UNITED STATES OF AMERICA

 

            FOOD AND DRUG ADMINISTRATION

 

     CENTER FOR DEVICES AND RADIOLOGICAL HEALTH

 

                JOINT MEETING OF THE

                 DENTAL PRODUCTS AND

         EAR, NOSE AND THROAT DEVICES PANELS

 

                     + + + + +

 

                    OPEN SESSION

 

                     + + + + +

 

                     WEDNESDAY,

                   OCTOBER 6, 2004

 

                     + + + + +

 

 

            The panels met at 8:30 a.m. at the Hilton

Washington, D.C./North, 620 Perry Parkway,

Gaithersburg, Maryland, DR. A. JULIANNA GULYA, Chair

of the ENT Panel, presiding.

PRESENT:

 

  ENT PANEL:

    A. JULIANNA GULYA, M.D., Chair

    KAREN H. CALHOUN, M.D., FACS, Consultant

    R. MICHAEL CROMPTON, J.D., M.P.H., RAC, Industry

       Representative

    HERMAN A. JENKINS, M.D., Voting Member

    ERIC A. MAIR, M.D., Consultant

    LISA A. ORLOFF, M.D., Consultant

    CAROLYN R. STERN, M.D., Consumer Representative

    DAVID J. TERRIS, M.D., Consultant

    GAYLE E. WOODSON, M.D., Consultant

    SARA M. THORNTON, Executive Secretary


PRESENT (Continued):

 

  DENTAL PRODUCTS PANEL:

    JON B. SUZUKI, D.D.S., Ph.D., M.B.A., Chair

    B. GAIL DEMKO, D.M.D., PC, Consultant

    ELIZABETH S. HOWE, Consumer Representative

    KASEY K. LI, D.D.S., M.D., Consultant

    DANIEL R. SCHECHTER, ESQ., Industry

       Representative

    DOMENICK T. ZERO, D.D.S., M.S, Voting Member

    JOHN R. ZUNIGA, Ph.D., D.M.D., Voting Member

 

  FDA REPRESENTATIVES:

    A. RALPH ROSENTHAL, M.D., Director, Division of

       Ophthalmic and ENT Devices

    M. SUSAN RUNNER, D.D.S., M.A., Chief, Dental

       Devices Branch, Captain, USPHS

    ERIC A. MANN, M.D., Ph.D., Chief, ENT Devices

       Branch, Captain, USPHS

    HEATHER S. ROSENCRANS, Director, Premarket

       Notification Staff

    KEVIN P. MULRY, D.D.S., M.P.H., Dental Officer ‑

       Dental Devices Branch


                      I‑N‑D‑E‑X

 

AGENDA ITEM                                     PAGE

 

Call to Order                                      4

      A. Julianna Gulya, M.D., Chair

 

Introductory Remarks                               7

      Sara M. Thornton ‑ Executive Secretary

 

Conflict of Interest Statement                    10

      Sara M. Thornton ‑ Executive Secretary

 

Branch Updates                                    12

      Captain Eric A. Mann, M.D., Ph.D. ‑

            Medical Officer

 

FDA Presentation                                  19

      Heather S. Rosecrans ‑ Program              19

            Operations Staff

      Captain Eric A. Mann, M.D., Ph.D. ‑         25

            Medical Officer

      Kevin P. Mulry, D.D.S., M.P.H. ‑ Dental     45

             Officer

 

Open Public Hearing Session                       64

 

Panel Presentations                               97

      David J. Terris, M.D.                       97

      B. Gail Demko, D.M.D.                      115

 

Panel Deliberations                              145

 

Second Open Public Hearing Session               324


                P‑R‑O‑C‑E‑E‑D‑I‑N‑G‑S

                                         (8:39 a.m.)

                    CALL TO ORDER

            CHAIRPERSON GULYA:  I now call this joint

meeting of the Food and Drug Administration Center for

Devices and Radiological Health joint meeting of the

Ear, Nose, and Throat Devices Panel and Dental

Products Panel into session.

            I see we have a number of individuals who

are interested in today's meeting regarding the

prescription versus the over‑the‑counter use devices

intended to treat snoring and/or obstructive sleep

apnea.  And I am very appreciative of that.

            I think we will quickly go around the

table and perform introductions here, starting on my

left here.

            DR. ROSENTHAL:  Ralph Rosenthal.  I'm the

Director of the Division of Ophthalmic and ENT

Devices.

            DR. RUNNER:  I'm Susan Runner.  I'm the

Branch Chief of Dental Devices and the Deputy Director

of the Division of Anesthesia, General Hospital and

Infection Control Devices.

            DR. DEMKO:  Gail Demko.  I'm a consultant

to the Dental Products Panel.

            DR. CALHOUN:  Karen Calhoun.  I'm an

otolaryngologist at the University of Missouri.

            DR. TERRIS:  Dave Terris.  I'm a

consultant as well.  I'm at the Medical College of

Georgia.

            DR. WOODSON:  Gayle Woodson,

otolaryngologist, consultant, Southern Illinois

University in Springfield, Illinois.

            DR. ORLOFF:  Lisa Orloff, consultant to

the ENT Devices Panel from University of California,

San Francisco.

            DR. MAIR:  Eric Mair, otolaryngologist

from Wilford Hall in San Antonio, Texas.

            MEMBER ZUNIGA:  I'm John Zuniga.  I'm a

member on the Dental Panel from UNC, North Carolina.

            CHAIRPERSON GULYA:  Julie Gulya.  I'm at

the National Institute on Deafness and Other

Communication Disorders.

            EXECUTIVE SECRETARY S. THORNTON:  Sara

Thornton, Executive Secretary for the Ear, Nose, and

Throat Devices Panel.

            MEMBER SUZUKI:  Jon Suzuki, Dental

Products Panel, Associate Dean at Temple University.

            MEMBER JENKINS:  Herman Jenkins,

Otolaryngology, University of Colorado.

            DR. LI:  Kasey Li, consultant from

Stanford Sleep Disorders Clinic.

            MEMBER ZERO:  Domenick Zero, Dental

Products Panel, Associate Dean for Research, Indiana

University School of Dentistry.

            DR. STERN:  Carolyn Stern, family

physician, consumer rep for the ENT Panel.

            MS. HOWE:  Betsy Howe, consumer rep for

the Dental Panel.

            MR. SCHECHTER:  Dan Schechter, industry

representative for the Dental Panel.

            MR. CROMPTON:  And Mike Crompton, industry

rep for the Ear, Nose, and Throat Devices Panel.

            CHAIRPERSON GULYA:  Okay.  Thank you very

much.  Without further ado, I will turn it over now to

Ms. Sally Thornton, our Executive Secretary.

                INTRODUCTORY REMARKS

            EXECUTIVE SECRETARY S. THORNTON:  Good

morning.  On behalf of FDA, I would like to welcome

you to the very first joint meeting of the Dental

Products and Ear, Nose, and Throat Devices Panels in

the Twenty‑First Century.

            (Laughter.)

            EXECUTIVE SECRETARY S. THORNTON:  Before

we proceed with today's agenda, I have a few short

announcements to make.  I would like to remind

everyone here to sign in on the attendance sheet in

the registration area just outside the meeting room.

All public handouts for today's meeting are available

at the registration table.

            Messages for panel members and FDA

participants, information or special needs should be

directed through Ms. AnnMarie Williams, who is

available in the registration area.  The telephone

number for calls to the meeting area is (301)

977‑8900.

            In consideration of the panel and the

agency, we ask that those of you with cell phones and

pagers either turn them off or put them on vibration

mode while in this room and make your calls outside

the meeting area.  We strive to make this a cell

phone‑free room.

            Lastly, will all meeting participants

please speak into the microphone and give your name

clearly so that the transcriber will have an accurate

recording of your comments.

            At this time, I would like to extend a

special welcome and introduce again to the public and

the panel and the FDA staff new panel consultants who

are with us at the table for the first time:  Dr. Gail

Demko from the Dental Panel, Dr. Kasey Li from the

Dental Panel, Dr. Eric Mair from the ENT Panel, Dr.

Lisa Orloff from the ENT Panel, Dr. David Terris from

the ENT Panel, and Dr. Carolyn Stern, the consumer rep

for the ENT Panel.  Those folks are joining us today

for the first time.

            There are two other announcements of note

that I would like to make at this time.  The first is

to recognize that ENT Panel voting members, Dr.

Julianna Gulya on my left here, who is Chair; Dr.

Herman Jenkins; and also Dr. Howard Francis, who is

not with us today, and ENT industry rep, Mr. Michael

Crompton, will serve on the ENT Panel today for the

last time in that capacity.  Their term expires on

October 31st of this year.

            We want them to know that their dedication

to the work of the panel has been much appreciated.

