U.S. FOOD AND DRUG ADMINISTRATION

CENTER FOR DRUG EVALUATION AND RESEARCH

FOOD AND DRUG ADMINISTRATION

NATIONAL TRANSPORTATION SAFETY BOARD

JOINT PUBLIC MEETING

Transportation Safety

and

Potentially Sedating or Impairing Medications

National Transportation Safety Board Headquarters

429 L'Enfant Plaza

Washington, D.C.

Thursday, November 15, 2001

8:00 a.m.

BERNARD A. SCHWETZ, D.V.M., Ph.D.

Acting Principal Deputy Commissioner

Food and Drug Administration

CAROL CARMODY

Vice Chairman

National Transportation Safety Board

Co-Chairs

STEVEN GALSON, M.D., M.P.H.

Deputy Director

Center for Drug Evaluation and Research

Food and Drug Administration

DR. VERNON ELLINGSTAD

Director

Office of Research & Engineering

National Transportation Safety Board

Technical Panel

On behalf of the Food and Drug

Administration:

DR. ROBERT TEMPLE

Director

Office of Medical Policy & Office of Drug

Evaluation I

On behalf of the Food and Drug

Administration:

DR. ROBERT MEYER

Director

Division of Pulmonary and Allergy Drug

Products

DR. CHARLES GANLEY

Director

Division of Over-the-Counter Drug Products

DR. RUSSELL KATZ

Director

Division of Neuropharmacological Drug

Products

DR. THOMAS LAUGHREN

Supervisory Medical Officer

Division of Neuropharmacological Drug

Products

DR. PAUL ANDREASON

Medical Officer

Division of Neuropharmacological Drug

Products

On behalf of the National Transportation

Safety Board:

DR. MITCHELL GARBER

Medical Officer

Office of Research & Engineering

DR. MARGARET SWEENEY

Transportation Research Analyst

Safety Studies Division

Office of Research & Engineering

MR. PETE KOTOWSKI

Motor Carrier Specialist

Office of Highway Safety

MR. RAFAEL MARSHALL

Project Manager

Office of Highway Safety

Invited Parties

Advocacy Groups

KAREN TARNEY

Citizens Against Drug Impaired Drivers

Industry

TODD SPENCER

Owner-Operator Independent Drivers

CORRINE RUSSELL

Consumer Healthcare Products Association

WILLIAM MAHORNEY

American Bus Association

NORM LITTLER

United Motor Coach Association

TOM FAULKNER

Air Transport Association

BILL BRADLEY

Consumer Healthcare Products Association

Operator Unions

KAREN HEAD

Legislative Council

CAPTAIN RANDY POPIEL

Allied Pilots Association

Government

ROBERT M. CLARKE

DR. FREDERICK TILTON

Professional

RICHARD GELULA

National Sleep Foundation

DARREL DROBNICH

National Sleep Foundation

 

A G E N D A

 

AGENDA ITEM: PAGE:

Administrative Announcements and Opening 328

Remarks

Witness Panel V - Education 329

Kenneth Edgell

Office of the Secretary of Transportation

Office of Drug and Alcohol Policy and

Compliance

Washington, D.C.

Natalie Hartenbaum, M.D., M.P.H.

Occumedix

Maple Glen, PA

Allen Parmet, M.D., M.P.H.

Midwest Occupational Medicine

Kansas City, Missouri

Questions from Technical Panel/Parties 346

and Discussion

Witness Panel VI - International 428

Jenny Bergin

Pharmacist Consultant

National Secretariat of the Pharmacy Guild

Australia

Asbjorg S. Christophersen, Ph.D.

Associate Director

National Institute of Forensic Toxicology

Norway

Dr. Johann J. de Gier

Ultrecht Institute for Pharmaceutical Science

The Netherlands

Questions from Technical Panel and Discussion 459

 

 

 

 

 

A G E N D A

AGENDA ITEM: PAGE:

Afternoon Session

Witness Panel VII - Warning Labels 495

Ruth Day, Ph.D.

Duke University

Durham, North Carolina

R. William Soller

Senior Vice President and Director,

Science and Technology

Consumer Healthcare Products Association

Washington, D.C.

Bert Spilker, Ph.D., M.D.

Pharmaceutical Research and Manufacturers

of America

Washington, D.C.

Michael Wogalter, Ph.D.

North Carolina State University

Raleigh, North Carolina

Questions from Technical Panel/Parties 521

and Discussion

Adjournment

 

 

 

 

 

 

 

 

 

 

 

 

P R O C E E D I N G S

8:06 a.m.

Administrative Announcements and Opening Remarks DR. ELLINGSTAD: Welcome back. We're off schedule already. I'm sure we'll make up for that.We'll have three panels today. A couple of announcements first.

Again, as -- as yesterday, questions from the audience may be given to one of the staff members who's -- who have the index cards, and if you get that -- give -- give those questions to them we will ask that at the conclusion of the round of -- of questioning.

We also will -- have scheduled a 1:00 audience discussion session as we had yesterday for those who have -- have preregistered to make some remarks. At the moment no one has -- has registered for that, and essentially, anybody that wishes to do so should do that by the time of the first break. What is likely to happen is that we will move up the start of our afternoon panel to 1:00. So, we -- we possibly will -- will be able to exceed the schedule that we have printed up here.

Are there -- you have, Steve?

DR. GALSON: Just very quickly. The reason this meeting is running so smoothly is because of a lot of hard work of -- of -- and planning and also running the mechanics of the room, and I just want to acknowledge the hard work and assistance of those folks. From FDA, Lee Lemley and Anne Henig, who are standing in the back. From NTSB, Carolyn Dargan and Mary Jones. I'm not quite sure where they are but they're around. And then, helping us in the room is Antione Downs and Will Scholochenko. Thank you very much. Doing a great job.

DR. ELLINGSTAD: Thank you. We'll begin this morning with our Education Panel. And our first panelist is Dr. Natalie Hartenbaum from Occumedix in Maple Glen, Pennsylvania.

Dr. Hartenbaum?

Witness Panel V - Education

DR. HARTENBAUM: Thank you for inviting me -- that better? Okay. Sorry about that. Didn't sound like it was vibrating yet.

While I'm primarily going to address educating operators, I think it's equally important to look that we have to also educate healthcare providers, and this is not just the medical examiners that work for the companies but also the treating providers. While companies are aware that they do have a requirement to educate their operators, they do so in many different ways. I've spoken with several of my colleagues in occupational medicine, both in the corporate and private practice setting, to get a sense of what the different organizations are doing. I've also practiced in private practice and served as medical director of a Class 1 railroad, so I'm going to primarily address commercial highway driving and rail.

Many of the companies will advise their operators to talk to their treating providers and read labels, which is a nice start. Some of them will also tell them to have their providers or have the employees themselves talk to the companies' medical professionals to discuss the side effects of medications. This may work well in some cases but it doesn't work very well when we're dealing with over-the-counter medications where there are no medical professionals involved in the prescribing.

Some of the drivers may actually go ahead, take the medication insert, read it, pulling up their reading glasses first if they need to, and look for the great words that say, "Use caution when driving motor vehicle or operating machinery." These operators will indeed use caution. They will be careful. They will work more slowly. But they are still impaired. Evidence has shown that they cannot always adequately assess the degree of impairment these medications may cause.

Some companies do require that individuals in safety-sensitive operations provide information from their healthcare professional that the medication they're using is safe, medication they're using will not impair their operations. And what they will do is some companies will also ask that the medical examiners for that company interview and instruct.

For the rail industry, the only individuals required to have regular contact with health professionals are locomotive engineers. This occurs only once every three years and they're only required to address vision, hearing, and color vision.

For highway, the new medical examination reporting form requires the examiner to discuss with the driver the potential hazards of medications, both prescription and over-the-counter. But here again, the only thing the examiner can do is advise them to talk to their treating provider and read warning labels.

With very few exceptions commercial driving, the only -- there are very few specific limitations on medications. They are not supposed to be using any medication which is impairing or may be habit-forming. However, if they have a health professional who is prescribing a medication and states they are not impaired, they can continue to work in commercial operations.

Many examiners and many companies attempt to get this information from the treating provider and may give questionnaires similar to the one in the binder containing questions such as these. The treating professional looks at the patient -- their patient they want to keep happy and says, "Are you having side effects?" What does the driver or operator say? "No, I'm not." He knows if he answers he's having problems he'll be pulled from service. The healthcare professional says, "Okay. Fine. You're safe to drive," signs off the form, it goes back to the company. The company's medical examiner has no option but tries to challenge or question this medical professional. The response that they often get is, "I know this patient longer than you have and he's better now than he's been for the past five years not on the medication," not understanding the full implications of this partially incomplete assessment and the impairment that this medication may cause.

There are some guidance available for commercial driver medical examiners. In conference reports prepared by -- they were conferences sponsored by the Federal Highway Administration. These, however, predated the ADA. So, even though it contains recommendations on both classes of medications and specific medications, examiners for companies who try to prohibit this are challenged because they need to do an individualized assessment on each driver.

Some of the companies will have information such as the FDA does have a nice pamphlet called "Over-the-Counter Medications and Flying," maybe you shouldn't. There are also information prepared by -- pharmaceutical companies who try to reach out to the healthcare providers and explain to them the importance of impairing medication while at work, not just while driving.

The FAA has a bulletin available and the FTA also has a newsletter available that has in the past covered medication's potential impairment. The FRA and the FMCSA does not at this point have a vehicle for this. Labeling is one start but it's just as important to make certain that the health professionals, the healthcare professionals, understand the importance of a complete assessment and how impairing and how dangerous some of these medications can be.

DR. ELLINGSTAD: Thank you. Dr. Garber has reminded me that I've neglected to make the obligatory fire safety announcement. And in the event of an emergency such as a fire, the building fire alarm will activate and a voice message will instruct persons to vacate the building. If that happens, you should proceed to the nearest exit. There are emergency exits up in the front here on either side of the platform and at the back of the room. Sorry for having neglected that, intruding into the program.

Our next panelist is Dr. Allen Parmet, Midwest Occupational Medicine, Kansas City, Missouri.

Dr. Parmet?

DR. PARMET: Thank you for inviting me.

My background is about 25 years in the military medicine and about 10 years in private practice. The last six years I was medical director for an American Airline company, which was a not-for-profit company. It wasn't on purpose. Just kind of worked out that way. But back in private practice now.

I am a pilot and before I started all this I was actually an air traffic controller for the military, so I've been in this business a long time.

Our point of view from aviation is very similar. I'll have to preface my remarks by saying I totally agree with what Dr. Hartenbaum has said and want to build a few things with regard to aviation.

Our pilots and air traffic controllers are regulated and we have the FAA to rely on and often to blame. When we need somebody to blame, we're very happy to have them there because it gives us the opportunity to say, "You can't take any medications without approval." That's a blanket statement. Nothing. And at least in my company, our rule was that any medication taken must be reported to the company medical director and I personally reviewed all the reports that were submitted and had to approve somebody to return to work. I won't say that everybody actually did that, but that was the rule and it was enforced if somebody was found not to be compliant with it.

But across the board, the only regulations that really apply are to the pilots and air traffic controllers. We have other safety-sensitive personnel as well, including our mechanics, our flight attendants, and security people. And we certainly don't need a mechanic who is sedated and forgets to screw the bolts that hold the tail plane on. We don't need a security person who falls asleep and allows a few pieces of cutlery to go through the X-ray machine. So, our -- our needs are quite broad here.

And we can't use accidents as the end point because those events are so rare as to not give us a good statistical evaluation. We have to be able to evaluate cognitive impairment by a means less than that.

We also have to evaluate it over a very broad screen. We of course don't -- in -- general commercial aviation don't -- don't have any 60-year-old -- 61-year-old pilots, but we do know that -- that aging affects the results of some of these medications, so we have to look at that as well.

The other thing is the environment we operate in is not quite the same. Most of us operate at cabin altitudes equivalent to about 8000 feet. That's about 550 millimeters of barometric pressure and the oxygen levels have dropped from a normal -- the 160 millimeters down to 110. This hypoxia affects and magnifies the effect of any sedating medications. You put in at end of flight, long day, fatigue after a -- a maximum mission is basically equivalent to having about two drinks of alcohol. We -- when we add in any sedation from any medication, you get a sedagistic effect.

So, we've had company policies that work. We can try to educate individual practitioners. It's very difficult to do that because the individual practitioner is the advocate of the patient and will absolutely never tell their patients, "You can't do what you want to do." And I've seen extremes in this.

It -- really, to give you an example, I -- I had a recent case where a driver literally ran into a parked vehicle that had warning lights and a flagman, and the driver was taking prescription amounts of codeine and diphenhydramine and also had a blood alcohol of .18 and at the time his personal physician evaluated him had a blood alcohol level of .18. And his provider testified in court that that man was not impaired.

When you have these situations where the individual provider clearly is such an advocate for the patient, we're never going to see anybody say that there is no impairment unless they're independent, and they have to be independent to be able to -- to base it because otherwise we're -- we're winning individual freedom with no collective responsibility. And if we don't regulate this we're going to legislate -- we're going to litigate it. The lawyers are going to say who will be responsible and who's going to end up paying the bills, and that could be individual practitioners.

What we'd like to have is strong guidance. One could create a list. The -- the FAA has -- has already, as you've seen, Dr. Hartenbaum presented, a -- a pamphlet that is a very strong advisory for aviators. And it works if everybody reads it. But getting that pamphlet is not universal. Ideally, we'd like to have every single person aware of every medication they take and, even more ideally, the interaction between medications, which is much more difficult and in many cases remains unknown.

So, we're faced with a lot of dilemmas here and it's not an easy -- easy situation to -- to come to the ultimate conclusion of what is safe, what can you go safely and work with, what can you not, and what are individual variations. So, it's a tough problem. I don't have the absolute solutions for you.

DR. ELLINGSTAD: Thank you, Dr. Parmet.

Our third panelist is Mr. Kenneth Edgell with the Office of the Secretary of Transportation and the Office of Drug and Alcohol Policy and Compliance.

Mr. Edgell?

MR. EDGELL: Dr. Ellingstad, Dr. Galson, members of the panel, thank you for inviting me here.

I --

(Pause)

MR. EDGELL: Okay. Back on track. I am going to take the next few minutes -- I hope I can get through it in five or 10 -- to introduce this mountain of information that I have here on -- on the table and leave it with you and offer it as an example of DOT's contribution in the education area.

Safety is DOT's number one objective. It is -- we refer to it as our "North Star." DOT shares the concern of the NTSB and the FDA regarding the complications that can arise if caution is not exercised when any prescription medication and some over-the-counter medications are used. During the last decade DOT has issued extensive drug and alcohol regulations together with guidance and specific education and training requirements. The transportation industry itself has addressed the need for caution when using prescription and over-the-counter medicine.

DOT continually addresses this issue with periodic notices to the industry and with a wide range of educational and training efforts to those with safety-sensitive jobs and those --

DR. ELLINGSTAD: Could you pull the microphone a little closer?

MR. EDGELL: Oh, I'm sorry.

DOT continually addresses these issues with periodic notices to the industry and a wide range of educational and training efforts to those with safety-sensitive jobs, to those -- and to those physicians who are tasked with ensuring the medical qualifications. I'd like to go through some slides to point out some of the actions taken by each one of our operating administrations.

(Slide)

MR. EDGELL: The Federal Motor Carrier Safety Administration develops and periodically publishes easy-to-understand guidance documents and videos that advise medical providers and operators on the hazards of -- hazards of using medications while responsible for operating commercial motor vehicles.

As an example, Federal Motor Carrier Administration has developed an educational video that targets the motor coach industry. This video addresses the use of prescription and over-the-counter meds in relationship to fatigue.

Motor Carriers is working in partnership with the American Trucking Association on a train-the-trainer program for their Wellness Program which targets commercial drivers called "Getting in Gear." This program will address, among other issues, the use of over-the-counter medicine, prescription meds as possible hazards when operating a commercial motor vehicle.

The -- over 350 physicians, medical examiners involved in determining medical qualification for drivers have been trained by the American College of Occupational and Environmental Medicine and more physicians, approximately 3000, have purchased the DOT "Medical Examination Guidebook."

Motor Carriers has traditionally relied upon the medical community to advise drivers about the proper use of -- medications, both prescription and non-prescription.

(Slide)

MR. EDGELL: Federal Transit Administration has been very active in providing training for public transit agencies and their contractors the past two years. 13 fatigue classes, 15 substance abuse classes, eight drug and alcohol seminars, 13 seminars are planned for 2002. Special emphasis has been placed on education for both management and employees about the safe use of all medications, including over-the-counter drugs. All of the major transit systems have incorporated over-the-counter and prescriptive meds into their policies and driver training orientations.

(Slide)

MR. EDGELL: The Federal Rail has issued a safety advisory on the recommended practices for safe use of prescription and over-the-counter meds by safety-sensitive railroad employees. That initiative involved into the Federal Rail publishing and distributing a compliance and enforcement manual which established the program standard for prescription and over-counter medication use. Federal Rails has also provided numerous presentations and classes to railroad labor and management leaders which underscore the seriousness of their training efforts.

(Slide)

MR. EDGELL: And as a follow-up to the -- the DOT's complete commitment to safety, when Lamar Allen, who was a panelist before you yesterday, does a railroad inspection tomorrow, I can assure you that he will look carefully at the railroad to determine that their policy that they have is fully implemented in this area of concern.

(Slide)

MR. EDGELL: Federal Aviation has published information for airmen which addresses the dangers associated with the use of specific over-the-counter drugs as well as the dangers associated with the use of prescriptive medications. Examples include the "Aeronautical Information Manual" developed for civil aviation pilots which devotes an entire chapter to the medical facts for pilots; the "Medical Handbook for Pilots," which contains a chapter "Drugs and Flying;" and from the "Medical Facts for Pilots" a brochure entitled "Over-the-Counter Medications and Flying."

In addition, the FAA has developed information specific for the aviation -- for their aviation medical examiners. These include quarterly publications from the Federal air surgeon and the medical bulletin, which contains relevant articles and technical reports on the effects of medications and flying. A series of presentations has been developed by the Civil Aeronautical -- Aero Medical Institute. These are known as CAMI's aviation -- courses. CAMI has also developed the basic and beam aviation medical -- examiners' seminars which are conducted across the country and two self-administered training courses.

(Slide)

MR. EDGELL: U.S. Coast Guard has the Motion Marine Personnel Physical Examination Report. This is a report -- this is a form that standardizes the physical examination of all holders of Coast Guard-issued licenses and merchant mariner documents. This form is used for navigation and vessel inspection circular, which specifies -- specifically addresses dosage, purpose, and side effects of medication.

The Coast Guard has embarked on a new crew alertness campaign. The Research and Development Center has been working with the maritime industry in generating interest and awareness of crew alertness and crew endurance management. This system was designed to allow company management and crew members to use objective methods to constantly improve the work plan, the safety, and the personnel endurance.

(Slide)

MR. EDGELL: National Highway Traffic Safety Administration is involved now in the large truck crash study with the Federal Motor Carrier Safety Administration. This study is to determine the causes of serious truck crashes so that most -- so that the most effective measures -- countermeasures to reduce the occurrence and the severity of the large truck crashes will be implemented. The study will determine the causes of serious large truck crashes and the part of the assessment includes significant information related to the use of prescription and over-counter medications, asking about 41 different prescriptions and 15 over-the-counter medications. Data will be collected on a voluntary basis but not from the standpoint of toxicological testing by the National Automotive Sampling System and law enforcement at 24 sites across the country.

This is a four-year effort, 250 of a planned 1000 accidents results have been collected to date and a final draft report and preliminary results should be available in 2003.

(Slide)

MR. EDGELL: The DOT strongly supports clear, consistent, meaningful, easily recognizable warning labels on prescription drugs and over-the-counter medications. Such a meaningful label would be helpful as a tool as a constant reminder of the side effects of medication. A meaningful warning label would be an excellent memory jogger for all of those involved in transportation.

The DOT's position is that we believe that the underlying medical condition for which these listed medications are taken is of utmost concern; that individual reactions to medications vary, creating a case-by-case determination; that drug interactions are another highly confounding concern that, again, leads to a case-by-case evaluation due to beliefs that the solution is very complicated but it centers around a system of continual education of all the key safety components, the DOT medical examiners, and the DOT safety-sensitive employees. Thank you.

DR. ELLINGSTAD: Thank you.

Questions from Technical Panel/Parties and Discussion

DR. ELLINGSTAD: We'll turn to the Technical Panel. Lead-off questions from Dr. Garber.

DR. GARBER: Thank you. Thank you all for -- for being here and thank you for your presentations.

I'd like to start out with a couple of points of clarification from Mr. Edgell, if I may. The training, the American College of Occupational and Environment -- Environmental Medicine training that -- that you listed under the FMCSA actions, is that DOT-sponsored? Does the DOT pay for that?

MR. EDGELL: No, not to my knowledge.

DR. GARBER: Okay. And --

MR. EDGELL: -- that's one-day training. That is -- would be paid for by those participating.

DR. GARBER: Does the DOT in any way fund that training?

MR. EDGELL: Not to my knowledge.

DR. GARBER: Okay. Does the DOT publish a book that goes along with that training?

MR. EDGELL: I'm not sure.

DR. GARBER: Okay. So, in spite of the fact that this is an FMCSA-listed activity, the FMCSA in fact does not have any role in providing that training?

MR. EDGELL: I'm actually not sure what the Federal Motor Carrier Safety Administration's role is in the administration of that training, if they participate in the training. They could very well. The Department of Transportation, and I'm speaking of other types of training or perhaps this is an analogy to be made here, we train medical review officers.

DR. GARBER: Right. No, I'm sorry --

MR. EDGELL: Now, --

DR. GARBER: -- I guess -- I guess the question really was to that specific issue of the -- of the training provided by the FMCSA.

MR. EDGELL: They -- they -- they -- they could participate in that with staff members. I personally do not know. I can find that out for you --

DR. GARBER: Does --

MR. EDGELL: -- and give you that information.

DR. GARBER: -- I know that Dr. Hartenbaum is a member of the American College of Occupational Medicine and also the -- the -- the editor of the text used, I believe, in that training. Can you comment on that, Dr. Hartenbaum?

DR. HARTENBAUM: Actually, there are several pieces. First of all, the textbook is not through ACOM. It's not through the American College of Occupational Medicine. It was an independent book put out, really, as a result of the negotiator rule-making committing merging the exam and the licensing process.

We recognize that information was available but it was not easily accessible. You had to all the agency and request the conference reports. What we did at the time was we took the conference reports and basically summarized them. We included information on the medications as it was listed in the conference reports, which were recommendations. It also included recommendations for an FHWA-, at the time, accepted and trained psychiatrist to evaluate the use of any of the psychiatric medications.

So, the book came out of the conference reports. They were recommendations. They had no regulatory force and could not really be held to a standard.

Of course, this came a couple years later. It is fully run by ACOM -- ACOM members. We did have a member from the FHWA speak several years ago, just talking about the regulatory issues.

What we've tended to present, again, are recommendations, regulations, and guidance material where any exists. Much of it is many years old. Our examiners continually tell us that they really can't enforce many of the recommendations on medications because it's a matter of opinion. These are recommendations. They're not codified. There's no supporting material available and there have been numerous lawsuits filed against companies and examiners that say, "I'm sorry. I can't qualify you while you're on Xanax or while you're on Adivan." And they go back and they get the treating professional to fill out a questionnaire and he says, "He's safe to drive. He's fine to drive."

ACOM would welcome an opportunity to work with the agency to get this sanctioned information. Right now it is independent and partially opinion.

DR. GARBER: Okay. And just, again, so -- so that I'm -- I'm very clear on this. And this is something that is independent of the DOT, this -- this guidance and these courses? Okay.

MR. EDGELL: But if I could add here, these courses in training the medical examiners would no doubt rely heavily on the DOT-published regulations, such as 391 which covers the medical examination criteria and the support information, the question and answers, additional guidance that is published to go along with 391.

And all of this is available on the DOT Web site. There's a very elaborate Federal Motor Carrier Safety Administration home page with this information spelled out categorically. And I would think that -- that the Motor Carriers would work very closely with ACOM or any organization to try to train to be in -- in a cooperative partnership. I just can't imagine anything else.

DR. GARBER: Which -- which actually brings me to my next question. Dr. Hartenbaum, do you believe that the guidance that is available that Mr. Edgell just described on the Web site and through other DOT sources, regulatory or official guidance sources, is adequate for the average commercial vehicle operator, commercial truck driver in particular, out on the -- out on the roads? Are they able to make a determination with the resources they have available as to whether a medication should or should not be used by them?

DR. HARTENBAUM: What the first -- is do medical examiners know the information is even out there? We've trained 350. There are thousands of individuals who can do these exams, from physicians, both M.D.s and D.O.s, nurse practitioners, P.A.s, and in some states chiropractors can medically qualify a driver as being able to drive. That includes evaluating the medication. So, first of all, we're not even coming close to reaching the -- the examiners.

Secondly, the information is incredibly vague. The recommendation on -- is very clear and it says that Elavil should not be used. But that's not codified. If an examiner or company says, "I'm sorry but you're on Elavil. I can't qualify you," there have been and there will continue to be lawsuits because these are not codified or officially -- recently updated regulations. They come from conference reports that are about 10 years old and that is where we're getting our resources from.

We are with the second edition of the book, with the new recourses, we're trying to pull from medical literature but it's still recommendation and that's only reaching a very small percentage of the examiners.

DR. GARBER: And with regard then again to the drivers themselves, would -- would you suggest that -- that a large percentage or a small percentage of them is in reach of this information?

DR. HARTENBAUM: That'd be a very small percentage. If there was a brochure or pamphlet available similar to what the FAA has produced, that could be distributed either through the companies or through the examiners. That would probably be a good starting point.

DR. GARBER: Thank you. And Dr. Parmet, sort of a similar question. Is the -- is the guidance that is provided by the FAA currently effective in reaching the entire pilot community? And again here, I recognize that a lot of your experience has been in the commercial air carrier operations where there -- where there's often a physician such as yourself supervising. But in air taxi operations or commuter operations where there may not be as -- as robust a medical program, do you feel that those pilots are getting the official and -- and necessary information to make the appropriate decisions?

DR. PARMET: I think initially the information's available. And when we're dealing with pilots we have a different group of people who are more interested in what's going on because the tolerances are so much tighter. Certainly, at the fundamental level of the medical examiner we have a very different environment. We only have about 7000 aviation medical examiners in the country. You cannot just pick up and do a physical. You must go through a mandatory 40-hour training course from the FAA. You not only -- having done this, every exam you do is reviewed by the FAA. Your -- everything you do is tracked by the FAA. You must have continuing education and document that in the FAA courses.

There is no way that any medical exam in contact with the medical community through the FAA is done without FAA information, sponsored oversight, and continuous training. The FAA provides us with a newsletter that comes out on a periodic basis. So, medical examinations have continuous input from the FAA with advice to the medical examiner and we pass that on to our pilots.

And at the commercial level it works extremely well. At general aviation it's much less so and a lot of it's relied on their private organizations, particularly AOPA and EAA, which are very helpful and they work closely with the FAA on that issue.

In between are air taxi, some charter operations, and what we -- we like to call Agro Americans out in my part of the world, crop dusters and agricultural aircraft. And a lot of these folks, even if you gave them the information, wouldn't pay any attention. So, it's -- these are sort of our -- our equivalent to independent operators from the truck drivers.

But the information is -- is much more readily available. There are FAA publications that are -- that are reasonably good. I'd like to see more detail and better labeling on the issue, but we're in a much better situation on the aviation community than -- than the other agencies are.

DR. GARBER: Thank you. I think those are all my questions for now.

DR. LAUGHREN: I want to try and contrast this with -- with the -- the program late in the day yesterday when the military was talking about their approach to -- to controlling medications. So -- just so I can understand exactly how it happens in commercial transportation in this country, for example, a commercial truck driver is having problems sleeping, so goes to his physician and gets prescribed a medication. Does that have to be cleared with -- say if it's a -- if it's a large company, large trucking company. Does that have to be cleared with the medical examiner at the company?

DR. HARTENBAUM: In the majority of companies, no. Some large companies may require reporting. Most of them do not. Most of them leave it just to the -- talk to your doctor and discuss it.

DR. LAUGHREN: Okay. How about in -- in commercial air? Would -- if a pilot is prescribed a hypnotic, would that have to be cleared with -- with the medical examiner in the company?

DR. PARMET: Well, the answer is individual companies might have a policy yes or not, but absolutely every pilot would be knowledgeable that if they're on a prescription medication that must be reported to the FAA before they're cleared to return to service. And most commercial air operators would tell any -- any pilot if you have newly prescribed medication you are not cleared to fly and not cleared to return to duty until you have -- and blessed by the FAA or you're no longer requiring that medication.

DR. LAUGHREN: Okay. So -- so, --

DR. PARMET: We fail safe, basically.

DR. LAUGHREN: Okay. So, it would have to be cleared by -- by someone presumably following FAA policies about that. Then, my question is, what -- what are those policies? Do you have -- do you have lists of -- of hypnotics that are acceptable or not acceptable in the same sense that the military might -- might have those?

DR. PARMET: For most of the hypnotics the blanket answer's no. They're -- none of them are accepted.

DR. LAUGHREN: Even a very short half-life one would not be acceptable?

DR. PARMET: Yeah. In -- in general, they're -- and I could be corrected because I can see that Federal air surgeon has a representative, but in general, no, they're not permitted. If somebody is not actively flying and needs to take something, they cannot fly for at least 24 hours so that the effects of that are worn off before they return to duty.

DR. LAUGHREN: Well, it sound -- it sounds like that's an even more severe policy than is applied in the military. I mean as I -- if I understood it yesterday, very short half-life hypnotics were considered acceptable. I think the term was "bottle to throttle time" four hours or something like that. So, it sounds like it's -- it's even a more strict policy than in the military.

DR. PARMET: Well, the military is mission-driven. And if they want somebody to get their rest right now they tell them to get their rest right now. And when I was in the military we would prescribe what we called "no-go pills." We would give you a medication to put you to sleep now and then when we wanted you awake we would give you a medication to make you alert, even to the point of prescribing amphetamines. And we know short-term that this is safe. But we also had much higher acceptable level of risk in military aviation. There's people shooting at you.

