTING CHAIR LASKEY:  That's actually Part B of the question.

            DR. KATO:  Oh, sorry.

            ACTING CHAIR LASKEY:  That's okay.  Thank you for the segue.  But I guess we don't have to have consensus here.  You just need to hear our thinking; is that the gist of this?

            DR. ZUCKERMAN:  We want to try to put things together in the best way possible.  So at this point we heard comments that have ranged all over the block.  Certainly the panel has indicated that there are certain problems with the adequacy of the testing, the representativeness, et cetera, but, Dr. Ornato or others, would you submit that even given the limitations of the testing together with some of the other external data that you're aware of regarding the PAD trial and other sources of data that together there's enough or does, you know, 1(a) still bother you?

            This is a very important question to see if we can get some better consensus.

            DR. ORNATO:  Dr. Zuckerman, if you're asking for sort of a personal opinion, which I guess is the only thing I can provide.  I'm comfortable that although not idea, I think I've seen enough that I'm comfortable that we will likely be doing enough benefit.  In other words, enough people, I believe, will likely be able to use this device in the setting for which it appears to be intended that I'm comfortable, you know, with what I've seen so far.

            DR. VETROVEC:  To some degree this is a device that once it's off prescription, it is going to be driven by the interest of various members of the population, and I would guess that the survey probably came close to fitting the individuals that will buy this device.  And it's not prescriptive, and that may make sense then.

            Is the population that we would expect to use this device going to be able to operate it?  And I think the answer to that is yes.

            DR. SOMBERG:  I'm not sure how usability testing and product labeling really changes much from the current device that is approved versus the 510(k) application which takes away the physician prescription requirement, and I think it's the same device out there, and my comment may relate to a lot of other questions.  And for the brevity of the meeting, I think we should try to focus on the charge of the committee, which is the recommendation to take that away.

            Because I have a lot of comments on the device and what could be done to make it better, et cetera, and I think some of the things that were said today about the pediatric considerations were very much appropriate, but once again, I can't see how that relates to whether a physician gives a prescription or doesn't give a prescription.

            If someone can explain that to me, I will not bring it up again.

            DR. ZUCKERMAN:  Okay.  We're still on one ‑-

            ACTING CHAIR LASKEY:  Of course, that's not the question, John.  The question is has what we heard today met the needs of adequacy of the information base.  Let's try and stay focused here.

            And the answer seems to be -- yes, Bill. Sorry.

            DR. MAISEL:  I was just going to add if one of the concerns -- it's not one of mine -- but if one of the concerns is regarding less educated people, perhaps less data than on high school or college educated people, I guess I would ask the question:  what if that data did not look as good?

            I think the sponsor has done a very good job of making things as simple as possible, and if someone is told to remove their clothes and cut them off, if necessary, and they don't and they still put pads on, those people can't be helped.  I mean, I don't know what more you can do.

            (Laughter.)

            DR. NORMAND:  Well, I guess in terms of the question that was raised, and I realize I don't understand the barrier or non-barrier of a prescription.  I don't know if there's a selection process that the physician makes about, you know, who's smart enough or facile enough to use the device.

            But all I'm saying is that if you were to look at that, that is not representative of the population, and you know, that may or may not have anything to do with the removal of the prescription.

            However, that does tell me in a very simulated, pristine experimental setting, I'm going to get an overestimate of it.  Those are the numbers.  Now, if you're going to tell me they're all going to fail if I've got a lower educated population, maybe the company might change something and do something a little bit differently.

            I'm not saying that they need to or that they must, but surely the fact that the distribution, the demographics of the population that participated in the simulated testing situations were different, and I think that we can't guess, you know, sort of which way it's going to go.  I don't make up data.

            DR. KRUCOFF:  And my understanding of the intent of the question is that if this device is shifted from a physician prescription to OTC, that part of the assurance that we're being asked to evaluate with this question is even if the physician currently isn't doing his job, that's not the issue.  Currently if a physician write a prescription, they're in the mix, and some of the responsibility for how the device performs, the physician is in that mix.

            If we take the physician out of the mix, is the labeling construct and in this case is the surveys or experiments that have been done to assess the materials available to the consider sufficient to have them operate the device?

            And that is where to me the question on this particular aspect lives, and it seems like we have sort of a range of feelings.

            DR. SOMBERG:  I must say that I don't see how the physician is in the mix when we talk about the overwhelming majority of uses of the device has been in the public arena.  You don't know who you're going to prescribe the device to be used on or who is using the device.

            DR. KRUCOFF:  No,w John, you're talking about reality thought, and I think what we're talking about is --

            DR. SOMBERG:  Yeah, that's all I ever do.  That's all I ever do.  I'm not a dreamer.

            DR. KRUCOFF:  I think the issue here is a regulatory issue.  If you take the physician out of the mix.

            DR. SOMBERG:  No, but I think what a regulatory issue should be focused on is there any special population we need to protect, et cetera, special testing that needs to be done, usability, et cetera, that the physician would identify or would have identified, and that would change the device, and I'm just saying, you know, 95 percent of the uses are in the public arena, that the physician really doesn't do any of the screening, is saying the device has worked out very effectively from all data we can get, and it's a lot better than some of the prescription devices we've talked about, even implantable devices, in the past.

            So I'm just very impress by that, and I don't see why we should, you know, go over and over.  You know, maybe we could be helpful in another forum, but over and over a device that's approved.  We're just asking for one thing.  Should a physician interpose himself, and I haven't seen any data to suggest that taking that away would place any increased risk, and the experts have testified that it would increase the potential benefit.

            ACTING CHAIR LASKEY:  Well, you keep going there, John, but we're still trying to answer the question.  So that's --

            DR. SOMBERG:  Well, I can say that the question is --

            ACTING CHAIR LASKEY:  Yeah, I think Dr. Zuckerman and the agency have probably heard the spectrum of opinions up here on the adequacy of the testing that was performed, which I guess is one way to view this, is just the patient brochure.

            DR. KRUCOFF:  Warren.

            ACTING CHAIR LASKEY:  Yeah.

            DR. KRUCOFF:  Can I risk -- you know, part of the flavor of this to me does suggest that if it was not unduly burdensome that providing some additional similar information in an independent population that maybe leans a little more toward the less educated side would probably be reassuring if it had similar looking profiles to what's been demonstrate.

            ACTING CHAIR LASKEY:  I'm not sure I'd say less educated.  I'd just say more representative, but ‑-

            DR. KRUCOFF:  Well, I didn't mean that in a derogatory way.  I meant in an identifying, you know, sixth grade level, seventh grade level population, that it would be reassuring.

            ACTING CHAIR LASKEY:  Perhaps it's tangential.  I don't think so, but we've heard the theme repeated that this is not just the box.  It's the system here that we need to think about, and the support system, the EMS system, the whole aspect of getting the ancillary care going.

            So let's not forget that it's just the box that we're evaluating here.  It's also the 911 aspect and all that ensues from that.  The box, as someone pointed out, wouldn't work very well without the infrastructure.

            And I can't even begin to think of the impact of this on 911 calls, but let's move on.

            Since actually, Norm, you already took a crack at (b), is to comment on whether it's necessary to establish other aspects of usability such as self-training, storage, and maintenance as a prerequisite for removing the label.

            DR. KRUCOFF:  Well, I think that's true.  I think there must be more data regarding self-training, storage, and maintenance before you can removal that label.

            ACTING CHAIR LASKEY:  I guess my question is:  how do you simulate shelf life?

            DR. KRUCOFF:  I'd have to defer to an engineer about that, but there must be a way to do that.

            DR. MAISEL:  Or perhaps simply just stating explicitly what the recommendations are would be a step in the right direction.

            DR. KRUCOFF:  This was one area where I think the track record of the previous platforms actually I found to be helpful, and I'm not an engineer, but we deal a lot from the device side, but I see no radical change in the platform, and at least as the company has reported, their self-test environment seems to be pretty robust over at least the generations of a device sitting on the shelf for years at a time, as long as somebody knows to listen for a beep.

            We didn't see data on people listening for a beep, but this was the one aspect that I found, the longevity of the platform in the self-test environment not having been associated with problems, that to me was a little more interpretable and a little more reassuring.

            DR. KATO:  I guess my concern was going to be that as the device gets mass produced or produced in greater numbers, then the manufacturing process is going to change also, but right now --

            DR. ZUCKERMAN:  But that's not the point of the question.  Let us assume that the engineering will be fine.  It's an approved device right now.  the problem is:  does the lay user need to have some education, testing about storage, maintenance of this device?  It usually sits on the wall.

            You know, the actual testing concentrated on a specific component of the device history.

            DR. RINGEL:  Maybe I missed it on the last round.  I apologize if I'm retracing.  If this device has been approved, I don't understand how the removing the prescription changes storage and maintenance, for instance.  If someone says, all right, if you write the prescription, then there's going to be some training given, I can understand that when we discuss prescription and training.  But I don't understand how prescription and storage and maintenance has a role in our discussion today, whereas it should have been maybe contemplated when the device was originally approved.

            So I'm just asking the question again.  i know that it was just discussed in Part A, but I don't understand why this was a factor here.

            DR. SOMBERG:  I'm not going to say anything.  I'm sorry.

            ACTING CHAIR LASKEY:  No, no, no.  I think we can let the agency -- it seems that the question was directed to the agency.  What's different now than before?

            DR. ZUCKERMAN:  Well, I think the sponsor would agree with Dr. Ringel, and that's why they concentrated on the adequacy of testing to show that in an acute arrest situation that lay users could use the device appropriately.

            However, we're just trying to do our due diligence, cover all of the broad strokes.  If you think that those aspects of potential training covered in 1(b) are self-obviously, then you agree with the sponsor and they don't need to be further demonstrated in this OTC scenario.

            DR. RINGEL:  So we can review issues that were more appropriate to its approval as a device at all is what you're saying.

            DR. ZUCKERMAN:  Yeah, the strategy that the sponsor chose was to concentrate on 1(a).  We're just asking from the FDA's perspective:  is that an appropriate strategy to take here?

            DR. KRUCOFF:  So that's where I see 1(b) as a beep and a light, that basically they've gotten the system down over the years to a beep or to a light that is not ready, and to me that's probably more likely to be readily translatable to a consumer population than the vicissitudes of call 911, then open the package, then peel it.

            So I would support their emphasis in terms of 1(b).

            DR. NORMAND:  Yes, and I also support their strategy.

            DR. VETROVEC:  I support it, too.

            ACTING CHAIR LASKEY:  That sounds like consensus.

            MS. WOOD:  let's move on to Question 2.  Safe and effective use of the device may depend on the ability of the untrained lay person to determine in what situations the AED should be used.  Please comment on the adequacy of the testing that was performed in the product labeling and training materials that are provided to support the notion that lay users would know when to use the product.

            ACTING CHAIR LASKEY:  Yes.

            DR. SOMBERG:  I thought that was very well done, and as I said, I think there are some target populations that could be identified where certain cards could be given, and there's additional work that could be done in this area, as well as areas related to -- I mean, you know, just because this device is approved doesn't mean there's going to be updates and improvement, and I think this company has shown -- what is this, the third generation or fourth of your products? -- I think they're going to be able to do that, but I think this has been well demonstrated.

            ACTING CHAIR LASKEY:  Well, well demonstrated in the adult population.  I guess we should be specific because Rich's concerns are completely valid with respect to the differential diagnosis in a child when they're --

            DR. KRUCOFF:  Well, they're recognizing that this really applies to the user, not the patient, and there, again, I agree with what sounds like other voices, that it's down to patient is down, not breathing right.  When in doubt, use it.  That's pretty good by me.

            ACTING CHAIR LASKEY:  Fair enough.

            MS. WOOD:  If you do not believe that the testing and/or labeling are adequate in Part A above, please comment on the type of testing or type of labeling changes that would be necessary to support the removal of the prescription label.