And we are very grateful for their willingness to

serve.  FDA owes you a resounding thank you for all

you have given us.  And we will be sending you a

special remembrance for your service.  Please join me

in thanking them.

            (Applause.)

            EXECUTIVE SECRETARY S. THORNTON:  The

second is to announce the voting members who will

begin their terms on 11‑1‑2004.  They are Drs. Eric

Mair and Lisa Orloff, whom you have just met, and Dr.

Kathleen Sie, who is with the University of Washington

in the Children's Hospital Medical Center in Seattle,

Washington.  Dr. Mair will be the new panel chair.

           CONFLICT OF INTEREST STATEMENT

            EXECUTIVE SECRETARY S. THORNTON:  Now I

would like to proceed with the reading of the conflict

of interest statement for this meeting.  "The

following announcement addresses conflict of interest

issues associated with this meeting and is made part

of the record to preclude even the appearance of an

impropriety.  To determine if any conflict existed,

the agency reviewed the submitted agenda for this

meeting and all financial interests reported by the

committee participants.

            "The conflict of interest statutes

prohibit special government employees from

participating in matters that could affect their or

their employers' financial interests.  To determine if

any conflict existed, the agency reviewed the

submitted agenda for this meeting and all financial

interests reported by the committee participants.

            "The agency has no conflicts to report for

today's agenda.  However, we would like to note for

the record that the agency took into consideration

certain matters regarding Drs. Gail Demko, Eric Mair,

and David Terris.  They reported interests in firms at

issue but in matters not related to today's agenda.

The agency has determined, therefore, that they may

participate fully in all discussions.

            "In the event that the discussions involve

any other products or firms not already on the agenda

for which an FDA participant has a financial interest,

the participants should excuse him or herself from

such involvement, and the exclusion will be noted for

the record.

            "With respect to all other participants,

we ask in the interest of fairness that all persons

making statements or presentations disclose any

current or previous financial involvement with any

firm whose products they may wish to comment upon."

            Thank you, Dr. Gulya.

            CHAIRPERSON GULYA:  Thank you very much,

Sally.

            While proceeding along on our agenda, we

will next hear from Dr. Eric Mann, who is the Chief of

the Ear, Nose, and Throat Devices Branch.

                   BRANCH UPDATES

            DR. MANN:  Good morning, distinguished

panel members, FDA colleagues, and guests.  The last

meeting of the Ear, Nose, and Throat Devices Panel

occurred in August of 2002.  And we would like to take

this opportunity to give you a brief update on the

branch and some of its activities since that last

meeting.

            We have had a number of staffing changes

within the branch recently.  Aside from myself as

Branch Chief, we have Ms.

Karen Baker as our nurse consultant.  We have two

audiologist reviewers:  Ms. Teri Cygnarowicz and Dr.

James Kane.  Dr. Vasant Malshet is our branch

toxicologist.

            And we are very pleased and privileged to

have two new reviewers within our branch as of last

fall.  Dr. Srinivas Nandkumar is an electrical

engineer with signal processing background.  And Dr.

Antonio Pereira is a practicing otolaryngologist/head

and neck surgeon, who also serves as a part‑time

medical officer for our branch.  And Dr. Pereira takes

over for Dr. Sid Jaffee, whom some of you may recall

has served our branch so well for the pst years.  We

wish Dr. Jaffee well in his retirement.

            We have had one original PMA approved

since the last panel meeting.  The Karl Storz

autofluorescence system was approved in December of

2002 for the indication of use of white light in

autofluorescence bronchoscopy to identify and locate

abnormal bronchial tissue for biopsy and histological

evaluation.

            The target patient populations for this

new device are patients with suspected bronchogenic

carcinoma, those previously diagnosed with lung

cancer, and those patients who demonstrate abnormal

sputum cytology, abnormal chest X‑ray, CT scan, or

other similar technology.

            Here is a photograph of the entire

autofluorescence system.  On the left, you can see

consists of a bronchoscope, a light source with a

variety of filters, a camera, and a video output

display monitor on the top.  On the upper right‑hand

photograph, you see a photograph of the lower airways

with white light used during a traditional white light

bronchoscopy.

            Below that, you see the same area

illuminated with the autofluorescence mode of the

system.  And you can see several areas of reduced

autofluorescence, which indicate possible areas of

abnormality and may require biopsy.

            We have had quite a number of PMA

supplements submitted since the last panel meeting.

And I would like to share a few of the more important

ones related to cochlear implants.

            Cochlear Americas received approval for a

design change to their electrode for their Nucleus 24

contour system.  The new electrode is a longer,

specialized electrode tip, which is shown here.  The

new electrode is called the soft‑tip electrode.  It

features an advance off stylet insertion technique.

I think you can see the stylet here on the left side

of the figure.  The new electrode tip is advanced off

of that stylet into the cochlea with the aim of having

a less dramatic insertion into the cochlea and

ensuring a more consistent perimodiolar placement of

the new electrode.

            We also approved an advance off stylet

insertion tool in October of 2003.  It's shown here on

the left.  This insertion tool is to be used with the

new electrode and permits the surgeon to use a single

hand insertion technique during the implant surgery.

            MED‑EL Corporation received approval in

August of 2003 for a medium active electrode array.

This new design features contact spacing, which has

been optimized for special difficult cases of cochlear

implantation, specifically those patients who have

cochlear ossification or congenital malformations of

the cochlea.

            Like the standard array, it consists of 12

pairs of electrode contacts, but they are compressed

together at the distal end of the electrode, as shown

in this figure here, which facilitates a higher

likelihood of complete insertion in these more

difficult cases.

            The company also received approval for an

MRI indication.  The device can be used with MRI at

0.2 tesla field strength.  However, proper positioning

of the patient within the magnetic field is necessary.

And the imaging facility is directed to contact MED‑EL

prior to the MRI study to ensure that proper

procedures are followed during the MRI.

            Finally, the third manufacturer of

implants within the U.S., the Advanced Bionics

Corporation, received approval for a major repackaging

design change to their implantable cochlear

stimulator, shown here on the left.  The new

stimulator is called the HiResolution Bionic Ear

System, or HIRES 90K for short.  It features a

silicon‑embedded titanium case.  This is a smaller

case compared to the previous generation of the

CLARION device, which was made out of ceramic.

            The agency also granted approved for a new

HiFocus Helix precurved electrode, which is shown here

on the lower left.  The electrode achieves this

precurved configuration, perimodiolar configuration,

within the cochlea after removal of an insertion

stylet.

            Finally, the company received FDA approval

for MRI compatibility with their device at field

strengths of 0.3 and 1.5 tesla.  Prior to the MRI

study, the magnet within the implanted device has to

be removed.  The MRI study is conducted.  And then the

magnet is replaced with minor surgical procedures.

            As you may be aware, Advanced Bionics

recently issued a worldwide voluntary recall of all

unimplanted clarion and high‑resolution bionic ear

systems.  The company undertook this action in

response to the finding of moisture within the implant

case of explanted devices, devices that had been

explanted for either medical reasons or for device

failures.  In some cases, they were able to link the

moisture within the implanted case with the actual

device malfunction and failure.

            The company is currently taking steps to

address this by looking at their manufacturing

processes, but in the meantime, FDA has worked with

the company to draft notification letters for doctors,

patients, and hearing health care professionals.

These letters went out last week.

            Of note, FDA is not recommending removal

or replacement of normally functioning implanted

devices.  And the overall failure rate for these

devices to date has been relatively low.

            Finally, I am very pleased to announce

that within the next week we will be making available

a CDRH cochlear implant Web site, with the Web link

here.

            The target audience for this cochlear

implant Web site is current and prospective cochlear

implant users, their parents, families, educators, and

health care providers who may be involved with these

users.

            The content of the Web site includes

information regarding cochlear implant design and

function, including some very nice animated graphics,

gives details about the cochlear implant surgery, and

addresses some frequently asked questions.  A very

nice feature also is that it provides easy links to

FDA regulatory approvals for these devices.  So we

think this will be a significant contribution to the

resources out there available to the public on

cochlear implants.

            This concludes the branch update.

            CHAIRPERSON GULYA:  Thank you very much,

Dr. Mann.

            We do have a very tight morning schedule,

but I feel it incumbent upon us to at least be given

the opportunity to have some burning questions

answered.  Are there any such burning questions for

Dr. Mann before we proceed to Ms. Rosecrans?

            (No response.)

            CHAIRPERSON GULYA:  Okay.  Great.  Ms.

Heather Rosecrans, please?  I think you were next on

our schedule for a presentation.  Most of you should

have a copy of her slides as a handout.

                  FDA PRESENTATION

            MS. ROSECRANS:  Thank you very much.

            I'm here this morning to just briefly

discuss with you a subject that I am sure you are

familiar with, which is prescription and

over‑the‑counter use.  I just want to give you a few

examples and briefly go over the regulations we use to

distinguish these two was of regulating and labeling

devices.