In civil aviation, you don't have to go. We can get somebody else to do your job, so we don't have to accept that risk. We can bring in a back-up pilot to fly that flight. Why should -- why should we accept the risk that somebody may be compromised in their cognitive ability?

DR. LAUGHREN: I guess the only difficulty then is that if -- if the -- if the consequence of taking a hypnotic to a pilot is that he or she won't fly and if they, you know, they feel they need that, then it might encourage deception.

DR. PARMET: This is true, and this does happen. And I -- you know, I've had informal conversations with the Pilots Union physicians and they're aware of it. And the pilots are aware of it. We haven't quite figured out how to get around it yet.

DR. LAUGHREN: I guess the only other point I wanted to come back to -- this is for Dr. Hartenbaum. I had -- had the sense from what you were saying is that -- that one severe limitation on -- on what kind of education you can provide is the information available on drugs and in particular the fact that it's hard to distinguish among drugs based on -- on, for example, prescription labeling, that -- that the information is often somewhat vague. It encourages caution but doesn't really make the kinds of distinctions that might be -- might be useful to an examiner in making recommendations about, you know, one drug versus another for any particular class of drug.

DR. HARTENBAUM: Most of the examiners are seeing the driver for one time over two year exposure. The person who is prescribing are the treating professionals. And when you go back and say, "Is this person having side effects? Are they safe on this medication?" invariably the treating will say, "He's fine. He's not having side effects." So, until there's a list that says, "These are not permitted" -- right now the -- FMCSA prohibits the use of insulin and medications for seizures if you're driving a truck. And we still have neurologists and endocrinologists who keep writing, "Okay to go back to work. Safe to drive," yet he's on insulin. But we don't have the same kind of force behind saying, "He is on Elavil. He really isn't safe to drive." "No, he's my patient. I know him. He's better now than he's ever been." And the companies will try and deny that and we'll end up in court.

MR. EDGELL: One of the things I would like to add on your first statement, just to point out that it is a requirement of any driver -- and -- and drivers, that's the -- the largest portion of the transportation industry. 7 and a half million, we estimate, out of the 8 and a half million safety-sensitive employees regulated by the Department of Transportation. Those drivers are required to any time they go to a physician are -- and have medication prescribed are required to tell that physician, "I'm a driver," so that the physician can provide the proper warnings with any medication.

And maybe it's -- the defense -- being somewhat defensive or -- or just naive in this area, but I would like to think that these individual providers are more than advocates of the patient in doing these physicals, that they are advocates of safety. That's their purpose in this. And -- and we are having faith in that system.

DR. GALSON: Your colleagues next to you are shaking their heads.

DR. HARTENBAUM: I'd like to respond on that one. There's really two different --

MR. EDGELL: They are the physicians. I'm not.

DR. HARTENBAUM: There's really two different examiners we're referring to. One is the medical examiner that the company may send the individual to, and that contact is only once every two years. The other is the prescribing physician, who actually may end up being the examining physician because some companies allow a driver to go to their own personal physician, who generally doesn't even --

We have found in occupational medicine that we frequently get return-to-work notes. "Can return to work." But he's having passing-out episodes. "Do you know he works at heights?" "Oh, I didn't know that." "I started him on insulin. He had a seizure last month. He's fine to go back to work." "Do you have any idea what he does for a living?" or even ask what the person's job is? And doctors prescribe the sedating medications. I'm not sure why they would prescribe it without thinking that they're driving a car or just working around with other equipment at home.

So, I think too often physicians just really don't think about the potential side effects of their medications or what the person does for a living.

DR. TEMPLE: Mr. Edgell, you just -- before I get to my main question, you said that drivers are required to tell their treating physician their -- what their job is. What does that actually mean? How are they required -- what if they violate -- is it a law?

MR. EDGELL: It is -- it is a -- requirement of DOT regulation for motor carriers and it is to be conveyed to the driver by the employer that if you go to a physician that you tell that physician that you are a driver when they're prescribing any medication in the interest of safety. And that is to be conveyed by the employer to the driver, and we write our rules addressing the employer as well as the driver.

Also, companies are authorized to have policies that if you're on prescription medication it's the company's -- is the -- is authorized to know that -- stated that most companies do not have those policies in place. I would think that the large companies do. They have a greater appreciation for litigation liability. But we are a small business industry.

DR. TEMPLE: Well, one of the things people ask us more and more at FDA is whether we know how our various risk management programs are actually working. We have all kinds of labeling and advice and if it was followed everything would probably be perfect. But we know that people don't follow it.

Really, for all of you, do we have any idea how much transmission of knowledge and then -- and then appropriate performance there is? There's -- it sounds like there's masses of literature that give all good advice people would need if they became aware. Do we have any idea what the penetrance of that is? Do most people know? And if they do know, do they say, "Oh, well, I just -- I've got a cold. I'm going to take that stuff"? Any -- I mean these are susceptible to surveys and sampling. Is there any of that?

DR. HARTENBAUM: I guess just even looking at some of the accident reports that's come through the NTSB where operators at all commercial modes have been found to have things like Benadryl in their system.

As far as reporting to your personal physician, I'm not sure that even makes a real difference. We had an accident in New Orleans a couple years ago where every treating physician knew he was a bus driver. It was on every hospital admission, it was on every hospital form, every physician encounter, and yet they kept releasing him back to work despite medical problems and despite medications.

So, I think educating the healthcare provider has to be an important part of this process. We can't just stop educating the employee because they'll go back and talk to their doctor and the doctor will say, "Oh, I guess you're fine."

DR. TEMPLE: But it -- it would be possible, for example, to conduct a survey among practitioners, wherever the people who are doing this, to learn about the level of consciousness of those things. I mean those are all expensive and I understand why things don't get done, but there isn't -- nobody's tried to do that sort of thing, I take it?

DR. PARMET: Well, --

DR. HARTENBAUM: I'm sure the College -- the American College of Occupational Medicine would be thrilled to work with the FDA in --

DR. TEMPLE: DOT --

DR. HARTENBAUM: Whoever wants to work with us.

(Laughter)

DR. HARTENBAUM: We'd love to get the grant.

DR. PARMET: Well, let me -- let me say, the FAA has actually been doing this because they have a much tighter control as well as investigating all the fatal accidents, and they've got a continuing surveillance both by FAA and NTSB together. And they have the statistical data. I mean when you look at that end point, rare as it is, you find that between 25 and 35 percent of fatal accidents have some sort of drug on board at time of the accident. Some of these drugs are prescription drugs that are prescribed and approved by FAA. It's just a survey that's been done. But it's -- some of them, about 15 percent, are over-the-counter drugs. And a small percentage are controlled substances that it was illegal to fly with under the DOT 5.

So, we -- we know it's out there even in a organization and a group of -- of pilots who are aware of the risk. They're much more aware, they're much better educated on the average than the other agencies. They're much better controlled. The examiners are all trained, which you cannot say in the other agencies, except the Coast Guard is working on theirs.

But certainly, the DOT examiners of -- of commercial drivers, I would say the majority of them have had no training whatsoever. They're just told to do the physical, and they don't have to be a physician, they don't have any training, and there is no feedback as to whether they've done the job correctly or not. I can't tell you how many drivers' physicals I may have failed somebody on and the individual go down the street and have someone else do it and pass them for egregious conditions.

DR. ELLINGSTAD: Could I interrupt? To follow up on that point, we -- we've got representatives of all of the transportation modes here and we're participating and we're sort of pretending that we have equivalent kinds of systems going on. But we're certainly hearing of substantial differences in terms of the kinds of infrastructure both to monitor and regulate operators as well as to provide education and training and information.

Perhaps it would be helpful, maybe starting with Mr. Edgell, if you could just explain for us what the infrastructure is with -- in each of the -- the modes with respect to the -- the medical examiner, you know, cadre and what -- what role they have with respect to operators either to monitor what they're -- they're taking or to -- to deliver this kind of information?

MR. EDGELL: The -- starting with the Federal Motor Carrier Safety Administration drivers, the drivers are the safety-sensitive position. And they are required, if they're driving interstate, to have a physical to determine their medical qualifications for driving.

DR. ELLINGSTAD: Who delivers the physical, and does FMCSA license or -- or otherwise --

MR. EDGELL: They --

DR. ELLINGSTAD: -- certify these examiners?

MR. EDGELL: They -- the Motor Carriers allows the states to determine the -- who -- who a medical examiner may be: physicians, some places physician's assistants, nurse practitioners, and at this point or not even chiropractors if they're allowed to do physicals in that -- in that state.

The intrastate drivers, most of the states have incorporated the requirements of the regulation that I mentioned, 391, for their state commercial motor vehicle operators. Aviation has specific physical requirements that have been discussed on the regular basis, periodic basis, one to two years, some three years.

The transit industry does not have specific requirements for physicals. However, most of the transit operators are strongly influenced by Motor Carriers and by the rail industry and have incorporated those same physical requirements in their transit operations -- all of the major transit systems have physical requirements -- medical qualifications for their operators.

And the maritime industry has medical qualifications for anyone with documents, issued licenses and merchant mariner documents.

DR. ELLINGSTAD: One follow-up. I assume from what I've heard that someone could probably produce a list of all of the FAA-certified medical examiners by this afternoon if we asked. Could the same thing be done for any of the other modes?

DR. HARTENBAUM: No.

MR. EDGELL: No, I don't believe so.

DR. HARTENBAUM: No. There's no way you can do it for highway, and you can't do it in rail, either. It can also take a little bit for transit. I know transit right now -- a large number of transit operators are covered either under FRA or FMCSA requirements. And the companies that have those requirements are meeting them.

For their operators who do not fall under one of those two agencies, there are often -- maybe some similar exam but not always, not requirement. For highway, the examiner can be anyone who is licensed by a state to do an exam. There is no formal training requirement. The examiner is expected by regulation to be aware and knowledgeable of regulations and training and -- regulations and additional material.

There was an informal study done about six years ago asking occupational physicians if they were even aware of the conference reports or the advisory criteria that was available and a significant portion of them said they had no clue it even existed.

There was also a study done in the midwest with eight states where they were looking at every single examination done, and over half of them had errors made and these were examiners that knew they were being reviewed.

For rail, the company can -- can have the exam done by any examiner they choose. And it's only -- locomotive engineers are required to be examined and it's only vision, hearing, and color vision.

DR. ELLINGSTAD: Thank you. I'm sorry, Dr. Temple.

DR. TEMPLE: No, that was very instructive, actually. I think I'm -- I'm done.

DR. SWEENEY: I have a question for probably Mr. Edgell. What has DOT done for non-commercial drivers in terms of informing them about the dangers of medications?

MR. EDGELL: Non-commercial drivers?

DR. SWEENEY: Yes.

MR. EDGELL: Taxi cabs? Private autos?

DR. SWEENEY: Passenger cars, yeah.

MR. EDGELL: Passenger cars? I really can't address that question. I mean we have not -- we participated with this -- with the City of New York when they had some questions regarding drug testing their -- their taxi drivers, but on -- on request we will provide information. But specifically providing information to private drivers, I'm not aware of anything specific that we -- anything targeted that we have in -- in the Department.

DR. SWEENEY: And yesterday -- for any of the panel members here, yesterday we heard in the late afternoon about the expanding role of pharmacists in counseling patients who come in for prescription medications. Have any of the modes worked in the -- with the pharmacy industry?

DR. HARTENBAUM: I know that at least one pharmaceutical company has been working with the American College of Occupational Medicine trying to make sure that the op docs know about the sedating versus non-sedating antihistamines. But not directly working with the pharmacists.

DR. GARBER: I've just got one point of clarification. There -- there is -- is there in fact any list, either permissible medications or non-permitted medications, that an operator could access if they wanted it that is approved by the DOT? In fact, does -- does the DOT publish any list of either approved or non-approved medications that an operator could use either in conjunction with their physician or -- or on their own to determine whether a medication should or should not be used?

MR. EDGELL: We do not have an approved list.

DR. GARBER: And again, just as a point of clarification, I know Dr. Parmet indicated that certain hypnotics would not be permitted for 24 hours, but my impression is that that was more of a guidance either provided to the medical examiners or something that the company provided rather than FAA guidance, is that correct?

DR. PARMET: For -- for general purposes that's correct. The FAA does have an internal list that they use with their air traffic controllers, but in theory -- not supposed to be using.

DR. GARBER: Okay. And then, just -- I really -- I know that I've -- I've probably been a bit harsh in my questioning, Mr. Edgell, but I did want to point out and -- and perhaps give you the opportunity to point out how -- how much leeway does the DOT actually have in enforcing any rules that it would -- might require with regard to medications? I mean how would the DOT in fact be able to enforce any rules were they to put them in place that were specific to specific medications?

MR. EDGELL: Well, enforcement is certainly a big concern with the Department of Transportation because we have so many companies, so many employees. In the motor carrier industry alone you're talking hundreds of thousands of employers, millions of employees. It -- it would be quite -- quite difficult because the enforcement is only -- it's most effective when done at the company's -- at the employer's principle place of business. And the resources are -- are a problem.

DR. GARBER: Thank you. I think that's all we've got for now from the Technical Panel.

DR. ELLINGSTAD: Thank you.

This morning I think we'll start with the Transportation Industry group.

DR. FAULKNER: Tom Faulkner, ATA. I have a question from colleagues here for Dr. Hartenbaum. Is it your position that all medical providers performing DOT medical examinations be trained, certified, and/or registered on an approved DOT list similar to what the FAA has?

DR. HARTENBAUM: That's a difficult question. My personal opinion is, yes, there should be some mandatory information dissemination, mandatory requirement that they demonstrate that they understand the questions.

There was a committee formed several years back and we've been waiting the past three years I guess now for a rule-making where the question of should there be certified examiners. One group proposed certified examiners similar to the FAA system. One group -- one party of this committee said, "We'll sign a form that we'll do the exams right," which clearly they're already signing the form, they're still not doing it right. And the third group recommended giving the information out and answering a series of questions and answers to demonstrate understanding.

Part of the problem with certifying is that there are not absolutes. Intentionally, a lot of these are left to the discretion of the examiner. There is not a pass-defer type system as there is in the FAA. An AME can examine an individual and say, "You don't meet these criteria. I defer you," and that goes to the regional flight surgeon and it goes up the ladder for review.

In highway, the medical examiner, whoever that might be, whether they have the information or not, has the final answer. There is no appeal. There is no further up-the-ladder to go. So, my concern with certifying is how do you test an absolute yes-no answer when there is no absolute yes-no answer? You have to look at each individual basis.

Do I feel there should be mandatory training? I do there -- do feel there should be some mandatory training of some sort. Does it need to be for the FAA? No. We would love to work cooperatively with, you know, the agency on these courses.

DR. FAULKNER: Another question. We will be hearing from the International group, but for instance, in France they have by mandate so many doctors per so many employees, a pretty tight ratio. And as we heard yesterday with the military, one flight surgeon will be serving, you know, maybe 100 pilots along with the other personnel. In the States here 7500 AMEs, or aviation medical examiners, to half a million pilots.

What's the panel's thought about something similar to what they have in other countries where you have a mandatory number of physicians, maybe increase the number of AMEs to be more -- better resource or accessible to employees in the transportation industry?

DR. HARTENBAUM: -- doing commercial driver exams?

DR. FAULKNER: No, I -- well, that's another thing is to have a, maybe, combined specialist that, you know, we've heard here a maritime ground transportation -- commercial driver's license, aviation. Individuals that know the very limits and the training in that and have that safety responsibility rather than -- I mean they're still patient advocates, obviously, but again, the -- the public good, shall we say, in mind as well.

DR. HARTENBAUM: That's probably not a bad step but I think you could do it a simpler way by making certain that examiners -- there are sufficient examiners and they're sufficiently provided the information.

DR. PARMET: If I can address that -- I was part of one of the pilot programs about seven years ago. And we trained all the individuals in the State of Missouri who were going to do DOT driver examinations. We got organized, we trained everybody in a series of seminars. It wasn't nearly as extensive as -- as the FAA, but we weren't dealing with the same demanding environment of altitude and acceleration. And we were also dealing with people who were fairly experienced already. We certified the people in short order.

I think we greatly improved the awareness and the quality of the examinations done. For the first time people began to get feedback on the examinations they were doing. Somebody was looking at their product and giving them a grade. Because right now there is nothing done. For the majority of these examinations under DOT commercial drivers there is absolutely no feedback. You don't know if you're doing a good job or a bad job. You may be the best, you may be the worst, and you have no idea. And I think it's very feasible to do that and we've proved it.

So, I -- I actually support something parallel to the FAA system. I think that would be an excellent idea. It would promote safety. It's going to cost, but it would promote safety.

MR. EDGELL: We certainly -- if I could comment on that, the advocates of safety are also advocates of training. If we get to establish a -- a way to get this information to the physicians in a better way I think the Department would certainly promote that idea. We do have guidelines that have been put out that I mentioned. The Motor Carrier industry has developed a physical examination form that we certainly want to have in the hands of all of those examiners doing these physicals and a better way to get that information out.

We certainly -- I think what I hear is that we need to do more and the needs are very broad -- tremendous amount of individuals -- it's a huge problem. Huge, huge issue.

DR. FAULKNER: Last question, actually, is -- it's from the -- since I gotcha, Mr. Edgell, comment. Any plans on the horizon to change the DOT 5 drugs tested for?

MR. EDGELL: They're at the -- at OMDCP, the Office of Management and Drug Control Policy and Health and Human Services Drug Testing Advisory Board, there has been a lot of attention lately made to the ecstasy drug. And that is -- has been proposed in some guidance -- some efforts by the Drug Testing Advisory Board on their -- on their guidance for alternative specimens to add that drug. But the protocols are not developed. It would be an amphetamine class and that is the only thing -- and I'm not saying we're going to do this. I'm just saying that that -- that is the one that's making its way towards the stove and could be a possible addition to the amphetamine class of drugs. That's the only one that I'm aware of.

That is -- if we did that, it would -- sometime in the near future, two, three years probably.

DR. FAULKNER: Final question. This is more, really, for the panel. What about -- there's been approaches from some people or employees in particular saying when it comes to labeling perhaps putting "DOT-prohibited drug." Your thoughts on that?

MR. EDGELL: The idea of a list, a tremendous amount of medications, these medications, the condition is more important than the medication you're taking. The physicians yesterday were talking about it. Can I produce a list that is -- is totally safe? And one physician says, yes, probably -- only problem in one in a thousand. One in a thousand with 8 and a half million people still gets you a pretty large number that could be potentially problematic.

Everyone said that, well, you have to have a caveat here that taking it at the proper dosage because if you're using it incorrectly -- and then the -- the cross reaction with other medications you might be taking. So, once again, you ask tough questions.

DR. PARMET: I -- I'd like to think that would be a great idea, but the -- there are some -- some medications that even at minimal dose would not be safe. The problem is that you say "no go" and the assumption is that that -- if that's not on the label everything else is okay.

DR. HARTENBAUM: I think having a list of at least some absolute "nos" would provide some start, a way of getting around this for both examiners and for providers. I used the example of Elavil earlier. It was recommended Elavil should not be permitted but it's recommended. We know Elavil is significantly -- its effects last for a -- really, for a long time. If we had something that said that these are absolutely nots and these are to be reviewed, it would give the companies and the examiners something to stand on.

DR. PARMET: You could in fact have a prohibited label, a mandatory "you gotta check before you can do this," and then this is generally okay. Although I -- I can tell you in my workers' compensation practice I have a lot of people who tell me they can't possibly work if I put them on ibuprofen. It puts them right to sleep. Now, if they're taking it for a headache it's okay but not with a work-related injury. Everybody's individual.

(Pause)

MR. SPENCER: I'm Todd Spencer with the Owner-Operator and Drivers Association. And I'm not going to contend or -- that I'm going to speak for anybody else at the table, but yesterday I had -- I had real difficulty with the sedating effects of this particular meeting.

Now, this morning --

(Laughter)

MR. SPENCER: -- I've had no such condition. I felt the arrows several times and I think now and then somebody really needs to speak up and say, well, wait a minute, let's get with the real world.

Clearly, I think the best we can hope for from this meeting is some guidance about what is acceptable and what's not. Largely everything else is a gray area. It's important, I think, for us to realize the people that we're working with.

Now, in -- for example, I don't know very many people of any occupation and doing anything that aren't aware that things like Benadryl and other over-the-counter cold remedies or -- or drugs for allergies can make you -- can make you drowsy. It doesn't make any difference what they are. Most people know those things already whether they're truck drivers or pilots, and I cannot imagine any scenario where pilots or truck drivers or other operators of equipment aren't especially aware and keen on those particular issues. And those are -- any kind of over-the-counter stuff you're only going to take as a last resort if -- if -- because the symptoms of the problem are going to create more of a safety problem than the condition that might result from taking an over-the-counter medication.

Now, in regard to -- so you're not going to do that unless you -- unless you really have no other options, and then you're aware of those things.

In my experience in commercial trucking, oftentimes -- oftentimes doctors are going to be conscientious. If it's your personal physician, then he's going to know something about you. And yes, he's going to be your advocate but he's also going to be -- he's also doesn't want you to die. Now, that's going to be a personal physician. So, he's going to tell you straight in terms of -- in terms of what effects any kind of a prescription medication might have on you. He's going to provide you the information.

Now -- but not all doctors are going to be equal when it comes to this. We hear -- there are instances where there are company physicians with motor carriers. Now, the way the motor carrier industry works is that -- is that they need -- they need drivers. The -- the biggest segment of trucking is the truckload carrier industry and this is the segment that goes through drivers like oats to a horse.

A hundred percent turnover is the industry norm. Now, do I think a company's medical doctor is going to necessarily be more conscientious about things like that? Not a chance if they've got a truck that needs a driver. Not a chance. They'll send him down the road.

Now, in the practical world, in the -- in the practical world, we have anywhere from 5 to 7 and a half to 10 million commercial drivers. I don't care whether the driver works for a small company or the biggest company in the world. None of those drivers are going to report to the company that they're taking medications. They're not going to do it and there's absolutely no power on this earth that would make them, no law we could pass. It's simply not going to happen.

We need to provide better education to truck drivers and perhaps to pilots and some others. Right now there's no formal education of any kind, not in driving or anything like that required, for truck drivers. None whatsoever. And unless -- unless it's mandated there -- there won't ever be any real meaningful training that truck drivers get. There won't be any.

There are opportunities, as I said previously. Many -- most people are aware of side effects that are common with some substances but not all. In the trucking industry what we've seen over the past decade is a tremendous growth in immigrant drivers operating trucks. Many don't speak English. I'm thinking they don't speak English and I'm thinking they would be at a real disadvantage in any of these types of things because I'm not aware of any over-the-counter substances that basically come with different languages on the label. Maybe there are some, but I suspect we have problems there that could be addressed. I'm not exactly sure how we do them.

Now, is -- and I know there are -- I would agree that there should be substances that should be simply "yes" -- "yes" or clearly "no." But in other instances I think drivers can safely drive with over-the-counter medications and -- and many -- many, many, many have done it for years.

Now, probably to underscore my comment about how trucking works, a few months ago there was a driver that took a truck into the capital in California. Now, in retrospect, I kind of wish that driver had have had some Elavil in his blood because maybe he wouldn't have made that decision. But -- but that's basically the way trucking works. Thank you.

DR. ELLINGSTAD: Was there a question embedded in there, Todd?

(Laughter)

DR. HARTENBAUM: If there was I'd like to make a comment on that.

DR. ELLINGSTAD: I -- I am glad that -- that we aroused you a little bit. I -- I despaired of surviving an entire public meeting without a word from Todd Spencer.

(Laughter)

MR. SPENCER: Actually, I need to add one more just to set the record straight.

(Laughter)

MR. SPENCER: I mean it's important that you have an accurate picture of the real world if you're going to be talking about policies that are going to have any meaningful impact. Dr. Parmet suggested a while ago that independents could somehow be some special problems. Now, I understand the term "independent" covers lots and lots of different areas. The particular organization that I'm here representing are -- is made up of individuals that own -- that own and drive their own trucks. They do this for a living and most do it for careers. In terms of frequency of accidents and severity of accidents, they are the best and safest drivers on the road today. So, I'm hoping that wasn't the "independents" that you might have been suggesting.

DR. ELLINGSTAD: Well, we don't want to cast dispersions on the crop dusters that he was talking about either, so we'll move on to the unions.

DR. PARMET: That's the highest risk activity you can do, so they naturally have more accidents.

DR. ELLINGSTAD: The union table?

CAPTAIN POPIEL: Pretty hard to follow that speech.

(Laughter)

CAPTAIN POPIEL: Randy Popiel, APA.

(Pause)

CAPTAIN POPIEL: -- the FAA actually has a -- a very strict tolerance on -- on hypnotics and depressants. And I guess it's curious to me as to why the DOT wouldn't follow through with -- with something like that, something as to their strict policy with -- with any operator of any -- of any motor vehicle. I think in commercial aviation the -- the grounding time is -- is more than the magnitude of the depressant -- certain depressants that have been prescribed to an aviator are in the -- in the area of -- of three to six months away from the -- of the cockpit of an aircraft.

Any idea why -- why the severity or the -- the concern doesn't follow through into DOT's enforcement of -- of other activities, other drivers?

DR. PARMET: Well, I think in terms of use of antidepressant medications the question is less the medication than the underlying disease, both of which have to be addressed for safety. So, with regard to a minimum of six months -- and in fact right now the FAA will not approve somebody returning to flight duty who's taking an antidepressant medication. If they stop the medication and -- as most of these mental health problems do resolve, we can return to some -- I will have to say for our other safety-sensitive people a lot of them do work on antidepressant medications. About 25 percent of my flight attendants are taking some sort of psychoactive drug and we are aware of the process of reviewing if there is a safety impact.

But again, we're looking more in those cases to the underlying disease process, not the use of medication. The -- the comments earlier were a short-term grounding if somebody was using a medication on a one-time or two-time basis for sleep or some acute problem. It's -- it's not -- not really a disease going on, it's simply a situation that is -- is going to pass in a day or two.

CAPTAIN POPIEL: In the -- in general aviation and also commercial aviation there are mandatory disclosures either on a -- depending on which area you're operating in, mandatory physicals at -- at six months or a year, depending on -- on what your -- your position is in the aircraft and up to two years in general aviation between -- between physicals. And on each one of those the FAA requires a mandatory disclosure of doctors visits and medications being prescribed. Is there any -- is there any follow-up policy with -- with the other industries that require mandatory -- mandatory disclosures?

DR. HARTENBAUM: For rail, no. For highway, the exams are at least every two years and the new form does include a space for any physician you've seen, any medications you're taking. So, that's there.

The -- the driver is required to sign that the information they've provided is accurate and true. So, that's, I guess, the closest you can come to a mandatory. But it's two years.

If a person starts on the medication during that two-year period there is no flag to pick that up. And you know, the ideal waiting period, talking about a period of time until you adjust to the medication and develop a tolerance to the side effects, there's nothing to really educate the drivers that they shouldn't drive until they develop a tolerance or have gotten used to side effects.

MR. EDGELL: The form used in maritime also has similar questions -- past --

CAPTAIN POPIEL: In both -- in both commercial and transportation operators are international drivers and operators held to the same standards as far as disclosures? Is that a question you can answer?

DR. HARTENBAUM: I can answer for highway. There's been agreements both with Canada and with Mexico through NAFTA that we will accept their statement that their drivers are medically qualified. Canada has a rather interesting system with a very detailed book put out, essentially approved by the government, on medical conditions and what's qualified and what's not qualified. Very detailed.

Mexico, we're really not quite sure what they have. But the U.S. has signed an agreement that we'll accept their medical qualification.

CAPTAIN POPIEL: Same hold true with aviation?

DR. PARMET: With aviation we have a requirement that anyone that flies a commercial aircraft into U.S. air space must meet U.S. FAA requirements. And we participate with ICAO, the International Civil Aviation Organization, whose regulations are similar -- tougher than FAA. FAA's actually one of the more liberal organizations in having carefully evaluated pilots for use of chronic problems and chronic medications and permitting them to return to flying. But they have the largest database in the world as well, so I think their -- their decision on that is sound. The aviation community internationally is close to --

MR. EDGELL: Just to add one thing that of the -- with the exception of just a handful of Mexican employers -- carriers, while they do enter the United States they are limited to the travel within the commercial zones -- U.S.-Mexico border. We're still in the process of -- of working that issue for --

DR. ELLINGSTAD: Thank you. Now we'll go to the pharmaceutical industry.

MS. RUSSELL: I'm Corinne with the Consumer Healthcare Products Association. I have two questions aimed at any or all of the panelists. Are you aware that the over-the-counter drug manufacturers have an extensive and ongoing consumer education program aimed at all consumers? And as consumers we know there are many drivers who are drivers, and this campaign is aimed to provide important guides for safe medicine use. And continuing with that same question, I -- I wanted to know if you're aware of an organization called the Council on Family Health, which is a consumer education foundation funded by industry that has averaged over 194 million impressions with print, broadcast, and Internet materials designed to educate people about consumer proper medicine use. And CHPA, our association, has distributed over 6 and a half million copies of various publications, again, about safe medicine use over the last three decades or so. That's one question.

And the other is, what suggestions do any of you have for the OTC industry about groups we can work with to further get out messages that would specifically help the transportation industry? Because we do partner often with Food and Drug Administration, with a host of consumer groups, minority groups, senior citizen groups, et cetera. So, we'd like your suggestions.

DR. HARTENBAUM: I think the first issue is that we're dealing with a different population. I had not heard of the second organization you mentioned. I'm aware of OTC, information that's out there. It recommends don't operate machinery, don't drive until you know how this affects you. The problem is, is the individual has that choice. I can say, "Okay. I have a cold. I'm not going to go drive today or I'm going to drive from here to the supermarket."

With commercial drivers, we're dealing with those who need to show up at work or they're going to get disciplined or they're going to lose their pay or are driving 10 hours, according to our service regulations. So, the amount of driving they'll do is different.