            ACTING CHAIR LASKEY:  Well, fortunately, we do believe that it's adequate.

            MS. WOOD:  Okay.  Number 3 --

            DR. RINGEL:  Well, on Number 2 I guess I didn't speak up again because I had said it earlier.  I think that there does need to be something included in the package that makes it clear that infants and toddlers are different.  Airway, breathing, circulation is the mantra, and I don't think that's been changed at anytime recently.  So I think it has to be stated.

            DR. SOMBERG:  Didn't they say that when you put in the pediatric paddles the voice algorithm changes?  So isn't that in the system?

            DR. RINGEL:  But it's not in the brochure, and it's not difficult to put it in the brochure.

            DR. SOMBERG:  Oh, no, I agree with that.

            DR. RINGEL:  It's not difficult to include just  few lines about infants and toddlers, airway, breathing, circulation.  That's all.

            MS. WOOD:  The timing of CPR relative to  defibrillation is one concern for this type of device as it impacts survival in certain cases, such as asystole or pulseless electrical activity.  According to the current American Heart Association recommendations, CPR should precede defibrillation in the chain of survival.  The Philips device addresses the need for CPR in two ways:  by identifying the need for AED CPR training in the labeling and by including device prompts during the defibrillation process that are based on the patient's underlying rhythm, such as normal sinus rhythm, ventricular fibrillation, PEA, asystole.

            Please comment on whether these recommendations regarding CPR are enough or whether other measures are needed, and please comment on whether the concern is unique to an over-the-counter AED or whether the same concern exists for the prescription version of the device.

            DR. ORNATO:  I'll be happy to start with that.

            First, the question is flawed.  The second sentence is incorrect.  The American Heart guidelines do list in the chain of survival early CPR, but it's not meant to imply that that is to precede defibrillation if there's a short bound time interval.

            However, the question is, in fact, otherwise a superb question, and is the source, as Dr. Becker and others have pointed out, of intense  scrutiny and controversy and discussion and will be materially, I think, dealt with to some degree at the next guidelines conference, which will be occurring within a few months.

            That said, I think most of us who kind of work in this area basically accept the notion which was presented earlier, which is that there likely are several phases of resuscitation, and that first four or five minutes is an electrical phase, and early defibrillation really appears to be the best intervention that we have.  There's really not even a close second.

            And so in that sense, I think this device and the entire family of AEDs have it correct.  I think the real issue is what do you do about the individuals who were down longer than four or five minutes, and right now, none of the devices, none of them, even the ones that we have for medical use by physicians and paramedics that are FDA approved can really answer the question of when is it time to turn to shocks as opposed to priming the pump with CPR.

            There is a whole science that has evolved in the last decade looking at the VF waveform, such things as median frequency and other fast 40(a) transforms of the VF waveform that appear to give us somewhat of an index of the state of ATP in the myocardium and whether you should shock or not, and I'm optimistic that in future generations of defibrillators in general will probably have the ability for defibrillators to look at the waveform and then be able to tell whether you need CPR then or defibrillation.

            But we're not there yet.  The science is not quite there yet.  So my answer to this question is I think the device is doing all it can do, which is to follow the consensus American Heart and international guidelines on CPR. 

            They may change this year.  I think the real issue to me is, you know, can this device change relatively easily to conform to whatever modifications are made in the guidelines, and that's a technological question.

            I think we got a hint of it.  It sounds like the device has some configurable features now and has the ability to be upgraded by software with a main-in.  If that, in fact, is the case, then I think I'd feel comfortable that the device is where it needs to be, given today's science.

            ACTING CHAIR LASKEY:  That being said, nothing in here that we've heard today is stratified by tying down.  Should there be some specific language that this is the way to go when it's witnessed or sort of witnessed or within --  there is no language in here that alludes that that and then that leads into do you do CPR.

            I found it notable that the CPR recording wasn't playing this morning when we saw the demo.  That's out of that particular record.  So I think we ought to --

            DR. ORNATO:  The current AHA guidelines don't stratify in that fashion.  However, the Scandinavian paper, Dr. Wik's paper and Dr. Cobb's observational report in JAMA a few years ago from Seattle would, in fact, support the notion that the first four or five minutes probably are different than what comes in the next five or six minutes.

            However, as I've indicated that's a subject that's going to be, I think, greatly and hotly debated at AHA guidelines this year, and it may or may not result in any modification in the guidelines recommendation.

            So I think, you know, the only standard I think we can reasonably and fairly hold a manufacturer to is what is the current recommendation right now, with the notion that they need to have the flexibility to modify if the AHA and International Liaison Committee on Resuscitation make a substantive change in the recommendations.

            DR. SOMBERG:  Warren, can I?

            ACTING CHAIR LASKEY:  Yeah.

            DR. SOMBERG:  I agree with Dr. Ornato's statement that this device lives up to the current guidelines.  I'd also say that if we were a panel and had to make a decision on changing the guidelines for time, there's such a paucity of data, 200 patients, the study design, the observational study.  You'd go crazy.  Our statistician would go crazy with that data.  So let's not approve something based on that data.

            And lastly, I would say we have to be careful as a panel not to go from extreme to extreme.  We wanted a simple device, a device that the average person could handle with the average education, et cetera, and now we're asking people in a time of emergency where time tends to stop, et cetera.

            I mean I always have time.  Someone comes up to me and says, "You've been coding the patient tangentially on this for, say, 15 minutes or so," and I think it's only three minutes or something like that.  So it's very, very difficult to put a time configuration in there.

            So I'd be very concerned about -- and then maybe the machine went on.  Maybe the machine, you know, could go off and then put on again.  There's even a timer on a machine might be questionable.

            So I would say, you know, this is field tested.  It's approved, and what we're asking to do is take away the prescription thing, and therefore, let's not change.

            I'm afraid any change in device may open it to more problems than less.  So a device that has validated itself to this point is the safest device to put out there that will do the most good.

            ACTING CHAIR LASKEY:  Nevertheless, we recognize the need that the IFU may change as the body of evidence changes.

            DR. SOMBERG:  That's right.

            ACTING CHAIR LASKEY:  It's not written in stone.

            DR. RINGEL:  So, again, this is overlap, I guess, with the previous question, but since it's asked, again, the recommendation of CPR and not enough of the peds. should be -- and again, I don't want to make peds. as a broad category, but infants and toddlers -- the comment should be that the documentation is probably not adequate to make it clear that CPR should start before defibrillation.

            And then the voice prompt would come already after you've gotten the machine, put it on the kid and so forth.  So that would be not the recommendation of the AHA.  You start the CPR first, or the American Academy of Pediatrics.

            ACTING CHAIR LASKEY:  Yeah, I guess insofar as (b) goes, the same concern does exist for the prescription version.

            DR. RINGEL:   Correct.

            ACTING CHAIR LASKEY:  Number four.

            MS. WOOD:  Over-the-counter, nonprescription products, such as cold medicines , typically it's just the layperson in determining whether they need to buy the product by presenting in the outer packaging information describing the intended use of the product.

            Please comment on the adequacy of the external carton labeling in conveying important information to the lay user that would allow them to know whether this product is right for them.

            DR. NORMAND:  The only comment I'd like to make, and maybe it's already on the package, but the issue about the Spanish, in the Spanish label or in the English label that the automation is in English because I think that's an important point.

            DR. KRUCOFF:  To me one of the ironies here is what I actually think would belong on the outer part of the box if consumers are going shopping.  If you think you need one of these, you probably should talk to your doctor.

            (Laughter.)

            DR. KRUCOFF:  You may not need a prescription, but at least to alert them to think about it.

            DR. ZUCKERMAN:  Okay.  So, Dr. Laskey, is there some consensus on four or were these just comments?

            ACTING CHAIR LASKEY:  Seems to be.  I mean we could obviously do due diligence with this one, too, but I think we have consensus that it's  -- I don't know.  What does it say on the outside of the box?  If you're deal you open this?  What does it say?

            (Laughter.)

            ACTING CHAIR LASKEY:  I see the picture.

            DR. KRUCOFF:  No, if you see somebody else dead, open this.

            ACTING CHAIR LASKEY:  Yeah.

            DR. SNYDER:  Actually, to Dr. Krucoff's point, it does say, "If you have concerns about your health or an existing medical condition, talk to your doctor.  A defibrillator is not a replacement for seeking medical care."  It's right here.

            DR. KRUCOFF:  Yeah, you mentioned that earlier, too.

            DR. SNYDER:  It basically identifies the product.  It's the HeartStart Home Defibrillator.  It says it's used to treat victims of sudden cardiac arrest who are not responsive and breathing normally, and if in doubt to apply the pads.  Treat sudden cardiac arrest by delivering energy to the heart.

            ACTING CHAIR LASKEY:  I mean, I guess --

            DR. SNYDER:  It also reinforces the time of the essence defibrillation within the first few minutes provides the best chance of survival.

            DR. SOMBERG:  Well, you've also got to remember that you buy it in the carton.  It's going to be put in this little carrying pack.  It's going to be kept in the carrying pack.  Probably the carton -- I mean it's like antiques.  You know, antiques are much more valuable if they have the carton because 90 percent of them are thrown away.

            So, I mean, this is what someone would read but not necessarily the user will read.

            So can I ask you?  With that said, what is the little pouch thing?  And maybe it's advisable to put all of these good things in the pouch.

            DR. KRUCOFF:  Or a wall mount.  Is there a wall mount?

            DR. SOMBERG:  And there was a lot of handouts.  So if you tell me it's all on that, I apologize.

            DR. SNYDER:  The labeling on the first of the quick reference guide is check for signs of sudden cardiac arrest.  Unresponsive, not breathing normally, and then it has the one, two, three operations of the device.

            DR. SOMBERG:  And I just might suggest on the cover of that thing, you also have the physician admonition as well.

            DR. VETROVEC:  This is an interesting point because a cold tablet is inside the box, and there's no reason that someone would have it outside the box.  So you'd get other information when you were looking at it in a drug store.  It's likely Wal-mart would have this open so you could look at the product, and you wouldn't necessarily read the box when you were looking at it, and maybe the compromise here is the information that's on the box should be displayed prominently at the advertising site.

            MS. MOYNAHAN:  Can I make a comment?

            This is Megan Moynahan.

            The question was worded specifically to ask you whether you felt that the external carton labeling would allow users to know whether the product was right for them, meaning should they buy it at all, and the reason we're asking that question is because there may be some considerations they should think about.  For example, if they do live alone, this might not be the best product for them.  Can they physically work with the product?  Do they know that they have to get down on their knees to help the patient?  Do they know that they have to be able to listen to audible alarms or things like that?

            And this is more the question of can the user in a store situation determine for themselves whether they need to buy the product?

            DR. VETROVEC:  Well, if you're really asking that question, it seems to me that then the statement needs not so much the disclaimers of where it might not be useful to the person, but maybe it ought to have some statement about the incidence of sudden death and people unsuspecting or something like that and increasing with age.

            That would be the sort of information that might be important to a user.

            DR. RINGEL:  When I had looked at the materials, I must admit I hadn't thought of it in exactly that way, but if you're asking the question of can you get an education of who needs the product by looking at the box, I don't think the answer is yes.  I think most people at that level of education would not know what defibrillation means.

            It doesn't say anything about heart attacks, which is what most people think.  It says things like sudden cardiac arrest, you know, or something like that.  Most people, I guess, wouldn't know what that is.  I mean, most people only know the term "heart attack."

            And I think many people don't know what defibrillation is.  They know what shock is, but I don't know that they know what defibrillation is.

            So if you ask purely not knowing anything else and you just look at the box, I think it might be a problem. 

            What does the rest of the group think?

            DR. MAISEL:  I was just going to say I think if you asked what is the single piece of information a person should most have if they're about to buy the product, for me it would be what is my risk or the risk in my environment of needing to use the device.

            In other words, what is the risk of sudden cardiac death if it's for themselves or their family.