            Basically it surrounds adequate directions

for use, whether or not there can be adequate

directions for use written for a lay person.

Generally we're looking at the sixth or seventh grade

level, considering how to write that labeling for a

lay person, or if adequate directions for use cannot

be written for a lay person, it would be considered a

prescription device.

            Our regulations, or actually our labeling

regulations, are found in our Code of Federal

Regulations in chapter 801.  They describe the

over‑the‑counter devices, again those for which

directions for use can be written for a lay person, as

well as prescription devices, which are exempt

technically by our regulations, exempt from adequate

directions for use, meaning for a lay person, but

obviously they have directions for use for the

licensed practitioners.

            We also have what is considered under

prescription devices prescription home use.  So that

would be a prescription device that you send home with

the patient to use.  for example, prothrombin time

tests used in cardiovascular disease are given by the

physician to the patient.  They pick them up at the

pharmacy and then use them in their home and report

back to the physician.

            If a firm had a prescription device and

they wanted to market it over the counter, that would

require a new application before the agency.

            And, lastly, I wanted to mention that we

do have many devices that are both prescription and

over‑the‑counter.  Someone can actually come in to use

with a submission for a device that is both

prescription and over‑the‑counter.  The distinction

would be how they are going to label the product.  And

obviously they would be packaging it differently as

well, but it could be that's the very same device.  A

good example of this would be pregnancy test kits.

            Okay.  So obviously I'm sure you're very

aware the over‑the‑counter devices are available for

purchase directly by any lay person or consumer.  And

they involve self‑diagnosis, et cetera.  Again, they

require adequate directions for use for that lay

person.

            A prescription device ‑‑ and this is the

definition from our regulation ‑‑ is a device which

because of any potentiality for harmful effect or the

method of its use or the collateral measures necessary

to its use, it's not safe except under the supervision

of a practitioner licensed by law to direct the use of

such a device and, hence, for which adequate

directions for use cannot be prepared, again meaning

for a lay person.  As I just said, they would be

exempt for a lay person.  And, again, they include

those home use devices.  That's considered

prescription.

            The labeling that we require in our

regulations would be "Caution:  Federal law restricts

the device to sale by or on the order of a."  And

that's to be filled in with any one licensed by the

state to use that prescription‑type product.  Okay?

            And, again, the states enforce these

prescriptions, even though the federal law requires

the statements.  Normally we allow the states to go

ahead and enforce them because every state, as I'm

sure you are very well‑aware, is different in what

they allow.  And also the method of its application

for use has to be addressed.

            I just wanted to, lastly, just go over a

couple of examples for you that you may be familiar

with.  Recently, I think in September, we just cleared

under the 510(k) process, actually, a device that went

from prescription to over‑the‑counter.

            And there was a public panel meeting in

July.  Those are the automatic external

defibrillators.  We just cleared our first

over‑the‑counter one.  Previously they were

prescription and then prescription home‑use.  And,

again, now we have cleared our first over‑the‑counter

one.

            I should also let you know that in the

510(k) program, which I know you have had training on,

if a device has been cleared for prescription use and

they want to market it as a prescription home use

device and they make no other changes to the product,

that would just involve they would be adding labeling

for the home use environment.  That does not require

a submission to the agency if it's accepted medical

practice in the United States.  If in the PMA area it

went from prescription to prescription home use, that

does require a PMA supplement.

            A couple of other examples of things that

we have in the near recent past cleared as

over‑the‑counter would be the cryotherapy systems for

warts have recently gone over‑the‑counter through the

510(k) process.  As I said, pregnancy test kids; the

prothrombin test again would be prescription home use.

Ovulation predictor test several years back went

over‑the‑counter through the 510(k) process.

            And examples such as over‑the‑counter

strep tests and over‑the‑counter gonorrhea tests have

actually not been allowed to go to market at this

time.  It was determined the impact on public health

was too great and had significant safety and

effectiveness concerns.  So, therefore, to date we

have not allowed those over the counter.  But, as you

are aware, I am sure, we have allowed the AIDS test to

go over the counter.  And the risk‑benefit decision

for that was met before a panel.

            So that's what I have for you today.

Thank you.

            CHAIRPERSON GULYA:  Thank you, Ms.

Rosecrans.

            MS. ROSECRANS:  Thank you.

            CHAIRPERSON GULYA:  Are there any

questions at all from the panel?

            (No response.)

            CHAIRPERSON GULYA:  Okay.  Thank you very

much.  Next we will turn to Dr. Mann.

            DR. MANN:  Again, good morning and welcome

to our distinguished panel members.  This certainly is

a rare opportunity for us here at FDA to have access

to such a wealth of clinical experience from both the

Dental and the ENT Advisory Panels.  We very much

appreciate your willingness to attend and prepare for

this meeting and to share your knowledge with us as we

consider important regulatory questions related to

over‑the‑counter use of medical devices for the

treatment of snoring and obstructive sleep apnea.

            I would like to open this morning's

session by giving you a brief history of the subset of

ear, nose, and throat devices which have been proposed

and in some cases cleared for over‑the‑counter

treatment of snoring and obstructive sleep apnea.

            The purpose of this slide is to basically

demonstrate that although we have had many devices

cleared in the past for indications related to snoring

or obstructive sleep apnea, we don't have a single

division or branch within the agency that deals with

that indication, snoring or obstructive sleep apnea.

            In fact, we have at least four branches

within our office that have been involved in a review

of these devices.  The Dental Devices Branch obviously

would review things like oral appliances, jaw

positioning devices, and also an assortment of other

devices, such as palatal implants and the Repose

tongue base suture system.

            Our branch, the Ear, Nose, and Throat

Devices Branch, has reviewed nasal dilators, cervical

pillows, and a category that I will define a little

bit later called mandibular support devices.

            The Anesthesia and Respiratory Devices

Branch has regulated the wide variety of CPAP devices

currently out on the market, which are obviously a

mainstay of OSA treatment.

            And the General Surgery Devices Branch has

regulated devices with more generic surgical

applications, such as the lasers and the devices using

radiofrequency technology.

            Now, despite the fact that these devices

are all in different branches, I would emphasize that

there is extensive formal and informal consultation

that goes on between branches if there are clinical or

technical issues that arise.  And I would also

emphasize for the purpose of the panel discussion

today, we are not addressing CPAP devices and the

surgical devices, which obviously would not be good

candidates for an over‑the‑counter indication.

            So, with that, I will be focusing my

presentation this morning on the three categories up

here on the left, which have been proposed for

over‑the‑counter use.  So I will begin with the nasal

dilator, which is defined within the Code of Federal

Regulations as a device intended to provide temporary

relief from transient causes of breathing difficulties

resulting from structural abnormalities and/or

transient causes of nasal congestion associated with

reduced nasal air flow.  The device decreases airway

resistance and increases nasal air flow.

            These devices were the subject of an ENT

Devices Panel classification meeting back in October

of 1990.  At that time, it was determined that they

would be regulated as Class I devices.  I would point

out that since that time, all of the indications that

have been cleared pretty much have been

over‑the‑counter indications.  And the early

indications mainly focused on things like reduction in

nasal airway resistance and increase in nasal air

flow.

            This slide illustrates that the regulation

also kind of breaks down nasal dilators into internal

and external variations.  The external variation,

shown on the left here, basically consists of a skin

adhesive coupled to a spring‑like material.  It is

placed over the dorsum of the nose and pulls the

lateral walls of the nose out laterally to expand the

nasal airway over the region of the nasal valve.  Here

is an example of one, the Breathe Right Nasal Strip,

which most of us are familiar with.

            We also have a variety of internal nasal

dilators, a good example being the Breathe With Eez

nasal dilator shown here.  It is a stainless steel

wire frame that is inserted into the nostril and

basically supports and expands the distal nasal

airway.

            We also have on the market a device called

Breathe EZ, which again goes into the nostril but in

this time it's actually straddling the columella and

compressing the septum bilaterally.

            Finally, I would call your attention to

the Nozovent device here at the bottom, which consists

of a spring‑like center strut and two flanges on

either side.  This is inserted into the nostrils and

presses out laterally on the lateral nasal airway to

expand the distal nasal airway as well.

            As I mentioned on the previous slide, the

indications for these devices early on basically

centered on things like reduction in nasal airway

resistance and increases in nasal air flow.  But the

Nozovent device down here at the bottom was actually

the first device that came in seeking an

over‑the‑counter snoring claim.

            This was back in the early 1990s.  The

company recognized that the over‑the‑counter snoring

indication consisted a new indication for use, and

they did submit a 510(k).  Within that 510(k), they

presented clinical data to support the safety and

effectiveness of the Nozovent device for snoring.