The information provided includes, "Be careful." And the drivers are being careful. The problem is there's difficulty in recognizing the level of impairment and in essentially multi-tasking. You can concentrate on one activity. But if you have a car coming at you from the right, another one coming from the left, and they're walking across in front of you, you may not have that reaction time to respond appropriately. And the exposure time and the potential hazards are very different from the private drivers that's into commercial driving.

As far as organizations, I can give you, "Gee, I can suggest." Probably afterwards would be --

MR. EDGELL: The -- specifically as -- since we are mainly talking about the Federal Motor Carrier Safety Administration, a good point of contact within Motor Carriers would be the Physical Requirements branch.

Also, it sounds like that just physicians in general would be an excellent place to start to provide this information since they -- they are what we are relying on -- who we are relying on for safety of -- of the drivers.

MS. RUSSELL: Thank you very much.

DR. ELLINGSTAD: Thank you. Next we'll move to the Professional Sleep group.

MR. GELULA: Thank you. I have a question first for Dr. Hartenbaum and then Dr. Parmet, and it's the same question. At this hearing yesterday the Delaware deputy attorney general cited an egregious example of a failure to adhere to established trucking hours of service rules resulting in that case in a catastrophic collision. And I'm wondering if you would explain the hours of service work rules for commercial drivers and, Dr. Parmet, for pilots and then address how such work rules would create drowsiness and sleepiness for many, if not most workers and interact with sedating medications?

DR. HARTENBAUM: Okay. They're very detailed. It's basically -- I'd might defer from -- details, but they can operate 10 hours without a rest period. And I believe they have to have eight hours -- it's 60 hours a certain number of days, 70 hours other days. There was a new hours of service rule proposed -- it's been put on kind of indefinite hold -- which was more based on giving them adequate rest areas and looking at some of the studies to see people don't rest during their time off.

MR. GELULA: But those work rules have not been implemented. The existing work rules, as you said, 10 hours on, eight hours off, and then 10 hours on and eight hours off. So, there -- isn't there a circadian effect there?

DR. HARTENBAUM: Absolutely. There's a maximum number of hours you can put in over a seven-day period. But getting yourself regular sleep when it's required is definitely a problem.

MR. GELULA: How would that react -- relate to sedating medication?

DR. HARTENBAUM: Certainly not helping.

MR. GELULA: And -- and for pilots, could you also explain, Dr. Parmet, the distinction between flying time and duty time?

DR. PARMET: We clock them in when they -- they actually push back, so that's when their flight time begins. They do have an 80-hour work month. But they may put in 160 hours to get their 80 hours because they're going to show up, report for duty, and brief their flight, pre-flight the aircraft. If there's a delay there's going to be more -- more time before they actually push back and start the clock. They will have a limited duty day and we forecast a particular flight -- run a flight crew out we have to put a second crew on board the aircraft so that one crew takes off and the other crew lands. They have mandatory rest periods.

We work very hard in the commercial industry to make sure where people are staying is adequate, quiet so they do get good rest. We -- hotels to make sure that we get our -- our people appropriate rest.

In the air taxi operations, however, the rules are considerably looser and you'll find that somebody's -- may put in two or three hours in the morning and then be back in the afternoon and put in three or four more hours the same day. Certainly, there's -- teeing is an issue here.

Circadian synchrony, or jet lag some people call it, is -- is a major problem because when we're trying to have someone operate when their body clock says sleep, your performance goes down. And as I mentioned earlier, that can be the same as having several drinks of alcohol. When you add any sedation whatsoever to that from a medication, even one that someone is well adapted to, as we mentioned, -- which people typically don't have sedation after a week or two on that medication. Put them into a situation where they're fatigued because of duty time, working, and they're out of their daily body synchrony, now you have a synergistic effect and it all adds up to create an unsafe situation.

We try by scheduling to avoid that in commercial airlines. We work pretty hard -- we're not there yet -- working -- our pilots' unions are trying to make sure we work on it.

MR. DROBNICH: One quick question. You did a pretty good job of covering all the different modes but what I didn't hear a lot about was light rail and bus operators, which concerns me very greatly. Can you describe any educational efforts aimed at transit operators or are they covered by any rules or regulations from Department of Transportation?

DR. HARTENBAUM: Light rail are generally covered under the FRA, so they'd be under those regulations.

The buses are often CDL holders and will fall under the FMCSA standards. The ones that are not covered of the FTA are the subway operators. And it really -- I noted the FTA has put out both a -- has a newsletter that goes out to the examiners and several companies have gotten together and they do have questionnaires that are sent to the employees asking them to fill out by the treating physician, "Are you safe or are you not safe?" So, we're kind of back to the same question as before.

MR. DROBNICH: Does the FTA have any rules or regulations covering Metro rail drivers or bus operators?

DR. HARTENBAUM: Rail and -- under highway. The -- there was a letter issued -- you know, I have the least knowledge about FTA or FAA. There was a letter issued by the secretary about two years ago reminding transit companies that they need to educate their operators. I do believe that most of them have now standardized the form and do educate their operators.

MR. DROBNICH: Is the panel aware of any educational efforts towards transit operators on this issue?

MR. EDGELL: Transit has over the past two years run a number of training operations on fatigue classes, substance abuse classes, drug and alcohol seminars. And they've continued to plan for those in the future as well. And Doctor's correct that transit is very much influenced by the rail industry or the motor carrier industry because of the obvious association -- your large transit operators, say, in total are very aware of the medication issues, as I mentioned before, and have those in -- in driving training orientations.

DR. ELLINGSTAD: Thank you. We'll go to the Government group. Mr. Clarke?

MR. CLARKE: If I can -- let me just clarify on that last point before I get into my questions. The FTA does not have statutory authority to issue safety regulations for the transit authority. What they do have statutory authority for is to require that transit authorities as a condition of -- of being funded by FTA for capital programs have safety programs in place. But our authority to approve or disapprove those plans is tenuous, and so I think the answer to the question, "Do we have direct control over -- over transit operations," we at the Federal level, the answer is "no." But we certainly work very closely with transit operators to help them do the right thing. And I think the point that's being made here is that they are conscientious and responsible.

MR. DROBNICH: Just to follow up on that, has the FTA given guidance in this area to the transit authority?

MR. CLARKE: Well, I think Mr. Edgell pointed out that there's been a series of classes and training exercises done in which this is part -- this issue is part of that subject.

Let me go on to some of my questions. Dr. Hartenbaum, there was some back and forth earlier on about FMCSA's role in -- in your -- and ACOM's activities in training. Can you explain further whether or not -- it's my understanding that they have had some more than small amount of involvement and cooperation with you folks on that work, is that -- is that not true? In terms of guidance or support or coordination?

DR. HARTENBAUM: No.

MR. CLARKE: No? You've had no contact with them at all?

DR. HARTENBAUM: No. We've had contact. We've actually had much more earlier on where we did have someone from FMCSA speak one of the lectures -- two of the lectures much earlier. We actually asked -- we discussed the possibility of working more closely and were kind of told that the agency couldn't sanction one training program over another. We also have a newsletter that's put out through ACOM which we have -- I sent an open invitation to the FMCSA and also the NTSB to submit articles. And you know, they've had the time to answer specific questions when they've been posed.

But no, the -- is not overseeing it, it is not reviewed, it is not sanctioned by the FMCSA. The information we present is primarily from their regulations and their conference reports although the conference reports are many years old.

MR. CLARKE: Are you familiar with FMCSA's waiver program for disability folks?

DR. HARTENBAUM: Well, there's the skill forms evaluation certificate, which used to be -- orthopedic waiver program. And yes, I also am aware of what used to be the waiver program for vision and diabetes. It was then changed after being challenged to an exemption program. I know there was a "Federal Register" announcement about two or three, maybe six months ago concerning the option of exempting insulin-requiring diabetics. I believe at this time there's only exemption or waiver programs that are under consideration.

MR. CLARKE: And there's a testing program associated with that, too, is that --

DR. HARTENBAUM: The only testing program is for the skill performance evaluation certificate, former orthopedic, requires a road test.

MR. CLARKE: Is it your -- is it your sense that that's an involved process?

DR. HARTENBAUM: Yeah, that is an involved process. The processing of the vision waiver, which is the only waiver currently being -- vision exemption. The wording was changed in 1998 -- required an ophthalmologist to say the person is safe and that their vision hasn't changed.

MR. CLARKE: Does this go before some kind of board or --

DR. HARTENBAUM: It's published in the "Federal Register." There is a required public comment period for this exemption.

MR. CLARKE: Would you see the same kind of thing evolving if this was to expand to kind of -- in fact, he was talking about here. In other words, folks looking for waivers and --

DR. HARTENBAUM: I think the program could exist and would be very well -- well based if there was a decent review mechanism in place. Unfortunately, the individual who's saying that he is safe is the person's treating physician.

MR. CLARKE: Right.

DR. HARTENBAUM: The waiver program in the FAA has individuals who are trained and understand flight. They understand the medical conditions that occur in flight. Right now what the FMCSA does for their waiver programs is they put it back to the treating provider. You know, I've --

MR. CLARKE: But still, I'm talking procedural. What -- what is -- what is the process involved in attempting to get one of these things in terms of due process and -- and amount of time spent to do all this?

DR. HARTENBAUM: There's two different pieces. First is the orthopedic piece where the motor carrier or the individual can submit to a state or regional director of the FMCSA that they're, first of all, otherwise medically qualified, what their orthopedic limitation is, how long they've had, what kind of vehicle they're operating, how long, and all the details that go along with that. They then undergo a road test.

MR. CLARKE: So it's an involved process?

DR. HARTENBAUM: That's an involved process. The other waiver program or exception program is vision and there they submit an application to the Federal agency, who gathers information including their safety record, and gets information from an ophthalmologist about their vision, about whether it's stable or not.

MR. CLARKE: Any sense as to how many folks total might be involved in both these, then?

DR. HARTENBAUM: Yeah. There's probably about 400 in vision exemption right now and -- better number on that. There are also a number, probably about 1500 who have been in the original waiver program for vision and I think about 200 may still be floating out there who have been in the insulin --

MR. CLARKE: Would you like to venture a guess as to how that process might work? Because the number was 3 million or 4 million or so.

DR. HARTENBAUM: I think at --

MR. CLARKE: Attempting to get those kinds of waivers.

DR. HARTENBAUM: I think it would be overwhelmed, the system. But I think that even the way it works right now I have concern about, you know, there's -- put the information out. On one hand, there's a report that just came out sponsored by the -- the FHWI that the vision requirement is necessary and in fact to recommend that the field of vision be expanded to include a vertical requirement, not just a horizontal field of vision as it now exists. Yet, we're -- they're granting exemptions --

MR. CLARKE: I guess my question goes to the process, not the -- not the criteria.

DR. HARTENBAUM: The process -- I think there needs to be a better medical body that reviews this than just the person -- personal physician.

MR. CLARKE: But -- but in your opinion, how would that work if the numbers were on the order of millions?

DR. HARTENBAUM: It wouldn't work.

MR. CLARKE: So, how would you -- how would you suggest, then, if something like that --

DR. HARTENBAUM: I think you would need a system similar to the FAA where there is a group that is dedicated to looking at the waivers and has sufficient staffing and funding --

MR. CLARKE: And how many --

DR. HARTENBAUM: -- and expertise.

MR. CLARKE: -- how many folks do you think that would take?

DR. HARTENBAUM: I couldn't begin to --

MR. CLARKE: Do you want to guess?

DR. HARTENBAUM: How many does the FAA use? Multiply it by a factor of --

DR. PARMET: Well, --

DR. HARTENBAUM: -- 10.

DR. PARMET: -- right -- right now I think the FAA has about six full-time physicians. Is that right, Doctor -- down at -- down at CAMI who review 7000 field examiners. You would probably need some --

MR. CLARKE: And that's for a population of how many -- how many --

DR. PARMET: We -- we have around 600,000 pilots.

MR. CLARKE: How many commercial?

DR. PARMET: Commercial, I think it's around 150,000. I'm -- it's in that area.

MR. CLARKE: So, we're talking a population of 100-, 150,000 commercial operators?

DR. PARMET: Right. You would have to proportionally be on the same ratio. If you have enough people, your process will work properly. But that's what it requires, enough people to properly access, review, and analyze each individual case.

MR. CLARKE: So, we're talking hundreds of thousands of -- of field examiners, the equivalents of AMEs --

DR. PARMET: Right -- right now you have no clue as to how many examiners you have. It's theoretically every licensed exam --

MR. CLARKE: Physician.

DR. PARMET: -- P.A. in several states. You know, you're talking millions. You have no idea who --who's out there.

MR. CLARKE: No, but I mean in the system --

DR. PARMET: And no idea --

MR. CLARKE: -- in the system that's been suggested here, do you want to hazard a guess as to what the scope might be as it relates to the commercial driving population?

DR. PARMET: It -- it would be proportionately large. You'd probably need around 100,000 examiners.

MR. CLARKE: Or more.

DR. PARMET: It's -- possibly, yeah. It's -- it's doable.

MR. CLARKE: And a review mechanism associated with reviewing what -- what those --

DR. PARMET: That -- that's right. You'd have to meet proportionally that kind of training system set up to do it. But you could do it. It's not impossible.

MR. CLARKE: No, no. I'm not suggesting it's impossible.

DR. PARMET: Been working for the FAA since 1926.

MR. CLARKE: Are you suggesting, then, that -- that you think in -- in -- in your opinion that some system like that -- of that magnitude is -- is -- is practical and warranted?

DR. PARMET: I -- I think it's warranted. I think it would be practical. It's -- if you do it computer-based, which is how we do it with the FAA, 99 percent of the routine physicals are absolutely standard and they're reviewed on a computer base compared to published regulations. And you know the person meets the standard. When they don't, then they require review.

DR. HARTENBAUM: One comment on published standards. The published standards for pilots is much more detailed than for highway. The cardiac one for -- for highway states that they can't have cardiac insufficiency -- I forget the exact wording right now. I should know that -- or any other medical condition likely to result in loss of consciousness, syncope, or congestive heart failure. But it doesn't give guidance as the FAA's does on how long they need to be -- after an MI, what's required after a heart attack, whether they can have a pacemaker or not, what kind of -- they can have. So, the specifics --

MR. CLARKE: As a --

DR. HARTENBAUM: -- of the regulations are very different.

MR. CLARKE: -- as a practical matter, all of that, if it were to be done, would have to be done in a rule-making process.

DR. HARTENBAUM: That would be correct.

MR. CLARKE: And -- and all of it would have to be subject to the scrutiny of -- of the rule-making process in excruciating detail on every aspect of every guideline.

Is it -- do you have any sense as to whether or not the new Motor Carrier form has helped at all in terms of highlight -- or heightening doctors' awareness of the need to be sensitive to this issue?

DR. HARTENBAUM: The issue in general or just sedating medications?

MR. CLARKE: Medication.

DR. HARTENBAUM: I think it has made them more aware, those that read it. We know a lot of them don't read it, especially the ones who do one or two a year. They are instructed to discuss with the driver. But even just discussing it doesn't always solve the problem because the drivers don't understand how much impairment they may have and the treating providers don't understand.

MR. CLARKE: So, in your --

DR. HARTENBAUM: I think there's improvement. Do I think it solved the problem? No.

MR. CLARKE: But there has been improvement?

DR. HARTENBAUM: Some.

MR. CLARKE: Thank you.

DR. ELLINGSTAD: And finally, we turn to the Evidence group.

MS. TARNEY: Two questions for Mr. Edgell. What do you know about training of pharmacists and physicians during their professional schooling, if any, on the issues of driving and medications?

MR. EDGELL: I really can't comment on that at all. I have very limited knowledge. Physicians might be better to address that question.

DR. HARTENBAUM: I'll handle that one. Not very much at all. I gave -- rounds at a hospital recently. Not even looking at commercial drivers but just reminding them that there are medical standards for private drivers and a significant physician -- significant proportion of practicing physicians weren't even aware that there were medical standards for private drivers. They weren't aware that -- I live in Pennsylvania -- that Pennsylvania has a mandatory reporting law. So, these are practicing physicians.

In private -- in medical schools they're not taught at all.

MS. TARNEY: Is the DOT working with the AMA,the American Medical Association, for general physician education?

MR. EDGELL: Specifically, I'm not -- I -- once again, I'm not able to comment on that specifically.

MS. TARNEY: We have two questions for Dr. Hartenbaum. Along with your talking about generating a -- you'd like to see a list of -- of drugs generated that are absolutely on a unsafe list, would it also make sense to you to have your examiners trained on the issue of impairment and not rely totally on medications so that variations can be included -- individual variations can be included?

DR. HARTENBAUM: I would love to see examiners properly trained on impairment, on medical conditions, on prognosis, on understanding that if a person has a small heart attack they're not necessarily safe to go back to work one week later because that small heart attack may extend out, become a large heart attack. So, there's a lot of education that needs to be done.

But what's important is we need to have support -- companies and the examiners need support to make a decision and not constantly be challenged, as we're seeing right now.

MS. TARNEY: In the courts?

DR. HARTENBAUM: Yes.

MS. TARNEY: Another question for Dr. Hartenbaum. Are you aware that the Australian truck drivers operate without any limiting hours of service and that surveys have shown that up to 25 percent of them use amphetamines to stay alert and to keep driving? Could you describe some of the psychomotor degradation and cognitive impairment that can result when drivers operate trucks for very long consecutive hours and are actively using drugs to stay awake?

DR. HARTENBAUM: No.

(Laughter)

DR. HARTENBAUM: It's not a good combination, but I am not a psychopharmacologist. So, I -- I was aware that Australia did not have hours of service regulations. I was not aware that that many of them operate with enhancing medications.

MS. TARNEY: Do you think there's that many in -- in this country? I hear rumors all the time that there's that many and more using amphetamines.

DR. HARTENBAUM: There may be. We have run into a problem where providers will prescribe ritalin for drivers who have, quote, "ADD" to help them stay alert while they're driving. You know, we do have to talk about the underlying condition, if they truly have ADD. Again, there's medical -- medical literature out there that drive -- individuals with ADD don't drive safely. However, the physicians swear that they're safer because they're on the amphetamine.

So, you know, it's really the information and getting it out there and having support to make these decisions.

MS. TARNEY: Thank you.

DR. ELLINGSTAD: Thank you.

I believe we have a couple of questions from the audience. Dr. Galson?

DR. GALSON: Let me just start with a question of my own. In the air transport sector, how are sedating antihistamines treated with regard to their stature on these lists?

DR. PARMET: All sedating antihistamines are not --

DR. GALSON: If some --

DR. PARMET: -- are not -- sedating antihistamines are not approved. The so-called "non-sedating antihistamines" must go through a trial period and then we can submit the individuals for approval to be chronically on them, keeping in mind that about six percent of people are sedated by the -- the non-sedators because they don't have the enzyme in the brain that actually pumps the -- the drug back out.

DR. GALSON: Great. Okay. From the audience, if medical examiners will be required to be certified, what would be the impact on the number of medical examiners that would be willing to continue conducting exams? This is for anyone on the panel.

DR. HARTENBAUM: Well, I think that's been a concern all along is that the number of examiners will go down. I think we're now seeing with the medical review officers as they're now required to be trained and pass an exam that the numbers will drop off. So, I think the -- the number will go down. There also is concern that as the number goes down, the cost may go up both because of the cost of training and the decreased access, supply and demand economics.

DR. PARMET: When we did the pilot program in Missouri we had a whole lot of -- that's a technical term, "whole lot" -- of -- of educational programs to certify people. We went all around the state and made it as convenient as we could. We maybe had a drop-off at 20 percent of folks but there was no increase in cost because we went out of our way to make sure that everybody who wanted to take the training could go through it.

Yeah, there would be an impact but that's -- that's the effect of every regulation we do. We have to -- have to weigh the -- the cost of the benefit.

DR. GALSON: Okay. This is a -- specifically for Dr. Parmet. If -- if a pilot flies with a company without a treating medical -- and is prescribed a medication not recommended for flight, what mechanism is there for forcing the individual to report to his AME or company or FAA?

DR. PARMET: Well, the individual's required by Federal Air Regulations to report that. And the treating -- if the treating physician's in the AME, then the AME knows that that has to be reported. But just like with drivers or any other agency, if the treating physician is not the medical examiner they may not report it. They may not even know. So, we -- we, as everybody else, have to rely on the individual pilot or driver to report and basically ground themselves in those situations.

DR. GALSON: And the follow-up to that, isn't it true that many of these drug uses are never reported?

DR. PARMET: Absolutely.

DR. GALSON: And then the last one, isn't it true that this reporting is largely voluntary? And I think you've already answered that.

DR. PARMET: That's correct.

DR. GALSON: That's it.

DR. ELLINGSTAD: Okay. I think we have a couple more from the Technical Panel. Dr. Garber?

DR. GARBER: Yeah. Just one -- one distinction that I'd like to draw would be the -- we spent a fair amount of time discussing certification of examiners or -- or examiner systems. And obviously, that could conceivably play an important role in regulating medication use by operators, particularly for chronic conditions. But I do want to draw a distinction. What about for the acute conditions? The -- many of our drivers, many of our pilots will be using, say, a benzoanasapine as prescribed for muscle relaxant properties or other central nervous system acting medications for that. For an intermittent problem that they may have they may be using the over-the-counter substances for intermittent problems that they have.

Even if you do have a -- a -- a large systematic program by which an individual has intermittent contact with aviation medical examiners or other certifying officials, how do you get to that issue? How do you get to the issue of the intermittent use of various medications, hypnotics for sleep aids, variety of different things that we -- that we commonly see prescribed and commonly see used by -- by people out in the community that would not be listed as a medication that they were currently using?

DR. HARTENBAUM: One way of doing that, the FAA's pamphlet, informational booklets that are given to AMEs to give to their pilots. Having something similar prepared to be given to commercial drivers. Just kind of a little bit of an education piece. Will it stop them all the time? No. Will it at least make them stop and think? Yes.

DR. PARMET: With regard to the individual practitioners, we're talking about every single licensed provider in the country and how do you get that information to them? One might have to actually change the labeling within the "Physician's Desk Reference," which is probably on every provider's desk in the country since it's provided to us for free. That's -- that's the best way I -- I buy that book.

But if it actually had a label on each drug that says, "This may not be used by a commercial pilot without approval by the FAA," "This should not be operated in commercial vehicles," kind of a labeling issue on that end. That brings awareness to the individual providers who may not even know that their -- their patient happens to operate hazardous equipment.

DR. GARBER: And -- and one -- one question related. For the medical certification system, we've been discussing either an FAA-type system or a system in which, essentially, every licensed practitioner can -- can allow or certify operator. Presumably, there are variations in between these two systems. And I thought I heard Dr. Parmet discuss a system in Missouri which was somewhere in between and did or did not have Federal funds or Federal requirements attached to that? Perhaps you could elucidate a little bit more on how that worked and whether that sort of system might be useful in conveying medical information -- medication information to operators?

DR. PARMET: That -- that was a pilot program under the aegis of DOT. So, the state was educating every physician. In Missouri it's only physicians and nurse practitioners can complete the DOT form for drivers. And that was just a pilot program under one year.

And we -- we actually modeled it on the FAA system using a new form that required the driver to fill out everything they were taking, including medications, and then sign it under penalty, which didn't exist in the regular commercial driver's market.

DR. GARBER: If -- would -- in your opinion, would the system that was initiated as a pilot program in Missouri at that time be as unwieldy for handling as many commercial drivers as the system that would be proposed that would be a Federally centralized system from the -- from the -- from a FAA-type perspective?

DR. PARMET: I think it has the same issues because it had to be managed at the state level. And the state Department of Transportation was having the same issues with -- with manpower as well as trying to be consistent. And you've got every jurisdiction in the country.

So, I'm not sure you would get uniformity at -- at the state level. Certainly don't have it now. It would certainly improve the system in terms of education, and drugs and sedation were addressed in that program.

DR. HARTENBAUM: With the negotiation of that rule-making committee, one of the concepts was to make a system not quite as unwieldy as the FAA system where all the information is, first of all, updated and, secondly, sent to all examiners that you're not on the approved examiner list, you just don't do it. And I would also provide a mechanism that when there's new drug information available that could be sent to the examiners and then relayed to the drivers when they show up at their exams. Kind of a cross breed between the way it is and the way FAA has it.

DR. PARMET: I'm not sure the FAA system is unwieldy, but it's -- it's more structured. It does respond. When we have a problem we get good response out of it, so I -- I wouldn't say they're unwieldy. They're a highly structured system and it's been in place for over 75 years, so it knows what it's doing. And our -- our regulations are -- that we operate under are straightforward. I've got three pages of guidance for cardiac conditions, not three sentences.

DR. GARBER: Thank you. And I believe Dr. Sweeney has a question as well.

DR. SWEENEY: Earlier the question was asked about the feasibility of a "DOT-prohibited" label. What about the alternative of a "DOT-approved" label? Your opinions on that?

DR. HARTENBAUM: That would probably work just as well. Yeah, then you would address what do you do about medications that are not on that list? There would need to be a mechanism to review those as they come along.

MR. EDGELL: I think any list would certainly be a formidable task. The review, the development, the updating. Certainly a formidable task.

DR. GALSON: But it exists already for the FAA and the military has a list, so what -- why is that such a large endeavor?

MR. EDGELL: I was not here yesterday so I did not hear the military list and I think even when you were talking about it a moment ago you had some issues with it. The -- I'm -- the -- for the DOT to prepare this list.

DR. ELLINGSTAD: Mr. Clarke asked some questions about the staffing requirements to -- to hire all of these physicians and supervise them. If we're try -- if we're talking about some kind of a magnitude estimate of the task, what would it take to do that particular task of creating such lists? And I guess we probably should have asked our Air Force and Navy folks in terms of what their investment was. Do you have something to suggest in terms of -- of how big that -- that project would be?

DR. HARTENBAUM: First you start with what exists. You take the military list, you take the FAA not officially sanctioned list. You review it, you add to it, it -- that probably is somewhat more workable than the whole certification and review process for everything else. So, I think it's workable.

DR. TILTON: I have a comment that there is no FAA list, so I --

DR. ELLINGSTAD: Excuse me. Please identify yourself?

DR. TILTON: I'm Dr. Tilton. I'm the Deputy Federal Air Surgeon.

There is no FAA list, and -- and Dr. Parmet said there's an unsanctioned list which I -- I would say is a very loose definition because what I think he's talking about is the fact that we don't allow hypnotics and we don't allow a lot of categories of things. But there's no list of medications that we have either written or unwritten or sanctioned. So, I just want to make sure that we understand there is no list, and I agree with what Dr. -- Mr. Edgell said about the -- the difficulty of developing that list, number one, maintaining it, number two, and also, coming back to what we're really concerned about, is the underlying condition.

If you had an approved list, someone might say, "Okay. I can take Medication X," when in fact they shouldn't be taking Medication X because of the side effects they might have, number one, and also because the underlying condition they have, number two, would preclude them from safely operating whatever vehicle it is they're operating.

DR. PARMET: I think you do have a list you use with your air traffic control unit, which is not quite the same thing.

DR. TILTON: Well, I guess if we do I'm not aware of it, so. The air traffic control process is managed and -- and we actually, in my mind, we don't have an approved sanctioned list for air traffic controllers as well. But we would include them in the same way we would include pilots, which would be they're effectively controlling airplanes. And so, the list of kinds of things that we would prevent them from working with would be the same things: hypnotics and anything that would sedate and anything that would be psychoactive.

DR. ELLINGSTAD: Did you have another comment, Dr. Hartenbaum?

DR. HARTENBAUM: If we could get a -- even a list like that that was official in commercial drivers that we take out of the recommendations from the conference report and say, "These are officially recommended as not to be used without detailed review," it would help the examiner because a lot of them don't even know what to do with that list. They -- 10 years old.

DR. ELLINGSTAD: Thank you. Are there any --

MR. CLARKE: Can I make a comment? Can I make a comment, Doctor?

DR. ELLINGSTAD: Okay.

MR. CLARKE: There's been a lot of discussion about recommending and requiring, and just to clarify, in the context of -- of sanctioned programs, regulated programs like pilots and locomotive engineers and so forth there are no such things as recommendations. You either have a rule or you don't. You can -- and I learned this long ago from my lawyers, that if you want to put out a recommendation, they would say, put out a rule.

So, I think we have to be clear that -- that you can't deal with recommendations here in the context of official DOT-recommended lists. It's either a rule that would allow or prohibit or not. And therefore, I think we -- we have to be mindful of what all that entails to get such an official prohibition or approval in place. I think that's some of the distinctions that we're trying to draw here. Recommendations, trade associations, professional societies, the AME, for example, can make all kinds of recommendations about best practices and -- and professionally recommended ways of doing things, but officially sanctioned and prohibiting is a very different issue.

DR. GALSON: Just --

DR. HARTENBAUM: I --

DR. GALSON: -- just a quick comment. Sorry.

The Food and Drug Administration and I believe lots of other Federal regulatory agencies make recommendations that don't have the weight of law. So, there are officially sanctioned guidances or recommendations that the Federal regulatory agencies make. They wouldn't have the force of prohibiting but they can be used as guidances by industry and other groups, and that's fairly common Federal regulatory practice.

DR. HARTENBAUM: The conference reports I refer to are -- were sponsored by the FHWA and it does say, "These are not officially sanctioned recommendations." But they are what the medical examiner tries to use to give some guidance to these very vague regulatory pieces. And because they're only recommendations from a conference that hasn't been sanctioned, they really don't carry any weight and that is very frustrating.

MR. CLARKE: Right. But that goes to the next step you talked about: people then looking for official ability to go back to work or not go back to work or prohibiting people from going to work.

DR. HARTENBAUM: The examiner's looking for guidance, whatever way we can get it. And the -- the guidance from the conference reports are many years old. And anyone who tries to stand behind them and say, "This is what the recommendations from this group of specialists -- representatives suggest we do" are challenged. So, the examiners try to follow it but are really given a hard time.

DR. ELLINGSTAD: Okay. Anything else from the Tech Panel?

(No response)

DR. ELLINGSTAD: Okay. I'd like to thank the panel very much. Any effort here that keeps Todd awake all morning is -- is --

(Laughter)

DR. ELLINGSTAD: -- certainly worthwhile.

We will reconvene at 10:30 for our International Panel.