            DR. RINGEL:  Do they understand?  Do your patients understand sudden cardiac death as opposed to heart attack?

            DR. MAISEL:  Well, they don't have to.  It's just of needing the device.  Whether they understand that it's a heart attack or a sudden cardiac death, I don't know that there's an easy way to present that on the outside of the package, other than perhaps  some graph or chart of, in people with no prior medical history, of unanticipated sudden cardiac death by age or something like that, but I don't know that that's a realistic option on the back of a package.

            DR. KRUCOFF:  I guess what I'm hearing is more like does there need to be a bullet list on the side of the package like what does it take to operate this thing and you need two double A batteries and a flashlight and a wrench, and that that somehow -- you're forewarned of that so that you don't buy somebody a Christmas present that when they open it they can't use it.

            So, you know, I think some of the ergonomic features, if that's really the question -- I wouldn't want to substitute that for having on the front where they got it, but you know, you probably should talk to your doctor,b ut maybe on the side, if there is a bullet list of specific ergonomic features, that would mean if you buy this thing and somebody in your house arrests, you're not going to be able to use it, that that wouldn't be a bad bullet list to put on the side, and it doesn't sound like it would be too much more complicated than the things you all had pointed to.  You may have to operate it on the floor to maintain it.  You may have to be able to hear a beep.  You may need a sixth grade education, you know, to play the --

            ACTING CHAIR LASKEY:  There's a lot of writing on this box right now.  So I --

            DR. SOMBERG:  But can I?   This is a very involved device.  it's going to take more than the outside reading of a box.  I think the manufacturer has spoken to its confidence in trying to deliver the message to the person by giving them 30 days to look through this.

            I mean it's not that you buy it and you're stuck with it.  You have 30 days to go through that and you can --

            DR. KRUCOFF:  You can generally use it in those 30 days.

            DR. SOMBERG:  well, you may use it the next day.  That's not true.  You'd be surprised how many people run out, especially if their physician is away at an FDA meeting, right?

            But the point is I think there's a whole manual there.  Someone has to go through it, and what we've heard, we've each learned a little about this device today.  Nobody can understand it in a minute by looking at the box, and I think you have to read the manual and it will tell you that, you know, you need people at home.  You need people that can handle this.  You need to host things, and some people are going to be overwhelmed, and then they'll give it back, and in fact, what's the incidence of people giving it back?

            Less than one percent.  Well, obviously there are a lot of cognitive dissidences they'll tell you in marketing school, but --

            DR. KRUCOFF:  -- by airports.  I mean, if you get into homes, it may be different.

            DR. SOMBERG:  That's a good point, too because it's a live public access.  The building or the airport doesn't give it back.  You're right.

            But I would say go to the manual for this type of info.  That's my message to the FDA.

            DR. KRUCOFF:  Well, I would respectfully disagree.  I think a bullet list on the side that had specific ergonomic features, that if you can't do this, you can't use this, would be simple, reasonable, and for all the writing could be discrete enough to be useful.

            DR. KATO:  Yeah, and I'd like to agree with Mitch.  I mean, many of the products that we buy now all have that.  Software, hardware for computers has very explicit listings of what you have to have in order for it to work.  I think that's reasonable.

            ACTING CHAIR LASKEY:  How would people feel about a bullet list that said you may be at increased risk of sudden cardiac death if you -- bullet, bullet, bullet, bullet, have had a heart attack?

            DR. VETROVEC:  I would agree with that.  I think the ergonomic issues, I think you need to -- if the goal is to make it like cold remedies on the supermarket, then you need to tell people who might benefit from it.

            ACTING CHAIR LASKEY:  And you have to have a cold, and I think that's the problem here.  These people don't have a cold, and they haven't been survivors of sudden cardiac death.  They are at risk of, but we can't quantitate the risk.  Nobody can.

            So I think that's just opening up a hornet's nest.  I mean, we all agree it's for the treatment of someone that drops dead, but to go home and to ask that person to do some risk stratification in their household for who is at risk for sudden cardiac death is (a) unfair, (b) impossible, and I just -- the language here of is it right for them is just so vague, and I think if we cleaned up the language a little bit in the question, we might be able to help you more.

            But I think that's ultimately what the morning's discussion was about, was the inability to quantify the risk.  You know it's there.  It's greater than zero, but how do you do that and how do you do it without making the buyer hysterical?

            DR. RINGEL:  I think I mostly agree with that.  The only thing is as I look at the packaging, it really -- for such a big life saving product I really now looking at it have to admit there's a real dearth of any usable information.  The only thing it says, and it's in about the smallest print on the package, it says, "Used to treat victims of sudden cardiac arrest who are not responsive and breathing normally.  If in doubt, apply the pads.  Treat sudden cardiac arrest by delivering energy to the heart."

            Very small print, and that's it.  So I guess I hear what the other panelists are saying, and it seems like maybe a little bit more information could be -- again, if the FDA is asking the question, and I hadn't thought of it until we asked the question.  If they're asking the question is it like a cold remedy that tells you why you need this product, this is even less than, you know, allergy medicine gives.  That's all.  It cold be a little bit more.

            DR. ORNATO:  But it -- I'm sorry to keep this going -- but it comes down to this fundamental issue of is this a medical device or is this a safety device, and that's really what I'm hearing out of this discussion that we're struggling with.  If this were to be viewed in the traditional paradigm of a medical device, then we would need all of those things, and it's perfectly understandable that our instincts are telling us to put those things for all of the reasons that you've nicely articulated.

            But what I've had to I think keep reminding myself as the day has gone on is that this problem of sudden death is totally unpredictable.  We don't know who the victim is.  We don't know who is going to be in the household when this happens, and ultimately 80 percent of the events occur in the household.  So if ultimately we're going to make a dent in this problem, it's very similar to the fire extinguisher issue.

            You know, I will have to go back and look at the ones that are in my house, but I don't think on the label of a fire extinguisher it tells you to restratify what you're likelihood is of having your house catch on fire.

            And although I don't want to make light of the comments that have been made, I think the difference is where we physicians and health care providers are in the mindset always of viewing this as the traditional paradigm of a single patient, a single device that we're prescribing.

            This is really a different animal, and I think that that's why we're having this discussion back and forth.  Maybe that will help.

            DR. RINGEL:  Even a small comment, I mean, because I've listened to what you guys are saying, and many people here feel the importance of making sure that the lay public is aware that they need to activate EMS and that this only buys some time, that it's not even a mention on the box.

            So someone could think, "Oh, all I need to do is take this.  We're going to go climb, you know, Mount Everest.  I'll take it up there and then we'll be fine."z

            I mean, that's why I said a little bit more labeling.  You could even say, you know, it gives you the extra time needed before the paramedics arrive.

            All I'm saying is it's really a dearth of information for a big product.  I'm not saying it has to label everything, and I know wheat you're saying.  It's a public safety thing.  It doesn't have to list all of the conditions that you might have, but it's a little bit sparse on information.

            DR. KRUCOFF:  Actually I kind of like that.  If they could wordsmith something that would on the front say that this thing is an adjunct to the knowledge of CPR and the use of 911 EMS services for in the home, you know, but actually if you could emphasize that it's important for you to know CPR and to know how to dial 911, and that this is an adjunct to that that you can keep in your home that, you know, bridges that little time period that can be so critical, I think that would be a really interesting way to put what it is right on the front of the box.

            MS. WOOD:  Number five, Philips is seeking over-the-counter status for this AED to be used with both adult and pediatric pads.  Both the adult and pediatric pads are already FDA cleared with prescription status.

            In support of the usability of the device with pediatric pads, the sponsor has provided the results of simulated use testing of pediatric electropatches with the AED performed on ten subjects.  The purpose of the test was to determine whether users could recognize the need to change from adult pads to pediatric pads.

            Please comment on whether this testing is sufficient to remove the prescription only label on the pediatric pads.

            ACTING CHAIR LASKEY:  So we'll defer to Dr. Ringel for the consensus.

            DR. RINGEL:  I was really hoping honestly that you guys would start because I'm really torn here.  A trial of ten is almost nothing.

            I was reassured by the comments after I asked the questions.  I still am troubled by the pediatric pads.  On the one hand, I would love to have the kids, the babies and infants and toddlers included in the over-the-counter use.  On the other hand, maybe there should be a discussion with their pediatrician about, you know, their child who they're worried about sudden infant death or their child who they're worried about, you know, this or that, and maybe they should discuss it with a pediatrician who can then tell them what to do.

            I don't know.  I'd really like to hear what the other panelists say because I'm torn on that one.

            DR. SOMBERG:  I would say if you don't take away the prescription for pediatric pads and just did it for adults, then you have a default mode and that you would vitiate the use of the pediatric because people who wanted to buy it would go ahead and buy the adult.

            And I am very concerned, and unless you correct me if I'm wrong, but let's say it was used in the infant population.  You're giving 150 Joules to an infant.  Would that not have the potential for myocardial damage?

            So I'd rather someone who is concerned about this have the same admonitions as the adult population.  You know, consult a doctor, and I also recommend strongly a pediatric card there to give a little more information about the use of this, et cetera, and I certainly wouldn't object if they order the pediatric paddle, you know, that this is all recommended.

            But if we just have the adult panels available to buy over the counter, then people are going to buy that and use the adult for the pediatric, and that is, I think, not as good as having the pediatric available.

            DR. RINGEL:  That was part of why I'm on the fence here, is the issue.  It goes like this.  I ask them why not include the pediatric paddles.  They say cost issue.

            Okay.  Then we go through, well, what are the chances that someone who's an adult and doesn't have any kids in their house are going to need pediatric paddles.  The answer is very limited, but then if you say people are buying it specifically because they have an infant who has been diagnosed as having sudden infant death or someone who has long QT, well, then they are plugged into the physician system anyhow, and they could get that prescription and get the pediatric paddles.

            On the other hand, the chances that apart from those rare conditions long QT or whatever, it's ‑- these are primarily respiratory events, and the chances of getting VF that would then meet an algorithm and get a shock is so small, and if you do get it, it's better just to shock the kid.  You may fry the heart a bit, but its' better just it's better just to show them.

            So it's tough.  If they're not going to include the pediatric pads, the chances that someone who does not have an infant that they're worried about in the house is going to spend the extra money, order the other pads and get them sent it small.

            I don't know.

            DR. SOMBERG:  I see your point.  I'd just add one more thing.  The one thing that really does disturb me in the last hour of the conversation, or two hours or three, is that they're not having the pediatric pads because once again, that adds a level of a complication, and I think although you buy it for the home use, et cetera, I can see how especially in neighborhoods -- I live in a country where there's a few acres between houses -- but if you're living where 50 feet down i the next house and the next house, someone knows you have the defibrillator.  A child has a problem.  It may be used on a child.

            So I really think the company, unless I'm misunderstanding it adds two, three, $400, but I really think that both sets of pads should be considered.  That's my personal opinion here.

            But, once again, this prescription removal, that's what we're here for today, and I would say if someone wants to buy it for the child and they decided not to consult the physician and they go ahead and buy it for the child and they only can get the adult, then they'll use the adult, and that's something we're making them do what we shouldn't make them do.

            You know, the companies have argued this.  We've argued this.  We don't know who it's going to be used on.  We don't know who is going to use it and for what, you know, whether it's in their house or someone else's house.  It should have both components to be reasonable, and I think both components are the pediatric and the adult because the machine only works partially.  It doesn't work giving you the other algorithm if it doesn't have those pediatric panels to convert it, and you need those voice prompts to be able to go to the ABC approach for pediatrics airway to be told.

            So I think it's an incomplete device if you don't give those pediatric pads.

            DR. ZUCKERMAN:  Dr. Ringel, are you any more convinced one way or the other?

            DR. RINGEL:  I really hate for this to be a sticking point because I think it is a very, very small point, and frankly, my major problem before with the pediatric pads had been my concern about them being erroneously used on larger people.