            While I can't disclose all of the contents

of that submission, some of the data used to support

the indication have been subsequently published, as

shown here and basically showed a reduction in

subjective snoring skills and so forth.

            Based on the clinical data provided, the

labeling submitted, and other information within the

510(k), it was, in fact, cleared in August of 1991 for

an over‑the‑counter snoring indication.  It obviously

opened up the doorway for other nasal dilators to come

in seeking a similar indication.

            So following the Nozovent clearance, the

FDA policy for nasal dilators seeking a snoring

over‑the‑counter indication has been as follows.

Assuming that the device has the same indications for

use or very similar technological characteristics to

the nose event or another suitable predicate device,

no clinical data has been required to support a

snoring OTC indication.  And typically what has been

submitted are things like design specifications,

material specifications, and some bench‑top testing as

appropriate to demonstrate substantial equivalence to

that predicate device.

            However, if there is new technology or new

indications for use, they would have to come in with

a 510(k) with clinical data.  An example of that would

be the Breathe Right Nasal Strip.  When they came in

seeking an OTC snoring claim, that was obviously

different technology from the internal nasal dilator

with the Nozovent device.  So they did submit clinical

data to support clearance of their snoring claim for

over‑the‑counter.

            Now, one of the things that happened in

the late 1990s was the passage of the Food and Drug

Modernization Act.  And under the provisions of this

act, the vast majority of Class I devices became

exempt from pre‑market or 510(k) notification.  This,

indeed, was the case for nasal dilators as well

effective April of 1999.  However, I would point out

that this exemption is subject to limitations.  And

any device which has new technological characteristics

or new intended use would still be required to come

into the agency with a 510(k) and clinical data to

support the indication.  I would point out that there

have been no obstructive sleep apnea indications

cleared for these devices to date.

            FDA has reviewed the labeling for these

products in the past for snoring indications and in

general has ensured that the adequate labeling

precautions and warnings are included.  The exact

wording of these precautions and warnings has varied

somewhat, but in general they all instruct the patient

to seek medical attention for any abnormal breathing

patterns during sleep, pauses, and breathing, daytime

sleepiness, difficulty breathing, gasping, choking for

air at night, and so forth, things that would indicate

potential for diagnosis of sleep disorder breathing.

            In addition, the labeling has also

included instructions to cease use if there is

evidence of skin or mucosal irritation depending on

whether it's an internal or external nasal dilator.

The consumer is instructed not to exceed the

recommended duration of use for the product.  And the

product has been labeled not for use in individuals

under the age of five.

            I did a quick search of our computerized

database of previously cleared nasal dilators that

have been cleared for this snoring claim and came up

with a quick list of about seven devices that we have

within our database, but I would emphasize that since

the FDMA was passed, many of the newer devices have

not had to come in with a 510(k).  So this is clearly

not a complete list of nasal dilators out there on the

market for snoring.

            So that covers the nasal dilators.  I'd

like to next move to cervical pillows, which have also

been regulated by our branch for these indications.

Unlike nasal dilators, we have no classification

regulation for cervical pillows for the indication of

snoring or obstructive sleep apnea, but the agency has

determined that these devices when they're marketed

for either a snoring or an OSA indication do fall

within the definition of a medical device because

they're intended to affect the structure or the

function of the body.

            In the early 1990s, we had quite a few

510(k)'s that had come in seeking a snoring

indication.  Based on the large potential number of

510(k)'s that would be coming in, the limited

resources of the agency, and the relatively minimal

risks associated with the direct use of a pillow, it

was decided that FDA would exercise regulatory

enforcement discretion for pillows being marketed for

the snoring indication.  I would emphasize this is for

the snoring indication only, not for any other medical

conditions, like obstructive sleep apnea.

            So under this regulatory enforcement

discretion policy, no 510(k) pre‑market notification

has been required for pillows just seeking the snoring

OTC indication.  There's been no enforcement of

section 807 of the regulations regarding registration

and listing requirements.  These devices still are

subject to adulteration and misbranding provisions of

the Food, Drug, and Cosmetic Act.  And FDA has always

reserved the right to change this policy if determined

to be necessary.

            Now, this exercise of regulatory

discretion has always been contingent upon the sponsor

agreeing to some labeling conditions.  As I stated

before, there can be no other medical claims for the

proposed device.

            In addition, we have insisted that they

include these warnings and contraindications,

essentially the warnings, instruct the patient to seek

consultation with the physician if they have signs or

symptoms of obstructive sleep apnea, such as excessive

daytime sleepiness or pauses in breathing similar to

the labeling for the nasal dilators.

            There were some contraindications that

were required in terms of contraindicating patients

with heart disease being substantially overweight.

And the product had to be labeled for not for use by

infants or children and to discontinue use if pain or

discomfort results.

            So this was the policy that was developed

in the early 1990s.  And since that time, many

manufacturers have agreed to abide by these conditions

and have been marketing their pillows for snoring OTC

conditions without submission of 510(k)'s to the

agency.

            The first cervical pillow that came to the

agency seeking an OSA indication was the

PillowPositive II Cervical Pillow.  This was back in

1999.  The sponsor was Life Sleep Systems.  They had

been one of the companies that had been marketing

their pillow for the snoring indication under the

terms of the regulatory discretion that I just

described.  But they did recognize that the OSA would

be a new indication for use and came into the agency

with the 510(k) seeking a claim for snoring and mild

obstructive sleep apnea.

            To support this indication, they submitted

clinical data.  Again, I can't go into detail about

everything within the content of that 510(k), but some

of that information has been published as well.  I can

include the references here.  And I think one of these

references is actually in the panel briefing packet,

basically demonstrating reduction of respiratory

disturbance index with use of the pillow compared to

baseline conditions.

            Based on the clinical evidence supplied

within the 510(k), review of the labeling and so

forth, this was, in fact, cleared in June of 1999 for

both a snoring and mild obstructive sleep apnea

indication.  This clearance was for prescription use

only.

            There were several instructions regarding

measurements that had to be taken of the patient,

fitting of the pillow to the individual patient by the

health care provider.  So it was labeled as a

prescription use only, and the sponsor did not request

over‑the‑counter indication for this pillow.

            The labelling for the patient did, in

fact, contain the same warnings and contraindications

that we have prescribed previously for snoring pillows

and nasal dilators.

            Now, since that time, we have had two

cervical pillows that have also been cleared for a

mild obstructive sleep apnea indication in addition to

snoring.  The first of these was the Popitz Pillow,

which came in in 2002.  It was similar to the previous

pillow in terms of the technology of cervical

positioning to achieve increased patency and stability

of the airway.  This pillow essentially places the

patient or the consumer in the snit position with neck

flexed, head extended to stabilize and open the

airway.

            The 510(k) was, in fact, cleared for the

snoring and mild obstructive sleep apnea indication in

October of 2002.  There were numerous factors that

went into that decision‑making process.  First of all,

the sponsor had submitted clinical data supporting the

effectiveness of cervical positioning and mild

obstructive sleep apnea, similar to the evidence

presented in the previous slide.

            There was a recognition that there may be

some fuzziness or crossover between patients out there

with primary snoring, snoring only in mild obstructive

sleep apnea.  We know that from night to night, there

is a significant variation in patient symptoms and the

results of studies from various centers using various

criteria.  So the distinction between snoring and mild

obstructive sleep apnea is not always that clear‑cut

on individual patients.

            Third, we had a long history of safe use

for snoring pillows over the counter, as I will get to

in a couple of minutes, but basically no significant

adverse events have been reported to FDA for snoring

pillows for the past ten‑plus years.

            Finally, it was felt that the sponsor had

submitted adequate directions for use for an OTC

indication.  In particular, this pillow did not

involve any sort of fitting or specialized

measurements that had to be taken like the previous

pillow.  And it did include all of the warnings,

contraindications, and so forth, in terms of

instructions to seek medical attention for signs and

symptoms of obstructive sleep apnea.

            So kind of based on all of these factors,

it was felt that adequate directions for use had been

supplied in submission.  And it was cleared in October

of 2002.  Since that time, we have received one

additional 510(k) for the indication of mild

obstructive sleep apnea and snoring.  It's the Soma

Pillow.  It was cleared in April of this year based on

clinical data with the pillows supplied by the sponsor

as well as consideration of the other factors

mentioned for the Popitz Pillow.

            So, in summary, we have basically three

pillows cleared for mild obstructive sleep apnea,

snoring, one of which is a prescription device and

these two of which are over‑the‑counter.

            I would like to finally move on to the

category that we are terming "mandibular support

devices."  These devices are essentially those that

support the mandible in the closed position.  I

downloaded some pictures of CPAP chin straps from the

Web.  This is basically what we're talking about when

we speak of mandibular support devices.  They're

basically supporting the mandible in the closed

position.