(Brief recess)

Witness Panel VI - International

DR. GALSON: Let's get started. Like to start with our sixth panel here, International, and give a special thanks to this crew that has traveled tremendously long distances to come give us the benefit of their expertise and input.

The first speaker is going to be Jennifer Bergin, who is a pharmacist consultant at the Pharmacy Guild of Australia. Thank you.

MS. BERGIN: Dr. Galson, Dr. Ellingstad, members of the panel, thank you very much for inviting me here.

(Slide)

MS. BERGIN: What I'm going to do today is give you an overview of -- overview of the professional and regulatory partnership that exists in Australia.

(Slide)

MS. BERGIN: Okay. Just by way of background, the -- approximately 25 percent of drivers -- of the 3400 drivers killed in Australia in road accidents -- yesterday one of the other speakers referred to Olaf Drummer's work. We -- we have evidence that shows that -- goodness. 25 percent have drugs in their system and of those people, 15 percent had cannabis, 13.4 had psychotropics, 4 to 4.4 percent had opiates, 3.8 percent had stimulants, 3.6 percent had benzodiazepines, and about 8 percent had both drug and alcohol in their system.

It's interesting to note that most cyclists had a higher instance of cannabis, some 17 to 20 percent, and as already mentioned this morning, truck drivers had -- had an incidence of 20 percent of stimulants. These -- these figures are similarly demonstrated in the seriously injured category.

And also, we have a -- a regulatory system that involves subsidizing medicines called "Pharmaceutical Benefit Scheme." And that largely determines how frequently a drug is prescribed because it is subsidized. And of the 250 frequently prescribed drugs, 25 percent are either known or suspected of being capable of impairing users' driver skills. And we have 120 drugs that are actually -- that actually require sedative warnings.

(Slide)

MS. BERGIN: The regulatory framework includes two main categories. The "Prescription Only" system is governed by therapeutic goods orders under the regulations and they require warning statements. As I said earlier, in the standard for the uniform scheduling of drugs and poisons there's an appendix with 120 drugs and pharmacists are required by law to label these with sedative warnings.

(Slide)

MS. BERGIN: In the Non-Prescription area we have two categories of drugs: Schedule 2 and Schedule 3. The -- these are known as "Pharmacist Only" medicines or "Pharmacy" medicines. In this category as a -- as a restriction to the licensing or the registration of the product the manufacturer has to include the warning statements on the packaging.

(Slide)

MS. BERGIN: In the Professional Framework we have a publication called the "Australian Pharmaceutical Formulary Handbook," commonly known as the "APF." In that book the counseling notes.

(Slide)

MS. BERGIN: There are 153 drugs that are listed as an instruction to pharmacists as to what -- what additional information to add to the counseling and also dispensing process.

So, if you can on that slide, there are lots of numbers and letters, and so something with a Warning 1 or a Warning 12 would indicate to the pharmacist that a stated warning statement would be required. We will go back to that in a minute.

These take the -- these take the -- SUSDP, the standard warning statements, of which there are three, a little further because they add drugs like antihypertensives and hypoglemics, drugs that may cause dizziness and lightheadedness or -- particularly in the early part of dosing or where the doses change, the pharmacists would use their discretion and add those -- add those -- not, no -- sorry. Not discretion. They would add the warning segment but they would also discuss with the person what would be the most appropriate label for -- depending on the person's intended use.

(Slide)

MS. BERGIN: The other link is that the -- the warning statements that are in the -- that are in the regulatory framework have been taken up by companies who produce these -- these -- these three stickers. Now, they don't quite match the warning statements of the SUSDP. The one on the right is a new statement, the use where the medication is a -- hypnotic and for nighttime use. But the -- these are produced by a company called Fieldlies.

Now, Mr. Fieldlies came to the United States 30 years ago and saw some warning -- warning labels here and he went back and he negotiated with the professional organizations, and as a result we now have these -- they're stick-on labels that the pharmacist adds to the dispensing label.

Now, what they do is processes that the SUSDP has produced -- so that's the regulatory framework. The professional framework is then produced and then the company who produces the stickied-up labels adds the colored statements. So, the one that I've decided is green, it will be in the next edition, the 18th edition of the APF. It's just being produced. The SUSDP. This is a new warning statement, Warning Statement 90, and so that was only just decided recently and it will be in the next -- the next production run of sticky labels.

(Slide)

MS. BERGIN: Okay. Now, the other link is the dispensing software. As you can see -- this is a screen dump from Winifred, which is a dispense -- dispensing software. All pharmacists in Australia use dispensing software. You can see on the -- the left-hand side -- what would you call it? "Aide de memoire" or something like that, but also a shortcut key for the pharmacist.

So, these are all the warning statements that apply to carbamazepine. And if a pharmacist wants to type in L12 or any of those other little shortcut keys on the left-hand side there, that will also appear on the dispensing label. And the person may -- the pharmacist may also then add the -- those little colored labels as well. So, there are sort of two -- two ways that you can add the label or you may want to have both.

(Slide)

MS. BERGIN: Okay. We also have professional standards and guidelines and other mechanisms to reinforce this activity. The Quality Care Program was introduced in 1998 and it's a whole series of professional standards that leads -- that eventually leads to the pharmacist becoming accredited. They are externally assessed against these standards. So, there is a dispensing standard and there is a -- a counseling standard.

The dispensing standard requires that the -- that the pharmacist adds the caution and advisory labels every time they dispense.

The other thing that we have to reinforce these are things called shelf talkers. Now, I'll have to hold these up. They're not on my presentation.

So, these are three shelf talkers that are sedating antihistamines, antihistamines for motion sickness, and antihistamines for use as sleep aids. Now, these are placed near the products. As I said earlier, we have -- we have either prescription or we have two categories of over-the-counter medications. The anti -- the antihistamines are both -- there are some in the Schedule 3 category and there are some in the Schedule 2 category. But where does the -- medications are physically placed within the pharmacy? These -- these little cards are placed and the consumer can look at them and look at the questions. And it says, "Are you driving or operating machinery?" So, it's a little check to the consumer to say, you know, "Why do I need to ask -- you know, I must ask why that's important" when they're still selecting.

But the -- the other part is that the -- the professional framework has what's called the S23 standards. So, the pharmacists -- required to take part in the supply of an S3 medication and an S2 medication where -- where warranted. And we've had this training program all around the country and in one of the states of Australia every pharmacy has now been through a behavioral modification change program where they've had a -- a -- a mystery shopper come in and report their behavior against these standards.

(Slide)

MS. BERGIN: Okay. The other thing we have is consumer hand-out information, and here I've given you an extract from temazapam. These -- this is a hand-out that comes with the dispensed medication. They are produced -- and they're currently being modified and performance-tested to be easily -- more easily being able to -- to be read and understood. But -- and they're given out with the medication. They are different from the product information, so that in particular, I've just given you the extract there from the one for temazapam.

(Slide)

MS. BERGIN: Okay. The other thing that we have in the pharmacy is the pharmacists' self-care fact card. That should have a link to --

(Pause)

MS. BERGIN: This is -- this is part of the pharmacy self-care program. Now, not all pharmacies have these. About -- about 40 percent have them. And what it is is a fact card about medicines and driving that the pharmacist can add either in talking to the person and counseling them when they give out the medication or in response to a request for a consumer about information about medicines and driving.

(Slide)

MS. BERGIN: And lastly, the way forward. We do have a multicultural society in Australia and, as was mentioned yesterday, not everybody has the level of understanding, can read to the level that these labels require. So, there has been some research that has been done in Australia to -- to indicate that not everybody has a full understanding from the labels. So, we don't really accept that labeling is the only way to go.

So, we -- we really do encourage the pharmacists' intervention in talking to people and helping them to understand. Some of the dispensing systems have language other -- languages other than English and in the guidelines pharmacists can add those labels to -- to the -- to the dispensed product. But we certainly see the use of picturegrams being used in the future and a colleague of mine suggested something like the one I have on the screen.

The Victorian -- the State of Victoria has been very proactive in this area. They -- they are advocating increased education and public awareness, and they have also developed a -- an assessment tool for practitioners which covers both medications and conditions. There are 30 checkpoints in the -- in this quite comprehensive document. They now have the power to test if they believe a driver is impaired and they test my understanding is over 100 medications. So, they don't just stick to the sedating medications. There are over 100 medications they can test for.

So, we would certainly like to see a greater public awareness. And a lot of my colleagues certainly in the Pharmaceutical Society and in -- members of the Pharmacy Guild work with organizations. It's not uncommon to see people doing driver education programs to do with medication. There is also another standard to do with health promotion and there are -- so this is not an uncommon activity. I thank you.

DR. GALSON: Thank you very much.

Our next speaker is going to be Johann de Gier, who's from the Ultrecht Institute for Pharmaceutical Science in the Netherlands.

DR. de GIER: Thank you very much for inviting me to speak here today. It's on, is it? Yeah.

(Slide)

DR. de GIER: Well, in the Netherlands we have had experience, I think, for over 25 years now in the field of drugs and driving, and we really take care of patients -- at least that's what we intend to at the School of Pharmacy in the Netherlands, especially since we all know that about 10 percent of the drivers, at least in the European countries on the average, is taking regularly some kind of psychotropic medication.

In the Netherlands we have had an -- a very longstanding tradition of affixing labels -- warning labels such as was just shown in the Australian example, and I will come back to that later in order to give you some feedback on the experience and evaluation of its use.

(Slide)

DR. de GIER: What I would like to do now is, first of all, to present you the most recent example of an international effort to implement what -- what we all have heard yesterday, the present knowledge out of experimental and epidemiological research in order to get the prescribers and the dispensers more active in this whole field.

What -- what I would like to do also is remind you that the report that I will present here, at least the recommendations of this report, they can be downloaded from this Web site of ICADTS. ICADTS, as you all know, the International Council on Alcohol, Drugs, and Traffic Safety, is an independent non-profit body whose goal is to reduce mortality and morbidity brought about by the misuse of alcohol and drugs, licit and illicit, by operators of vehicles in all modes of transportation. This organization was founded 50 years ago in Stockholm.

The working group that is -- actually was busy on the prescribing and dispensing guidelines was established in 1997 at the ICADTS conference in -- there was a -- specifically, the chairman of the Victorian Road Safety Parliamentary Committee who actually challenged the -- the scientists of the -- in the -- in the room and said, "Well, you all disagree," like we have seen meetings like this yesterday and in other parts of the worlds as well. But what is now really the next step to go forward in order to be more practical?

So, this -- this ICADTS working group started with 13 experts from eight countries, most of them out of Europe. We actually decided to go for a multidisciplinary approach because I think that the change of behavior of all the healthcare professionals is -- is our first priority target now and see how they can be involved but still also reminding you that sharing responsibilities and -- is, I think, the next issue, is how to achieve partnership with pharmaceutical industry, with drug regulatory agencies, health educators, and all those who have a responsibility, not in the least also to mention the patient.

So, I would like to give you the brief presentation of the report's recommendation and I'm of course most willing to respond to your questions afterwards.

(Slide)

DR. de GIER: I think the first recommendation deals with the regulatory authorities, the drug regulatory authorities. I think that implementing warning systems that are effective is -- is one of the priorities that we would like to stress. There is, I must say, hard -- hardly defined any studies that evaluate the effectiveness of affixing warning labels. And hopefully this afternoon you will hear more about this by midday.

(Slide)

DR. de GIER: There is some research in the Netherlands. I said we have started this -- this implementation in the early '70s but we found out that if the physician was not stressing anything or the pharmacist was not stressing anything in addition to what was on the label and specifically the label, "This drug can influence or might impair your driving performance" doesn't tell the patient much if there is no backup information from the professional to -- to point this out.

The red label, the one that probably also was in the -- in the Australian scheme that actually forbid the patient to drive, has hardly been used by the Dutch prescribers. And if you go into a Dutch pharmacy these days, they probably cannot show you the label anymore. This was just done by not using it.

Since the computer systems in the Netherlands and -- and also like in Australia took over most of the labeling processing of the information by dispensing labels, the information is now on the dispensing label. So, the -- I think half of the pharmacists in the Netherlands do not use those yellow stickers or yellow labels anymore because they say, "Well, the information is there. Now I don't forget to use it because the computer has taken care of it," so it's an improvement on that side. But it is not as alerting as it was in the -- in the early days.

(Slide)

DR. de GIER: In Norway, and probably you will explain a little bit more, the Red Triangle system was introduced in 1981 and later on in 1983 in all the Nordic countries. And -- but also here, hard to say how effective it was. In 1987 there was an evaluation in Sweden that actually explained that three years after the implementation that 50 percent of the patients receiving a medication with a red triangle on the medication box did not really understand the meaning of it. They thought it was something that indicated poison or that it was to keep it out of reach of children. So, there was not an understanding that all the patients understood what was going on.

And also in the Netherlands we looked at that and we found out that one-third of the patients receiving that yellow sticker actually took any action, which means not drive at all, drive less, or in some situations also stopped taking the medication, which of course is not the right thing to do if you are treating some kind of a disease.

(Slide)

DR. de GIER: So, what we would like to do is just focus on the -- the responsibility here with drug regulatory authorities, and I think that one of the ways we could actually go a step forward is to actually use the three tier categorization system, which I will declare in more detail a little bit later, because this is what we know at the moment based on -- on -- on experimental work and also based on the consensus among experts in the field who did this kind of research for more than 25 years at the moment.

We also should improve the structure to assist the drug -- drug manufacturers in drug testing because most of the research that has been submitted to the drug regulatory authorities as we have seen it, especially years ago, was not right useful in order to get some -- some -- some kind of a categorization system installed. That was also one of the reasons that ICADTS in 1991 presented another report with guidelines how to do a proper drug testing with respect to impairing properties of the medication.

The final thing we would like to -- to put forward here is the establishment of an -- an independent center for maintaining the drug characterization system. Since its introduction we have seen initiatives in Germany by the Pharmacists Association, in Belgium by the National Road Traffic Safety Institute, also permission by the government to do so, and most recently, last month in Spain by the Minister of Transport. They came up with a -- translated list of these original three tier categorization system. The only ones that really did an update on the original list were the Belgians but the others just translated this. But I -- I still think that there is a need to go forward here.

(Slide)

DR. de GIER: Well, this is about the categorization system as it was introduced in 1991 by a group of experts. This was actually a consensus survey with more than 50 experts all over the world at that time involved in this kind of research. And what we did was we actually assessed categorization according to these three scheme -- three-category scheme by looking at about 600 drug names and different doses. We looked at the acute and the agronic administration to see how that might affect the -- the categorization and also to look for the time after intake of -- specifically for the hypnotics where the residual effects of course are most important for the patient.

The -- the comparison with alcohol came in late. It was not the original scheme with the comparison with alcohol, and you have seen examples yesterday presented by Jim O'Hanlon who showed the experimental work where he used higher blood alcohol concentrations to compare with tests being indicated in this sheet here.

What the -- the status at that time was that it was adopted by the European Drug Regulatory Agency as a note for guidance and only for all new chemical entities. So, all the new medicines that were introduced as of the 1st of January '92, should have the -- at least have an opportunity to -- to come up with a categorization in this scheme. But since the Note for Guidance also allowed the pharmaceutical companies to ignore this and to come up with a pharmaco-dynamic profile with a long list of the reported adverse direct reactions, most of the drug companies actually choose for that -- that option.

And I have done a review, a survey, afterwards, five years after this implementation. I found out that actually no regulatory authority demanded this kind of information from the pharmaceutical companies. There were several reasons for it. First of all, of course, there are no guidelines on -- on -- for allowing the categorization. There was discussion on how -- difficulties -- descriptions, actually, were to apply even though we later on developed the scheme with the comparison with alcohol.

I think one of the basic issues in Europe at that time also was the priority that was given to a completely other type of problem with drugs and pregnancy. In that field there were categorizations and -- and code systems developed and people had some problems with it. And I think that that was also one reason that they didn't want another topic to go into the same kind of problems again. That would also be one of the reasons.

(Slide)

DR. de GIER: One problem that the European harmonization in this field actually caused was that they did decide to come up with class descriptions of impairment of driving behavior for -- for example, for all the benzos they came up with one same type of information, ignoring the possibilities and also having no opportunity to distinguish between the various benzodiazepines, as we have seen yesterday, from experimental work. I think that's a step backwards after doing research in 25 years in this field that the harmonization process in this particular area of drug regulation takes the other direction in not allowing you to give the difference between the different drugs.

(Slide)

DR. de GIER: Well, this has been shown yesterday. I will skip it. But this allows you also to see that these -- there's a risk ratios coming out from some of the epidemiological surveys show that not all the benzos are similar. Of course, they have a -- an increased risk but comparable to BAC levels of alcohol. But this kind of information you completely lose if you have one standardized sentence in the package insert which for all the benzos the same.

(Slide)

DR. de GIER: One of these studies by Garbone shows very clearly that if you look at the different dose levels that were actually defined according to the British National Formulary, low dose, intermediate dose, and high dose, that there is an increased risk for benzo users to be involved in a road traffic accident. And if you look at the -- the risk on the right-hand side, low bottom right, you also understand that this is about what you can achieve if you take alcohol in a blood alcohol concentration out to the legal limit in this country, .08, which of course is far more higher than the legal limit in most European countries where we have .05. So, the definition of impairment is slightly different, I think, if you compared it with alcohol.

(Slide)

DR. de GIER: Specifically for the professional organizations of physicians and pharmacists, we would like to have the report, as I indicated earlier, to be implemented in their professional activities and also encourage the membership to dispense the least impairing or safe medication if available. Of course, even if you have a safe or a relatively safe drug, there always will be a individual response, so specifically for the first week or two specific guidance should be given to the -- the patient. And therefore, we also come up with -- with more information than you normally can find in your package insert in order to give some more guidance and some more tools to the patient how to detect this kind of impairment.

Also, we would like to utilize information and communication technology for implementing these guidelines. We have developed a program, computer program, for pharmacies and general practitioners in the Netherlands where if they select the worst impairing hypnotic like, for example, florazepine, the system pops up with a decision support tool which actually allows them to select the least impairing one in the same class. This has all been supported by the users of the system. It's not mandatory. There is no -- no government that takes care of that, but the professionals themselves selected this kind of approach based on the categorization system.

(Slide)

DR. de GIER: Well, with respect to the responsibilities in transportation safety and public health, I think that even the existing systems but also if we would like to follow the Nordic countries by introducing the red triangle, we still need to have a good evaluation before and after implementation of the effect of this kind of warning system and we're still lacking that.

I think that there is a need to increase the knowledge regarding the relative risks of being involved in accidents by users of this type of medication. The research yesterday, the epidemiological research actually allows you to come up with -- with class -- direct class relative risk estimates, so all the different -- you can see in experimental work, if you would like to have that confirmed by pharmaco-epidemiological surveys, you probably need a lot more database -- extensive database than most of the research that has been done until today can show. But possibilities are available and I think that we should use them.

There is also a discussion going in the Netherlands and also in other countries like Belgium, Sweden, and Germany where they just a couple of years ago in 1991 introduced a new traffic law where it was -- a zero tolerance approach for illicit drugs. But knowing that this is only one to two percent of the driving populations that regularly take this type of illicit drugs and knowing that 10 percent is probably taking psychotropic medication, there needs to be something else also for that -- that population at risk.

So, the discussion in the task force in the Netherlands is now not to combine driving with benzodiazepines being used specifically, as the benzodiazepines are all half-life drugs, and also to look at the high levels of short half-life benzodiazepines. And the discussion now is whether this should be implemented in a law or that we first have to, again, try to do the prevention approach.

(Slide)

DR. de GIER: We also would like to have an encouragement of healthcare professionals to implement these guidelines with or without information technology. And this also should be looked upon in the -- in the sense of media campaigns, which of course are also very difficult to evaluate if you do not know the baseline, if you do not know the effects of other modes of information transfer.

DR. GALSON: Dr. de Gier, it's just a time. If you could try to finish up?

DR. de GIER: Yes. I -- I will --

DR. GALSON: Thanks.

DR. de GIER: -- close down with my last two ones.

(Slide)

DR. de GIER: The driving licensing authorities, I think, have been struggling a lot with this type of information, and also they ask for their -- the list of drugs and their categorization system. The European guidelines so far have not established what is a high dose not compatible with driving but it's stated that way.

And finally, the research and education as has been given before. I think we probably should think of presenting the categorization system on the Internet and try to find people to respond to that and hopefully this will improve the situation in the future. Thank you very much.

DR. GALSON: Thanks a lot.

Our last speaker is Dr. Asbjorg Christophersen -- I hope I've pronounced that right -- from the National Institute of Forensic Toxicology in Norway. Thank you for being here.

MS. CHRISTOPHERSEN: Okay. Thank you very much for inviting me to this seminar.

(Slide)

MS. CHRISTOPHERSEN: And first, I'll try to give a short overview of the drugged driving situation in Norway, including some general information on medicinal psychoactive drugs and accident risk.

(Slide)

MS. CHRISTOPHERSEN: The first picture, I think we have the goal -- flew very fast because this stuff was -- topic was covered very well by the speakers yesterday. However, this is a figure or a table which is a summary based on a large number of studies on psychomotor tests and driving tests. This was published last year in "Forensics and Science Review."

And this again show that benzodiazepines has very high risks and also the cyclic antidepressant and sedative and antihistamines, obits, and also the stimulants have -- considerable risk and to some summaries for accidents.

(Slide)

MS. CHRISTOPHERSEN: Go through this very fast.

Okay. And then I will go through an -- to the Norwegian situation. And then, first, the Norwegian Road Traffic Act showing that if this is not allowed to drive under the influence of alcohol and the BAC limit is 0.02, which was lowered this year, and it's also not allowed to drive under the influence of other intoxication or narcotic drugs, which also including psychoactive medicine and drugs.

(Slide)

MS. CHRISTOPHERSEN: The next pictures gives a very short overview of the handling of drugged driving cases in Norway. First, the drivers are stopped by the police and mainly due to an accident, reckless, or dangerous driving. The police make some private investigation by the -- at the roadside used during a DRE investigation and an alcohol test. If drugs are suspected, blood and drug samples are collected and at the same time a clinical examination are performed by physicians. The samples are sent to our institute, and these are standard -- and analyzed by a standard analytic program covering the most frequently used illegal drugs and also medicinal drugs. And after the report is sent back to the police, there is done a primary evaluation based on the analytical research and the clinical examination if this person was impaired or not.

And again, the police may also ask for an expert witness statement before the case end up in court.

(Slide)

MS. CHRISTOPHERSEN: The next picture gives an overview of the drug -- drunken and drugged driving situation in Norway for the last 15 to 20 years and which is shown -- shown or illustrated on the blue bars, there has been a decrease of drunken driving but at the same time this has been an -- an increase of drugged driving cases. And to -- to the end of 19 -- in the '90s, drugged driving cases was at the same level as drunken driving cases, or between 4500 to 5000 cases in a year from a population of 4.3 million inhabitants.

(Slide)

MS. CHRISTOPHERSEN: The next picture shows an overview of the most frequently detected drugs, with THC and amphetamines on the top, and then followed by some benzodiazepines.

(Slide)

MS. CHRISTOPHERSEN: On the next picture it is focused on the -- on the medicinal drugs where you will see that benzodiazepine and fluronitrazepine is the most frequently detected drug, followed by codeine and some other benzodiazepines, and also some muscle relaxants, but these drugs are detected not so frequently compared to diazepines to nitrazepines.

We have also performed some accident studies both of phantom accident and also in -- accident drivers. And these studies show that benzodiazepines after alcohol was the most frequently detected drugs. It also including both -- antidepressant and also sedating antihistamine in the studies but these drugs were not detected at all.

(Slide)

MS. CHRISTOPHERSEN: Who are these drivers? They are most oftenly a man between 20 to 25 years old misusing illegal drugs and also psychoactive drugs and often at high doses. They are frequent multi-drug users and they have also frequently been arrested earlier for drunken or drugged driving. And also, this driver has a very high mortality rate.

(Slide)

MS. CHRISTOPHERSEN: There are also some available information about medicinal drugs and traffic risk which has been developed in Norway. As has been mentioned earlier, the drug passage -- packages for psychotropic drugs has a red triangle systems. The practice for two years ago approximately was introduced package insert systems for all drugs with rather -- red triangle marks. There are information brochures at the pharmacies which should be distributed to the patients and oral information should also by given -- be given by the prescribing physicians and also the pharmacist, but however, this could be done much better.

There are also special literature available in Norwegian drug handbook system for physicians and pharmacists. And at last, there are lessons and courses are offered for physicians and pharmacy student at the university.

(Slide)

MS. CHRISTOPHERSEN: There you see an example of the red triangle system which has been in Norway -- used in Norway for about 20 years. And this red triangle is -- means that -- which is also in the Habsburg system and this information should also be given by the physicians or the pharmacists that for the first time when you start to use this drug you should not drive at all for the first -- first two to four weeks before you -- you can -- you know your reaction on these drugs. And when you continue on to use these drugs, you should never drive for the first two to four hours after you have taken the drugs.

(Slide)

MS. CHRISTOPHERSEN: And at last, there are also some special guidelines for keeping driving license. First, drivers misusing -- it has been documented that a driver misuse alcohol, illegal drugs, or high doses psychoactive and medicinal drugs, he should not be or she -- he or she should not be allowed to keep their driving license.

Another thing, we have also a narcotic drug law which also include both illegal drugs and psychoactive prescribed drugs, but if the person use this drug without any prescription. And if the persons are sentenced according to the Drug Use Law, it could also be decided by the court that this person should not keep their driving license because he is -- can be a risk for traffic safety.

And at last, there are special guidelines for patients on methadone treatment programs or other substitution programs. Thank you.

DR. GALSON: Thank you very much.

Questions from Technical Panel and Discussion

DR. GALSON: We'll move now to the panel -- the questions from the Technical Panel. NTSB, do you want to start? Tom, want to start?

DR. LAUGHREN: Is it on now? I'll start with -- with Dr. Bergin, but the other panelists should feel free to jump in as well.

I have a question about this red triangle. I was listening to each of you and looking at your slides. It -- it appeared to me that the triangle might have different meanings in different countries. As I understood Australia, what the red triangle means is that patients should be aware that the drug may be sedating and they should not drive if it affects them but that does obviously give them the option to drive, whereas in Norway, as I understood it, the red triangle means don't drive if you're taking the drug. And I wasn't clear on what it means in -- in the rest of Europe.

So, could you -- could you clarify what that -- what it does mean?

MS. BERGIN: I think your interpretation is correct that the patients do have the option to drive. It's -- of the three labels, Label 1 would be considered the -- the highest warning level, I suppose. The Label 12 is used with a range of medications but including the antihypertensives and the hypoglycemics and it is not as serious. So, I suppose the red triangle is an indication of the severity of the -- the warning, but yeah, you're quite correct. It -- we're just saying to people if affected don't drive.

Let me just refer to some notes here. I --

(Pause)

MS. BERGIN: The assessment tool that is used by mainly doctors but some -- but also occupational therapists, their assessment tool with medication is divided into categories of drugs, and in the, say, antihistamines, they -- they recommend that the non-sedating antihistamines be used. In the sedative hypnotics they advise people not to drive while being stabilized. So, their advice is that the chronic long-term use of these drugs does impair ability to drive and all patients should be cautioned and they should be asked not to drive while being stabilized. So, that's the assessment tool for a driving license.

DR. LAUGHREN: Okay. But that's -- that's separate from the product labeling. The product labeling, as I understand it, the strongest warning for any drug is that -- see how it affects you and then decide whether or not you can drive?

MS. BERGIN: Yes. In the labeling process. But in the course of talking to the person I think that the advice might be given not to drive, particularly in the early stages of the therapy.

DR. TEMPLE: How does the triangle and the conversation interact? Does the triangle carry the implication you should talk to your doctor about it? How do those two systems dovetail?

MS. BERGIN: Yeah. I don't think the triangle is really used as a tool, I -- I'd have to say, impact. Pharmacist is just aware of which drugs have the sedating or impairing properties and they talk to people without particular reference to the red triangle. But they certainly refer them back to their -- to their doctor.

DR. LAUGHREN: Is it different in -- in Norway? Does the red triangle have a different meaning in Norway?

MS. CHRISTOPHERSEN: Is it on? Yes. Yes, I think it's a bit different from what's in Australia. But of course, the patient is -- is responsible itself. But information should be given by the doctors and also a brochure should be delivered by the pharmacist and recommend that you should not drive for the first two to four weeks when you use this drug. But of course -- and if this patient is arrested by the police and it can be documented that you are impaired with a combination of analyses, what you detect in blood and also a clinical examination, the drive -- this driver can lose his driving license if it's proved that it -- he or she was impaired.

DR. TEMPLE: Impaired or -- or using?

MS. CHRISTOPHERSEN: Impaired.

DR. TEMPLE: And that's because what triggers the examination in the first place is the observation by somebody that person seemed to be behaving in an impaired way?

MS. CHRISTOPHERSEN: If it was -- if it can be proven for the court and the court accepted that this patient or this person was impaired.

DR. TEMPLE: Does that actually happen other than out with -- I mean does that happen with alcohol -- other than with alcohol or abused drugs? I mean have you actually had --

MS. CHRISTOPHERSEN: Oh, yeah.

DR. TEMPLE: -- some --

MS. CHRISTOPHERSEN: Yes, many times. Many times.

DR. TEMPLE: For -- for using a sedating antihistamine or a benzodiazepine?

MS. CHRISTOPHERSEN: Yes. If it has been proven for the court that this patient was impaired or influenced.

DR. LAUGHREN: Then I had a question for Dr. de Gier about the -- the three tier system. On face it's very attractive to have that way of categorizing drugs, just as it would be very attractive to have a list of drugs that -- that could be used or could not be used in someone who's going to drive.

As always, the devil's in the details, and how do you propose to actually categorize drugs? On -- on what basis? And is there any agreement in Europe on, you know, what kind of experimental data should go into that, what kind of epidemiologic data, and have drugs in Europe been categorized using this three tier system?

DR. de GIER: Well, the -- the system has been developed based on the -- actually, the discrepancies that existed for the dichotomous systems like we have in the Netherlands for many years. And also, the red triangle is kind of -- in the system.