            I'm not sure that three cases of a seven, eight year old and a ten year old convinces me that I don't have to worry up at the upper end, but the company seems very certain that this is the best way of providing pediatric defibrillation as opposed to any other techniques.

            Down at the lower end I must admit I don't have very much concern.  I think that parents who are going to bring it into the house for their infant or toddler, I know these parents.  They are way plugged in medically, and they will get the pads one way or the other, whether it's prescription or over the counter.  They will buy them.  They will hook them up.  If that's why they're buying the machine, they will get it.

            So I guess it's okay for over-the-counter use as long as the rest of the panel is not concerned about the upper end, which is you know bringing us up to having child pads in and then being used on adults, child pads in and then being used on the large eight year old.  If that doesn't bother anyone, then I think it's okay.

            DR. KRUCOFF:  Well, let me make the argument from the other side, which would be if the OTC version was really one format.  I mean maybe that's actually a whole lot smarter.  Just make the OTC version with the adult pads, recognizing that if you need something for an under 50 pound child that that's a parental or institutional decision that could involve a doctor where there's going to be a motivation to involve the doctor.

            What that interestingly takes away is the potential complexity and the general use that somebody with a sixth grade education actually gets confused and ends up putting the pediatric -- you know if you have both sets of pads in every unit, the potential is to get confused, and maybe what we could do is take away that opportunity for confusion, let the OTC version be one size and to --

            DR. RINGEL:  Well, there's no reason to deprive the pediatric population of an OTC device.  If you make the pads by prescription that's all you'd have to do.  You don't have to disable the whole device.

            DR. KRUCOFF:  Well, that's what I'm saying.  My understanding of this question is that one of the regulatory options here would be to make the whole device OTC, however make the pediatric pad configurations by prescription.  Same box, et cetera, but is that what's being suggested here, Bram, that that is at least an option?

            DR. ZUCKERMAN:  Well, it could be considered, but the easiest would be to make everything OTC if felt appropriate.

            DR. MAISEL:  I don't understand the rationale for making pads, pediatric pads which are markedly less complex than this complex device by prescription.  I think we can debate whether they're packaged with the device or not, but it seem ludicrous to me to make that by prescription and not the device by prescription.

            DR. KRUCOFF:  You could just package them separately.

            MR. MORTON:  Excuse me.  Could we go back to Megan?

            Excuse me.  It's me, Mike.  I'm sorry, Megan.

            What is the configuration of the device now?  Because that's really what we ought to be looking at is what they have submitted, what the sponsor submitted as to be reviewed for 510(k).  Is that an ancillary device, the pads?  Are they different models, pediatric and adult?

            MS. MOYNAHAN:  It's the same unit with different kinds of pads, and right now the home used system which has a prescription offers both adult and pediatric pads.  What the sponsor is asking for is removal of the prescription for the unit and the replacement adult and pediatric pads.

            MR. MORTON:  Okay.  I was just confused.

            DR. SOMBERG:  Well, that confused me.  You mean the current unit that is now available for prescription when you get a prescription and you purchase the unit, it has both the adult and pediatric pads in it?

            The sponsor is saying no.  It only has the adult, and you must request and purchase the pediatric material.

            MS. MOYNAHAN:  Right.

            DR. SOMBERG:  I must submit from my point of view it's hard to confuse.  You know, if the adult pads were connected, and that's the way the machine is configured and then it came in a box just as my camera comes with a lens or something else tucked in the back, pediatric pads, I don't think people would be very confused.  It's just those individuals who want the flexibility, you know.

            You have one neighbor who's potentially at risk, you think.  You have another neighbor that has an infant, and then you bought it for your spouse who had an MI.  I mean, you know, that's the options, and when you pay this much money for a device, you would probably want the maximum -- and we want to get the most out there, you know, the public health thing.  We want to get the most out.  So, I mean, you can make up all sorts of weird scenarios, but I think just having all options available makes the most sense to me.

            DR. MAISEL:  I don't feel that strongly about whether the pads are with the device or not, but if they're not with the device, then I think the packaging should be clearly marked that pediatric pad is not included.

            PARTICIPANT:  That's a good suggestion.

            MS. WOOD:  Number six, according to the AHA, the first link in the chain of survival is to activate the EMS system calling 911.  The sponsor has addressed this concern by placing a prominent sticker, call 911, call EMS on the AED case.  Please comment on the adequacy of this approach.

            DR. VETROVEC:  I'll make at least the first comments.  I've made comments before.  I think this is the single most important point to get across because this is where the individuals really are going to be the help they need in addition to what they can provide themselves.

            So having that on the way as soon as possible has got to be communicated critically.  I'm not sure.  I still think electronically it would be better to do it.

            DR. KATO:  I'd just like to see that the sticker be made permanent, etched on printing on the package.  When I was looking at the package before, I think that the sticker is part of the name, that you can write on it, which means that potentially you could lose it or if you give it to somebody else, they're going to want to put their name on it.

            So I'd like to see a permanent 911 paint job on the red bag.

            DR. KRUCOFF:  Yeah, I would agree with Norm.  I would like to see bigger, more prominent call 911 before use, but as elegant as the digital solution sounds, I mean, in my own home I don't have a cell.  My cell phone does not work in my own home, and the potential with the level of technology that we have available to think that you're called 911 or think this thing is going to call 911 for you when, in fact, it's in a dead cell I think would be very hazardous.

            But I do agree with norm.  It's so important, and it's so simple to do.  Just make the darn thing the biggest lettering on the box the way it would hang on the wall by the phone.  Just write right on the surface when you look at that, I think what you should see is, "Call 911 before use," while you're there at the telephone, and hopefully the instructions suggest as you guys suggested.  Keep it by a phone, mount it by a phone.  Start with 911 and then grab it and go.  I think that would be my suggestion.

            ACTING CHAIR LASKEY:  Pretty straightforward.  Is that there on the record?  If forgot.  When the recording starts, is that the first thing that comes up?

            DR. KRUCOFF:  No, there's a reminder later, after the first cycle.

            DR. SOMBERG:  WE had a conversation specifically.  They figured that if you were the lone one, you don't want to call 911.  You don't want to be running back and forth

            DR. SNYDER:  Correct.  The first layer of labeling is the sticker.  In the event that someone does that and we have no data in our experience with defibrillation to suggest that that's what's going to happen, but should it happen, what we're trying to avoid is causing the responder to have to go back and forth between the patient and the phone, all the time the patient not receiving either circulatory support or defibrillation.  So if they're not activated, we want them to deliver first shocks.  Then they get a reminder to go back and activate EMS.

            DR. RINGEL:  Just once again for my unintended consequences, so when somebody puts this in the house, this is going to become their reference for CPR, their reference for all sorts of CPR issues and, again, call EMS is not the first stage for single responder for kids.

            So when you do that, whatever card, whatever plaque, whatever you're going to do for the pediatric response, they have to be reminded that that's not the first link in the chain for pediatric resuscitation.  At least not yet.  It's do the breathing, get a minute in, then go to the phone.  So we just have to remember that if it's going to be marketed for kids.

            ACTING CHAIR LASKEY:  Just give BLS cards to everybody that wants one of these.  That's basically what.

            DR. RINGEL:  Yeah, and I"m not asking for much.  Just make sure it's in the documentation.  that's all.

            ACTING CHAIR LASKEY:  Good.

            MS. WOOD:  Number seven, automatic external defibrillators are currently track devices by FDA regulation.  Tracking requires the sponsor to have processes in place to promptly identify users in the event of a recall.  At this time removing the prescription labeling will not alter the tracking requirement for these devices.

            In Philips response to this question, Section 4 of the FDA review memos of the panel pack, Question 6, they state that they have submitted a petition requesting a waiver of the tracking requirements for its AEDs.

            Please note that the panel is not being asked to comment on the merits of such a petition.  Please comment on the adequacy of Philips' description of the methods they have in place to identify users in the event of a recall.

            DR. SOMBERG:  Warren.

            ACTING CHAIR LASKEY:  Yes, John.

            DR. SOMBERG:  I think it's important that there has to be a very detailed tracking system, and I don't know why that -- and I'm very disturbed about 46 percent being able to be identified.  I really don't understand why if you purchase this you don't get the card filled out immediately.  If the device is given to someone else, that is a problem, and you're probably only going to get feedback when they need some part of some maintenance, but at least get the name of one person and probably to suggest that if it's transferred a second for the warranty, you know, to sustain itself and to get an extra discount or something, you need to fill out another card.

            But it seems to me there should be a mandatory card filled out similar to a gun, and we k now that ATF has a lot of troubles tracing guns, but at least they know who the first purchaser was..

            DR. KRUCOFF:  I agree.  You know, I just think whether you did it at the time of sale, at least tracking through the first point of sale.  What if protocols really do change and you've got a big sticker on the front of all of these things that say call 911 for a pediatric purpose or don't call 911 for a pediatric purposes and the recommendations change?  I mean, I think at least that first  --

            ACTING CHAIR LASKEY:  And it needs to be a much tighter surveillance, and it's interesting how in the last sentence you left out the qualifier "promptly" because I liked that in the second sentence, but the mechanism to identify patients promptly.

            DR. VETROVEC:  I think it's important to emphasize, too, that the key may not be only identifying who purchased it.  It's conceivable some of these will be purchased as gifts, and so somehow you've got to have the question right or so forth as to who the user is going to be and the contact for the user.

            MS. WOOD:  Number eight, FDA develops an understanding of how devices are performing in the post market period by the reports that come into FDA through the medical device reporting or MDR system.  The sponsor has described the measures they have taken to encourage use of FDA's MDR system in Section 4, FDA review memos of the panel pack Question 12.

            Please comment on the adequacy of the response.

            DR. SOMBERG:  Warren, I thought the post marketing data was quite informative, and it's once again, I think, important to try to keep information on who has the device and every effort should be made to that, but I don't think that was the loosest link in the chain here.

            DR. KRUCOFF:  I actually think there's a huge Pandora's box that I have to admit I guess i see as burdensome here.  As this moves into a consumer population, we can't get doctors to fill out MDRs.  You know, as we move to consumers, I think the burden to dump this on the company, you know, I think to make efforts to track what's going on, I think one of the built in reporting at least data gathering mechanisms that they have, that they seem to have some real spirit toward maintaining is when a part replacement comes in, to go find out how it was used, how it did, what happened.  That would be very valuable data, and you might be able to get your hands on something interpretable.

            But you know, to talk to my grandmother about how it went when she defibrillated my grandfather or to ask her to fill out an MDR if he died, we can't get doctors to do that.  How can we expect them to get that in a consumer population?

            I just can't imagine.

            DR. MAISEL:  I do not think it's unreasonable to ask users to call an 800 number in the case of malfunction or suspected malfunction, but I agree with what you said.

            ACTING CHAIR LASKEY:  Yeah, it kind of segues into number nine.  I guess number nine has got more potential meat to it than number eight, but I think it's just not feasible, number eight.

            MS. WOOD:  The sponsor has proposed to conduct a post market evaluation of this device.  Section 5-7.  The primary objective is to assess the safety and effectiveness after use of the device.  Please comment on the adequacy of this proposal to collect information about the device used in a post market period.

            ACTING CHAIR LASKEY:  And we certainly applaud the efforts of Philips to come forth and propose a post market evaluation.  That's a key interest of the agency, and obviously as we go over the counter with this product in terms of the adequacy of the proposal, first of all the fact that you're doing it is a credit.  It wonderful.  It's probably the only way we're going to get information on the use of the device. 

            Any other comments about the program?  Yes.

            DR. SOMBERG:  I just have one comment, and you know, taken as a totality, this package, I just want to say I think it's unique to this particular product and not necessarily generalizable.

            ACTING CHAIR LASKEY:  What is unique?

            DR. SOMBERG:  All that we've talked about today, including the post marketing follow-up, et cetera.