            Like snoring pillows or cervical pillows,

we have no classification regulation for mandibular

support devices.  In fact, we have received no

510(k)'s for these devices to date.  The reason why I

am mentioning them during this meeting is that we have

received numerous informal queries from industry

regarding the types of studies and the types of data

that would be required to support safety and

effectiveness of these devices for either snoring

and/or obstructive sleep apnea.

            In general, the literature that has been

cited in support of these types of devices are those

such as I have shown here, which basically show that

the mouth open position is associated with increased

collapsibility of the upper airway and a narrowing of

the airway, so the presumption being closure of the

mouth with one of these support devices would enhance

patency and stability of the airway.  So I raise this

as a possibility of things that we might be seeing in

the future.

            Finally, I would just like to give you a

brief overview of our post‑market adverse event

experience with these three categories of devices.  We

did a search of our computerized database, the MAUDE

database, which captures both voluntary and mandatory

adverse event reports dating back to the early '90s.

With respect to nasal dilators, we have had four

adverse event reports.

            Two were related to skin irritation with

the use of an external nasal dilator, nasal strip.

One reported eye irritation related to use of a nasal

strip, although it was unclear how the eye irritation

was tied to use of the device.

            Finally, we have one report of an internal

nasal dilator that was actually displaced into the

posterior nasal cavity.  We have received no adverse

event reports for cervical pillows for the snoring and

obstructive sleep apnea indication to date.

            Finally, even though we have had no

510(k)'s for the mandibular support devices, we do

have one event reported in the database of transient

airway obstruction in a patient using an illegally

marketed device.  They basically woke up gasping for

air, pulled off the strap.  Fortunately, there was no

significant sequelae related to that, but it was

reported in our database.

            In general, the ten‑plus‑year experience

with these devices has demonstrated that there have

been relatively few adverse events reported.  And

those reported have, by and large, been minor in

nature.

            That being said, I think it's given that

there is a significant under‑reporting of minor

adverse events.  Dr. Mair has published a very nice

study, prospective study, of experience in a patient

population with these over‑the‑counter devices.  As I

understand it, a number of those patients experienced

some minor adverse events.  So I'm hoping this

afternoon perhaps he can share the knowledge that he

gained from conducting that study with us.

            So that concludes my portion of the

presentation.  If there are no questions, I will turn

things over to Dr. Kevin Mulry, who will be discussing

the dental devices and their history.

            CHAIRPERSON GULYA:  I think in view of the

time, we will proceed with Dr. Mulry's presentation.

Then we can hopefully interweave questions after we

have our open public hearing session before we dive

into our deliberations.  Thank you very much, Eric.

            DR. MULRY:  Good morning.  I would also

like to add my welcome to the panel and thank you for

taking the time today to come and join us in this very

important discussion of devices for the treatment of

snoring and/or obstructive sleep apnea.

            EXECUTIVE SECRETARY S. THORNTON:  Kevin,

you can move that up to your mouth.

            DR. MULRY:  Thank you.

            EXECUTIVE SECRETARY S. THORNTON:  But we

need you to speak closely into it.

            DR. MULRY:  Okay.  Dr. Mann has presented

the ENT Branch's perspective on the regulation of

these devices.  I am now going to present the Dental

Branch's perspective on the regulation of these

devices.

            So the scope of the dental devices that

we're going to discuss today includes intraoral

devices only.  They are devices that are fitted over

the teeth and tongue and are removable.  I want to

reiterate that the discussion to date does not include

implantable devices, surgical devices, CPAP, or

diagnostic devices.

            The regulatory history for the dental

devices is that the panel met, the Dental Products

Advisory Committee, met in November 1997 to classify

intraoral devices for the treatment of snoring and

obstructive sleep apnea.

            The panel recommended that these devices

be classified into Class II with special controls in

order to provide reasonable assurance of the safety

and effectiveness of these devices.  This means that

sponsors need to submit a 510(k) or pre‑market

notification to the agency for market clearance.  And

a special Class II special controls guidance document

was published in 2002 as the special control for this

Class II regulation.

            In some sponsors, one of the impetuses for

the meeting today is that sponsors have requested that

these devices be made over the counter.  That is the

reason we are asking for your input today as to what

data sponsors should submit to provide reasonable

assurance of safety and effectiveness for

over‑the‑counter use for dental devices.

            Intraoral devices are cited in the Code of

Federal Regulations under 21 CFR 872.5570.  The

regulation states that intraoral devices for snoring

and intraoral devices for snoring and obstructive

sleep apnea are devices that are worn during sleep to

reduce the incidence of snoring and to treat

obstructive sleep apnea.  The devices are designed to

increase the patency of the airway and to decrease air

turbulence and airway obstruction.

            The agency published a Class II special

controls guidance document, which I believe was

provided in your panel packs.  The document is

intended to inform manufacturers regarding the data

needed in a 510(k) submission.  In developing this

guidance document, the agency has considered it the

least burdensome approach to resolving the statutory

requirements.

            The guidance document includes the risks

to health generally associated with the use of these

devices and recommends measures to mitigate the

identified risks.  The guidance document also includes

recommendation for biocompatibility testing for the

devices, clinical testing that may be needed based

upon the individual devices, and labeling.

            So what are the types of dental device

designs for intraoral devices?  The classification

includes three basic designs:  the tongue retaining

devices, the mandibular repositioning devices, and the

palatal lifting devices.

            The tongue retaining device are intended

to increase pharyngeal space to improve the patient's

ability to exchange air by supporting the tongue in an

anterior position.

            The mandibular repositioning devices are

designed to move the mandible into a more anterior

position and provide support for the jaw at rest.

This is intended to create a larger airway space,

thereby decreasing airway turbulence, tissue

vibration, and airway obstruction.

            The palatal lifting devices are designed

to lift the soft palate, thereby increasing airway

patency.  The device is designed to support the soft

palate, thereby decreasing tissue vibration and

decreasing the intensity of the snoring.

            Intraoral devices for snoring and

obstructive sleep apnea have been cleared for the

treatment of snoring and the treatment of snoring

and/or mild to moderate obstructive sleep apnea but

not severe sleep apnea, and they have been

prescription use only.  All dental devices have been

prescription use only.

            This slide demonstrates some examples of

the types of device designs.  The one on the left is

a tongue retaining device.  It contains a bulb into

which the tongue is placed.  And the tongue is held in

place by suction.

            The mandibular aspect here is fitted over

the teeth to stabilize the device.  And the device is

held in this anterior position through the pressure or

the resting of this aspect of the device depending on

the design against either the lips or the jaw.  And

also the mandibular aspect since it is fitted to the

teeth also prevents the device from moving in a

posterior direction.

            The device on the right is a mandibular

repositioning device.  It depicts the mandible in an

anterior position to centric occlusion or your normal

bite.

            You can see here that in the anterior

area, there is an open space for oral breathing.  That

is one of the things that we have required in all of

the submissions for intraoral devices, that there be

a mechanism for oral breathing since these devices can

be somewhat obstructive due to the nature of the

devices.  And also we have concerns about those

patients who might have nasal congestion.

            I would also like to point out the

mechanism for advancement on this type of device.

It's a keyed type of mechanism, which can unless the

device can be advanced either by the doctor or the

patient and it's a very gradual type of advancement

and may be able to advance due to 20 to 40 different

types of physicians.

            I would like to contrast that with the

boil and bite mandibular repositioning devices that we

are seeing today.  These tend to be a thermoplastic

material with slotted groves in the anterior of the

mandible aspect or the mandibular tray.  There's

usually a pin or a stylus attached to the maxillary or

upper tray that fits into the slot of the lower tray.

This then has preset slots or preset advancement

settings.  And there are usually two or three types of

settings on these types of devices.

            Then on the right is the palatal lifting

device, which has a button, which is gradually

adjusted in a posterior direction back to the soft

palate towards the uvula.  This is done in a very

gradual fashion because patients need to adjust their

gag reflex to the presence of this button as it can be

for many patients a difficult adjustment based upon

the natural gas reflex.  The button is intended to

support the soft palate and, therefore, reduce the

vibration of the soft palate and reduce the intensity

of snoring.

            Also, I want to go back just for a second

and say that the amount of advancement that we usually

see with these types of mandibular repositioning

devices has a wide range.  It is usually about 50 to

75 percent of the maximum protrusive position.  The

slotted mechanism is preset, and the advancements are

usually approximately 4 to 5 millimeters for the

treatment of snoring and approximately 8 to 10

millimeters for the treatment of obstructive sleep

apnea.

            So what are the trends the Dental Devices

Branch has seen in the few years with these devices?

The majority of the early designs for the mandibular

repositioning devices require that a dentist take an

individual impression or a custom impression of each

individual patient.  They contain a lot of orthodontic

hardware, hinges, wires, et cetera, and also that they

had self‑adjusting advancement mechanisms that could

be adjusted by either the doctor or the patient.