As long as you do not take into account dosage that has been prescribed for -- and/or the formulation of the drug, it could be very difficult to use only the -- the drug name on the list. So, I think the system allows you at least to have that kind of specific categorization of the impairing drug included.

The categorization system has been supported by the experts in that -- in that survey that we did in 1991. And we -- we looked at specific expertise among these experts, and if there were five or more experts responding to a specific drug name, dose, and/or formulation and no more than -- 15 percent of them were in disagreement with what the outcome of those five experts or more experts were, then we -- we call it an agreement and a consensus. This was based on the knowledge we have in the -- in the period of the '80s. It has not -- not been updated ever since.

As I explained earlier, the Belgian police did for their support of their introduction of the new traffic law in 1999 did a exercise to cover the Belgian market within the place and that is what I can -- I can explain as the -- the latest development.

The drug regulatory agencies, as I explained in the Note for Guidance, also offered you opportunity not to use the categorization system. And also, they indicated that for -- entities this would apply if possible. And since 1992 -- and I did a survey, an experience that no -- no example of a categorization application of the system in the specific -- entity market authorization was -- was discovered. So far, no one has really used it.

DR. LAUGHREN: What about the factor -- in addition to dose, what about the factor of time? You might imagine that a drug like -- like zaleplon within the first couple of hours would -- would have a -- you know, might have a severe categorization but at eight hours might -- might have no effect.

DR. de GIER: That's true, and that's -- that's also the reason why Dr. O'Hanlon yesterday explained this with this particular type of medication. There is an extension to the categorization system that you indicate to the -- the time after -- after intake of the medication. And that is an extension as it's been used. And also the -- the possibility to indicate whether they use an acute drug situation or a chronic drug situation.

So, these -- these type of extensions are possible.

DR. TEMPLE: The -- for the places that have red triangles now, who decides whether a drug gets one or not? You may have explained this and I may have missed it, but in Australia how is that determined? It looks like it's on but it looked like a -- oh, no, that was the other-- that was the -- it looks like it was on the unit of use package. Somebody must have decided that it goes on there. Who does that?

MS. BERGIN: That red triangle is only on the labels produced by the company that produced -- produces a range of labels. It's their decision, I think, in consultation with the Pharmaceutical Society to put that red triangle.

The regulatory framework only list the 120 drugs that have to have the warning statements either on the packaging or by the pharmacist. So, --

DR. TEMPLE: This is part of the drug approval system in Australia?

MS. BERGIN: Yes, yes, yes.

DR. TEMPLE: And it's -- and it's specifically a recommendation for the bottle, is that right? This -- this isn't -- this isn't the packing --

MS. BERGIN: It depends whether it's a prescription or -- Schedule 4 -- no, I shouldn't say "prescription." Schedule 4 or Schedule 8 or a Schedule 2 or Schedule 3. So, Schedule 2 and Schedule 3 is the over-the-counter -- are the over-the-counter categories. They have to have it on the packaging. The other two have to have it when it's dispensed, so they have to have it on -- on place by the pharmacist.

DR. TEMPLE: Okay. But that is determined by the regulatory authority?

MS. BERGIN: Yes.

DR. TEMPLE: And is that also true in the Netherlands?

DR. de GIER: In the Netherlands the yellow sticker or the label was introduced in 1973 by the National Association of Pharmacists and the National Association of General Practitioners. And this was not a regulation that was just a voluntary system. And as I said, it's been actually diminished its use by the introduction of computerization in pharmacy.

DR. TEMPLE: And -- and has there -- are -- is there discussion with the regulatory authority about it? Do they interact and decide together or is it completely independent?

DR. de GIER: Well, in the situation at this moment I think that there is a discussion how we can implement a new system if you would like to do that. We look very carefully at the evaluations from the Nordic countries. The red triangle is -- is an attractive one but still it's not an improvement if it's still a dichotomous system. If you cannot differentiate for dosage for time after intake for chronic and acute situation, it probably is not an improvement.

DR. TEMPLE: So, you think it's not optimal because of that. So, you -- are you thinking some text in the little box or something?

DR. de GIER: Well, it was a surprise to see that some of the regulatory authorities who was -- I was talking to who said, well, actually, the information from the industry is there because probably for liability issues they need to have all those long lists of the first direct reactions stated there. But to give a -- a warning level with a categorization indication in itself could help the people leading that put some reference over that type of information.

And a quick reference, of course, is to see how in bearing it should be and if you compare it with blood alcohol concentrations that people are most aware of.

DR. TEMPLE: Some of the information in boxes, does it come from standardized tests? Is every potentially sedating drug in any given country or in Europe subjected, for example, all the time to a driving test like we heard about yesterday or I guess simulation isn't widely available so that couldn't be it. Do they all have that? Is that where the linkage to a particular blood alcohol concentration comes from? Where -- how do those numbers get created?

DR. de GIER: As far as we have received the attention, I think, from the industry as Dr. O'Hanlon expressed at yesterday, all the new antidepressants, all the hypnotics, all the antihistamines that are entering the market are probably taken to a schedule where you also look at driving tests or over-the-road driving tests as we have established that in the Netherlands -- I know a company who recently indicated that they did not have that driving test achieved in their approach and they were considering this because as a result of that we do not pay any priority attention to this kind of drug if there is no information on the type of a driving test that is available. That's not used.

I think that in the situation in the Netherlands where it is the professional group physicians and pharmacists who decide in particular on how to use the warning label that they can decide whether -- whether or not this will be a drug to be mentioned as an alternative to a situation where the older drugs are sedate or heat-bearing.

DR. TEMPLE: Would -- would -- would the -- going through Dr. O'Hanlon's or his -- or his successors' system become a de facto requirement for a drug in the Netherlands as a regulatory matter?

DR. de GIER: Well, it -- in Europe at this time the -- the regulatory system is centralized as much as possible by the -- in London. And as Dr. O'Hanlon indicated, the driving test has been approved as a reliable tool for this kind of testing. And I think this is probably a matter of time in order to get this accomplished.

DR. LAUGHREN: Could I come back to Australia for a moment? Again, as I understand it, here in Australia the red triangle is a regulatory requirement as opposed to the Netherlands. It's part of the regulatory process as opposed to an independent group.

MS. BERGIN: I don't believe so.

DR. LAUGHREN: Oh, oh. It's -- it's not?

MS. BERGIN: No.

DR. LAUGHREN: Okay. Well, that --

MS. BERGIN: No.

DR. LAUGHREN: -- that's --

MS. BERGIN: Appendix K, I think, in the SUSDP, which is the Standard of Uniform Scheduling of Drugs and Poisons, lists the drugs that have to have the warning statement 39, 40, or 90.

DR. LAUGHREN: Which is -- which is sedation?

MS. BERGIN: Or to aid sleep. The new one is 90.

DR. LAUGHREN: Okay.

MS. BERGIN: That's only been introduced in the last few months.

DR. LAUGHREN: Okay. So, the red triangle is basically voluntary wherever it is?

MS. BERGIN: Yes. In fact, there's only one company that produces the labels that the pharmacists use to affix to the packaging when they put the dispensing label on, and so all pharmacies have these -- these warning -- these range of labels --

DR. LAUGHREN: And the --

MS. BERGIN: -- and they're the -- they're the ones they use.

DR. LAUGHREN: And the basis for the decision to use a red triangle as opposed to some lesser warning is -- is what?

MS. BERGIN: Well, it's the -- as -- I suppose I still have a level of cognitive impairment because I have sleep deprivation in getting here. But -- and I know I was nervous when I first started so I apologize for that.

DR. LAUGHREN: Don't drive.

(Laughter)

MS. BERGIN: No, I won't. What happens is after the SUSDP, after the scheduling process this Appendix K is produced. Then the Pharmaceutical Society produces the instructions to pharmacists, I suppose, the counseling notes. And then the company that produces the labels, then they follow on and produce the labels.

Now, the professional organizations go further than the regulatory process and add other drugs to the list where they think the warning statements should be, and they -- they add -- they have a sub-category of the label 12 where it -- they believe it's only important in -- in change -- in the initial part of treatment or in changes of dose. So, that -- that's the link between the regulatory process and what ends up in the dispensing systems and also the labels that are affixed to the -- to the products.

DR. TEMPLE: Are there -- I can imagine why one might believe they'd have an effect, but are there actual studies that suggest that people pay particular attention to red triangles or yellow boxes or any of these things as opposed to just words? Has that actually been looked at or compared?

MS. BERGIN: Not to my knowledge, so -- but only -- the evidence, I guess, that we have is the anecdotal evidence in the interactions between -- because this is such a high level of intervention and discussion when these products are dispensed or supplied, I'd say that the feedback is that there is a level of understanding. Whether that translates into a change of behavior I am unable to say. But certainly, there's a pretty good attempt to make sure that there's an understanding.

DR. TEMPLE: Would you know from surveys or, you know, sending shoppers in that there usually is a discussion of the effects on, say, driving with the pharmacist when they go get either a prescription or an over-the-counter drug? Do those interchanges actually take place as you hope they would?

MS. BERGIN: Certainly, the feedback from the S23 Standards Project that has been going on for the last year or so indicates that that level of -- there is a high level now of interaction that is going on. I guess the difference is a lot of yesterday focused on sedating antihistamines and -- but in Australia the non-sedating antihistamines are available over-the-counter. And so, part of that interaction would be if there was a request for a particular product would be a discussion with the person on those factors that might make -- you know, what are they going to use it for, what have they used before, and -- and -- and steering them towards a non-sedating medicine.

DR. TEMPLE: But you -- how do you know those things occur? What -- it sounds like -- they're obviously good things. How do you know that they occur? Anecdotes or people tell you or you send shoppers through or --

MS. BERGIN: The -- the -- the S23 Standards Project had a mystery shopper.

DR. TEMPLE: Uh huh.

MS. BERGIN: Yeah. So, what they did was they sent in -- first of all, they sent in a facilitator to explain that the project was going on and to make -- increase the awareness of the standards. And then later on they -- they sent in a mystery shopper who tapes the experience. And so, then they -- they -- they measured, I guess, the baseline behavior and then the -- after -- with the mystery shopper behavior. So, they had a reasonable awareness of that -- a good awareness now because, as I said, in one state every pharmacy has met the standards.

That's not to state -- to say that there is an interaction -- every man, woman, and child in Australia visits their pharmacy 14 times. I'm not confident to say that there would be a pharmacist intervention in every visit, but I think we're getting to a better level of intervention.

DR. TEMPLE: Is the report -- is what you just described in one of the things that's included in the --

MS. BERGIN: No, it isn't. And I would -- I'm not -- when I talk about that high level of intervention they -- I know that they were talking about analgesics. I just can't remember whether the -- one of the product groups they targeted was antihistamines.

DR. TEMPLE: Actually, anything that describes an assessment of an intervention or an assessment of a program would be of interest to us.

MS. BERGIN: I can certainly get -- that project is just winding up and will finish in February, so I can certainly get -- get you the final report when it's available.

DR. GALSON: Okay. Unless there are any pressing questions from the Technical Panel, I think we'll move on to the parties. Start with the Government table. Are there any comments from this group?

MR. CLARKE: I don't have any questions.

DR. GALSON: Okay. Advocacy table?

(Pause)

DR. GALSON: While they're thinking about it, in the Professional table? You guys?

MR. DROBNICH: Just a quick question for Dr. de Gier. Obviously, you've had a lot of experience with these issues. Having heard what you've heard over the last two days, what are the one or two things you really think the government or the professional groups should focus on to tackle this problem? Should it be media education first, campaigns first, or should it be professional education?

DR. de GIER: I think that one priority should be given to the educational part of it and specifically for physicians and pharmacists. The discussion yesterday was also on the movement of pharmaceutical care and that'll -- at least and also in other European countries this is catching up, which means that there is a -- more attention to the needs with respect to the -- the drug use and the problems that they may cause for the patient.

I think that by having that approach established you can also start thinking of a better warning system, but as long as it is not an improvement of what we already have, I would not recommend to use that. At least in our government, the discussion is on that if we start only by switching from the yellow label to the red triangle this will not really help. If it is not a safety system or a different -- approach in that respect.

Furthermore, I think that the -- the prescribing and dispensing guidelines, as long as they are here, if they are being adopted by the professional -- health professionals, then the next step will be how to apply these. And I think that what we have seen with all this new development, like pharmaceutical care practice standards and guidelines in -- in -- in the medical and the pharmaceutical field, that as long as this is not being implemented into any practice in a computerization it will not be applied as easily as it is intended to be.

So, I think information and communication technology will push this forward as long as we can first of all adopt this. And the information campaigns as they are being developed or will be developed, they will support on each of these specific areas, so as well in the professional as in the patient and the public field.

DR. GALSON: Advocacy Group, question?

MS. TARNEY: We have two questions. In the ICADTS Dispensing Guidelines under Number 4 and Number 8 they generally refer to the physician and the -- the pharmacist having some -- some interaction and having the patient return to the pharmacist. In this country it would seem that the patients if there's a problem with the drug or there's a question that they generally go back to the physician and not the pharmacist. Is that -- does it really show itself differently in the Netherlands or in Europe? And who has the regulatory authority over those pharmacists to follow up?

DR. de GIER: Well, there is a change in the reimbursement system for pharmacists in the Netherlands, which means that they should provide -- approve of their documentation system, of their -- the use of practice guidelines and standards and protocols as they do, for example, with asthmatic patients who have their instructions by first-time use of the aerosols and other treatments. If they can show that they can do that -- do that practice by following the protocol and also document this intervention, they get a better reimbursement scheme for their -- for their activities.

The reason for referring patients back to the pharmacy is based on what in the Netherlands has been established as a pharmacotherapeutic review committee concept of a local scale that the pharmacist and the prescribing physicians together decide on a sort of formulary, what type of medication should be used in specific medical situations. And these are all based on the accepted medical standards in the professional groups, so the government is very keen on having this kind of discussion going because it's -- it turns out to be, at least in the Netherlands, that this will lower the cost in medication, the total healthcare costs proportionately. And I think that this will allow the pharmacist and the patient also to -- to collaborate in a more professional way.

MS. TARNEY: So, your physician has let go of a little control?

DR. de GIER: Excuse me?

MS. TARNEY: Your physician is -- has let go of a little bit of control, then?

DR. de GIER: Yeah. Well, the situation, as I said, that the insurance companies actually make the contracts with the pharmacists and the physicians and they can also require to use protocols, to use documentation systems in order to -- to control the drug bill.

MS. TARNEY: And we have one other question. What kind of mass media campaign was done in any of the countries on these labels so that people really understood what -- what they meant? And do they identify with the intended use of the labels?

MS. BERGIN: I'm aware of one campaign in 1995 where there was a mass media campaign which was just -- judged to be successful, and the assessment, however, was made by the pharmacies on the number of people who came in to discuss their -- sedating medication or the medication that may affect driving performance as a result of the campaign. To my knowledge, it didn't address the level of understanding.

I'm only aware of one study which has looked into a person's ability to understand and label in general and, certainly, that recommendation from that report was that a lot of people -- sorry, I can't remember the percentage -- require someone to assist them in interpretation of medicine's information so that in a certain level of reading ability, I suppose, and understanding.

DR. GALSON: Did you want to add something, Doctor?

MS. CHRISTOPHERSEN: Is it on? Yes.

In Norway the mass media or the newspapers and television very often focus on -- on the drugs and driving, showing that this is an increasing problem and also give information on what the special drugs -- medicine drugs which may affect your driving. So, I think that many people, hopefully, are aware of this problem. So, in this case, they are also doing a good job.

DR. GALSON: Okay. Industry table? The Transport?

MR. BRADLEY: No.

DR. GALSON: No questions? Consumer Healthcare?

DR. PARMET: No questions at this time.

DR. GALSON: Okay. Union?

CAPTAIN POPIEL: No.

DR. GALSON: Okay. Circling back to the Technical Panel, are there any questions that you wanted -- go ahead. Okay.

MS. BERGIN: Excuse me. Could I just add something else to that last question?

DR. GALSON: Certainly.

MS. BERGIN: One of the things that has happened in Australia, it's a government-funded system. Because there was, I guess, skepticism by medical practitioners about the information provided by drug companies there was a call for unbiased, evidence-based material for physicians, doctors. And so, the government has set up a -- a system called Divisions of General Practice, and so there are 123 geographical areas in Australia that have -- it's an infrastructure where general practice sort of manages public health programs and other -- other activities and -- including computerization of the profession.

But one of the major activities is called the National Prescribing Service. And they are -- they -- they have some -- they have facilitators in each of those divisions that is linked to the National Prescribing Service and they provide information on -- this unbiased, evidence-based information that the -- they're an independent drug rep, I suppose. They go out and do practice visits and provide this information or they may hold education sessions within a division. And they have targets within their division to reach, you know, reach the number of general practitioners in their division. And that's proven to be very, very successful. They've only been in operation a couple of years, so I guess it's another medium -- I guess it's another mass media sort of approach to drug information for it.

And the other thing that we are doing which may help is we've just launched a program called Home Medicines Review, which is a collaborative medication review. The doctor refers the person formally. Any member of the healthcare -- healthcare team can trigger you, but the doctor formally refers the person to the pharmacy of their choice. And the pharmacist goes out and conducts home medicines review. And so, they are able to see what -- the complete range of medication the person is taking, what problems they have, and how -- what problems they have in taking it, including the complementary medicines. And also, what we are seeing is in increasing the sedating medications and -- and medications that are level -- labeled 12 contributing to falls and that's a focus in -- in Australia at the moment in -- to decrease the number of falls that are related to medication.

And so, I think that system will be -- also be very effective in increasing the awareness about drugs and driving.

DR. TILTON: Could I make a clarification for the record? This is Dr. Tilton over here.

DR. GALSON: Certainly.

DR. TILTON: Going back to our previous session, the elusive list that was referred to. Actually, about three years ago a list was developed and it was developed in conjunction with our Air Traffic Controllers Union because they asked for some direction on what kind of medications we might consider that if they were on they wouldn't be allowed to control traffic. So, in conjunction with the union and the negotiated process we developed a list which is not exhaustive. It's not used and it's not reported to be -- to them that if they're on a medication or not on this medication that they will or will not be allowed to control traffic. It's a list that informs them that probably if they're taking such a medication they'll not be allowed to control traffic and it could be temporary or permanent depending on the condition.

It's not exhaustive. It is not used -- it's only updated once a year per the negotiated union agreement, and we do not put medications on or off that list during the year. If something were new to appear on the market we wouldn't go back and update that list, so nobody's in charge of the list other than every year we update it. And we do not use it in conjunction with any of our pilots. So, there is -- there is a document out there that we use but it is not -- it's not a list that we refer to when we're doing our certification process.

DR. GALSON: Thank you for that clarification.

Is there more points of --

DR. LAUGHREN: Yeah. One more question. And this -- this is for Australia or -- or the other panelists could respond, too.

This is a question about the number of -- of warning labels that might appear on a prescription bottle and -- and the effect that that might have on, I suppose, in a sense desensitizing patients to warning labels and therefore decreasing the impact. Has that been a problem in Australia?

MS. BERGIN: Well, as it hasn't been evaluated I -- I can't really give you a definitive answer. I think most pharmacists would -- in the list I have in the kit you can see things like "swallow whole" or "take after food" would be in the text but the warning statements, generally they would use the colored labels. Some of them might put it on and have both, but -- so, you would probably not see more than one or perhaps an -- an additional expiry date label or something like that.

So, I think they do -- they are -- they are aware of information overload, I suppose, and -- and that people just don't see things after they become used to them, so I think that there would be selective use. But as it hasn't been evaluated I can't say for sure.

DR. LAUGHREN: Thank you.

DR. de GIER: The -- the Netherlands discussion went on -- after introducing the computerization 20 years ago, at that time we were applying different colors and different shapes of stickers and labels. And it was decided by the -- by the pharmacists that they would like to have the -- the most important ones on the dispensing label printed by the computer so that it will not be a -- a manually tasked -- manual task for the person -- person in the pharmacy to do. And ever since, as I said, this has been used with great enthusiasm and -- and people don't like to -- to stick labels anymore.

DR. TEMPLE: Whether we're talking about a triangle or a sticker or whatever, would people be entitled to assume that if a drug doesn't have one it's okay in this respect? Which really involves mostly a question of whether you've gone back to look at the older drugs that may have not been -- may not have been subjected to driving tests and so on. Would -- would -- would that be what you'd expect people to assume? No sticker, no triangle, no problem?

DR. de GIER: Well, the -- the information with the older drugs is -- is, as I said, not being tested as -- as extensively as with the new ones. But on the other hand, that the -- the Netherlands at least, the local formulary committees and following these practice standards of the medical and pharmaceutical professional organizations, they don't pay attention to the older drugs anymore. They actually go for the safer ones in this respect.

As soon as you take the next step, legislation, and you would like to have traffic -- traffic law developed with some kind of a list of drugs, then of course the -- the risk might be that people who do not see the name of the drug on a particular list that has been regulated by traffic law, they probably would look for an alternative with -- with a drug which has a constituent that is not on the list. And that discussion is -- is being taken up by the task force that I was referring to. So, we -- we identified the problem and they're still working on how to improve this situation.

DR. TEMPLE: So, ideally at least, any system like this should try to be comprehensive and go back as well as forward or --

DR. de GIER: Exactly.

DR. TEMPLE: -- or it would be misleading?

DR. de GIER: That's correct.

MS. CHRISTOPHERSEN: Could I address that statement? I think that based on some interview investigation in Norway it's a change between the older generation of the pharmacists to the younger one. It's maybe that it's based on better education but the younger one are more aware of their -- that they are responsible to give information to the patient. I'm hopeful also that drug package inserts with written care information would also -- will improve the situation.

DR. GALSON: Okay. I think we've got -- we have a question from the public, so let's do that and then we'll come back.

DR. ELLINGSTAD: One question for Ms. Bergin. How is the consumer to determine whether or not they are affected by a medication? Doesn't your labeling imply that it is okay to drive if you don't feel sleepy?

MS. BERGIN: Yes. The Warning 12 talks about mental alertness. I mean as we heard -- well, as we've heard from a lot of speakers, people may not be aware that their driving is impaired. So, I -- I accept the point that there is -- it appears that we are saying that you -- you only shouldn't drive after you self-assess that you have a level of impairment.

I'm not answering this very well but, yeah, I -- I -- there's not that link that you --

DR. ELLINGSTAD: I think the point is, is there any instruction given to the -- the consumer themselves to make that determination?

MS. BERGIN: On how they know that --

DR. ELLINGSTAD: Right.

MS. BERGIN: Only in the discussion, I guess, between the pharmacist and the -- and the person. I mean, certainly, the fact card recommends that -- that they should take alternatives like a taxi or a friend. But I suppose after a period of stabilization of medication, then -- then I guess we -- we are relying on that -- their own subjective assessment of their ability.

DR. ELLINGSTAD: Thank you.

DR. TEMPLE: Of course, that's -- that's an interesting question because, as we heard yesterday, people can have impairment on the simulation test and not feel sleepy, not feel impaired, and in fact they can even have decreased sleep latency and not feel sleepy, all of which makes you wonder about how well people can assess their own abilities.

MS. BERGIN: However, in speaking to colleagues before I came over here who have worked more in the -- the testing field and -- they made the comment that people adjust their driving habits and in fact may be adjusting to the more cautious or safe zone when they drive because they know they're on medication. I think we've seen in the relative risks studies that those that are on cannabis have -- tends to have a lower relative risk. And it -- my -- one of my colleagues made the comment that if you are anxious perhaps you are better on an anxieolytic than -- and driving than if you are not.

So, it's a multi-factorial --

DR. TEMPLE: Right.

MS. BERGIN: Yes, so -- system and, certainly, I mean I accept that through courses that were given yesterday, but it's -- it's not an -- it's not as simple, you know, how you -- it's multifactorial.

DR. GALSON: One more question.

MR. MARSHALL: There was a little mention yesterday about drug recognition experts in the United States, and I was just wondering what sort of training do law enforcement get to recognize drug impairments or things such as that?

MS. CHRISTOPHERSEN: In Norway all of this is implemented in the education for the police officers. And it's also from post-education courses offered for the traffic police. So, I think, yeah, at the moment very many in Norwegian Traffic Police has these special courses. But the Drug Recognition Expert Program, they use, it's something similar to what they have in United States, and I've seen -- lots of things have been taken. For the -- but it's something more simple than -- simpler than it is in -- in United States because if drugs are suspected then there -- we will follow by a clinical examination performed by a physician. So, the investigation they do at the road is not so many different tests as in -- I know it is for the program in United States.

DR. GALSON: Okay. Any other pressing questions from the Technical Panel?

DR. GARBER: Just briefly, and -- and maybe this panel can't -- can't fully answer the question. But is there any specialized guidance provided to commercial vehicle operators separate from what's provided to the general public in -- in the organizations from countries that you represent?

MS. BERGIN: The -- only in the area of the assessment tool that I mentioned, the fitness to drive. There are two levels. One is for more of the general public and then there is a commercial assessment tool that's at a high level.

DR. de GIER: Similar in -- I think there is, according to European guidelines. This is all over the European countries. It's a similar thing.

MS. CHRISTOPHERSEN: Same in -- in Norway.

MS. BERGIN: I mean what was referred to earlier that was the use of stimulants, it's certainly a major problem in Australia in that pseudoephedrine is available as a Schedule 2 medicine and certainly pharmacists are applying a much greater level of scrutiny in the supply of that product. That's my -- but I think the people who are buying it for -- well, for both diversion and also inappropriate use know the correct answers to all the questions anyway.

DR. GALSON: Okay. I think we'll end this session now. Thank you very much, witnesses. Very informative.

I do want to make an announcement about the scheduling. We were scheduled to have lunch now and then have an open audience discussion at one. However, no one has registered for that session. So, we'll break for an hour and start with Session VII after lunch, and we have been in touch with all the witnesses. I think all but one is already here and that one's going to come early. So, we will aim to start in an hour on the next panel. Thanks.

(Whereupon, at 11:58 a.m., the meeting was adjourned for lunch, to reconvene at 1:00 p.m., the same day.)

 

 

 

 

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

1:03 p.m.

DR. ELLINGSTAD: Okay. Let's get started. We have some new faces at the Technical Panel table, so why don't those people introduce themselves?

DR. GANLEY: Charlie Ganley from the Division of Over-the-Counter Drugs, FDA.

DR. TEMPLE: Bob Temple, also FDA. Director of the Office of Medical Policy.

DR. SWEENEY: Meg Sweeney, National Transportation Safety Board, Safety Studies Division.

MR. MARSHALL: Rafael Marshall. I'm with the Office of Highway Safety.

DR. ELLINGSTAD: Okay. Thanks.

Witness Panel VII - Warning Labels

DR. ELLINGSTAD: We'll start now with our final panel for the meeting. And this panel will discuss warning labels. We'll start with Dr. Michael Wogalter from North Carolina State University.

Dr. Wogalter?

MR. WOGALTER: Thank you.

I'm Mike Wogalter. I'm from North Carolina State University, part of the Ergonomics Program there, Cognitive Ergonomics. And I've been doing research on warnings some 15 years or so.

And it's hard -- it's hard to distill a lot of research that has been done. There are books that have been written on the topic. I brought a few. This is "Warnings and Risk Communication." It has a -- several -- many chapters on warnings and various studies. And also, there's collections books of various articles. These two books contain approximately 120 research articles, empirical experiments, and so forth.

In the five minutes that I've been allocated I'm just going to gloss over some things, try to introduce you to the area. Thought I'd introduce the very first thing that is probably a safety principle, engineering principle, and it's a hazard control hierarchy which basically says that if you've got a hazard, first of all, you have to determine that there is a hazard. And then, if you're able to, you try to design out the hazards. You try to eliminate the hazard, and that's -- that's probably the best strategy.

If you can't do that, then you try to guard against the hazard in some way to prevent people from getting to the hazard or getting near the hazard.

Then finally, if you can't do those things well then you warn and you try to warn as best you can. The problem is that warnings are not 100 percent reliable. And so, the best you can probably do is try to maximize effectiveness.

And there's a bunch of methodologies out there now across the last 15 years that one could use to evaluate warnings. That includes subjective studies where you compare different warning labels. There's latency studies, reaction time studies where you try to find out how long it takes for them to find a warning label. There's comprehension types of studies; after you've exposed them to the label what did they get out of it, what -- do they remember it? You could ask them about attitudes and beliefs and so forth.

There is a -- a national standard. American National Standards Institute over in Arlington area, I think, has a Z535 standard, and you probably have seen similar kinds of warnings on machinery and so forth. It has the warnings with a triangle, exclamation point with the "danger," "warning," "caution" header with -- in different colors. It also specifies certain things that go into warnings, and that includes stating what the hazard is, describing the hazard, telling people what to do to avoid the hazard, and the consequences of what would happen if they fail to comply with that hazard.

They also recommend certain kinds of format, things like bullet points and putting it in outline format. That is, not putting it in continuous text, giving it a certain amount of white spacing and so forth. They also recommend if it's possible to use a pictorial symbol, one that would reach 85 percent comprehension in a test and have no more than five percent critical confusions. And by critical confusion, what that is is an interpretation perhaps opposite of what it's intended or at least a very wrong interpretation that could lead to some problems. You can't have more than five percent.

I thought the -- just the remainder of my five minutes is to show you an information processing. It's kind of a -- a combination. I call it the Chip Model.

Let's get that up there. I -- I -- I spent lots of money to get prepared here.

(Slide)

MR. WOGALTER: It's -- I call it the Chip Model and it's described -- each one of these stages is -- has a chapter in here that goes through the research regarding it. And it's kind of a sequential model, but you'll see that there's looping-backs and feedback loops.

Well, the first stage is the source. And that's who it's -- the warning is coming from. And some research has suggested that if it's, for example, government warning on alcohol. That -- that -- that actually seems to lend more credibility to that warning, or surgeon generals as opposed to just, you know, no -- no source there.

The next is the channel. And warnings is a fairly broad area. It doesn't just include labeling. It's -- we had some things on education and pamphlets, mass communications such as advertisements, commercials. There's indirect warnings where someone -- for example, a physician may receive a warning and relay it to a patient. So, there's many different -- also auditory warnings, another way.