            Do you want me to elaborate more on that?  I think Bram is understanding my particular comment that this is -- I think you need to be this system and not necessarily generalizable to every defibrillator in terms of the safety, in terms of the validations, in terms of everything else, and really since this is an important issue, it would have to be gone through with each different item.

            DR. ZUCKERMAN:  Right, but now we're trying to define the goals of the post market study, and although the sponsor has indicated that they will commit themselves to a post market study, we've heard today how there are a lot of extrapolations being applied here because the data in the intended patient population isn't quite there.

            So what goals does the panel have in the collection of these 200-odd uses?  There aren't any hypotheses defined in the last section of your panel pack.  Are there certain questions that you would like answered?

            For example, going back to Question 1 of the FDA questions, there's really a lack of data perhaps when use of this device is looked at as a function of educational level.  That could be looked at more closely.  In this post market study proposal so far, the prescription and OTC device uses are being combined.

            Is that what the panel really wants to see or do we want to see a series, an adequate series of OTC cases that can be compared to a prescription control to make sure that all of these extrapolations that have been talked about today can be confirmed?  What are some reasonable goals here for this post market experience?

            DR. KRUCOFF:  My prediction, Bram, in a realistic sense is that with a diligent effort supported by the sponsor, you might get some information on the former, on the 1(a) confirmed in real use, in real world use.  Do people at different educational levels actually know where the yellow pads are?  And can they get it to operate?

            I think as much as all of us would love to have the data of something more elegant, like a comparative with and without prescription, I think the likelihood that you could get that  meaningfully, in my opinion, meaningfully out of a post market experience would be a huge clinical trial.

            You know, what we might hope would be that some of the NIH sponsored data that might give us some explanation, although the flip side is if this goes OTC, it may undermine the NIH's ability to do this trial altogether.  So not that that's the issue for this panel, but I think realistically in the post market environment that learning more about 1(a), the operational, can people use it, do they get confused, and relating that to educational level or other things would be learning something.

            ACTING CHAIR LASKEY:  I think we need to be extremely modest in our expectations, but there are some glaring gaps in the information base, which can be obtained at minimal cost, I would think, but we do need to be modest in the expectation.  So certainly general use as a registry approach to this , just one cross-sectional swipe or, better yet, just a look at the beginning and a look after a year, but you'd have to evaluate the cost of doing that, but I think we've outlined enough areas where we need filling in without designing a parallel cohort.

            DR. ZUCKERMAN:  Right.  MY comment was not to design a parallel study.  the way the protocol reads right now, it's unclear in this case series of 200 uses how many would have to be OTC.  It's a pooling of prescription of uses and the relevance of the prescription data I'm not sure is what is needed right there.  Or I may be wrong.  That's where I'm going.

            Mitch.

            DR. KRUCOFF:  Well, okay.  So good point, and I really missed it.  I mean, one thing would be to simply start the data gathering during that overlap period, and then you're going to get to a point where you're going to have pure OTC data.  That's not a randomized experience obviously or even a parallel experience.  It's just done by calendar time from point of release.  Would that add importance?  I mean, unfortunately I think what to me a lot of the message of today is is that the prescription component of this gadget has been to some degree a barrier or let's say more a barrier than a thoughtful addition to how the device is used or who it reaches.

            So I guess my expectations that somehow the prescription  versus OTC versions would actually look any different if using the same device are -- I like Warren's word -- I would be very modest in my expectations of what we learned across that boundary.

            ACTING CHAIR LASKEY:  Well, and even more directly, we're assured of the safety of this device.  If you could get some effectiveness, that's really what we're after.  We don't have a handle on effectiveness by geography, by age, by class, by so much.  That would be helpful.

            DR. NORMAND:  If I could say something, I know we're not supposed to be designing anything, but it looks like you're going to use the telephone research as well, and I would urge you to have information on the missing data.  This is standard in any analysis that is conducted.  So we're going to be modest.  We're going to collect data on geographic distribution, educational and some demographics on the population that are using this.  Just standard that you should be thinking about collecting information and it being reported back to you.  You've got the numbers and things such as that.

            I'm not sure about the prescription and OTC, and I'm not sure if you're sort of wasting resources by getting it on both groups of patients.  I understand the desire to have both, and it wold be nice to have both pieces of information, but I'm not sure where the 200 came from.

            Did you say 200 sample sign?

            DR. ZUCKERMAN:  It's not defined right now.  It was derived.

            DR. NORMAND:  Okay.  Because I don't know where that --

            DR. MAISEL:  It does state 200 in the --

            DR. NORMAND:  I don't know the justification for that particular sample size.  I don't know what that's based on.  It's pulled out the air in my mind.

            But in any event, if you wanted to estimate something, wouldn't it make more sense to use to make it for the OTC population?  I feel like you're going to be wasting some money and we're going to get little information on both groups.  So focus on one and do it well I would suggest.

            DR. MAISEL:  I agree with that, and I think it should specify home use.  I don't think we need more information about use of this in public access areas, you know, in a shopping mall or something.

            DR. KRUCOFF:  I agree with that.

            DR. VETROVEC:  This may be too mundane, but it would seem to me if you're calling people and finding out how to use certain information, the obvious things that you would like to know is were there any difficulties with using the device or what information would have been helpful to you to know ahead of time.

            You might be able to learn a lot about how to reconstruct the information going forward.  So I wouldn't be --

            DR. KRUCOFF:  You know, that also triggers towards in Sharon-Lise's sort of emphasis.  I think one of the critical pieces in gathering some of these data is to find out the patient's outcome because if the people who don't respond to your survey are the ones who are depressed because they die, the use died, boy, would that be the wrong kind of slant.

            So, you know, I think at some point putting the energy into making this a meaningful data set would be extremely valuable if you can keep your arms around it.

            ACTING CHAIR LASKEY:  Okay. 

            DR. RINGEL:  I'm sorry.  I've missed this before, and I just have to ask this quickly.  On the front cover you have a little thermometer, and I had meant to ask this early one, and it says that if it's stored under 50 degrees less tha 48 hours.  Does that mean the whole thing has died in two days if it's left out in your car in Minnesota nine months out of the year?

            DR. KRUCOFF:  Yeah, but everybody is so hypothermic they live forever.  So it doesn't make--

            (Laughter.)

            ACTING CHAIR LASKEY:  Dan Power.

            MR. POWERS:  The indicator on the box is really about shipping and how you would treat the device.  We don't want it just sitting out on shipping docks where it's very hot because heat affects pads and battery shelf life.

            DR. RINGEL:  So it's not in actual use.

            MR. POWERS:  At 48 hours it' snot going to like suddenly vaporize or anything.

            ACTING CHAIR LASKEY:  Okay.  We are moving into the home stretch here.  The last portion of our session today is the open public hearing.

            DR. KRUCOFF:  Warren. I'm sorry.

            ACTING CHAIR LASKEY:  Yes.  Sorry.

            DR. KRUCOFF:  Can I?  Just before we leave questions.  I just want to suggest wording going all the way back, but just to wordsmith a suggestion on what might go on the front of the box, who buys this thing.  It might say for emergency use in conjunction with CPR of unresponsive subjects while awaiting 911 rescue response.

            I just wanted to suggest a ballpark of wording of if you want to know who ought to buy this thing or what it's about, but something in that flavor which is just what we are talking about.  I just wanted to put that on the record.

            DR. VETROVEC:  The definition of what it is, I'm not sure it still addresses who ought to buy it.  I think it still needs a list of at least the people who are at greatest risk and the concept that half the people who die suddenly didn't know they were sick.

            ACTING CHAIR LASKEY:  I think we've raised enough issues for the agency and the sponsor to ponder for quite some time.  So if we can now again move to the open hearing, the first speaker this afternoon that has requested time is John Gregoire.

            I hope I've pronounced that right.

            MR. GREGOIRE:  Yes.  It's John Gregoire.  That's a tough one there.

            Good afternoon.  I appreciate the time to speak with you folks today.  My name is John Gregoire, and I'm a sudden cardiac arrest survivor.

            Philips is paying my travel expenses.

            MS. WOOD:  Just keep the mic close, please.

            MR. GREGOIRE:  Okay.  Philips is paying my travel expenses for attending this event today.  I live in Dallas, but I took a day off from my family  vacation in Hilton Head, left them there to attend this event because it's very important to me.

            I'm here to void my support for the elimination of the prescription requirement.  I know first hand the importance of this technology.  On June 23rd, 2002, while working out at the Plano YMCA with my two sons and wife, I experienced sudden cardiac arrest.

            A heart surgeon who happened to be working out at the club at the same time recognized that that was what had occurred with me and began applying heart massage as well as CPR.

            Due to that early intervention, I have no heart damage, brain damage, actually any evidence of even the event occurring.

            He asked the club if they had a defibrillator.  The YMCA in Plano had bought one just a couple of months prior.  They used it to restore my rhythm, and you know, clearly was very blessed and lucky to be in that place with someone who gave that care, as well sa having the technology.

            Unfortunately many other people aren't so lucky.  The survival rates for SCA, as everyone knows, are low primarily due to two reasons:  time and technology.  Additionally, the public safety net of paramedics and ambulances can't get to victims' locations and time.  So the elimination of the prescription requirement in my opinion will get more defibrillators out and available to where these events occur and will save lives.

            Now, in my particular case, I had 99 percent, 99.9 percent blockage in one of my major arteries, and 50 percent in a second artery that two stents today now keep open nicely.  The problem for many people, including me, is there were no symptoms, no pain, no shortness of breath, no warning of any kind.

            Even when SCA occurred, it was like a light switch.  There was no pain.  there was no chest clutching.  Just darkness.

            So even after this event happened to me, I waited 18 months believe it or not before I got a home defibrillator.  After such a traumatic event, you're in denial that it's necessary, that it's important, and other barriers, such as the prescription requirement, makes it even easier to ignore.

            Relatives and friends that looked into purchasing a defibrillator for me when they ran into the prescription barrier just kind of moved side and didn't take that next step.

            Today I bring my defibrillator to my office daily.

            So in conclusion, lives can be saved with the availability of defibrillators.  The removal of the prescription obstacle will allow consumers to act on their needs and have this proven, safe technology available for themselves, as well as others.

            Thank you.

            ACTING CHAIR LASKEY:  Thank you, sir.

            Next on the roster is Dr. Graham Nichol, or at least a statement from Dr. Nichol.

            DR. NICHOL:  Good afternoon.  I'm Graham Nichol.  I'm here as a representative of the American Heart Association.  I currently chair the Heart Association's Automated External Defibrillator Task Force.

            Before I make the core of my remarks, I'd like to declare some potential conflicts of interest.  I have a clinical practice in the emergency room of Harborview New Medical Center in Seattle.  I am Director of the University of Washington, Harborview research and training center for pre-hospital care, and also my associated with University of Washington clinical trial center.  Both of those centers enroll patients or coordinate trials in a number of industries and agency sponsored trials evaluating resuscitation, interventions.

            I also hold an investigational device exemption from the FDA for a randomized trial of wearable cardioverter defibrillator.  And I previously received grants from several AD manufacturers for an out-of-hospital cardiac arrest registry.

            However, I hold on relevant to equity, and I've never taken any salary support, speaker fees or consulting fees from any device company or from the Heart Association.  The Heart Association does not endorse any drug or device, but we endorse all efforts to reduce death and disability due to cardiovascular disease, obviously a major cause of cardiovascular disease is out of hospital cardiac arrest, which is common, lethal, debilitating, and costly.

            Many of those events, as you have heard earlier, occur in the home and most EMS systems, if they arrive quickly are able to get good results, but are not able to arrive quickly.

            So in 1992 we previously challenged manufacturers to make small, simple, easier to use, automated external defibrillators that could be made available to lay responders to use at the onset of cardiac arrest before the arrival of the MES providers.