            The newer devices that we are seeing ‑‑

and there has been an increased interest in these ‑‑

are the boil and bite types of devices.  These devices

vary in design but tend to have in common that they

have a thermoplastic material, which is heated and

then placed in the patient's mouth.  And they have

preset advancement mechanisms.

            This is important in that we will ask you,

the panel, today to consider the different types of

designs in the discussion of data that should be

submitted to the agency if you were to recommend that

over‑the‑counter devices be approved.

            I just want to reinforce the concept of

the differences in the types of designs.  Again, the

one on the left is one that is a generic type of

device.  I will just use this, but there are many

different types of devices with a lot more wires and

a lot more complexity.

            The issue here is that for this type of

device to be fabricated, it needs the dentist to take

an impression of the individual arches, both the upper

and lower arches; requires that it be poured in stone;

be sent off to a lab; the wires need to be fabricated

to fit the individual patient; and then they need to

add the advancement mechanism.

            This is in contrast to the boil and bite

types of devices that are noted here that you can see

that there are slotted mechanisms on the mandible,

some type of pin or stylus on the maxillary or upper

aspect, which fits into the slots here.

            So I just want to draw the contrast in the

types of devices that we have.  The boil and bite

devices don't need to be sent to a laboratory, nor do

they need to be customized for each individual

patient.

            The Class II special controls guidance

document made labeling recommendations that were based

upon the discussion of the Dental Products Panel

meeting in 1997.  The guidance document lists

contraindications of central sleep apnea since these

devices, really, the intraoral devices, are intended

for obstructive sleep apnea, not central sleep apnea,

severe respiratory disorders, severe asthma, et

cetera, concerns for obstructing the patient who may

already be obstructed.  Loose teeth or advanced

periodontal disease, these devices, especially the

mandibular advancement devices, put a lot of pressure

on, in particular, the lower anterior teeth and the

upper anterior teeth.  And if a patient has loose

teeth or advanced periodontal disease, it may

compromise the dentition further.

            We have contraindicated these devices in

patients under 18 years of age because we do not

believe that they should be used during the growth

phases of the jaw and the TMJ.  In edentulous

patients, these are intended to be fitted over the

natural dentition.

            The guidance document also provides

warnings that the use of these devices may cause tooth

movement or changes in dental occlusion.  That may be

a long‑term effect of using these types of devices.

            Dr. Demko will be presenting on those

issues a little bit later, gingival or dental

soreness, especially the ones that need to be

individualized and custom impressions need to be

adjusted for each individual patient to prevent

impinging on the tissue.

            And the pressure from the advancement may

cause some dental soreness, pain or soreness of the

TMJ with the advancement of the mandible.  It may

stress the TMJ or the muscles surrounding the TMJ,

obstruction of oral breathing.  And, as I have said,

we have required a mechanism for oral breathing on all

of these appliances in excessive salivation.

            So what types of clinical studies has the

Dental Branch been reviewing?  For simple snoring, the

studies have included performance measurements that

include the rate of reduction of snoring based on

clinical observation.  This may be as simple as a

recording of snoring pre and post‑insertion of the

device measuring the intensity or loudness of the

snoring.

            For obstructive sleep apnea, the clinical

data includes baseline and post‑insertion

polysomnograms measuring the apneic events, the

apnea/hypopnea index, oxygen saturation, and other

measurements.  These data are provided in a 510(k)

submission when there is a new design dissimilar from

designs previous cleared in a 510(k), new technology,

or new indication for use.

            So what differences are there between the

Dental Branch and the ENT Branch in regulating these

devices?  All dental devices for snoring and

obstructive sleep apnea are intraoral, and all are

prescription devices.  That is, no intraoral dental

devices for the treatment of snoring and/or

obstructive sleep apnea have been cleared as

over‑the‑counter devices.

            Also, due to the dissimilarities in

design, intraoral devices for both snoring and

obstructive sleep apnea pose similar risks based on

the correct selection and fitting of the appliance, as

opposed to perhaps an external nasal strip, for which

fitting is not as critical as the selection of the

correct device for the treatment of snoring and/or

obstructive sleep apnea.

            As noted in Dr. Mann's presentation

earlier, the ENT Branch has cleared over‑the‑counter

devices for snoring and mild obstructive sleep apnea.

            So why has the Dental Branch cleared these

devices as prescription‑only devices?  These devices

present different risks perhaps from the ENT devices.

The devices are varied in design.  As I have

discussed, there are three different designs that are

included in the regulation to date.  Within those

designs, there are subsets of those designs.  And also

sometimes there are combinations of the designs in one

device.

            And the application based upon the degree

of advancement may present some other risks.  These

devices apply forces on the teeth, tissue, and the

temporomandibular joint, which makes correct selection

and fitting of the device along with adequate

follow‑up important in preventing injury.

            Critical care by a dentist is critical in

the diagnosis of periodontal disease, decayed,

missing, and filled teeth, the maximum protrusive

range and the range at which the mandible should be

advanced, the status of the temporomandibular joint,

and also the diagnosis of parafunction, such as

clenching, grinding, which may impact the type of

device that is used and also the fitting of the

individual device.  All of these assessments are

important to the safe use of these devices.

            The Dental Devices Branch has received

clinical protocols from sponsors to support

over‑the‑counter use for the treatment of snoring and

anticipate receiving protocols also for obstructive

sleep apnea.

            Some of the issues that have been

addressed in these protocols include the intervention

of a dentist or other competent intermediary to assess

the general health status, the oral health status,

and/or the appropriateness of the individual device

prior to the patient receiving the device.

            The Dental Branch has not viewed these

protocols as representative of consumer use studies

for over‑the‑counter devices.  For example, they do

not seem to reflect the experience of a consumer going

to a pharmacy, picking a device up off the shelf,

taking it home, reading the directions, fitting the

device accurately, and then being able to make an

assessment as to whether the device is the correct

device and also whether the device is effective.

            Other issues discussed in these protocols

include lay person self‑assessment of snoring versus

obstructive sleep apnea and directions for use for

self‑fitting the oral appliances and self‑assessment

of the fit.

            These are issues that we would like your

input in your discussion today to assist us in

determining what would be adequate protocols to

support over‑the‑counter use of these devices.

            As Heather Rosecrans presented earlier,

over‑the‑counter devices require adequate directions

for use for the lay person.  The questions that have

come to the Dental Branch's mind in looking at these

devices are:  Can the lay person accurately

self‑diagnose their medical condition?  Can the lay

person accurately self‑diagnose their oral health

status?  And can the lay person choose the correct

oral appliance and fit it accurately such that the

device is safe and effective and does not cause

adverse events?  And also are there different

considerations for snoring versus obstructive sleep

apnea?

            We have developed some questions to assist

you in your discussion today.  What I would like to do

is present the three questions that we have developed.

These questions apply both to the dental and ENT

devices and just hopefully will focus the discussion

to assist us in gathering the information that we

would hope to receive today.

            Question 1 is, as noted in FDA's

presentation, the following types of devices may be

considered for or have already been cleared for

over‑the‑counter status for the indications of snoring

and/or obstructive sleep apnea.  Please discuss the

risks and benefits of allowing devices to be marketed

over the counter for the treatment of snoring and also

mild, moderate, and severe obstructive sleep apnea.

            And, in particular, please discuss the

overall risk‑benefit ratio assessment as it relates to

the level of disease severity and discuss the

potential risks related to delay in professional

diagnosis and treatment resulting in over‑the‑counter

availability or use of these devices.

            We have developed a chart to go along with

question 1, which lists the different types of

devices, and then the snoring and the different

degrees of obstructive sleep apnea and whether these

devices have been presently cleared as prescription or

over‑the‑counter devices.

            Question 2, if after your discussion of

question 1 you believe that certain devices would be

appropriate for over‑the‑counter treatment of

obstructive sleep apnea, please discuss the following:

how adequate product labeling can be written to assist

the user in self‑diagnosing and differentiating the

severity of obstructive sleep apnea he or she is

experiencing to ensure proper use and also any other

general or specific labeling restrictions which you

believe would be appropriate for over‑the‑counter

devices to treat snoring and/or obstructive sleep

apnea; for example, any specific types of

contraindications, warnings, or precautions which you

believe should appear in the device labeling.

            And then the final question is, please

discuss the following aspects of the clinical data

which may be appropriate to be included in marketing

submissions for snoring and/or obstructive sleep

apnea:  a) the general clinical study design,

including control group, if needed; b) the endpoints

which would be acceptable for the assessment of the

effectiveness of treatment; c) the degree of

improvement for each of the endpoints which would be

clinically meaningful assuming an acceptable adverse

event profile; d) the specific adverse events, if any,

which should be carefully assessed by FDA from the

clinical trial; e) whether any of the responses to

3(a) through 3(d) would be different based on the

severity of snoring and/or the degree of obstructive

sleep apnea:  mild, moderate, or severe; f) any

specific considerations in trial design for

over‑the‑counter indications; and g) any specific

device types or indications which would not require

clinical data.  Again, we will put these questions up

later for you to assist you in your discussion of this

topic.