So, all -- if you have a warning hopefully it gets delivered to the receiver, and you can see that it's a communication -- a simple one, source-channel-receiver, but inside the -- in the receiver there's certain processes that must go on if you expect the warning to have some effectiveness.

And by effectiveness, there's three basic ideas or what's the purpose of the warnings. One is to inform. Another one is to facilitate compliance, compliance behavior. And then, sometimes also it's added that it should be a reminder if you already know that information.

So, basically, with the attention, you need to make it noticeable. There's lots of clutter out in the environment. On labels there's lot of information. You need to have it stand out. There's things like color, bigger print, pictorial symbols, and so forth that would enhance the likelihood that someone would see it.

Then also, in the attention part is there's attention maintenance. So, after you've captured attention, how do you hold attention there so that they actually read it? Well, you have to have, like, good legibility. And legibility is -- is important because a lot of folks don't have great vision, presbyopia. And if you have four point font there a lot of people are not going to be able to read that. You need it a certain level above that.

You've got to make it kind of interesting. Some of the white spacing and -- will help maintain attention. Think comprehension real briefly. The warning has to provide information. It should be -- the research suggests that it should be explicit. It shouldn't be just general warning, "This may be bad for your health" or "bad for driving" or whatever. Generally, the more explicit, the better.

With pictorial symbols you have to make sure that they understand it and don't misinterpret the pictorial symbols, and it's hard to design with pictorial symbols. It's not as easy as one might think.

Then, after that, so you've captured attention, you got to comprehension, then you may want to change attitudes and beliefs if they're wrong. For example, people may believe that over-the-counter drugs are safe. Well, how are you going to convince them that there may be some harm there or you may need to give a strident message, a firm message. It may come back to the source, giving it from a credible source and so forth.

And then lastly, your motivation. There's various factors that affect that whether it's low cost of compliance, whether it's easy to do. If it's very difficult to do or something is getting in the way people are not likely to comply. Whether they're under time stress. That hurts compliance. And whether they're social modeling, whether they can see other people complying effectively.

And lastly -- well, I'll -- I'll hold off. I do have some example pictorial symbols but I'll wait until, maybe, after Ruth Day gives some of her presentation. That's all with me.

DR. ELLINGSTAD: Thank you.

Our next panelist is Dr. Ruth Day from Duke University.

DR. DAY: Good afternoon. I can have the first slide.

I'd like to begin by telling you I do research on the cognitive accessibility of drug information. And by cognitive accessibility, I mean the ease with which both providers and patients can find, understand, remember, and use drug information and do so in an efficient and accurate manner.

Our research examines drug information from many sources, from the PBR and pharmacy leaflets to TV ads, Internet Web sites, and packaging. I'm hoping our first slide comes up because it cues the topic for today and has an interesting pictogram on it.

I may pause for a moment.

(Pause)

(Slide)

DR. DAY: Ah ha. Thank you.

So, today I'm going to begin by focusing on pictograms and ask whether they can help. And the first question we want to ask is what kind of help would that be? Well, we'd certainly want them to enhance cognition processes such as pattern recognition, comprehension, memory, problem-solving, and decision-making but ultimately we would like to be able to change behavior. So, when a person is taking a drug they might reconsider whether they should drive. When they must drive, they might reconsider whether they ought to take a certain medication and ultimately improve driving safety.

(Slide)

DR. DAY: In order to examine how we might study this problem, I'd like to take a look at one of the experiments that we've conducted, and here is the packaging for the antihistamine Benadryl. Very well-known one. The top of the display is the front of the package and the bottom of the display is the back.

There's a terrific amount of information here. In order for you to see it better I've enlarged it in the next slide.

(Slide)

DR. DAY: And I might ask you, where is the warning and what does it say? For most people, it takes a long time to find it, the warning about driving and perhaps they don't find it at all. In order to enhance the chances that people will take away the information that there may be some problem driving while on this medication, we've created a variation on this display using this pictogram.

(Slide)

DR. DAY: This pictogram comes from the pictogram library of the U.S. Pharmacopeia. It's part of one of their pictograms. It's a very strong pictogram. It doesn't say, "Use caution." It essentially is communicating, "Do not."

In order to determine the effect of this pictogram on cognition we did an experiment where some people saw the previous display, the packaging without the pictogram, and the other half on a random basis saw the same thing with a pictogram embedded.

Now, there are many locations where you could put this pictogram. For this particular experiment we put it up top, large -- in large size, and right by the drug name to really make it stand out, so we've been quite heavy-handed here.

The procedure was a study test paradigm. During the study phase people were actually comparing packaging for two drugs in the same category in order to ostensibly determine which one they would buy. And then, afterwards in the test phase we asked many different kinds of questions and one of which was about warnings, what are some of the warnings for this medication. And the results were that the people who had the pictogram added did do better. They did three times better in terms of their ability to report that perhaps driving was not a good thing to do while using this medication. Well, that's the good news. A threefold increase in performance.

The bad news is shown on the next display, --

(Slide)

DR. DAY: -- which shows that almost no one got it anyway. So, the -- it's well below 10 percent overall.

So, we might ask why? Why aren't people picking up this information? One answer is, of course, potentially information overload. But we asked about other things on this packaging. For example, we asked what are some potential side effects? The next display shows that people did quite well.

(Slide)

DR. DAY: On average, half the people reported that drowsiness could occur and it didn't matter whether they got the pictogram or not. So, they got this information from the packaging.

But did they really? Perhaps they got it from somewhere else, namely prior knowledge. In other studies we have asked people what are some possible side effects that can occur when you take medications in general? And as you can see, drowsiness is the most often reported likely side effect. It's twice as great as any of the others, and so people have general prior knowledge that drowsiness can come from taking medications.

By the way, many of the other things that came to mind are also not good for driving, such as dizziness, et cetera.

So, people don't seem to be making this causal link that they have prior knowledge about drowsiness. They may pick up some of it when they read the packaging, but they don't then make the link about driving.

So now, why is performance so poor? Why don't they get this warning in -- in -- in a -- in a good way? Well, there are a lot of other potential factors, and I think by going back and looking at the warning section again, and I've just blown it up and given it more favorable thought and so on so that you can see it.

(Slide)

DR. DAY: It is still a big block of text. A big block of text makes it hard to search, find, understand, remember, and use information. In order to enhance the exact same information here, the next slide shows how we can pull this information out and chunk it.

(Slide)

DR. DAY: Chunking involves just separating each chunk from the next chunk in a variety of different techniques that you can see on the display. There's a terrific amount of research that shows that when information is chunked people are much better at being able to remember, learn it, and use it later.

Another cognitive principle beyond chunking is coding. An easy way to describe this is that if you can put a name to it then you might be able to remember it more readily. So, the next display takes the exact same information of the previous slide and chunks it and codes it, both giving it a name and doing it in color.

(Slide)

DR. DAY: I'm not recommending we should go to displays like this. I'm using this as an analytical tool today.

And when you look at this slide, you'll see that there's a lot of jumping around of topics. So, you start out in the beginning with side effects, go to contraindications, then more side effects, then more actions, warning interaction, contraindications, storage, and overdose, which leads to another cognitive principle, and that is clustering -- put together which goes together in terms of the semantic or meaning basis.

So, we would recommend that a variety of cognitive principles be taken into account in analyzing current materials and designing new materials, principles such as chunking, coding, clustering.

(Slide)

DR. DAY: By the way, we have done a lot of work with the pictograms themselves. And as you can see here, the first choice that you -- you need to consider, one of the first ones, is whether the -- the pictograms are information-sparse or information-rich. That is to say, do they have a lot of intrinsic meaning in and of themselves? There are advantages and disadvantages to both types.

(Slide)

DR. DAY: Information-sparse pictograms are harder to learn but -- and they have less intrinsic meaning so they can be misunderstood. And different people can take away different meanings, as we heard in some of the discussions this morning. On the other hand, they can then be applied to a wider category of things, different types of warnings, not just the driving while medicated.

(Slide)

DR. DAY: The information-rich pictograms contain the meaning within it more readily and the top one has done very well in our test. They actually combine with other things in the U.S. Pharmacopeia pictogram library. For example, the middle one shows the causal link. You take the drug, you get sleepy, therefore don't drive. In some of our testing we find that when people first see the top of this pictogram they think the person is laughing or screaming or smelling one's own breath. I mean the interpretations are quite remarkable. Over time with a little bit of education hopefully this will go away. Far less education with these pictograms than with the information-sparse ones.

(Slide)

DR. DAY: Final issue is who's going to be designing the pictograms? Well, of course the experts will. I would love to give the job over to Mike Wogalter here and he'll get you a good pictogram. But we still have to take into account the prior knowledge of the people who are going to be using these, the general public.

And so, what we did was to give people what the current language is in the packaging, which is "Use caution when operating a motor vehicle or operating machinery" and ask them to design a pictogram. Could be a rough sketch. Drawing ability didn't count. And people did this and this display shows you the percent of times that different semantic components were included. Just about everybody has a car and the cross-out. And so, those are the two basic elements that need to be in the pictogram as far as just everyday consumers go.

A lot of them want to have a person and steering and some intention of driving in it rather than just interpreting it that if you're in a car you might get seasick or not feel well if you're taking a medication.

There are a variety of other things they put in. Machinery, we had a lot of buzz saws and other kinds of things but there was no consensus. So, when there's no consensus for how to represent a semantic component it's probably not a good idea to include it.

The last thing I'll mention on this slide is only a quarter of the people did anything about indicating that causality, the causality which goes from take the medication, maybe get side effects, maybe get impaired, back to the fact of driving.

(Slide)

DR. DAY: So, in conclusion, let's step back here -- oh, this -- this slide just shows that we've done work with a variety of other kinds of drugs, both OTC and prescription for allergies and other types of indications.

The last display comes back to this whole issue that we want to enhance cognition and behavior about the drawing -- driving and warning. In order to do so, we need to take a lot of approaches. I was distressed this morning when people said, "Well, we tried this and it sort of worked and then it fell off. We tried that, it didn't work." Pictograms are going to work in and of themselves but also in the wider context of the entire information.

So, there are a lot of issues to be addressed about what pictograms, should they be information-rich or sparse, where do you put them, et cetera, et cetera. But at the same time we have to take into account the linguistic information that's being presented as well. Chunking and coding and various kinds of language structures are important to take into account as well. And when you put together both linguistic and pictorial information about the same warning, that really enhances the chance that many more different people are going to get it and the people are going to have the information enhanced with both types of representation.

So, to conclude, there are many cognitive principles that are well-rounded and empirical studies that have gone on for the last 40 to 50 years. These principles work. Let's use them. Let's use them to analyze the existing materials and test the consequences for cognition and action. Then let's go into the redesign phase and let's redesign using these principles to enhance cognition and action, then retest. Let us test the consequences before we then put them out in the public view and only then begin the efforts on education programs. Thank you.

DR. ELLINGSTAD: Thank you, Dr. Day.

Our next panelist is Dr. Soller from the Consumer Healthcare Products Association.

DR. SOLLER: Could we go back one slide?

(Pause)

(Slide)

DR. SOLLER: Thank you. Good afternoon. I'm Dr. Bill Soller with the Consumer Healthcare Products Association.

My comments focus on OTC drug labeling, the OTC drowsiness warning, the new OTC drug facts label, public education, and a brief comment by way of conclusion.

Yesterday I presented this overhead which represented the summary of our AER postmarking surveillance analysis. Over this 10-year period '91 to 2000 there were 23 serious AERs with antihistamines as primary or secondary suspect drugs and with an accident term in any field of the AER no more than four per year and about 850 million OTC packages for adults alone sold over this particular period. And it's on this background that I make my comments.

The current OTC label has specific components that are arranged in a standardized flow of information, including active ingredients, uses, warnings. Within warnings, absolute contraindications, relative contraindications, in-use precautions, directions, other information, inactive ingredients, and questions.

I say the "current label." This is the current drug facts label format.

The important point to glean from this is that all of this information is important and it should be presented in a consumer-friendly way that has low to no potential for interrupting the standard flow of medical information, particularly in the warning section.

(Slide)

DR. SOLLER: This is an example of the drowsiness warning for OTC antihistamines. "When using this product marked drowsiness may occur. Avoid alcoholic drinks. Alcohol, sedatives, and tranquilizers may increase the drowsiness. Use caution when driving a motor vehicle or operating machinery. And excitability may occur, especially in children."

(Slide)

DR. SOLLER: And here we have the pre- and post-drug facts labeling. I think you can see there's quite a difference. The presentation we just saw did a study on the old drug facts label, the one on the left. And the new drug facts label has an outline format; the use of bullets to chunk information; the information is clustered; prominent, consistent placing of the drowsiness warning. I don't have a pointer here, but if you go down about halfway on the label you'll see "When using this particular product." And it's a consistent, standardized, rational flow of medical information starting from the top and moving down that would be replicated across all OTC products, all categories, thereby having an educational component to the consumer as they're using many different OTC products.

Most antihistamine-containing products have already been relabeled with this new drug facts format with full compliance May 16th, 2002.

(Slide)

DR. SOLLER: Given the lack of data to demonstrate that OTC labeling should be changed, the focus here should be on the core public educational message "Read the label, read the entire OTC label." The new drug facts box allows a renewed emphasis on this core message in an attractive way, noting, for example, more prominent and consistently placed warnings. Awareness and education about the need to read and heed the entire OTC label should target operators and consumers, and CHPA has traditionally partnered with outside groups and governments to promote this core message as noted by our Vice President of Public Affairs Corinne Russell this morning.

(Slide)

DR. SOLLER: Now, in relation to pictograms and symbols, this matter was thoroughly and publicly reviewed during the development of the final rule on drug facts labeling that took place over many years. FDA found that pictograms and symbols may be used voluntarily in addition to required warning language but, and I quote, "A symbol or pictogram that directs attention away from the required information or one that is ambiguous or can be misunderstood by consumers may render the products to be misbranded."

Pictograms and symbols are unproven in any in-use situation for OTC medicines that we're aware of, particularly as it would relate to the drowsiness label as it might affect accidents. They are potentially open to misinterpretations. Study -- studies supporting their ability to clearly communicate are, in our opinion, at best mixed. A number of studies show very poor understanding. Others show that -- or another shows that an illiterate population did not achieve understanding equivalent to a literate person reading the label. Another reports an ability to improve the communication of the pictogram but leaves unanswered the question whether the pictogram translates to real world views and benefit in a nationally representative population.

And with misinterpretation can come misuse and potential misbranding, and in our view this is an important limitation even in a small percentage of cases.

Pictograms and symbols would crowd the limited -- the label, limiting the amount of white space and space without wording and therefore make it less attractive, less readable, less consumer-friendly. They would work against the "read the label" message by potentially interfering with the flow of information in the drug facts label by distracting the reader to start at an icon if it were placed midway in the drug facts label rather than at the top of the label.

And I think potentially they would in fact represent a way for a reader to speed-read the label. This is particularly important because you have to ask the question, "Where would you stop?" Which is more important: a drug interaction label, a pregnancy label, "Keep away from children," driving, diabetes, the list goes on and on. And the potential of having multiple icons and then using that to speed-read -- changes to label I think detracts from the basic message of "Read the entire OTC label."

(Slide)

DR. SOLLER: In conclusion, OTC antihistamines have a demonstrated history of safe and effective use when used according to label directions. They are appropriately and adequately labeled. Pictograms and symbols are unproven in any in-use situation for OTC medicines that we're aware of. The issue is read and heed the entire OTC label. CHPA believes that it's important to maintain an ongoing program of consumer education on the importance of reading the label. Thank you very much.

DR. ELLINGSTAD: Thank you, Dr. Soller.

Our final panelist is Dr. Bert Spilker with the Pharmaceutical Research and Manufacturers of America.

DR. SPILKER: Good afternoon. I'm Dr. Bert Spilker of -- as you just heard, and in regard to the subject for this panel's focus I wish to make four points.

First, all investigational prescription drugs are thoroughly evaluated for ADRs by the sponsors that are developing them. One of the most commonly reported ADRs is drowsiness, and this often finds its way into the label of products across many different therapeutic classes.

Two, drowsiness is a subjective measure and is not always correlated with performance impairment in clinical studies. It is often very difficult to know if drowsiness is drug-related, related to the underlying disease for which a product is prescribed, or related to other factors.

Three, the sponsor's evaluation of drowsiness may include testing of drugs versus placebo, different doses of a drug to evaluate those relationships, and drug versus active agents from the same class with an incidence of drowsiness. Statistically it's different from placebo if applicable.

Any adverse event occurring at a rate greater than a pre-defined threshold which is usually on the order of .5 percent or one percent or any adverse event of clinical significance or any adverse drug reactions that occur during clinical development will be placed in the drug's labeling. All data are evaluated by the FDA and are supported by adequate and well-designed clinical studies. When clinical trials document the drowsiness due to a drug as statistically significantly greater than placebo, it may require a label precaution.

Lastly, current FDA-approved label language is adequate to present this information to the physicians and to patients. Warnings and product labels currently exist to alert prescribing physicians to the potential hazards of vehicle operation while using medications that can cause drowsiness. These safety warnings are communicated to subjects when physicians prescribe to their patients. Patient package inserts when provided reflect these warnings in easily understood language for the public.

Pharmacists are already required in many states to attach a peel-off label on the pill bottle mentioning when a drug may cause drowsiness and also to avoid using with alcohol or other depressants. In addition, many pharmacies hand out patient information leaflets informing patients of safety-related information when purchasing their medication.

In summary, there currently exist ample opportunities for physicians and patients to be informed about a product safety profile. We recommend that there not be any changes to FDA's current practice of label design for prescription drug products.

Thank you for this opportunity to make these comments, and we'd say that copies of this text are available on the desk outside.

DR. ELLINGSTAD: Thank you.

Questions from Technical Panel/Parties and Discussion

DR. ELLINGSTAD: We'll turn to the Technical Panel, and I believe our first questioner will be Dr. Ganley.

DR. GANLEY: Thank you for the presentations. They were very good.

I'm going to -- I have a bias towards OTC products right now so I'm going to sort of focus on -- on that right now. Oftentimes we see label comprehension studies that suggest that there's a comprehension of a certain warning, yet when an actual use study is done the actual behavior of the individual is not predicted by that label comprehension. And I can give you an example. Two years ago we looked at a muscle relaxant and it was reviewed in front of an advisory committee and there was data presented there where comprehension of -- not to drive if using this product was in the 95 percent range. Yet, in the actual use study 50 percent of people used the product and went out and drove.

And so, I guess the -- the issue for me is does a pictogram actually just highlight something for a patient to see? Does it help them comprehend it better? Or does it help change behavior? Because we're really interested in changing behavior here because I think whether you use words and, you know, in the chunks now that Dr. Day had presented, which I think is sort of how our -- our new labeling format is presented. You know, the issue is how do we change behavior? What -- what information do we have to include in there to change behavior?

MR. WOGALTER: Well, if you remember the Chip Model that I mentioned earlier, there was comprehension as an earlier stage and later there was behavior. You still had to go through attitudes and beliefs and motivation which could, if they don't believe that it's hazardous or it's too difficult to read the label, then you're going to get the possible decrease in -- in behavioral change. They may understand it when you show it to them but in actual use they may not believe the information or that it's for somebody else, not them. That's the problem.

The other thing about the pictogram, there's several different uses of the pictogram possibly. The one that's usually attributed to it is the comprehension aspect of it, but there's also the attention-getting aspect. That is, that it will draw your attention to that pictogram even if you don't understand it -- what it is. People are kind of curious about that and of course you don't want them to make an error in what it means, okay, so you have to look for the critical confusions.

The other aspect of pictograms is the reminder aspect, that if they do know the information just by a quick glance they can get that information.

DR. DAY: I would like to add something about the high level in comprehension studies. I've seen quite a few comprehension studies which have a high percent comprehension score and when you look at the methods I don't think that's necessarily what you can conclude. In some research that we did sponsored by the U.S. Pharmacopeia we did a levels of processing approach in looking at people's understanding of pictograms and other information in the pharmacy leaflets and things that go in the bags. And you can ask a general question, "What does this mean?" or "Did you see any" and "What were they about?" and so on. And as you get deeper and deeper, you find that maybe people don't really understand.

So, what is being taken as a comprehension score? And I think one of the best techniques is using what we call a problem-solving scenario task where you say -- say you're taking this medication and such and such happens. Is it all right to continue to use this drug? And half of the examples or scenarios you give, the answer should be "yes" and half should be "no." You mix them all in so you're not just asking, "Is it okay to drive with this drug?" And when you do that you see that comprehension scores often go way down.

So, I think we have to take a multiple level approach to understanding what these comprehension scores mean in the first place.

DR. SOLLER: This is Dr. Soller. I have three comments, Dr. Ganley. The first is that this may be drug-specific, and that's one thing to always consider, that the effects seen and how people are behaving to a particular warning may be impacted by the -- sort of the intrinsic toxicity of the drug itself and how they're using it. And I would guess that some of those answers would come out in the -- new study in terms of perhaps some of the compliance measures that will come out. So, sort of that said.

The second is, of course, and you know perhaps better than anybody in this room, that the label comprehension study and the actual use studies iterative process and there's always the potential to make the label better, test it again, and see if you can refine and get a better behavioral intervention that you'd hoped for.

And my third comment is the -- I think the importance of perspective here to step back. It's something that we've tried to share in terms of our comments and our thinking in this area, and that is that we are here in the very narrow focus of transportation. And when we sort of step up and we consider other special interest groups, people that are interested in accidental child ingestions, people that are interested in the effects of drugs on pregnancy, the issue of don't mix drugs, and on and on, you ask which is most important that we're going to put on the particular label. Or are we going to emphasize the basicness as you're reading the entire label and then use educational programs to have perhaps -- particular different parts of that basic message.

DR. TEMPLE: I guess even if you thought that the best thing is for people to read the entire label, it still seems likely that some presentations might be better than others.

I guess the first question I have is there seems to be at least a little bit of a contradiction. Dr. Day showed some evidence that pictograms have a little bit of effect. It wasn't very large and it was after all a very small pictogram. You could have made it much bigger. And it wasn't reproduced down among -- down in the text to sort of link the two. One can think of various ways of seeing if pictograms could work -- could work better.

But, Bill, you seem to think that there was really just no hope that there was any likelihood they work, so I guess I'm curious whether people think this is something to be explored more if you had a particular part of the label you wanted to draw attention to. Of course you want everybody to read it all, but you still might want -- you still might want to emphasize one part.

DR. SOLLER: Well, --

DR. TEMPLE: I take your point that every group will want to emphasize the part that's of interest.

DR. SOLLER: Yeah. And I think we fought about this. We've fought about this for many years during the development of the final rule on drug facts labeling and there was a thorough discussion of this. And I think that FDA netted out with the right kind of policy letting it be voluntary but noting that it was misinterpretation, you're open to misbranding. That makes sense. So, given that and then stepping back and saying what are we really trying to achieve as the new drug facts labeling is rolled out? We are taking the broader view and, yes, we are saying that in the context of pictograms this may not be the best kind of approach for this particular situation and for various reasons that I gave.

There's another study that shows that you can refine the symbol and come up with somewhat greater comprehension than was shown by Dr. Day, but that still leaves you with the question of how that translates out in a multicultural society and whether it's universal.

Another study has shown that if you really focus in on the cultural differences that people have and make your pictogram defined in that context your comprehension goes way up and the question is how do you translate that over here and in a multicultural society? And so, looking at what you -- what you have in terms of the outline format where you have the ability to -- for people to scan the label, if you're looking for memory the outline format of being able to scan through and get a quick re-recognition of what's important exists in the drug facts labeling. And that's an important feature of it.

The ability to use educational efforts, particularly with an industry that is interested in doing even more, is an opportunity to highlight drug facts labeling and even pulse different messages within that, within the basic one of "read the entire label."

DR. TEMPLE: I don't think anybody's suggesting that you have pictogram and no text or have text and no pictogram. It's the question of whether combinations of those things are worth exploring to see if you can do better. You wouldn't say that that isn't worth thinking about. What I understand is you're saying don't do it until you have a good idea whether it works.

DR. SOLLER: Well, I think --

DR. TEMPLE: Right?

DR. SOLLER: -- it's important to have a data-driven approach to labeling and you've heard me say that on other occasions, so --

DR. TEMPLE: Okay. But that -- does that include the possibility that a pictogram might be shown to be useful in a particular area or -- or do you think it's a settled issue?

DR. SOLLER: Well, I wouldn't necessarily exclude the potential that we can do even better on labeling. I mean we may find -- you take almost any category of OTC medicines and as new information emerges I think it's important to think about what we're doing. And I know you are involved in doing that on a daily basis and -- and that's something that happens on the OTC arena as well.

But I do say and I do think that you have done, you as an agency have done a very thorough examine -- examination of this. There hasn't been any new information that really has come forward that would change the considerations that you already had and I think that the policy that you have for the voluntary use with the proviso vis-a-vis misinterpretation and misbranding has set the right arc for what we know now.

DR. DAY: I have a comment about the data that you referred to. Not many people reported the driving warning. Keep in mind what the nature of the cognitive task was. People were given two packages and told to look at them to decide which they would buy. And they could take as much time as they wanted to and some -- one -- one experiment and another they were limited to a certain amount of time. Didn't make any difference. Those were the data I showed you.

However, if the task is take a look at these packages so that you'll be able to take this medication in a safe and effective way, then things do go up and that's a major point I would like to make in all the studies that a review -- that are cognitive or any sort at all. What is the nature of the task that people are being asked to do? And people get in information in different ways, and then the way you ask for it to come out can determine what you get.

And just one other point. In the displays that I showed it was the old labeling for OTC medications for antihistamines. We are also doing studies on the new labeling so we will have empirical evidence of the extent to which those are enhancing -- this and other information. There weren't enough data available in order to present that today.

DR. TEMPLE: Do you have data in order and how it matters? I mean you can't help but notice that in the label that was shown the first things mentioned is that children get excited on Benadryl. Not exactly the most important thing to know, you might think.

DR. DAY: That's true on this one --

DR. TEMPLE: I mean I guess you could argue that, but it doesn't seem to be.

DR. DAY: That's true in this one, not in clortrimaton and other things. But Dr. Wogalter has done a lot of research on the order of information.

MR. WOGALTER: Yes. We've published a number of studies looking at prioritization of different label components. As it turns out, there is an article in the "Drug Information Journal" that looks at what -- what -- what order of the different sections might be in different scenarios. For example, when you first purchase the product, if you're giving it to someone else, and pretty -- and we used different populations: older adults and students and so forth.

Basically, what the results were were very close to the new drug facts label. The real exception to it was that regular folks were not that interested in the active ingredients being first and they had it later down in the label, but pretty much the rest of the components were ordered in multiple different scenarios.

DR. TEMPLE: What about within a paragraph of text? There's a single paragraph that talks about five different things. It takes a little while to get to the sleepiness part.

MR. WOGALTER: Yes.

DR. TEMPLE: Could that -- could that interfere with understanding if that's important? I mean everybody runs off and worries about giving it to their children first and they forget that they're supposed to worry about driving.

DR. SOLLER: Just -- go ahead.

MR. WOGALTER: Well, you could -- that's true. I mean if you read a lot of instruction -- I mean a lot of warning materials, gives some really obvious things up front. And that leads to people saying, "Well, I already know this stuff." And so, whenever you have something further down even in the section or in any kind of text, you're going to get less likely that they're going to get to that section. So, you could prioritize within that section, I suppose.

DR. TEMPLE: I should say I'm not offering judgement here. We happen to be focusing on sleepiness now and maybe that's not what we were doing then. I'm just wondering about whether if one wanted to focus more on sleepiness one would think about rearranging the order.

MR. WOGALTER: Yeah. No, I understand.

DR. TEMPLE: And not intended as a nasty comment.

DR. SOLLER: Didn't take it and didn't think you needed a disclaimer. But my comment really reflects on the discussion, the very depths of discussion that we had with FDA. And we had a difference from an industry standpoint than FDA wanting to have directions higher in the label than it is. And in fact, we were -- even within our own group we were debating whether that should be.

But the basic order in terms of actives, uses, the question was directions or warnings. And warnings and directions I think also was engaged in a concept of whether this should be the consumer driving what they think they ought to have or whether there should be a medical overlay in terms of helping the consumer access the right information first. And part of the reason the active ingredient was -- was first was in relation to the brand name and ensuring that consumers understood the differences and what impactors were there.

Use is next. What do you use it for? And now that you're thinking you might use it, your first self-selection, the question being are there any absolute contraindications, "Do not use." Are there any relative contraindications? "Ask a physician before using." And then in-use precautions, and that's the standardized order for the warning section. I'll return to that in a minute.

And then, pregnancy and breast-feeding split out separately. And then directions, which you've gone through all of that in your self-selection. Then you move to the directions, and that makes sense as you asked for order.

Now, as it relates to drowsiness, for the antihistamine single-ingredient labeling, for example,

"When using this product marked drowsiness may occur," and that occurs within a sub-box within the overall drug facts box, so it is prominent. It's more --

DR. TEMPLE: Well, but it's --

DR. SOLLER: -- it's more conspicuous.

DR. TEMPLE: But it's late in the sub-box.

DR. SOLLER: Well, --

DR. TEMPLE: It's not the first thing in the sub-box. That's really all I'm asking about. I wasn't --

DR. SOLLER: That would be -- yeah.

DR. TEMPLE: -- trying to restructure the whole label.

DR. SOLLER: Yeah. And I -- and I think that's important to think whether you put drowsiness, and I'll return to that if I may by way of putting this whole thing into perspective, or whether you think about that it's important that a person ask a doctor before they use it if they have glaucoma and trouble urinating due to an enlarged prostate or a breathing problem such as emphysema or chronic bronchitis. That's a medical judgement. And the judgement was made during the discussion in a fair amount of discussion on that that you want to put the contact with the doctor for a medical condition like that first.