            The National Heart, Lung, Blood Institute and American Heart Association and others sponsored the public access defibrillation trial or PAT trial to test whether defibrillator by lay responders in public settings was effective and cost effective.  The results of the primary analysis will be published shortly in the New England Journal of Medicine.  Included in the study were community units, for example, shopping malls, recreational facilities and apartment complexes randomized to receive either structured and monitored emergency response system with lay responders receiving training in CPR or CPR and AED capability.  About 20,000 volunteers participated in the study.  There was a significant important difference in survival observed in these CPR and AED group compared to CPR alone.

            This demonstrated that training, equipping, and maintaining volunteers to provide early defibrillation within a structures response system improved survival to hospital discharge from cardiac arrest in public locations.

            Currently the National Heart, Lung, and Blood Institute and Philips are sponsoring the HAT trial to test whether defibrillation by lay responders in the home setting is effective and cost effective.  However, regarding device safety as part of our ongoing review of the scientific literature to update our emergency cardiovascular care guidelines, we recently systematically reviewed Medline and M-BASE from 1966 to the present to identify any adverse effects associated with use of defibrillators.  There were actually six published cases.  In one case the individual who was shocked inappropriately died.  In five other cases there was no adverse effect.

            Also, in 1990, Gibson and Eisenberg reported eight accidental shocks to EMS providers in King County, Washington.  Most of those were the result of accidental contact with the patient.  There were no fatalities.

            Note, however, that both the intentional and unintentional inappropriate shocks that I just described were all with manual defibrillators.  There is no published or unpublished evidence that we are aware of which demonstrates harm with inappropriate, intentional or unintentional shocks.

            And also in the PAD trial, which Dr. Ornato and Dr. Becker and others have alluded to today, there were no adverse effects associated with inappropriate shocks from the AEDs.

            Therefore, we recommend that use of AEDs by lay responders in public or home settings should include training and device maintenance.

            To summarize, we are unaware of any published or unpublished evidence that the requirement of a prescription prior to dispensation of an AED increases the likelihood that a responder will be able to use an AED better, nor are we aware of any published or unpublished evidence that the prescription requirement decreases inappropriate use or adverse effects.

            Therefore, we support removal of the prescription requirement for automated external defibrillators.

            Finally, as I was listening to the comments today, perhaps we may make some extemporaneous remarks about the notion of physician prescription and Web dispensation of AEDs.  That makes as much sense as the notion of physician prescription and Web dispensation of pharmaceuticals.  It is not getting you what you want.  It makes no sense.  We think the prescription requirement should go away.

            Thank you.

            ACTING CHAIR LASKEY:  All right.  Thank you.

            Next up is Michael Willingham.

            MR. WILLINGHAM:  Good afternoon.  Thank you for the opportunity to speak before the panel today on behalf of my company, Medtronic.

            My name is Mike Willingham.  I am the Vice President of Regulatory Affairs for Medtronics Emergency Response Systems Division, formerly known as Physiocontrol.

            I have no financial interest in the sponsor.  My salary is paid by Medtronics, and my expenses to travel here today are covered by the company.

            I should also mention that I also serve as the co-chairman of the American National Standard Committee for Performance and Safety of External Defibrillators.

            Medtronic is the leading producer of external defibrillators and  AEDs.  The company conducts research, designs, manufacturers, sells, and services its defibrillators, and we have been doing so for nearly 50 years.

            We introduced the first AED model specifically designed for lay users in the home in 1986 and received FDA 510(k) clearance for that use.  The LifePack 100 was sold to physicians and prescribed to individual patients with high risk for sudden cardiac arrest.

            The physicians trained the patient's spouse or caregiver in CPR skills and the AED operation.  The device was nicknamed the HomePack defibrillator.  It was very small in design and similar to today's AED designs.  It was small, lightweight, simple to operate, and had instructional prompts to guide the user through a resuscitation attempt

            However, this device was ahead of its time.  While it was effective for its intended use, public awareness of sudden cardiac arrest and early defibrillation programs was still years off, and as a result, the sales of LifePack 500 were limited, and the production was discontinued just a few years later after introduction.

            Nonetheless, this device demonstrated that AEDs could be used safely and effectively by lay persons.  Fortunately today public awareness of sudden cardiac arrest and the willingness of the general public to volunteer as a rescuer for a sudden cardiac arrest victim has increased dramatically, and while tremendous effort and progress has been made in recent years, the survival rates for sudden cardiac arrest, as everyone here has mentioned, are still abysmal.

            Hundreds of thousands continue to die every year, and we encourage FDA to keep the enormity of this public health issue in mind as we consider the relative risks and benefits of over-the-counter availability of AEDs.

            Medtronics supports any movement  to increase the awareness of sudden cardiac arrest and to promote the methods and tools to treat this disease.  We encourage the FDA to thoughtfully consider removing the prescription requirement for certain models of AEDs that are designed and proven as safe and effective devices for lay users.

            AED designs have continually improved in recent years, and several clinical studies have shown very promising results in public access defibrillation programs with dramatically improved survival rates.

            Large scale studies of home  AED use are already underway, and we should all be encouraged by these developments.

            The Emergency Care Research Institute, based in Pennsylvania, issued a comprehensive report in June 2004 evaluating and comparing the majority of AED models on the U.S. market today.

            ECRI is an independent, nonprofit research company and serves as the consumer reports for the medical device industry.  ECRI considered several factors in evaluating these AEDs for use by lay users.  The report provides an excellent detailed review of each model for comparison, and  ECRI concluded that several models of AEDs are appropriate and safe for lay use.

            We recommend that FDA review this report and its assessment of over-the-counter sales for AEDs.

            AEDs today are already being sold with prescription and increasing numbers to individuals and organizations that have never owned a defibrillator before.  We understand that consumers and non-medical organizations need help in establishing early defibrillation programs, and we offer support services through companies that include medical direction, CPR and AED training, device registration with local EMS, post event medical review, liability protection and, if needed, physician prescription for the sale of an AED.

            It's our experience that obtaining a physician prescription is relatively a minor consideration in cost in the overall consumer purchase of an AED.  From the purchaser's perspective, there are many considerations.

            Nonetheless, FDA authorization to market an AED without a prescription would give the consumer more confidence the device is safe for use by the general public, and hopefully it would encourage wider adoption, and we encourage the FDA to consider this benefit.

            Federal prescription requirement is just one of many controls placed on AEDs today.  Consumers must also consider state legal requirements, and nearly all states have Good Samaritan liability protection laws around the ownership and use of AEDs.  Some states also require prescription for the sale of AEDs, and nearly all states require a state licensed physician to be involved in the AED program, and require users to attend approved training.

            We currently offer most of these support services.  However, they add cost and complexity to the purchase, and they inevitably impede the adoption and deployment of AEDs.

            We encourage legislators and regulators to balance the need for these controls; that the need to increase availability of AEDs to aggressive improve nationwide survival rates from sudden cardiac arrest.

            My final point would be that earlier this year FDA publicly proposed to reclassify AEDs from Class III to Class II.  Per the regulation for Class II, FDA intends to provide guidance for special controls to AED manufacturers in the near future.  Special controls may include labeling requirements conformance to recognized performance standards and post market surveillance.

            A new edition of the American standard for external cardiac defibrillators was published just last year.  The standard includes specific requirements for AEDs, including those designed for infrequent use and public access in home settings.  It includes requirements for ECG analysis algorithm performance and defibrillator waveforms.

            Medtronic encourages FDA to develop a special control guidance document for AEDs and to provide the industry with a common set of requirements for future market clearance of AEDs.  This guidance document should provide the foundation for any unique controls for OTC AEDs.

            ACTING CHAIR LASKEY:  Mike, excuse me.  We're well over the allotted time.  So if you can summarize or wrap up.

            MR. WILLINGHAM:  And I am done.  Thank you very much.

            ACTING CHAIR LASKEY:  Oh, great.  Thank you very much.  It's just in fairness to all the other speakers today who are trying to adhere to the allotted schedule.

            The next scheduled speaker is Mary Newman.

            MS. NEWMAN:  Good afternoon, Dr. Laskey and members of the panel.  Thank you for the opportunity to speak here today.

            I represent the National Center for Early Defibrillation, which is based at the University of Pittsburgh, and with me today is Dr. Vince Mosesso, the Medical Director for the National Center for Early Defibrillation, who is also an associate professor at the University of Pittsburgh School of Medicine, Department of Emergency Medicine.

            In the interest of disclosure, our organization is funded by two corporate foundations, seven AED companies, and two private foundations.

            The remarks I'm about to share with you have been provided to you in your packets, and also I'd like to mention that Dr. Mosesso co-authored these remarks.

            The National Center for Early Defibrillation, a nonprofit, vendor neutral, information clearing house and resource center based at the University of Pittsburgh, supports a change in the Food and Drug Administration to enable over-the-counter sales of AEDs to consumers for personal use.  The rationale for this recommendation follows.

            Number one, sudden cardiac arrest is the leading cause of death in the United States affecting about 1,000 people every day.  It affects more people than the number who die from breast cancer, prostate cancer, AIDS, handguns, house fires, and traffic accidents combined.

            Number two, despite the fact that efficacious therapies exist, only seven percent of sudden cardiac arrest victims survive.  This dismal survival rate is due to the fact that most victims do not receive effective treatment, that is, a combination of CPR and defibrillation in a timely manner, and as you know from all the other remarks, this has to occur within minutes for it sot be successful.

            Without treatment sudden cardiac arrest leads to death.

            Number three, AEDs are safe, user friendly, computerized devices, things to voice and visual prompts that can be used effectively by trained and lay persons.  While training is recommended, the devices have also been used effectively by untrained lay persons.

            Further, AEDs cannot harm patients.  They will not deliver defibrillatory shocks to individuals who do not need to be shocked.

            Number four, while some individuals at high risk for sudden cardiac arrest can be identified in advance and these individuals may benefit from implantable cardioverter defibrillator therapy, most cases of sudden cardiac arrest are unpredictable.  Sine sudden cardiac arrest occurs most often in the home and sudden cardiac arrest is predominantly unpredictable, it stands to reason the consumers who are aware of this information who are conscientious about family health and safety and who wish to prepare for sudden cardiac emergencies may seek to purchase AEDs and have these devices available in their homes and personal vehicles.

            Currently consumers first have to get a prescription to purchase the device, which is an unnecessary impediment to optimal resuscitation readiness.

            Number five, despite the increasing attention to deployment of AEDs in public locations, most cases, 70 to 80 percent of cardiac arrests occur in private residential settings, and research indicates that when sudden cardiac arrest does occur in the home, the event is witnessed in 54 percent of cases.

            Therefore, in about half the cases that occur in the home, someone would be available to administer defibrillation, potentially leading to many more lives saved than the penetration of all public venues with AEDs.

            Number six, the concept of medical oversight is beneficial in specific settings.  AED programs and community-wide and large public or private facilities are strengthened when there is strong medical oversight.

            However, medical oversight of home AED programs is impractical and not warranted.  The benefits of medical oversight can be provided through appropriate labeling and inclusion of instructional and reference materials with the device.

            Further, the typical medical oversight prescription model does not apply to consumers and their families since both the victim and rescuer are unknown.

            Number seven, a change enabling over-the-counter sales of AEDs to consumers has the potential to have a strong positive impact on sudden cardiac arrest survival nationwide, without incurring any risk to future sudden cardiac arrest victims or their rescuers.

            We do not believe that the prescription requirement provides significant efficacy or safety benefit for personal purchase and use of AEDs and, indeed, is an impediment to more widespread availability of this life saving therapy in the setting where it occurs most often.

            However, we also feel that with the elimination of the prescription requirement there should be comprehensive user friendly instructional materials.  These should clearly and thoroughly explain and demonstrate device operation and maintenance.

            For all of these reasons, the National Center for Early Defibrillation urges the FDA to eliminate the prescription requirement for purpose of AEDs for personal use.