            I want to thank you for the opportunity to

present today.  And I will answer any questions if you

want.

            CHAIRPERSON GULYA:  Thank you, Dr. Mulry.

I think in view of the time, what we will do is we

will hold questions for all of you speakers, Ms.

Rosecrans, Dr. Mann, and yourself, of when we start to

embark upon our deliberations.  So thank you very

much.

            DR. MULRY:  Thank you.

             OPEN PUBLIC HEARING SESSION

            CHAIRPERSON GULYA:  Next on the agenda is

the open public hearing segment, for which we have 30

minutes allocated.

            While I am going through the rest of this

material, I see that we have five presenters listed

here:  Dr. Steven Merahn, Dr. Lawrence Epstein, Dr.

Kent Moore, Dr. Keith Thornton, and Mr. George Dungan.

If you would be so kind as to arrange yourselves in an

order so you could be proximal to the microphone so as

to minimize transition time in between speakers, that

would much appreciated.

            The open public hearing segment provides

the opportunity for members of the public who have an

interest in addressing the panel on today's topic;

i.e., over‑the‑counter/prescription use for devices

for the treatment of snoring and/or obstructive sleep

apnea.

            Each presenter should state clearly for

the record their name; affiliation; interests in the

topic at hand; any consulting arrangements or

financial interest with medical device firms; and if

travel expenses have been paid, by whom.

            Now, I have been asked by the FDA to read

this into the record.  This is the introduction to the

open public hearing general matters meeting.  Both the

Food and Drug Administration and the public believe in

a transparent process for information‑gathering and

decision‑making.  To ensure such transparency, at the

open public hearing session of the Advisory Committee

meeting, FDA believes it is important to understand

the context of an individual's presentation.

            For this reason, FDA encourages you, the

open public hearing speaker, at the beginning of your

written and oral statement to advise the Committee of

any financial relationship that you may have with any

company or any group that is likely to be impacted by

the topic of this meeting.  For example, the financial

information may include a company's or group's payment

of your travel, lodging, or other expenses in

connection with your attendance at the meeting.

            Likewise, FDA encourages you at the

beginning of your statement to advise the Committee if

you do not have any such financial relationships.  If

you choose not to address this issue of financial

relationships at the beginning of your statement, it

will not preclude you from speaking.

            So, as I said, we have 30 minutes for this

session.  We have a number of speakers.  And I

understand all of you have been asked to hold your

comments to five minutes.  And out of fairness to all,

I ask you that you hold yourself to these limits.

            I do have one of these neat little timing

devices that hopefully I can use without blowing this

all up.  We will try and use that to help encourage us

to stay on time.

            So we have as our first open public

speaker Dr. Steven Merahn.

            EXECUTIVE SECRETARY S. THORNTON:  Either

the podium or the table, whichever is more comfortable

for you.

            DR. MERAHN:  Good morning, everybody.

Thank you.

            EXECUTIVE SECRETARY S. THORNTON:  Dr.

Merahn, do you think we could dispense with the slides

at this time in the interest of time?

            DR. MERAHN:  I don't have slides.  I'm

just going to read off my screen instead.

            EXECUTIVE SECRETARY S. THORNTON:  Okay.

Fine.

            DR. MERAHN:  No, I wouldn't put you

through that.  I'm a no PowerPoint.

            EXECUTIVE SECRETARY S. THORNTON:  Okay.

I wanted to make sure you got your full five minutes

here.

            DR. MERAHN:  Okay.  Good morning,

everybody.  Thank you.  Thank you for allowing me to

present today.

            I am a physician and founder of the

American Academy of Sleep Disorders Dentistry, which

is a private education and professional services

organization with the objective of increasing the

number of patients identified and treated for

airway‑relate sleep disorders via collaboration

between physicians and dentists.

            It is our position that a collaborative

interdisciplinary approach to sleep disorders

management offers the most responsible and effective

means of reducing the significant public health and

economic impact of obstructive apnea.

            Our founding members include over 40

dental and medical professionals from all over the

country, mostly from working knowledge in the use of

oral appliances for the treatment of sleep disorders

as well as TMJ and other forms of craniofacial pain.

            The academy is almost entirely funded by

fee for service for educational and professional

activities.  I have no other related conflicts of

interest.  And, in fact, the funding for my trip today

came out of my own pocket.

            The specific question at hand today is

whether oral appliances for airway‑related sleep

disorders, such as snoring and sleep apnea, should be

permitted to be sold over the counter or should remain

prescription devices.

            On that question, our recommendation is

that they remain prescription devices, largely

because:  first, the risks of self‑diagnosis are too

high.  There was a complex differential diagnosis

associated with the signs and symptoms of

airway‑related sleep disorders, the primary symptom

excessive daytime sleepiness, is a symptom of many

serious medical conditions, including anemia,

hyperthyroidism, and others.

            While we do not believe that a full

polysomnography is required to diagnose an

airway‑related sleep disorder, a trained health

professional and in our vision a physician‑dentist

team should be involved in the screening, assessment,

and diagnostic process.

            Second, there are potential adverse events

related to the airway jaws.  Tongues and teeth tend to

be associated with unmonitored mandibular positioning.

Oral appliances are serious therapy and can have a

significant adverse impact on airway function if not

properly fitted for optimal therapeutic efficiency.

There is no one size fits all solution.  The

literature is quite clear that the efficacy is largely

a function of the degree to which the appliance is

titrated to patients' anatomy.

            However, the issues underlying the

specific question in front of you today should not be

lost.  The interest in over‑the‑counter status for

oral appliances is driven by the compelling need to

manage the overwhelming public health threat posed by

airway‑related sleep disorders.

            As I am sure the Committee is aware, sleep

apnea affects millions of individuals, more than

asthma and diabetes and is increasingly recognized as

a cause of hypertension and cardiovascular events as

well as impairments of cognitive function,

interpersonal relationships, and workplace

productivity.

            Our academy recently commissioned a study

which looked at the public health and economic impact

of current treatment paradigms compared to our

collaborative therapy model.  While these data are

being prepared for publication, I would like to share

one or two conclusions with the Committee.

            While CPAP is the gold standard of

treatment with virtually 100 percent efficacy after

titration, the data on compliance does not support

CPAP as meeting the public health needs related to

apnea.

            There are some patients who with a more

properly fitted and evaluated oral appliance will

offer 100 percent efficiency without the burden of

disruption of CPAP, but for even those who do not

receive 100 percent efficiency, there is a compelling

reason to use oral appliances to manage OSA.

            Our study developed a population impact

factor for each therapy, a therapeutic index derived

from fixed appliance data.  For oral appliances, the

impact factor is 60 percent.  While CPAP is

approximately 45 percent, this population impact

factor is derived from efficacy and compliance data.

            Based on these findings, oral appliances

should be repositioned, so to speak, as a first‑line

therapy in a step‑wise approach to management using a

collaborative primary care model.  This will

significantly reduce the costs associated with sleep

apnea.

            Untreated apnea adds approximately $1,800

to the lifetime costs associated with MI and stroke.

Based upon our population impact factor, oral

appliances will lower that cost to $650 while CPAP

actually only lowers it to $993.

            If we substitute oral appliances for any

percentage of patients entering the system, we will

save significant amounts of money with little

epidemiologic impact.  In fact, the academy supports

the increased use of oral appliances as first‑line

treatment for airway‑related sleep disorders in a

collaborative care model but does not support their

becoming available over the counter.

            And while this may not be in the

Committee's purview, we recommend shifting the

responsibility for the treatment of apnea to an

interdisciplinary team of physicians and specially

trained dentists as a method to achieve the public

health objectives but alleviate the risks of

self‑diagnosis and unmonitored treatment associated

with OTC oral appliances.

            Thank you.

            CHAIRPERSON GULYA:  Thank you very much.

            DR. MERAHN:  I can breathe now.

            CHAIRPERSON GULYA:  Yes, you can.  Any

pressing questions from the panel for Dr. Merahn?

            (No response.)

            CHAIRPERSON GULYA:  Okay.  Thank you very

much.

            DR. MERAHN:  Thanks.

            CHAIRPERSON GULYA:  We will next proceed

to Dr. Lawrence Epstein.

            DR. EPSTEIN:  Good morning.  Thank you for

the opportunity to speak on this issue.  My name is

Larry Epstein.  I am Board‑certified in sleep medicine

and head a sleep medicine specialty group in Boston,

Massachusetts.  I am instructor of medicine at Harvard

Medical School and the President‑Elect of the American

Academy of Sleep Medicine, the organization I am

representing today and who has paid for my travel

expenses.