And I -- I would add by way of perspective, and I was reflecting on this over lunch with my colleague Bill Bradley, and that is that we're -- we're dealing with about 100,000 crashes per year on drowsy driving. I'm not suggesting to minimize any one of those crashes. Don't misunderstand. Our understanding of the tremendous impact that that -- that that can have on a family. That's about 1.6 percent of the total 6 million or so police-reported crashes. Fatigue is the primary factor in all of this. Time of day is the most consistent factor with a peak that's right after midnight, another mid-afternoon. This is all off the Web page. With a feeling that the human circadian rhythm is the plain underlying factor as we're thinking about drowsiness.

Fatalities from drowsy driving is about 3.6 percent of all fatal crashes, and if you look at the NITSA prevalent study, you're dealing with alcohol over 51 percent prevalence. Antihistamines are about .6 percent prevalence. That very low involvement I think in terms of crashes overall is supportive of the AER survey we were seeing.

I think in that context as we're thinking about what to do, industry and FDA, particularly with the drug facts label, has done an awful lot, an awful lot in taking that paragraph format and putting it into a very prominent, consistently-placed type of warning within the warning section. And when you deal with what we had yesterday in terms of the ambiguities of extrapolating from the controlled trials and the simulator studies and the questions that we have about pictograms and whether they translate to changing in-use behavior, I think at this time our view is that as the drug facts label rolls out, as education is applied to that, the ability to hit certain specific messages perhaps on the warnings, that you've got the right kind of balanced approach already in place to address the issues that we've been talking about over the last two days.

DR. GANLEY: In the example that you talked about where there's an X-out of a car, does the consumer view an X-out as an absolute contraindication or a relative contraindication or does there have to be words attached to that?

DR. DAY: Most people interpret that "Do not." And most people, when I gave them the "Use caution" and they were to draw a pictogram, turned it into "Do not." Some people did use the caution, the exclamation point and the yellow triangle, but I think that the -- I don't have a position on this that we should or should not use pictograms. But if we were going to use them I think a pictogram should always be directly linked with the linguistic expression of the same information. And I can direct you to a paper of mine that goes into that and the whys and wherefores.

I do want to acknowledge Bill Soller's point, though, that too many pictograms can be distracting and you could have interference effects and so on, but all of these are empirical questions. We designed studies to test how many pictograms can a person handle and so on and so forth. And so, I think there are answers to these questions and I just want to point out that there's a huge body of literature and what's called dual coding theory. If you take some information and show it in both linguistic and pictorial information, people learn it and remember it better and they have more retrieval cues at the time of doing something else, behaving in the real world, whether they should take a medication or drive, that there will then be a retrieval cue. I saw some picture with a car and a cross-out, and that will then be more likely to cue them that this is a problem in this situation.

DR. GANLEY: Even if that -- the information that's attached to it is different? For example, if -- as we talked about earlier, some of these drugs may have a shorter effect than others so it -- there would have to be different information as to when you could resume driving, for example.

DR. DAY: Right. That's one problem. Another problem is it doesn't affect everyone in the same way. And so, I can understand that the pharmaceutical industry might be against having this as an absolute. It's not going to affect some people.

DR. GANLEY: What -- what about for prescription products where essentially a consumer is just given a container that has the drug and they may be given a slip alongside it? And, you know, the examples we saw earlier today, there was just a red triangle with the standard text that did not differentiate products. And how do you convey that information in the prescription setting? Does a package leaflet need to be attached that further explains that that would also have a red triangle? How do you accomplish that?

DR. DAY: Well, one way is to have the -- the pharmacy leaflet stuck in there. But we've done research on the best ones of those and find that the cognitive accessibility issues are still there. But we've also looked at the little auxiliary labels called the stickies that people put -- that the pharmacist puts on -- on the bottle. And I've tracked the same patient on the same drug, refills in the same pharmacy, and each time the labels were different across a couple of different drugs. So, sometimes it's without alcohol or with or without food or drowsiness and driving and there's no consistency. And that gets to the issue of mandatory versus optional use of these auxiliary labels.

Now, some of these software systems now do print out with the actual label who the person is and the prescriber and so on on the bottle, the little label that goes with it. But not all software does that, so it's up to the pharmacist to decide. If the phone rings and they're in the middle of getting the drowsy-driving auxiliary label and they answer the phone, they then may not get that label on.

DR. GANLEY: Is -- I guess then that would lead me to in the OTC setting, you know, one of the emphases, as Bill had pointed out, was this consistency that -- in terms of location of information. And you know, if the information isn't -- isn't there, is there an assumption that it's okay?

So, I guess one of the questions is should FDA develop a list of accepted and unaccepted drugs and label all medication whether they can be used if you're going to drive or use heavy machinery?

DR. DAY: Well, I'll comment about that and Dr. Wogalter might want to, also.

Any time you say "Don't" and you have a list, people interpret anything else as okay. It's not on the list, right? Anytime you say this is okay they don't necessarily to the same extent assume that things not on the list aren't okay. So, we were talking about the lists the military have and so on and so forth. It's not a -- it's -- it's not a -- a bi-directional thing that works in the same way. that is to say, when you say "Don't" people won't do that, they'll do everything else. If you say, "These are okay," they don't think about the others not being okay.

So, the -- the strength of the -- the warning is not bi-directional.

MR. WOGALTER: It's difficult to say whether people are going to interpret something that -- that it's okay if it lacks something there. It's kind of a gray area.

I have kind of like an anecdote where someone in my department used the "Mr. Yuck" label and put -- if you know what that is. It's the unhappy face with the -- the tongue sticking out -- and put it on all -- many of the products under the counter and all -- all -- all over the place, actually, and told their kids, "This is bad, this is poison, don't touch this," and then she brought home some other products and forgot to put the little label on there. And she comes home one day and sees that her little boy is spraying pesticides all over the kitchen and he said, "Well, it didn't have the "Mr. Yuck" on it." So, you never know how that's going to be interpreted.

One of the things that was brought up is the inserts. That's another place that perhaps you could add some pictorials, explain some additional things. We have published a paper which may be relevant -- I think it is relevant -- in the "Drug Information Journal" where we looked at inserts where it had eight different kinds of warnings on there and they either had both pictorials for all eight or they had pictorials for half of them. They were randomly distributed. Or it was just a verbal information or nothing. And we gave them -- at least those first three conditions for a limited amount of time and had people look at it.

And what we were really interested in is what happens to the things that don't have a pictorial symbol because you may not have a comprehensible symbol or something specific enough and will they ignore that information that doesn't have a pictorial? Well, it turns out if it had a pictorial they do get that information. That's the first thing they start looking at. They'll read the instructions right next to it. But they tend not to pick up the other things that don't have pictorial next to it. Basically, when they had pictorial symbols for everything they did great. It went very well. And if you ask consumers which would they prefer, they'd like to have the pictorial symbols. You just ask their subjective judgement, but there is a problem that you may not have a symbol for everything. And they're not specific enough.

The car there, is that going to fit a lot of things? You're leaving out perhaps the heavy machinery, whatever the heck that is, and, you know, can't fly a helicopter. It's -- you don't know how far they're going to take it. Now, if you had education beforehand it could serve as a cue or a reminder, "Oh, yeah, this comes under this auspices of not being -- use it while driving or use any other kind of machinery.

So, one possibility is to consider for alternative information to use pictorial symbols and maybe not have the problem with the misbranding, maybe if it came out with -- from other organizations as well. The pharmaceutical actual product where they may have some problems with litigation.

DR. TEMPLE: One of the points that Dr. Day made was that pictorial things should be linked to the text, so maybe that's part of the answer to that.

Can I ask a slightly different question? Do the pictograms have any potential role as a reminder function? Despite everybody's best efforts, it's hard to believe that people are going to re-read an entire label every time they get a familiar drug. Is it possible that, and has anybody studied this question actually, that this would be shorthand reminder of something that was important but that they may have forgotten? And I guess part of that might be when multiple drugs have the same brand name, could a pictogram help you tease your way through the thicket of different ingredients that bear the same class name?

MR. WOGALTER: I've done some research. It hasn't been on pharmaceuticals. It's been on other -- concerning other products where we give participants -- they think they're going to use a particular product and it contains an instruction manual with pictograms and the text. And if you were to ask them later on, "Describe all the hazards associated with this particular product," if they have a pictorial -- a pictogram at test that is serving as a reminder, they do much better in the hall.

DR. TEMPLE: Any other --

DR. SOLLER: I -- I think it's possible to generate hypotheses about what might happen in a situation. I don't have anything more to say about that relative to reminder except to ask whether you would be reminding persons not to drive a car and then ask what does that mean for truck. And I think what happens when you're looking at pictograms, you're balancing what might be done and certain benefits as you're suggesting perhaps as a reminder against what might be certain limitations, and I've elaborated those. I won't elaborate them again, but I think the universality is an issue. I think distracting -- the experts here, distracting information. Works well when there's a pictogram for a lot of the information. Doesn't work well if you only hit one, focusing only on that and get tired of reading.

So, I think it's a matter of balance. I think FDA did the right way. The evidence balance -- equation and came up with the right policy.

DR. TEMPLE: A lot of those questions sound potential of study. However -- I mean just as an example, you -- if -- if the pictogram reminded you that, "Oh, yeah, oh, driving," then it would remind you that -- similarly about all driving and you would -- you would, assuming reasonable intelligence, be able to realize that it applies both to driving a truck and a car. So -- but it doesn't sound like there's a whole lot of data yet on whether it can help your mind be -- of what you read in detail before. So, let's assume everybody's going to read it in full detail. Still might have that function.

DR. SWEENEY: Dr. Wogalter, you mentioned a minute ago the "Mr. Yuck" pictogram. How well recognized are some of these pictograms, the "Mr. Yuck", the biohazard pictogram? How well recognized are these ones?

MR. WOGALTER: Well, it depends on the population. We've tested "Mr. Yuck" over the Spanish-speaking population -- primarily Spanish-speaking, very little English, and they had no idea what that was. And they didn't attribute much hazard to it. And I think a lot of people haven't seen that for -- "Mr. Yuck" for quite a long time now.

As far as for aviation or biohazard or some other things, those are dealing with abstract concepts, things that are not really visible, and it's very difficult to create a pictogram for something that doesn't have a visual analog. You can make one for washing the hands. You could show water and a faucet with your hands there, but there's a variety of concepts that -- that is very difficult. It's not likely that they'll get it the first time. If they didn't -- weren't able to read the textual language and they didn't have any background training in it, they're not going to know what a biohazard symbol is.

DR. SWEENEY: Well, what is the role of education in developing some level of comprehension of pictograms?

MR. WOGALTER: Well, I think it's -- it's a good idea to have the education and I -- I've heard in some countries that they actually have some video games or a kind of a video game or you can give something like a coin in an airport and it gives you the pictorial symbols and you try to guess what it is. And it apparently earns some money, okay. So, that could be a way to educate folks. I think that's -- certainly there should be the education.

Let me just mention something about the warning system. The warning system is a very broad area. It includes the mass media, brochures, you know, variety of different things, including education that might happen in school. Each one of them are going to hit a different kind of population. We shouldn't assume that just one method is going to do it and by itself. I've run across certain situations where people don't get the newspaper or they get it just on the weekends and they don't watch Oprah or some of these other things. If I go into some of these hazards or -- you know, they have limited amount of exposure to what we might say is mass media. And so, you have to hit them in different ways.

DR. SWEENEY: How effective are labels right now for targeting a lower level population, people who may not have a high literacy rate? How effective are they for that population?

MR. WOGALTER: Well, I think they're improved. I think that the labels that are coming out, that have been coming out, the drug facts label, they use simpler language and I don't know of anybody who's actually evaluated the language. There apparently is some folks who have looked at some of the words and gotten some of the grade levels and tried to simplify it. There is -- the Spanish-speaking population does not -- unless they really are frequent words.

DR. SWEENEY: We just completed some studies on grade level analyses for prescription drugs and I think it's unwise to grade level overall without looking by semantic category. A lot of research in my lab is about benefits versus risks, within risks specifically side effects, let's say.

In the current TV ads that are running, 30 seconds, 45 seconds, or 60 second ads, we've done a lot of -- many different kinds of analyses, one of which is the readability level which also relates to comprehension on the auditory domain, and the readability level of the side effects that are given is much higher, something like 10th grade or 11th grade. I think -- yeah, it's 11th grade level whereas for the benefits it's much lower. So, you have to look within semantic categories within the type of information source, such as TV, Internet, package inserts, and so forth.

DR. SOLLER: Just a general commentary that when the drug facts label was developed industry and FDA independently brought in literacy experts to consult on that. Part of the final rule included what is called the interchangeability of terms with the idea of trying to go to simpler words, those with fewer syllables. And quite a lot was done. Very specific wording is part of that final regulation, all to help bring the -- the level of under -- well, the ability of the label to communicate to the individuals with a lower understanding of language.

DR. SWEENEY: Have there been any studies done comparing the effectiveness of a warning label versus a verbal warning from a pharmacist or a doctors in terms of behavioral compliance?

DR. SOLLER: I'm not aware of any.

MR. WOGALTER: I'm not aware either, at least as specifically as you've stated it. There are studies that have looked at auditory -- speech versus the printed information. And it depends on what the information is. If it's a complicated message, a long message, then that's better communicated via print as opposed -- and if it's a short message, easy to grasp, then the verbal -- the speech version is -- is sometimes found to be better.

DR. SPILKER: In terms of the question you asked, there are so may factors, even for a single pharmacist or a single physician, that I'd be very suspect about the data that they generate, just want to ask a lot of questions. For example, a physician or for that matter a pharmacist who's in a hurry is going to communicate differently than when they have enough time. If they have some personal interest, if they know the person they're talking to, if they're more empathetic, you know, I mean we can go on and on.

And so, to -- your question is a good one but I'd be -- I'm not aware of studies and I may be giving you one of the reasons why it's not easy to do that, because there are so many factors involved.

DR. DAY: Also, the extent to which pharmacists actually counsel is an interesting question. We heard yesterday about national boards of pharmacy having this be something that all pharmacists have to do and when a patient declines counseling they have to sign, "I decline counseling." But in fact, that part of the information is way at the top of the page. It's often on a clipboard, so the clip is over what that says there, and so people sign their name and the date, whatever it is. Most people believe they just signed, "I picked up this drug," and they don't know it's anything about counseling.

I stand in pharmacies and watch the extent to which pharmacists talk to patients. It's not very frequent.

DR. SWEENEY: One last question for me and then Dr. Marshall has a couple. Are there any companies manufacturing over-the-counter products that are using or contemplating using the voluntary pictograms?

DR. SOLLER: I'm not aware of a relation to the drugs that we've been talking about at this meeting.

MR. MARSHALL: During the session we've mentioned the Spanish-speaking population several times, and I was just wondering if you could tell us what sort of studies have been done on the cross-cultural effectiveness of warning symbols or --

MR. WOGALTER: Well, there really isn't that much on the topic. We've done a few because I've had some graduate students who were interested in that. We do have a recent grant that has -- but it's dealing with agromedicine and farmers and communicating things in Spanish or other means to migrant workers. We've done just -- I mentioned some pictograms earlier. They were just simplistic pictographs, and we asked them how hazardous these pictograms connote to you? They were kind of general pictograms: skull, the triangle-exclamation point symbol, and "Mr. Yuck" and so forth.

It turns out that the skull is recognized as being a hazard symbol but there is, I guess, another kind of anecdote that's described in a book that is kind of a reading book in human factors where they use the skull and crossbones. And the United States had put some skull and crossbones on some grain that was sent to, actually, Iraq to the Kurds and it had mercury. It was red-dyed. They weren't supposed to eat it. That was the idea, just for planting. And they discovered that they did eat it -- eat that because there were some droughts and things like that. And they asked them, you know, "What -- what about this skull and crossbones? Didn't you know what that was?" And they just said, "Well, it just seemed like a nice American symbol." They had no idea what that was. It's just like a logo.

And so, there is the problem with the -- in other cultures. There have been things like face memory and things like that. It's sometimes difficult to cross the cultures. Now, there may be more in Europe because ISO, the International Standards Organization, vice versa, the name, they do require for the testing of their pictograms three countries, three cultures to find that the pictograms are acceptable.

MR. MARSHALL: Another -- Dr. Day, do you have anything to add to that?

DR. DAY: No.

MR. MARSHALL: Another sub-population that the Safety Board is interested in is the older driver population since there is a growing number of older commercial drivers. And there's been a lot of research, obviously, showing that there's perceptual and cognitive changes that are associated with aging. I was wondering if there was anything that we can do or that needs to be done to make drug -- drug labels more comprehensible to this population?

MR. WOGALTER: I recently presented a paper at the Human Factors and Ergonomic Society in October and we looked at over-the-counter drugs and some different formats. It's kind of the older format that were out there. And we looked at size of print, white spacing. We looked at whether extended labels -- that is, fold-out labels so there would be some more information put on it. And we did a couple of different tests. One was subjective impressions, "Which do you like better?" And we also did a comprehension type of study where we handed the -- these containers that were manipulated on these dimensions.

And when the print was something like four point font or so we handed it to them. A lot of the older adults couldn't get a thing out of it. We even gave them questionnaires and they could look at the label and they were not able to get anything out of it. If it was seven point font, then they were able to get information out of it and you have a larger size there. So, you do have to be concerned about the size.

I think in the new labels there is more of a minimum size, around six or something like that, or at least that's the recommendation, which may be okay.

DR. SOLLER: That's right. There's a six point -- I don't know any studies that would specifically address an in-use situation a pictogram on an OTC label. There are studies -- where a co-worker looked at the lower literacy people and how -- on a variety of pictograms. Found a fair amount of miscomprehension.

But one of the things to think about that was -- hadn't really thought about it over the last two days, but dealing with the issue of pictograms, type, size, font, et cetera remind me of this. And that is that as you take these pictograms and start reducing them and you have a complicated picture that you're trying to convey in that, I think there is an issue that would relate to how easy it is to discern what is actually going on in that pictogram if you have -- and how low you can go. And that does impact, of course, then how large you want to make it, thereby impacting white space, amount of information that's not on the label, and believe it or not, that's extremely important in order to make people want to read the label. It's a lot -- you're more attracted to the diagram on the right side of the slide I showed than the one that's just one big, big paragraph. That looks daunting.

So, these are important issues when you start filling it up with a large pictogram so it's not going to be -- soon you're at a label where -- level where it's understood and you still have some of these other acuity issues.

MR. MARSHALL: So, were any focus groups or any field tests used to create the drug facts label that involved these sub-populations?

DR. SOLLER: There were studies that were done by FDA and there have been label comprehension studies and in-use studies with the label comprehension format -- the format that was developed through a label comprehension study that have been part of our -- switch applications that FDA's reviewed. I think in this room perhaps Charlie has seen more than anybody else in terms of those types of studies.

DR. ELLINGSTAD: Okay. Thank you.

Before we go to the -- the panels, most of this discussion has -- has focused on sort of a uni-dimensional, textual kinds of messages. A little bit of Dr. Day's discussions of pictograms sort of hinted at using more than one dimension but particularly redundant or partially redundant codes. Would any of you care to comment on that? And particularly, I'd be interested to know whether there has been any kind of a systematic examination of the benefits of -- of redundant coding, either fully or partially redundant coding? Start with Dr. Day.

DR. DAY: Oh, there's a lot of research outside of this content domain. So, if you repeat something more than once, learning and memory go way up. Repetition effects. There's hundreds of experiments on this.

The idea of having alternative representations of the same information is a powerful tool as well. And the tool coding theory I mentioned before, having linguistic and pictorial information, was developed by Allen Pavio, and there's hundreds of studies on that.

My own research has looked at alternative representations of the same information in a variety of content domains, and within the drug domain just the extent which people know what the side effects are after they read one of the pharmacy leaflets or the PDR, there's a tremendous information overload. So, in some of the drugs you might have as many as 52 side effects listed even on just the little in-the-bag pharmacy leaflet. And what we do is we ask people afterwards about how many side effects were on that leaflet? And they'll say, oh, about seven, and there were 52.

So, over and beyond knowing what they are, they're not picking up on what the information is. But if we take and then ask them to re-recall what they are, they can't remember many. But if we use more and more sensitive tests, they can pick -- we seem to pick up some information. But if we take and go away from the traditional ways of displaying the information and display it more spatially -- there is a series of fans and tree diagrams that people have never seen. They're unusual. But we can increase the ability of people to not only learn and remember but to know what to do if they got a side effect by 80 percent. And so, that essentially means a decrease by 80 percent of errors that people will make if they get a side effect: going to the ER when they shouldn't or not seeking medical -- medical attention when they should.

And these effects occur in providers and professionals as well as patients. So, we study doctors and pharmacists and providers as well. And although their overall performance is higher, they have more prior knowledge, the differential effects of alternative ways to display the same information is very powerful. Everyone benefits from some kinds of displays as opposed to others, which tells us something about the way that mental processes and cognition in general works.

So, yes, repetition. Yes to multiply ways to show information. But not all ways are good ways.

MR. WOGALTER: I agree with Dr. Day. There is quite a bit of research on multiple modalities. When you give them voice and print or pictorial and print, basically what the results say is that if you have both it's better. And it depends on the experiment which one of the individual, whether voice or print or pictorial of print, is better when you compare the single modality.

Also, on -- in the ANSI standards that I mentioned earlier, which are kind of a broad standard not necessarily for pharmaceuticals, they -- they include some redundant cues in their warnings. For example, the word "caution" is supposed to have a yellow background, so that's an extra thing. Or "danger" has a red background. So, that's just extra cues.

And people may miss one modality, as we know, and -- and pick up on another, so they may get information from their doctor but not read the label or not -- because they're sick or what -- the doctor doesn't give the information the way they understand. They might -- from the labels. Generally, more is better.

DR. ELLINGSTAD: Dr. Soller, in any of the work that you have done have you considered redundant coding? The color example is a good one in that other contexts, in displaying cockpit information or whatever, that kind of -- of redundancy within the -- the visual mode has been effective. Have you looked at it in this context?

DR. SOLLER: I'm not recalling -- I don't believe there were specific comments suggesting -- from outside parties that suggest that during the development of the drug facts label.

I would come at it from this standpoint, if I might. There are -- there's information that is suggested that there might be benefits on one side. We're aware of those. We look at how the drug facts label was developed and we consider that there are more disadvantages than benefits to pictograms in this area. And on coloring, it would be a similar sort of distracting mode. For example, if you had the warning section in yellow and I think there -- I think Giant, for example, did that for a number of years until the drug facts labeling came through. That is a -- that's something that draws your attention right to the warnings.

In terms of how we think how people should select the products, making sure that they don't cross dose, take the ingredient that contains one ingredient, picking up another product and taking that product that has the same ingredient, it's important to have the first actives first. Uses. That's how they're selecting. And then to go through the warnings. So, we think that there's a sequential -- I'll call it "coding" -- but a sequential acquisition of information that should be done. Putting colors or pictograms within the warning section we think would be distracting and take away from --

DR. ELLINGSTAD: Okay. But that's not based on empirical data? From what I'm hearing, this is a judgement that -- that someone has exercised that it's not based on some empirical findings. Is that --

DR. SOLLER: In terms of --

DR. ELLINGSTAD: -- a proper --

DR. SOLLER: -- deciding what the order of information should be, that -- I'm trying to think back in terms of the studies that FDA did in terms of different ordering. I believe that there is studies -- I think it was called Study A that was part of the drug facts rule that looked at different ordering of information. So, there is some empirical information that would support that.

Now, relative to the coloring, no, I'm not aware of any. That yellow box, for example --

DR. ELLINGSTAD: Dr. Spilker, are you aware of any?

DR. SPILKER: You would not find these, that I'm aware of, with prescription drugs. I think that -- I'm sure there may be some exceptions, but really, I'm not aware of colors being used.

DR. ELLINGSTAD: Thank you.

We'll go to the parties. Let's start with the Pharmaceutical Industry group.

MR. BRADLEY: I'm Bill Bradley with the Consumer Healthcare Products Association.

I thought it was very interesting that both Dr. Wogalter and Dr. Day made recommendations that have now been included in the new drug facts labels, such as chunking, bullet points, and so forth that do increase comprehension and make labels easier to read.

I don't know how to turn this into a question. Dr. Day's presentation seemed to show that consumers are most alert about drowsiness as a side effect and that may have something to do with the sometimes discrepancies we've seen in theoretically how things like antihistamines should perform and how they actually do, which they seem in actual life to perform much better than they would in theory. Do you have any comments on that?

DR. DAY: The study that I reported did not classify medications by OTC, prescription, or any indications. That study was very general. It was embedded in questions about a wide variety of products. And for that particular -- what are some common side effects of medications. And I think it did say prescription medications. And we have studies in the works now which do say "over-the-counter medications" and "safe or antihistamines" and -- or "anti-depression drugs" and so on, so we'll know a little bit better. But that's just what is off the top of the head when you ask them about side effects and medications in the same sentence.

MR. BRADLEY: Thank you.

DR. ELLINGSTAD: Thank you.

The Professional group?

MR. DROBNICH: Yes. I just have a -- a basic comment. I want to clarify the statistic that was thrown out from NITSA. I guess if I had a warning label it'd be warning "Don't cite NITSA statistics about drowsy driving."

I want to clarify that. When NITSA did that study there was 10 states that did not even have fatigue on the police accident report forms. So, if you look at international studies and at population surveys such as the National Sea Foundation's, five of the last six consecutive years 50 percent of Americans surveyed said that they've driven drowsy in the past year. One-fifth have actually dosed off at the wheel. And 23 percent said that they actually know someone who's had a crash in their lifetime due to falling asleep at the wheel.

Now, with that said, we still don't know what medications is part of that -- that drowsiness or fatigue or drowsy driving.

But if you look at international studies, 10 to 20 percent of the crash problem has been attributed to drowsiness.

So, I just wanted to make the point is if you're going to use the statistics as a consideration when prioritizing what goes up on the label make sure that we have all the -- all the information.

DR. SOLLER: Oh, I -- I take your point. I'm -- when I started off with the umbrella I was funneling down, and I could -- relative to the point I was trying to make and what we understand in terms of contribution of antihistamines based on the epidemiologic studies.

I would still stand by my point and take your clarification relative to the broad statistic -- gets us into that discussion.

MR. DROBNICH: Right. Absolutely. We have no idea, really, that I know of of studies showing how much sedating medications are part of that drowsy driving problem.

The -- the caveat to that is we know about two-thirds of Americans don't get proper sleep. So, if you imagine the interaction between sedating medications and underlying sleep debts, it's a much larger problem. It's like people walking around if they drank two beers a day and then take a sedating medication. And we do know that when people take medications it's often because of a cold or a chronic illness that may be contributing to an already sleepy state.

DR. ELLINGSTAD: Thank you.

Let's go to the Union group.

MS. HEAD: No questions.

DR. ELLINGSTAD: And the Transportation Industry?

PARTICIPANT: No questions.

DR. ELLINGSTAD: The Advocacy group?

MS. TARNEY: The first question's for Dr. Soller. Are you aware that highway authorities have moved strongly to the use of symbols and signs in lieu of word messages for many sign legends because of improved driver comprehension and with no adverse liability impacts on state departments of transportation?

DR. SOLLER: Yeah. The issue of something like "stop," which is sort of an all or none. I could see where moving to a legend and as we have that in terms of what becomes a necessary shorthand and a very quick information acquisition moment is an important thing to do. But where you have the label and the ability to read the label and take the time to read the label as you should we think there should be full conveyance of information and that the message should be, "Read the entire label." That's a very important public health message to be sure that we don't short-circuit.

MS. TARNEY: Our experience in -- in -- the kinds of questions that we get on our Web site often relate to questions regarding the side effects of medication, particularly on driving. And often that information is on the label already, which leads me to believe that people don't take the time to -- to read a whole label or the picture of a mother shopping with a couple of kids and she's trying to decide which over-the-counter medication to pick, and I think what she's looking for is a quick reference to the kinds of questions she might have. "Will this impair me?" And I'd like somebody to address those kinds of issues.

DR. SPILKER: I'd make one comment on that, although this is not just for prescription drugs. And that is that the individual variability is so enormous and we heard, which I totally agree with, that if any of us are sleepy or sleep-deprived for a number of hours, that's going to influence our reactions. Possibly, if you're taking other drugs, if you've just had a full meal, if you've had some alcohol, depending upon your mood, it can go on and on. For one individual let alone a lot of others, yes, it would be nice to be able to do that, but these are medically less feasible than we would wish for.

MS. TARNEY: I think we're trying to breach a wide gap between what is -- what is medically sound and what the non-medically-educated public will often want to look for and think is sufficient to keep them safe.

DR. SPILKER: Well, no, there is another issue we haven't brought up which really relates to the gap you're talking about, and that's liability. For the companies to go out and say, "Well, you know, really, this product hardly ever causes it," and this and that, drowsiness, so let's just say this is fine or let's go the other way. I think you get to the point that companies have to be concerned about liability issues and that does enter into this in different ways, I mean not just one way. And it's unfortunate, but I think that's one way -- one reason why companies are certainly going to be less willing to be crystal clear as you would like to see or the consumer would like to see when they shop for a product and they're picking up two things.

So, when the FDA is class labeling and the FDA has certain types of organization for data, we in the industry think that that's -- creates more or less a level playing field. It protects us as well as I think providing, Bill said, enough information so that when someone reads it they can get the information they need. Unfortunately, as you rightfully say, people want a real quick way to get the information.

MS. TARNEY: What happens to the liability issue, like, for instance, use the example of somebody's gone to the emergency room and the physician may say, "Go to the drug store and buy some Benadryl." And so now they've had a referral from a medical authority and they're not going to bother to read the label. What happens to the liability issue in that case?

DR. SPILKER: I think it kind of depends upon what happens --

MS. TARNEY: Well, assuming --

DR. SPILKER: -- situation.

MS. TARNEY: -- that it's not a good outcome.

DR. SPILKER: Well, of course. I mean -- well, I shouldn't say "of course." Benadryl may be the right product and maybe that person is being driven to the pharmacy by their spouse or someone else, they get the Benadryl, and it really doesn't work as the physician intended.

MS. TARNEY: I guess I'm assuming that they did their own driving.

I'd like to ask one further question. Often people comprehend or see when they say "Do not operate with heavy machinery," they see that as a forklift or a tractor and they don't separate that out to a motor vehicle. Is there any objection or recommendation to adding "motor vehicle" to "heavy machinery"?