            Thank you.

            ACTING CHAIR LASKEY:  Thank you.

            The next scheduled speaker is Carol Spizzirri.

            MS. WOOD:  Actually she sent in a statement to be read into the record.  This is from the Save a Life Foundation. 

            "Dear Ms. Wood:

            "Although AEDs are a valuable tool in the resuscitation of lives, they should be lower in cost and more available.  They should be managed by the medical community so a fear factor is not created in purchasing them without an educational component and CPR and their use, including the general maintenance of the unit so they work when needed with regular practice to create a comfort level by the user.

            "Lastly, it is important to redefine the Good Samaritan law and promote it at the national level to protect individuals against frivolous lawsuits."

            This is signed by Carol J. Spizzirri, R.N., President/Founder, and Mark Mitchell, D.O., Chairman.

            ACTING CHAIR LASKEY:  I guess you're going to read a statement from Mr. Grogan then?

            MS. WOOD:  Yes.

            ACTING CHAIR LASKEY:  Okay.

            MS. WOOD:  This is dated July the 13th.  "I am writing this letter to convince you that the FDA prescription requirement for the purchase of AEDs is an impediment to their deployment and, by extension, risks the lives of future sudden cardiac arrest victims.

            "More than a quarter of a million Americans suffer an SCA each year.  Only five percent survive.  I am one of the chose few.

            "My life was saved on November 16, 2002, on board United Airlines Flight 1540.  Dr. Hocksell (phonetic) Garcia began immediate CPR and United Airlines attendant Michael Braddock brought my heart back to a normal rhythm through the use of an AED.

            "I am a member of Sudden Cardiac Arrest Survivor's Network.  SCASN's parent organization is the National Center for Early defibrillation, NCED, which is located at the University of Pittsburgh.

            "Since my sudden cardiac arrest, I have developed myself to promoting greater public access to defibrillation.  This crusade has taken me into a wide array of venues:  Silicone Valley companies, fitness centers, police departments, as well as other public and private organizations.

            "In addition, given the fact that 70 percent of all sudden cardiac arrests take place in the home, I have also been a strong proponent of greater private access to defibrillation.

            "SCA survivors all have one thing in common.  An AED was available to them in their time of need.  Therefore, anything that inhibits AED deployment is life threatening to future SCA victims.

            "I have seen the chilling effect when people learn that they must have a doctor's prescription in order to purchase an AED.  The prescription requirement does nothing to improve the ease of the use or the life saving potential of AEDs.

            "At the very best, all that can be said about this regulation is that it makes it more difficult for anyone to acquire and deploy an AED.  In other words, this regulation stifles the proliferation of this miraculous piece of medical equipment.

            "The calculus of SCA is simple and indisputable.  As we increase the number of AEDs available in public and private venues, the SCA death rate will diminish.  Unfortunately the FDA prescription requirement is an impediment to this noble goal.

            "In conclusion, I strongly urge you to revoke the FDA regulation that requires a prescription for the purchase of AEDs.  By taking this step, you will improve the SCA survival rate.

            That's from Jack Grogan in San Jose, California.

            ACTING CHAIR LASKEY:  Thanks, Geretta.

            And if you have any more stamina left, you can read the last statement from Dr. Kellerman.

            MS. WOOD:  This is dated July 12th.  "To Whom It May Concern:

            "I regret that I will be unable to attend the upcoming meeting of the panel.  I am writing to express my opposition to the proposed premarket notification submission.  I am Professor and Chair of the Department of Emergency Medicine, Emory School of Medicine in Atlanta, Georgia.

            "I have conducted research on out of hospital cardiac arrest and the use of automated defibrillators.  My former mentor, Dr. Mickey Eisenberg and I, published opposing editorials on this topic in the September 20th, 2000 issue of JAMA.  A copy of my editorial is attached to this letter.

            "I have been employed by Emory University since 1993.  I own no stock in any device manufacturer, nor have I accepted salary support or honoraria from any manufacturer.  One manufacturer, Leardahl Medical Corporation, donated the devices that were used in my study of fire fighter defibrillation in Memphis, Tennessee.

            "Another company, Medtronic/Physio Control, recently agreed to loan my current institution equipment to study the utility of acquiring 12 lead ECGs in the field to improve the outcome of patients suffering from acute myocardial infarction.

            "The argument in favor of over-the-counter sales of automated defibrillators goes something like this.  Number one, heart disease is a major cause of death.

            "Two, ventricular fibrillation is a major cause of death due to heart disease.

            "Three, rapid defibrillation is necessary to save victims in VF.

            "Four, AEDs allow rescuers with minimal training to deliver defibrillatory shocks.

            "Therefore, widespread deployment of AEDs in homes will save thousands of lives following cardiac arrest.

            "There is solid scientific evidence to support statements one through four.  There is no scientific evidence to support statement number five.  Published studies on use of automated defibrillators by first responders, fire fighters, police officers, and other public safety personnel have yielded mixed results.  Interestingly clinical trials that have included a control group, as well as a treatment group, do not demonstrate the same degree of benefit reported by before/after studies that use historical controls.

            "When I was a member of the faculty of the UT-Memphis School of Medicine, I led one of the first major controlled clinical trial of first responder defibrillator by fire fighters.  Rather than equip all of our fire companies with AEDs and compare their performance to historical statistics, I equipped half of our companies with AEDs and retrained the other half to perform excellent quality cardiopulmonary resuscitation until the paramedics arrived.

            "During our two-year study period, the rates of cardiac arrest survival in our treatment or AED group was twice what we had observed in our historical controls.  However, survival doubled in the CPR, the control group, as well.

            "If we failed to include a control group, we would have reached the erroneous conclusion that AED use doubled Memphis' cardiac survival rate.  It didn't.  Simply conducting the study boosted cardiac arrest survival because it motivated everyone to do a better job.

            "In another study, researchers examined what happened when 19 urban and suburban communities in Ontario, Canada enhanced their emergency care system by equipping first responders with AEDs.  Following this innovation, cardiac survival increased from 3.9 percent to 5.2 percent, a modest but statistically significant difference.

            "However, most of this improve was due to a higher rate of survival from pulseless electrical activity, PEA, a condition that does not respond to early defibrillation.

            "Again, it wasn't the introduction of AEDs that made the difference, but probably better CPR.  The data on the benefits of widespread deployment if public access to defibrillators is even weaker than that reported for first responders.  The two most widely cited studies involved placing AEDs in casinos and on commercial aircraft.  Both are singular environments that they are little resemblance to the real world.

            "Casinos are an idea location for AEDs.  They are covered by surveillance cameras, feature roaming security officers who are trained to perform CPR and operate an AED, and they are filled with thousands of overweight, chain smoking patrons losing lots of money.

            "This environment bears little resemblance to Main Street, USA.  The widely cited study that put AEDs on the fleet of American Airlines saved six lives.  To achieve this benefit, the company trained more than 24,000 flight attendants and transported over 70 million passengers.

            "What do studies tell us about the benefits of placing an AED in the home?  Well, there aren't any.  To the best of my knowledge, the only published trial of placing a defibrillator in the homes of high risk cardiac patients produced negative results.  A larger study is presently underway, but its findings are not yet available.

            "For patients at significant risk for sudden cardiac death, an implantable defibrillator makes more sense because it operates itself automatically.  For the rest of us the odds that we will ever need a defibrillator are quite small.  If that time comes, the odds that someone will be nearby and know where the AED is kept are smaller still.  A clever salesman might argue that purchasing an AED for the home is no different than purchasing a fire extinguisher.  It is better to have one and not need it than to need one and not have it.

            "It is worth noting, however, that having an AED in the home might actually impair a person's odds of survival.  Will the family of a cardiac arrest victim lose precious minutes searching for the device rather than calling 911?  Will they focus so intently on operating the AED that they forget to perform CPR?  Will people who buy an AED place undue confidence in the device and either skimp on preventative care or fail to dial 911 at the onset of cardiac symptoms?

            "Obviously these are hypothetical concerns.  At this point the putative benefits of over-the-counter  sale of AEDs are hypothetical as well.  The FDA simply doesn't have the data it needs to reach an informed conclusion one way or the other.

            "Clearly, this is an instance when the commercial imperative to sell AEDs has outpaced scientific research on this subject.  With nothing more than device performance data you are being asked to authorize the unrestricted sale of a very expensive lottery ticket.

            "Thanks to the move Jerry McGuire, Americans are familiar with the express 'show me the money.'  Before members of the FDA Circulatory Systems Device Panel authorize over-the-counter sale of AEDs, they should shout, 'Show us the data.'"

            And that is signed Arthur L. Kellerman, M.D., MPH, Professor and Chair, Department of Emergency Medicine, Emory School of Medicine.

            ACTING CHAIR LASKEY:  All right. Geretta, take a break.

            Is there anyone else in the audience who wishes to address the panel today?

            I'm sorry.  How many -- I'm sorry.  Just so we can reschedule our time we're here.  Well, we heard from one this morning, right?

            If you want to come forth, sir.  Yes.

            So there are two additional?  Yeah, great, thank you.

            MR. BROWN:  Dr. Laskey and members of the panel, my names is Richard Brown, and I am a survivor of sudden cardiac arrest.  I am also President of the Sudden Cardiac Arrest Survivor Network.

            My life was saved because of the proximate availability and rapid deployment of an automated external defibrillator, but it could easily have been otherwise.  My SCA due to an artery blockage happened in a health club where approximately two months before another man died before my eyes.  He died because there was no AED at the facility at the time, and it took 45 minutes for an ambulance to arrive after 911 was called.

            My health club responded to my request to install an AED, and as good fortune would have it, I was the first upon whom it was used.

            On the day of my SCA, an emergency call to 911 from the health club generated a busy signal.  A member of the club who saw me go down ran across the street to the fire station and was told that they could not respond.  The station was in a different response district.

            Notwithstanding these impediments to saving me, the availability and rapid deployment of CPR and of an AED by some of the club's physical trainers saved my life.

            As President of the SCA Survivor Network, I have had the happy experience of meeting and talking to scores of others who have a similar story to tell.  I know survivors who have been rescued while at an airport, while at school, while at home, while at health clubs or a guy, while acting on stage, while at work, and while engaging sports.

            Easy was lucky to be near a defibrillator that was rapidly put into use.  Today you have the power to significantly take luck out of the equation.  If we simply contemplate where we spend most of our time, it is at home.  About half our time is spent there and on the average, that is where we can expect the majority of SCAs to occur.

            Elimination of the prescription requirement making the device a simple consumer purchasing opportunity will make AEDs more readily available to consumers and thus, to SCA victims where they most often need it.

            I'd like to think of this opportunity as not one confined to home use, by more broadly to personal use.  For the consumer defibrillator, it's not likely to be confined to some wall in the basement or attic. It will go on family vacations.  It will be taken to children's football soccer and basketball and hockey games and to swim meets and all other sporting events.

            There will emerge a two defibrillator family, one to keep at home and one to keep with you wherever you go.

            Who will be affected?  Contrary to what one might expect, the average age of our survivors in our group is relatively young, in the early 50s, and 14 percent of our group is comprised of teenagers.

            Survivor demographics span the highest level of consumer purchasing power in America.  SCA survivors are representative of an immense population that is in danger of dying of SCA.  At the same time they represent the group that is very likely to purchase personal AEDs.  That is why your decision is so critically important.  Since SCA cuts across all ages and is most likely to occur at home or where consumers are likely to take his or her person AED.

            Your decision to improve the availability of an AED as a consumer product will immediately save lives.  As more AEDs are sold in the consumer market, the price barrier will also diminish.  Look at the history of cell phones, of VCRs, DVDs and flat screen TVs.  The retail prices have dropped dramatically as more and more consumers learn about them and begin to appreciate your usefulness.

            And I hope that provides some insight, Mr. chairman, as to your concern before about this being available to people who cannot afford the present price.

            Removal of the prescription requirement for the sale of automated external defibrillators will have an immediate positive outcome in saving lives throughout the country.  Therefore, the Sudden Cardiac Arrest Survivor Network of NSAID urges the expeditious removal of this requirement.

            Thank you for your time.

            ACTING CHAIR LASKEY:  Thank you, sir.

            MR. BAUM:  My name is Jim Baum.  I primarily live in Lodai, California.

            I'm here today to urge that you drop the requirement for prescriptions to purchase AEDs, and I'm going to tell you the story of how the ones I purchased for my personal use saved my life.

            I read Monday's Wall Street Journal article.  Late Tuesday afternoon I was in my summer home up in northern Washington, and I got thinking about it, and I got thinking about it, and I thought, you know, we have to get more of these AEDs out where people can use them and save lives just like they saved mine.

            So I called Philips, and they said please get on the "red eye" last night.  "Come out here and tell your story."

            Last September I was going through O'Hare Airport on my way to somewhere that's not important, and I saw my first AED, that I had never seen any before, and I looked at that and I thought, you know, my neighbor on the west side of me in Lodai is 84 years old.  I own a winter home in Porta Vallarta, Mexico.  My neighbor on the north side that is 87 and his wife is 82, and the one on the south side is 78.

            And I'm looking at my own friends, and we're getting older, too, my friends around me.  I've got my own tonsils, my own appendix.  The worst thing I've ever had in my life is a cold.  I go for a check-up every couple of years.  No indication of any kind of heart problem whatsoever, any blockages of any kind.

            I got on my airplane and didn't think anything more about it, took my trip, came back, and as luck would have it a doctor friend of mine and I were having a cocktail one night at the bar, and he says, "Jim, I've got to buy an AED for my house.  Do you want one?"

            I looked at him, and I said, "Yeah, I want three, one for my house in Washington, one for my house in California, and one for my house in Porta Vallarta."

            Okay.  So in a week come three cardboard boxes.  I had never even touched one.  The one in the O'Hare airport was behind glass and said if I opened it a siren would go off and I would be arrested, you know.  So I looked at the thing, and I shook the box, and I got busy, and I threw the boxes over in the corner of the bedroom.

            Well, the three of them sat there for -- oh, I don't know -- probably three weeks.  We made our first trip down to the home in Puerto Vallarta in late October and we had a bunch of stuff to go.  So my wife didn't put one in the suitcases.

            We came back, and we went down again for Thanksgiving, and she had some room, so she threw one of these cardboard boxes in the suitcase.  And we go to Puerto Vallarta and got our shorts on and the beer out and the tequila, and threw the box up on the top of the dresser in the bedroom and thought nothing more of it.

            So it sat up there for ten days.  In the Saturday after Thanksgiving, it was kind of boring and I thought, "Oh, I've got to see what that thing looks like."

            So I got a box cutter, took it out on the patio with a cup of coffee, cut the box open, got the thing out.  Well, here's an instruction book, started reading the instruction book.  Well, you've got to install the battery to make it work.  It's not functional until you do that.  So I take the little bit off.

            And to make a long story short, I sat there and played with it.  I got my wife out there and showed her how to use it, and we had a house guest and his wife who as luck would have it, he was an oral surgeon, and the four of us sat out there and played with that thing and listened to it talk to us, and I was just amazed at the piece of equipment, how heat it was.

            And by that time it's cocktail time.  So it goes in and sits on the dresser again.  the next morning my friend and I took a long walk up the beach and had a good time, and came back.  We had our breakfast in a restaurant, and just as we got done, our wives came in.  Well, they wanted to eat, and I thought, "I don't want to sit here for an hour while they eat," and I'm feeling kind of punky and I don't really feel very peppy, and I said, "Guys, you go ahead and set.  I'm going back and lay down and take a nap.

            So I go back and I laid down, and the longer I laid there the worse I felt.  Pretty soon my wife and the two house guests came in, and I got my wife in there, and I said, "You know, something  is not right here.  I don't feel good."

            She says, "Well, let me get Bob in here."  Well, Bob hears the story.  Bob reaches over to take my pulse, and just as he's reaching out to take my pulse, I died.  Head goes back, eyes roll back, froth at the mouth, become incontinent.  I'm dead.

            Bob says, "Hand me the defibrillator over there, would you?"  He gets the defibrillator.  He turns it on, he sticks it on me.  The machine says, you know, "Stand back and defibrillate," and he pushes the button, and I woke up, and I looked around and I thought, "I went to sleep here while three people were talking to me.  How rude," and I started trying to pick up the conversation, and I became aware my left arm was shaking.

            And I said to my wife, "Why is my left arm shaking?"

            And she said, "We had to defibrillate you."

            Well, I let out a couple of four-letter words and said, you know, "That's stupid.  Don't play with me like that."  I looked down and, "Oh, my."  She was right.

            If I hadn't had that defibrillator I would not be here today.  And so I would urge you to reduce, to eliminate the requirement of having to have a prescription so that we can get defibrillators out where they will save lives in people's hands.

            Thank you.

            DR. ZUCKERMAN:  Sir, for the record, have you noted all of your potential conflicts of interest?

            MR. BAUM:  I don't think I have any.  Nobody has paid me anything.  Philips paid for my ticket last night to get out here, but they're not paying me here.

            DR. ZUCKERMAN:  Thank you.

            MR. BAUM:  I'm self-employed.  I don't make any money out of it.

            ACTING CHAIR LASKEY:  Thanks very much.

            MR. McNELLIS:  Good afternoon.  My name is Bill McNellis.  I'm from Stewartsville, New Jersey.

            I came here today, thanks to the Philips Corporation.  They invited me here to speak in front of this panel, and I thank you for the opportunity.

            We've just celebrated a two year anniversary of a gentleman who I work with who suffered a massive heart attack, and I use layman's terms because I am a layman at this issue.  As it stands right now, I'm probably more nervous standing here talking to you at the panel and the people in the room than I was when I used the AED.

            But as it stands my story goes we were at work one afternoon or evening about ten after six at night when one of the clerical staff came into my office and told me that one of our clerks was in the back in the computer room clutching his chest and he was profusely sweating and complaining of a lot of pain.

            So I immediately got up out of my office and went back and checked on our clerk.  Needless to say he had a vice grip on his chest so hard I couldn't hardly even move his arms.

            At that point in time I realized he was having a heart attack.  I contacted an associate of mine and told him to get the AED.  Our AEDs in our offices are located in such an area that they're accessible to all of our employees.

            I work in a food distribution warehouse, and our AED is located right outside on the floor, right outside of our office.

            So when I called on the radio to get the AED, my associate, a fellow supervisor of mine actually thought I was joking because we've had more incidences as the alarm, as people have stated before, on the box going off by people bumping it than we had any use for it.  We never had any use for it in our building

            Obviously at that point in time of the second request for the AED, he realized I was really serious.  So he ran in with the AED to me, gave it to me, and at that point we got our Mr. Duddar down on the ground, opened up his shirt, and applied the paddles.

            At that point he was still conscience.  With the expedience sake of using the AED and having it set up and ready to go, we applied he paddles prior to him actually going out.

            At that point it kind of more or less was a monitor, monitoring the event.  As time went on, he was complaining more and more of pain.  He kept telling me what he was going to die.  We had a lengthy conversation about that, and I told him there was no way he was going to die.

            At that point in time, he threw his head back, his eyes rolled, and he actually died.  At that point the AED did do its job and did shock the victim.  At that point we pushed the button and shocked the visit.

            At that time,  within seconds after the shock, he came back to life, and the first thing out of his mouth after he told me he saw a bright light was, "I remember everything you said.  What happened?"

            So actually at that time we had the paramedics on the way, but unfortunately they went to our mailing address versus our actual address.  So it did take a little extra time for the paramedics to do there.

            At which time we were almost in a stage of CPR and reshocking the individual, but luckily at that point the paramedics did show up.

            After reviewing the situation, the company and the paramedics, they took the AED with them and they downloaded all of the information at St. Michael's Hospital in Newark, New Jersey, which from what I was told was very helpful because it did give them insight to the whole event and exactly what did happen.

            When I spoke to the doctor the day I went to see Mr. Duddar in the hospital, the doctor said to me, "If it wasn't for the AED, Mr. Duddar would not be here today."

            The type of heart attack he had was massive, and that the idea of the AED being applied so quickly saved his life.

            So I'm very thankful for the AEDs.  Again, when Mr. Duddar and I talked, the first thing we did was a big hug and we love each other.  I mean, we were friends prior to this.  We are best friends now, and I will never let him forget the fact that, you know, you have to look at me and said, "I saved your life.  So don't screw up again."

            But as it goes, having the AED in a place of employment or in an airport is very, very important, but I also feel by being a rescuer that it's also important to have it available to the general public at home or anywhere, even in a vehicle.  You never know what may happen at home or you may never know what you may come across as a rescuer on the outside.

            So I do agree with taking the prescription plan off of the AED and having it available to all of the people.

            I thank you.

            ACTING CHAIR LASKEY:  And thank you.

            Are there any other requests to address the panel?

            (No response.)

            ACTING CHAIR LASKEY:  If not, I'd like to close the open public hearing and just kind of quickly wrap up here and ask Dr. Zuckerman:  does the agency have any additional comments or questions at this point?

            DR. ZUCKERMAN:  No.

            ACTING CHAIR LASKEY:  Does the sponsor have any final comments or questions?

            DR. SNYDER:  No.

            ACTING CHAIR LASKEY:  Ms. Moore, do you have any?

            MS. MOORE:  You don't want to hear my dissertation, do you?  Just joking because I am still concerned about that underserved population, but getting to the point, I do feel that the presentation was really quiet impressive, and as a lay person and a consumer, I believe that the use was simplified to the point that even the people who may be less educated than the test subjects should be able to understand what to do because of the voice prompts and the diagrams.  I think that they are really the thing that makes this really simply to use.

            I am concerned though about the box labeling.  I don't think that I would be prompted to purchase it just as it's labeled because you know when you go to the pharmacy or wherever you're going to buy it, the first thing you do, you read the box to see what it says, and I'm not convinced that the ordinary citizen would feel compelled to purchase this if that's all the information they have.

            However, if there is very aggressive marketing so that everybody knows what this is, then of course I believe the people would be compelled to buy.

            But I do feel that it was a very good presentation, quite, quite well presented, enough for even the lay members here to understand exactly that you are proposing to do, and I'm very please, but I'm still concerned about those people who may not have access to this lifesaving device.

            And once again, we would say that the underserved remain those persons who have less health care than the more affluent members of our society.

            ACTING CHAIR LASKEY:  Mike?

            MR. MORTON:  No comments from me.  Thanks.

            ACTING CHAIR LASKEY:  Well, it's my privilege then to ask for any final recommendations from the panel.  I think we've certainly given the agency lots of recommendations, but these are meant to be final recommendations, Mitch.

            DR. KRUCOFF:  I may step out of bounds, so Geretta, you can slap me, but this is actually to the ANA and other representatives of professional societies, and I speak as an embarrassed physician, that I think our professional societies need to do some education of doctors to get in the loop instead of being an obstruction to the loop, and I think we can follow that up in another venue.

            ACTING CHAIR LASKEY:  I certainly support that.

            All right.  Well, then I'm pleased to adjourn this meeting.  I would like to thank, first of all, the speakers who came forth out of their own time and energy and provided testimony for the panel.  I'd like to compliment and thank the sponsor, Philips.  That was just an outstanding presentation and thanks for hanging in there with us.

            And lastly, I want to thank my colleagues here at the panel.  They were just truly inspirational and supportive today.  So thanks.  Thanks, all.

            This concludes the recommendations of the panel regarding the over-the-counter use of Philips Medical HeartStart Home External Defibrillator.

            (Whereupon, at 5:55 p.m., the meeting was concluded.)