DR. SOLLER: If I could comment on that, that was a discussion within the development of the final monograph for OTC antihistamines. And I believe the first recommendation in that development was to use "heavy machinery" and it was FDA's determination that it should be "machinery" and "motor vehicle" does appear in the label.

DR. DAY: And I'd like to add to that that as long as the word "driving" is there the first thing that comes to people's mind is a car, and I don't think you need to specify that. So, you can leave in the "machinery" to then occlude everything else.

DR. SPILKER: But I personally react exactly as you do to the word "heavy machinery." I like the word "machinery" and take the "heavy" out.

DR. SOLLER: That's -- that's where it is.

MR. WOGALTER: I think that part of the problem is getting people to read the labels, particularly for OTC drugs. I -- I think that a lot of folks think that after seeing advertisements and the fact that they can get it without a prescription, they just generally think that they're safe. And we -- we're now in the transition from what I consider to be pretty bad labels on lots of products into much better labels. And I think that now when they're more attractive we may get some more people to read it.

There is a down side with standardizing these labels, is that, at least in psychology, you have the habituation phenomenon where they may be looking at some labels for one kind of drug or a few kinds of drugs and then they come upon one that is still an over-the-counter drug but looks the same, basically, and then decide not to read it, it's safe. So, it -- it's -- there -- there are certainly benefits in being able to locate the information, it's easier to read, but I kind of am worried that there is going to be some situations where people said, "Well, you know, it's the same old label and I don't need to look at it any further."

DR. SOLLER: I do have a question for you. We've done surveys over quite a number of years and typically people report that they do have a very high -- majority of people report that they do read the label before using the product the first time. I wasn't quite sure in your comment on downsizing -- did I hear that?

MR. WOGALTER: Down side.

DR. SOLLER: Down side? I'm sorry. I misunderstood. I beg your pardon.

But I think that is an opportunity that the drug facts label offers in terms of the kind of educational programs that can help them present this more attractive label in a way that is conveying that message --

DR. ELLINGSTAD: And the Government group?

MR. CLARKE: I just have one quick question. In either prescription or over-the-counter drugs, are any -- any of these warning labels under any circumstances say, "Do not take," for example, pregnant or any -- any set of --

DR. SPILKER: I believe that that's the distinction between precaution or warning and contraindication. Contraindication by its definition means "do not," and then it's usually "Do not take if you are," for example, pregnant. But you have a -- the way to think of this, quite frankly, is just as a simple hierarchy. So, you go from the contraindications and precautions -- warnings first, thank you, and then precautions, and then adverse reactions. And so, that's the way the physician certainly will look at this.

But in terms of the professional labeling, if you have labeling for patients they will not use those words in general but a pharmacist in those companies that make it up will say, "Do not take if you," bum bum bum, and then give some other -- through some other English words try to convey the distinction between something that's a stronger warning or a precaution and something that's been a reported side effect.

DR. SOLLER: If I -- oh, go ahead.

DR. DAY: I was going to say, and in some cases you will see "Do not take if you are," blah blah blah blah blah blah, "without consulting your doctor first." And so, sometimes people will say -- if you read the first part you toss it back on the shelf or get it home and then not take it. So, sometimes there's a warning that starts out one way and goes another way. And Johann de Gier from this morning has some examples of -- of those where within the same warning it's strong one way and then it takes it back later. So, I don't know --

MR. CLARKE: I mean even that -- even that sometimes can be better than -- than careful.

DR. DAY: Right. Exercise caution. By the way, some of the people in our studies when it says, "Use caution," they did not think it meant "Do not." They were going to do it anyway but they were going to be more careful. And you know what people do when they pay alcohol, they want to be more careful, they'll drive more slowly. Too slowly sometimes.

MR. CLARKE: Dr. Soller?

DR. SOLLER: Yeah, I just -- I had a brief comment. The OTC review began in 1972. That is some 30 years ago. And there is a huge information base and experience and policy base within the many "Federal Register" publications that came out of that.

An important aspect here is you think about what is behind the drug facts label is that the basic warning policy is that OTC warnings should be scientifically documented, clinically significant, and important for the safe and effective use of the product by the consumer as a base. And then as that has developed over the years to have a science base for what would go into the warning section, we now have the drug facts label that begins with, you know, in a kind of standardized way the absolute contraindication "Do not use." And there are "Do not use" warnings -- immediately come to mind right now and it doesn't matter, but -- specifics.

The second one is the relative contraindication, which is ask a doctor or ask a pharmacist before use if -- and there's a drug interaction section that basically is along those lines.

And then the next piece is in-use precautions, which typically will have embedded in there what might be emergent signs and symptoms as a person's taking care --

So, there's a very --

MR. CLARKE: So, there is a -- there is a category, though, of --

DR. SOLLER: Oh, yes. There's a category and there's also a -- what I wanted to share was that there is a very -- very strong policy base for how warnings are developed and put onto OTC labels.

MR. CLARKE: And I guess there's a hierarchy of concerns as to whether or not it goes in the "Do not take" or the advisory or the warning --

DR. SOLLER: Based on the science and in -- yeah.

MR. CLARKE: Thank you.

DR. ELLINGSTAD: We had another question from the Professional group?

MR. GELULA: Yes, thank you. For the panel, I'm curious. Is there any research about the effect of warning labels when a consumer or patient is uninsured, which is a condition of many non-unionized commercial drivers, and they may not be able to afford the optimal medications such as a non-sedating antihistamine? Will they heed or ignore the warning label?

MR. WOGALTER: I don't know of any research on that topic.

DR. SOLLER: I agree with Dr. Wogalter.

DR. DAY: As do I.

(Laughter)

DR. ELLINGSTAD: Thank you.

This has been a very efficient panel and you'll notice that we're a bit ahead of schedule. We do have a number of questions from the audience which Dr. Galson will -- will give to the panel in just a second, but what I would like to do is -- is alert the -- the various groups at the tables here that we will have an opportunity for a very brief comment. It doesn't need to be lengthy, unbridled sort of a thing, but we will be able to -- to make a pass through all of the groups before we adjourn, and if you have anything that you would like to say you'll have a few minutes to do that.

So, we'll -- we will -- you can be thinking about that while Dr. Galson gives the -- the questions from the audience.

DR. GALSON: Okay. The first one to the panel is, have studies shown that people ignore the "Use caution while driving" if they don't feel drowsy? We sort of touched on this but is there anything more you want to say?

DR. SPILKER: I want to comment about that, that many times whether you're taking prescription or over-the-counter products people have very simple mechanisms for avoiding drowsiness while they're driving. And that is they can speak with their spouse or someone else in the car, turn up the radio, sing, do all sorts of things to overcome or, you know, just be, you know, thinking about different problems, working it out. I think everyone has their own methods. But these methods I've noted anecdotally and -- with a number of people are ways to overcome them.

DR. GALSON: Any other responses to that?

DR. SOLLER: You asked for studies? I'm not aware of studies.

MR. WOGALTER: There's a general principal in the warnings research that if people perceive that the information is irrelevant to them they'll just skip over it.

DR. GALSON: Okay. The next question is sort of -- it's two parts. I'll read them both. The first is, do consumers read the entire label? We sort of touched on that. The second part is, after hearing yesterday's presentations on the disconnection between drowsiness and impairment do you think the need to find a way to explain this to the consumer -- in an upcoming label suggests that if you don't feel drowsy you won't be impaired?

DR. DAY: In many of the things that I reported today we just don't find that people have that causal link. Now, if you specifically ask them about it, ask them to reason it through, they would probably come to it, but it's very low in the cognitive deck. It's not at the top of the deck and they don't pull it out and substantiate it in everyday life.

DR. SOLLER: I answered that in part earlier but I would also say based on how we track our postmarking surveillance of our products and as we look forward to the promise of the new drug facts label, we think we're on target.

MR. WOGALTER: The first part of the question dealt with reading the entire label and just -- just a comment. Teaching at a university I have students come to my office and say, "I studied this material, I read the material," and they get a D. And so, when people -- if you were to get from a survey, "Did you -- do you read the entire label?" it may not be an accurate assessment of whether they got the information out of it.

DR. SOLLER: Just a comment. The experience with label comprehension and actual risk studies that would put that label on study into actual use has been part of the -- improvement process for -- in the '90s. And at least as far as I know, the experience with those products has been extremely good and I think that's -- that label. And the playoff on that is the development of the drug facts label for all products.

DR. DAY: I'd like to just comment that our XOTC switch process required the comprehension of -- is really wonderful. It's very nice to have that. I do think there are some drugs that haven't made it to the switch and it's partly because of whether people really understand the information. That may not be the fault of the format, however, as opposed to complexity of some of the drugs and what a consumer needs to understand about his or her own age and other health conditions in order to make the decision. So, not all drugs that have tried to go through the process -- prescription and OTC have made it partly based on comprehension. It wasn't necessarily related to --

DR. GALSON: Okay. Next question is addressed to Dr. Spilker in particular, and it says, does the package insert report the extent to which performance deficits have been found in -- psychomotor studies or the extent to which abnormalities have been demonstrated on physiological studies such as sleep studies? The FDA folks may be wanting to answer that.

DR. SPILKER: That's what I was going to say, that I'm sure the FDA group here would be in a wonderful position to chime in.

I think the first part of the answer has to do with the clinical significance of those studies. Keep in mind when a pharmaceutical product is tested during its investigational clinical trials, there are often up to 100 -- the average is supposed to be 68 clinical trials. Many, many endpoints measured, many tests, parameters measured, and there are often, for a variety of reasons, clinical -- well, sorry, statistically significant differences found between, say, one drug and placebo or active drug control or usual therapy.

And the question for both the company and the FDA is which of those differences are clinically significant and therefore are deemed important enough and relevant enough to be put in the label? I would imagine that for the most part in terms of the specific question there would be concurrence between FDA and the pharmaceutical manufacturer. I would imagine that when there were differences of opinion these would be discussed and an agreement reached and then when -- so the answer really is when it is relevant this information would be put in the package label.

Having said that and having read many package labels, I would say it is not very common that this specific information that the member who asked the question posed does make it to the label, and the conclusion would be that any differences would have been considered minor, mild, or not clinically significant if they're not present.

DR. GALSON: FDA want to add anything to that?

DR. TEMPLE: Only that while some labeling sometimes has the -- the qualitative statement about what the result was, say in effect on sleep latency, Sonata for example has statements that the next day nothing could be found on the following test. We've never actually put real numbers in like how much degree of impairment was largely because we don't think it would be easy to interpret. If -- if there ever were something that were readily interpretable I suppose we'd be willing to use it.

We actually haven't so far put in the results of driving tests. Again, with apologies to Dr. O'Hanlon, but the -- because we weren't sure that told you more than the fact that the drug -- that the drug makes you sleepy. I'm not totally sure that's true but that has been the position up to now.

DR. GALSON: Okay. Next question is about a specific kind of label. Dr. O'Hanlon showed pie charts that indicate the time course of sedation. Does the panel feel that this would be helpful to prescribers and consumers? These were pie charts, three colors. Red was one to four hours, yellow five to eight hours, green nine to 12 hours.

DR. DAY: I regret I wasn't here and didn't see it, but I think the coloring in and of itself is probably not the way to do it. If there would be a pie chart or anything else with an arrow and differential length of the arrow, that might be more effective. So, there might be some pictorial way to do it but I don't think color would do it. More color we put in for more different reasons and so on, it just gets confusing. But if you had, like, a full day as your circle and you had the arrow just went a little bit versus one that went a long way, that would probably be more --

DR. SPILKER: I'd like to comment that I don't think that a pictograph is the way to go with this. But I commented yesterday I think that this is important information if it is obtained and it is relevant to put in the label so that people understand what is the expected range of duration of effect on driving or other symptoms when they're deemed relevant. I think his data were quite important.

DR. SOLLER: Just a comment. I remember that they had red and green, if I'm remembering the circle, and I would just ask, you know, I hadn't thought about this before but you've got color blindness to consider yet again. And so, you know, some of these things seem like good ideas and then you kind of delve in and they eventually have limitations.

DR. GALSON: And the last question is driving and heavy machinery was mentioned on warnings. Was any thought put into operating aircraft and/or operating boats? We sort of talked about that.

DR. SPILKER: I would assume aircraft and boats come under the category of the machinery, heavy machinery. I think perhaps another term could be found involving transportation. I mean I think that'll be confusing too unless one can -- you have to draw the line somewhere. And if people say, "Well, I know I'm not going to operate a forklift, I'm just going to take out my F16 today, so" --

(Laughter)

DR. SPILKER: I mean you have to hope that people are wise enough to realize that even taking out a recreation boat with a motor does count as machinery.

DR. GALSON: Any other comments on that?

DR. SOLLER: I agree. I don't know that I would have done the F16-forklift analogy, but I --

(Laughter)

DR. DAY: I agree for a slightly different reason. If you put "heavy machinery" in then people might not think of chain saws because they're not heavy. So, I think just "machinery" without any adjectives.

DR. GALSON: Okay. That's it for the questions.

DR. ELLINGSTAD: Thank you.

The Technical Panel, do you have any more? Last chance.

DR. TEMPLE: Okay. Just -- just one. This has come up before. A lot of labeling says use -- you know, "Use caution if you're operating heavy machinery." We have collectively here reached the conclusion that that's meaningless gibberish. I wonder what you all think about that? We -- we can't figure out what a person's supposed to take from that. Do -- does it mean do it carefully, think about doing it, and we're fully resolved not to use that terminology anymore. I just wondered what you thought.

DR. DAY: The answer to your answer is yes, people take all of those possible meanings.

DR. TEMPLE: Which means it's meaningless gibberish, as I suggested?

DR. DAY: Not necessarily meaningless gibberish but differentially meaningful with lots of interpretations and behaviors. So, therefore, let's try to narrow the --

DR. TEMPLE: I'll buy your correction but it doesn't transmit very well. That's really --

DR. SOLLER: Well, I -- I'd make the comment, if I could, that "use caution" has been used in other product categories. It's used in the -- to separate dermatitis, eczema, monograph. It's used with the OTC stimulants, caffeine for example. The allergy, anti-emetic. So, it's used in a lot of different categories.

DR. TEMPLE: Is it clear what it means in each of those cases?

DR. SOLLER: And -- and I think that from the standpoint of looking at how the label is constructed where it says when using this product that you are potentially going to get this particular side effect, it may occur in terms of how this was constructed and how this was thought through. And then, in a separate section that says "use caution," I think when you put that together that there is a reasonable expectation that the consumer is going to do the right thing.

And we looked at that. We considered that and put that in relation to the evidence that is at hand to suggest that maybe this is not working. And I don't think we have it. So, we conclude that we think the label as it was constructed has been doing a pretty good job. We'll actually do a better job with drug facts labeling.

DR. TEMPLE: I guess I think you're posing a different question. Whether this is as big a risk as some people think it is is worth discussing but if we can't tell whether it means -- think about getting someone to drive you or pinch yourself a lot or open the window and sing a lot or -- or whatever those mechanisms, which I can assert do not work because I have a lot of trouble at three in the afternoon and those things don't help me at all.

DR. SOLLER: Well, I can tell you --

DR. TEMPLE: I think if you can't figure out which of those things it is, it's not communicating very well.

DR. SOLLER: Well, I can tell you I think it does. And I think it does because you're informing the consumer that marked drowsiness may occur. And if that occurs -- so use caution when driving motor vehicle or using machinery if that occurs. The very implied meaning is stop what you're doing or decide that you're not going to do it to begin with.

DR. TEMPLE: But -- but in some ways that's -- that's the point. It could say, "If you're very drowsy, don't," which would be one intelligent possibility, leaving aside the question of whether you do get appropriately drowsy as a signal. It could also mean do it -- be unusually careful with this F16 while you're using it, whatever that means. Drive it slow.

DR. SPILKER: Well, I have a --

DR. TEMPLE: Go extra high.

DR. SPILKER: I have a possibly slightly different take on this. I do agree with you that it does not convey much information. I think when you look at it the biggest problem is the word "heavy" in terms of heavy machinery, but why not say what you really mean? What we mean is the risk of accidents may be greater when you're taking this drug and you can describe what kind of accidents. But if you say something to that effect, you know, people understand -- that's -- that's the message, isn't it?

DR. TEMPLE: Well, that would leave the person free to decide how much they're willing to accept and --

DR. SPILKER: Exactly.

DR. TEMPLE: -- accidents, which at least makes sense. But "use caution," --

DR. SPILKER: Well, I mean --

DR. TEMPLE: Obviously, people can disagree on this.

DR. SOLLER: Yeah, and I stated the view that as we put this together with the experience in terms of the post-marketing surveillance and the idea that it is even better placed, provided my opinion in terms of thinking that it's doing the job.

MR. WOGALTER: I think it's an empirical question. I think that you need to give that original statement, see what people are coming up with. If it isn't what you intended, then try some more explicit statements.

DR. TEMPLE: I think we use it because we don't quite know what we intended. We're somewhere between saying, "Oh, really? Find someone else to drive you there," and you know, "Pinch yourself a lot." And we haven't really thought about it enough yet, but I'm sure we will.

DR. SPILKER: Well, I hope that when you --

DR. TEMPLE: With Bill's help.

DR. SPILKER: I hope when you think about it you consider at least saying what it is we all need, which is that the risk of accidents may be higher when you are operating machineries.

DR. TEMPLE: That has clarity.

MR. MARSHALL: Yesterday we -- we discussed several drugs that have caused or result in multi-fold increases in risk if taken and if the person drove afterwards. So, the question comes up is there any labeling on any drug that actually says, "Do not drive"? Would you know of any of them?

DR. SOLLER: Yes, I think there's prescription drugs. I don't have them off hand, but as I recall going through the PDR that I remember seeing that. But I don't -- I can't -- you have that information?

DR. SPILKER: I don't mean to be facetious and I don't mean it that way, but if you are having IV barbiturates or others, you know, obviously you're not going to be driving. And I think that there are a lot of things that, you know, it's not necessary to say it because people are not taking it. I defer to FDA to say if any traditional -- for example, if you're taking heavy sedatives or barbiturates, I mean do barbiturates say this?

DR. TEMPLE: We don't think they -- there's anything that says that absolutely, but we're not sure. We -- we don't know of any.

DR. ELLINGSTAD: Any final questions from the Tech Panel?

(No response)

DR. ELLINGSTAD: Okay. What we'll do now is -- is go and -- and provide an opportunity for each of the party groups to make any brief closing comment that they would care to make. Let's start with the Advocacy group.

MR. DONALDSON: I'm sure this is just a minor note struck in the symphony that we've heard for the past few days, but I just wanted to confirm Dr. Temple's remark and I'm probably almost certainly stealing the thunder from Darrel Drobnich over at the National Sleep Foundation. Pinching yourself, screaming at your spouse or friend in the car, opening the window, turning up the radio has an extremely fleeting alerting effect and drowsiness returns very, very quickly. And the only way to cure drowsiness is sleep, and unfortunately, a lot of people do it behind the wheel.

DR. ELLINGSTAD: Thank you.

Government group?

MS. TARNEY: I would --

DR. ELLINGSTAD: Oh, I'm sorry.

MS. TARNEY: I would like to make a recommendation that we do some further research and the combination of a written label with a pictogram with finding what the pictogram would be. I think there are -- still are a number of people that will not, cannot, and don't take the time to read a label or just are unable to. I think something -- even if a pictogram is not an ideal solution and I take the points that were made here this afternoon, I think something is better than nothing for some of those folks.

DR. ELLINGSTAD: Thank you.

The Government group, any concluding comments?

MR. CLARKE: First off, I'd like to commend both the FDA and -- and the Board for holding this hearing. This is a -- obviously been a -- it's a very complex subject, multifaceted, and not only in terms of determining when and under what circumstances drugs should or shouldn't be taken but also then what you do about it once you've made that kind of determination if such a determination can be made definitively.

In the -- the overall context that we've been discussing this thing which is the transportation arena, I just might highlight again the fact that we've been mixing and matching some of our discussions here. There is -- transportation is -- talked around has many aspects starting, obviously, in terms of modes but also in terms of population size of folks that we're dealing with and most importantly whether they're private or commercial operators. And -- and also whether or not -- and what levels of intervention, governmental intervention if you want to look at it that way, are available in those contexts.

Clearly, aviation -- commercial aviation is high on that list in terms of level of control. It's also in terms of commercial air transport operators of relatively small population, 100,000, thereabouts. We probably have less than that number, 50- to 100,000, I'm not exactly sure, locomotive engineers. We're dealing with thousands of transit operators and -- and mariners I'm sure it's on that order of magnitude whereas in the case of commercial motor vehicle operators we're talking 5, 6, 8, 10 million. I've heard different numbers.

The levels of control vary between highly Federal to practically no Federal in the case of -- of private motor vehicle operators. There is no direct Federal control of private vehicle motor operators -- private motor vehicle operators.

That's -- so, as we're considering this whole issue in total, I think we need to -- to keep in mind all those facets about how we would do anything relative to these various different populations in addition to the risks that may be associated with them and what those interventions -- what appropriate interventions are in each of those cases. Thank you.

DR. ELLINGSTAD: Thank you, Bob.

The Professional group, final comment?

MR. GELULA: Thank you. I will reiterate and agree that this has been a great meeting and we thank you all for pulling it together. I think in many respects it has also demonstrated that we're beginning in a lot of areas to find ways to recognize how drowsiness, whether it's caused by sedate -- sedating medications or other causes, is a factor in transportation and is a real concern.

I'd say from the Sleep Foundation's perspective sedating medications is an important issue but probably secondary to broader acts of omission rather than commission, such as general sleep deprivation that is pervasive in our society and has acute patterns in transportation. Issues of untreated sleep disorders as well as the interaction with sedating medications.

I'd say we -- there may have been something missing from the witnesses which might have been a scientist with a specialty in sleep to have introduced the interactive effect of sleep sufficiency versus sleep deprivation, the effects of sleep disorders, and the effects of circadian rhythms, particularly on shift -- shift workers, which is an endemic pattern in transportation industries.

Another point is -- that was made that I think was very important is that there is not always a signal of drowsiness prior to impairment. That's a special concern and why we need appropriate labeling.

We feel that the modal administrations in DOT are at this time all aware of drowsiness and sleep-related impairment, which given the relatively short history of -- of sleep sciences is -- is a significant advance. But to date there is not a sufficient priority given to this problem, resulting in a comprehensive and consistent high priority program. Education is a key. Labeling would only be part of the solution, so we need both together.

Finally, we think that labeling must be informed, and one example we would cite is the benefit -- potential benefit of short-acting prescription hypnotic medications for many people in the transportation industries who have to -- can only get sleep at times of erratic scheduling and in very unusual circumstances. Many times trucks with -- parked by the roadside with -- I think we have to take those circumstances into consideration and look at risk benefits and then form our labeling by them. Thank you.

DR. ELLINGSTAD: Thank you.

And the Pharmaceutical Industry, final comment?

MR. BRADLEY: We represent the manufacturers and distributors of non-prescription drugs, so our interest in this is on the over-the-counter drug side and that would be primarily the antihistamine as it relates to this hearing.

I think that we have seen over the past few days a lot of very interesting information presented. And certainly, one of the things -- yesterday we saw one of the panels unanimously agree that over-the-counter antihistamines did not seem to be much of a problem and we're glad to hear that. We also learned that indeed the Food and Drug Administration and our industry went in the right direction with the drug facts box, which makes the label easier to read and makes the warnings easier to find and makes them easier to comprehend due to the way that they're presented.

We also believe that any action that's contemplated further should be something that is shown to be needed on the basis of the evidence. It should be driven by data, not by anecdotes, and that anything that would be decided would be tested. Thank you.

DR. ELLINGSTAD: Thank you.

The Union group?

MS. HEAD: First of all, I just want to thank you all for putting together this meeting and in particular for inviting transportation labor to participate in this discussion.

My union represents transit employees and inner city bus operators and I think it's pretty clear that in both those industries there's a lot of confusion and -- about what is permissible and what -- what medications operators are allowed to take and continue operating.

I just want to say that we look forward to working with DOT and the NTSB and FDA in -- in taking steps to clarify and come up with some solid standards as to what it is our members can and cannot --

DR. ELLINGSTAD: Thank you.

And finally, our Transportation Industry group.

MR. MAHORNEY: I believe we all have short comments, but I'm Bill Mahorney with the American Bus Association. I think the things I've brought out of or at least that have really stuck in my mind the most out of the last two days is yesterday's panel that included the toxicologist that really indicated that therapeutic doses of antihistamines and some of these types of things are not necessarily a problem. Where the problem is is the improper use of some of these medications. You know, that could be anything from using when you're tired already to mixing them with the wrong kinds of other medications.

So, it seems to me that the way we get the most bang for our buck on this type of thing is education. And for commercial motor vehicle drivers, which is the folks -- what we at this table are concerned about is our drivers, is twofold in my view. One is educating the physicians who perform the examinations, whether that be a certification process, which we support. Maybe not necessarily something that is as in-depth as the FAA but certainly some type of certification and/or education program for those doctors that would include this type of information that they could convey to the drivers when they come in. Give them some basic information about what types of medications you should be very careful when you're using.

And the other thing is -- in my view is labeling of the medications themselves, of the OTC medications. You know, pictograms, of course, you know, intrigue me quite a bit but I think the bottom line is whatever we can do to make the label as clear and concise as possible in order to eliminate any possibility that whoever's taking that doesn't know what the side effects could possibly be is the way to go. Thank you. And thank you for -- for inviting us here.

MR. LITTLER: Norm Littler with the United Motor Coach Association. And first of all, I'd like to thank the NTSB and the FDA for inviting us here. This is an issue that we've been very concerned with for a number of years.

And over the last several days I think we've learned a great deal. And one of the things that comes out to us first and foremost is this is a question of choice: consumer choice, informed choice versus uninformed choice. And what we're seeing is several problems being highlighted here, and one is, first of all, the prescribed medications that the healthcare professional would prescribe and the pharmacist would dispense. To back up my colleagues' remarks, education is most important. Ask the patient what they do. Determine the risks. And from that point, then you can make the choices as to whether to prescribe a prescription drug that will best fit in what that person does versus possibly recommending an over-the-counter drug.

That takes us to the next question and the much more difficult one of the OTCs. And where you have medication, where you have a situation where somebody is self-medicating, and when you go into a store to make that informed decision, labeling is absolutely important. But I think before that what we -- what we're seeing -- what I heard yesterday was the comment relating to television or radio advertising. And in certain prescription medications now where warnings on adverse side effects are being made on prescription medications. We see a lot of advertising for the OTCs but we don't see the same level of warnings going on them. I think that's something that we would -- we would recommend and we would like to see.

And the other thing, again going back to the media, I think that the -- the FDA, the Department of Labor, and the Department of Transportation jointly or individually could take the message out to the public through the media campaign on the simply message that there are dangers present or possible risks involved with a range of medications when you're doing certain things, either operating machinery, operating motor vehicles, or other modes of -- transportation modes or doing other things. And this would cross the bounds of transportation into all job functions or even your private time, personal time.

But I think the message could go out and that could be something that could be done relatively quickly and fairly easily. And that's all I have. Thank you very much.

MR. SPENCER: I'll be real short because I think -- Todd Spencer, Owner-Operators -- I think most of these issues I'm going to be covering either have been or will be.

But of course, from our perspective, education has to be the key. For commercial operators, generally education -- at least commercial truck operators, education and training are largely non-existent and that is something that should be fixed. And of course, when you approach the subject of education I think a reasonable person should assume that any -- any substance you take can have an impact, a safety impact on your ability to operate that vehicle. And of course, I don't -- there -- there are lots of things we could do and none of them will be perfect when it comes to labeling and instructions and things like that, but to start out knowing that there can be an impact and knowing that you should be looking for that impact before you take it should be key and we need to remind people to do that at every opportunity.

And of course, whether we're talking about over-the-counter substances or prescription substances, the -- the condition we're addressing here is alertness or the lack thereof, and that happens for many, many reasons. I mean just in recent years we've started becoming aware of all of these -- all of these degrees and things are involved in sleep and things like that, and circadian cycles are going to happen to everybody every day whether you take substances or not. You need to be aware of those things and the impact that that can have on at least your ability to drive a vehicle and I would assume fly a plane and for that matter sail a boat.

But the key things have to start with education, and I do thank this committee for holding this hearing because I think it's going to be a benefit.

DR. ELLINGSTAD: Thank you. I'd like now before we conclude to call on my colleague Dr. Galson to first of all give us some administrative information about where we're going to be able to find all of the information that has been assembled and to make any concluding comments from the point of view of the FDA.

DR. GALSON: Okay. In case folks in the audience or the parties or the witnesses feel like they haven't had the last word and you want to have -- communicate more to us, our docket on this issue is going to continue to be open until December 17th and you can submit written materials to us up to that date. The information on exactly how to do that is in the "Federal Register" notice. If you need details, talk to the FDA staff in the back of the room or as you go out at the table.

We've enjoyed this meeting tremendously. I want to thank everybody for the time you've invested in letting us be aware of your views, and we'll take what we've heard very seriously in -- in making any policy decisions in the future on this issue, so for the FDA, thanks a lot.

DR. ELLINGSTAD: Thank you. On behalf of the Safety Board, I'd like to extend our thanks to all of the parties who have participated and kept our -- our witness panels hopping, to all of the witnesses who have explored these issues. This is -- has been very -- very informative. To -- to the -- those of you that have come and watched the proceedings and submitted your questions, we also appreciate that.

I'd particularly like to -- to thank the folks from both the FDA and the Safety Board who have served on our Technical Panel and done all of the -- the real heavy lifting to get this -- this whole activity underway and to -- and to carry it off. At the risk of -- of -- of bruising any other egos, I -- I do need to -- to particularly acknowledge Mitch Garber for the -- the efforts that he has made.

Our -- our support staff, Carolyn and Mary, I appreciate that -- all of the work that you've done.

And Steve, appreciate the opportunity to work with you.

Thank you all very much. We will take the information that we've obtained from these two days. It's probably going to take us a little while to -- to weigh and examine it, but I think that it will have a beneficial outcome for transportation safety. Thank you all.

(Whereupon, at 3:27 p.m., the meeting was concluded.)