            The AASM is the professional organization

for the subspecialty of sleep medicine.  The AASM

publishes practice guidelines and diagnostic criteria

to help provide the best care for patients with sleep

disorders.

            I have no other financial conflict of

interest with respect to the issue of oral appliances.

            Our organization and the individuals it

represents are concerned about the consequences of

possible over‑the‑counter use of oral appliances to

treat snoring and obstructive sleep apnea.  Making

these over‑the‑counter devices will increase their

availability but likely will not improve the care of

patients with obstructive sleep apnea.

            Oral appliances are valuable tools in the

treatment of sleep apnea.  Multiple studies have shown

their effectiveness for mild to moderate but not

severe obstructive sleep apnea.

            A review by the AASM using strict

evidence‑based review methodology, which is included

in our packet to you, which you should have, found

that oral appliances, though not as effective as

continuous positive airway pressure, were effective in

over half of the patients with sleep apnea.  However,

they are not uniformly effective and have some

significant complications.  For these reasons, the use

of oral appliances requires thorough evaluation and

follow‑up by medical and dental personnel.

            Several more recent reviews, which include

randomized trials in larger numbers, have reaffirmed

the findings in the original review paper.

            I would like to address two specific

questions from the Committee, though I have tried to

answer all of the questions in my written submission

to you.  First, what is the ability of the patient to

self‑diagnose and treat sleep apnea?  The most common

symptoms of OSA are snoring and daytime sleepiness,

which are sensitive but not specific for sleep apnea.

People trying to eliminate their snoring are often not

aware that snoring is a marker for the presence of

sleep apnea.

            Differentiating snoring from OSA can be

difficult for a trained physician, much less the

patient.  For example, in a young, non‑obese person

under 40 years of age, body mass index of less than

27, whose only symptom is snoring with no daytime

sleepiness or episodes of observed stopping breathing

at night, the chance of having obstructive sleep apnea

can still be up to 25 percent.

            Additionally, since obstructive sleep

apnea occurs while the person is asleep and unaware,

people are poor judges of the presence of sleep apnea.

Use of an over‑the‑counter oral appliance may improve

the symptom of snoring but leave the apnea untreated.

            I feel our organization is particularly

well‑suited to answer the next question.  What is the

role of medical and dental providers in the diagnosis,

treatment, and follow‑up of snoring and sleep apnea?

            It can be difficult to differentiate

between snoring and sleep apnea by symptom alone.

Multiple studies have shown that thorough clinical

evaluation plus objective testing, such as a sleep

study, are required to establish both the presence and

severity of OSA accurately.

            Patients who try to eliminate their

snoring with an over‑the‑counter device might delay or

avoid appropriate evaluation and remain untreated for

sleep apnea.  This increases their risk of developing

hypertension and other cardiovascular diseases and

increases the likelihood of workplace and automobile

accidents due to preventable hypersomnolence.

            The FDA has approved over 30 oral

appliances for the treatment of sleep apnea or

snoring.  They have different mechanisms and different

degrees of change in airway shape.  It is essential

that a dental professional trained in the role of oral

appliances and the treatment of sleep apnea and

snoring as well as all aspects of oral health and

dental occlusion be involved in determining the

appropriate device and ensuring appropriate fit.

            Although effective and well‑tolerated,

oral appliances are not always successful, often

require modification, and have both mild and

significant complications.  Jaw and teeth discomfort

and excessive salivation are commonly reported and can

be resolved with dentist‑supervised adjustment of the

device.

            Later complications include

temporomandibular joint discomfort and changes in

occlusive alignment, which can lead to chronic pain

and difficulty eating.  Follow‑up by medical and

dental care providers is essential for prevention and

treatment of these problems.

            Because oral appliances are not successful

at eliminating sleep apnea in everyone, it is

essential that the patients be checked for

effectiveness of the device.  Partial but ineffective

treatment can mask the preventive symptom of snoring

while leaving the most serious sleep apnea untreated.

            The AASM has published a clinical practice

parameter based on evidence‑based literature review to

guide practitioners in the use of devices.  This paper

is also in your packet.

            Our recommendations include the following.

One, the presence or absence of sleep apnea must be

determined before initiating treatment.  Two, oral

appliances should be fitted by qualified personnel who

are trained and experienced in the overall care of

oral health and temporomandibular joint, dental

occlusion, and associated oral structures.

            Oral appliances may aggravate TMJ disease

and may cause dental misalignment and discomfort.

Follow‑up care by dentists is necessary to assess the

development in any of these complications.

            In summary ‑‑

            CHAIRPERSON GULYA:  Okay.  Thank you.

Summarize real quick, please.

            DR. EPSTEIN:  Okay. Oral appliances are

valuable tools, but they need to be applied and

managed by physicians and dentists trained in the

treatment of sleep disorders and the management of

dental health.  Our organization and the practitioners

it represents requests that you not change the

guidelines at this time and do not make them

over‑the‑counter devices.

            Thank you.

            CHAIRPERSON GULYA:  Thank you.  Next we

will hear from Dr. Moore.

            DR. MOORE:  Good morning.  My name is Kent

Moore.  I am a Board‑certified oral surgeon.  And a

segment of my practice in Charlotte, North Carolina

focuses on treating patients with sleep‑related upper

airway breathing disorders.  I am the mediate past

Chairman of the American Association of Oral and

Maxillofacial Surgeons Clinical Interest Group on

Sleep‑Related Breathing Disorders and Obstructive

Sleep Apnea and currently serve as the President of

the Academy of Dental Sleep Medicine.

            The ADSM, the international organization

representing general dentists, physicians, oral

surgeons, orthodontists, prosthodontists, and

pedodontists sharing a specific interest in oral

appliance therapy and jaw surgery for treatment of

sleep‑related breathing disorders, is grateful for the

opportunity to address the FDA regarding consideration

of over‑the‑counter use of oral appliances.

            I have no financial interest in this

discussion, and my travel expenses have been paid for

by my academy.

            The ADSM is strongly opposed to OTC use of

oral appliances and feels that allowing OTC use would

present a significant risk to the greater public

health.  We do not feel there is sufficient data form

the body of scientific and professional literature

that substantiates the safety and efficacy of oral

appliances utilized in this manner and recognize that

unsupervisied utilization of these types of appliances

will cause significant morbidity to the population

involved as well as have detrimental effects in

preventing or delaying the diagnosis and proper

treatment of the underlying sleep‑related upper airway

disorder.

            The explanation for this position is

clarified blow in our response to the specific

questions asked by the panels.  That is, what is the

role of the medical/dental provider in the diagnosis,

treatment and follow‑up of snoring and sleep apnea?

            The ADSM's clinical treatment protocol,

which is attached in our written documents, documents

our position that the diagnosis or absence of OSA and

differentiation of primary snoring from OSA can only

be performed by a qualified sleep physician and

treatment therein coordinated and directed by the

diagnosing sleep physician.  Referral from the sleep

physician after proper diagnosis is made to the

treating dentist is necessary prior to fabrication of

an oral appliance.  These recommendations adhere to

the current American Academy of Sleep Medicine

Clinical Practice Parameter.

            Much of the effort of the ADSM is directed

toward training our membership regarding the

complexities of upper airway pathophysiology and need

for sleep medicine.  In order to modify complications

of therapy, once an oral appliance has been

fabricated, the patient must be followed clinically

for the length of time that the appliance is being

utilized.

            What is the ability of the patient to

self‑diagnose and treat obstructive sleep apnea?

Properly diagnosing the presence and severity of upper

airway disorders is a complex and potentially

complicated exercise.  The position of the ADSM is

that accurate self‑diagnosis on the part of the

patient is not a reliable method for diagnosis.

            People trying to eliminate their snoring

are often not aware that snoring is a marker for the

presence of OSA.  Differentiating snoring from OSA can

be difficult for sleep physicians without the use of

objective testing, much less an untrained person.

            Use of OTC oral appliances may improve the

symptom of snoring but leave the OSA untreated,

exposing the person to the risk of developing

hypertension and cardiovascular disease as well as

increased rates of workplace and motor vehicle

accidents.

            Also essential prior to treatment is the

need for proper diagnosis of the severity of the upper

airway disorder in order to help direct the proper

intensity of therapy.  The literature documents that

oral appliances are statistically more beneficial in

patients with mild to moderate OSA; whereas, those

patients with more severe degrees of OSA possess a

less statistical chance of obtaining a cure with oral

appliance therapy.

            Allowing any user to obtain an OTC version

of an oral appliance and treat themselves without

proper diagnosis exposes many patients to potential

under or inadequate treatment of their airway

disorder.

            Additionally, when a user fails to get an

adequate response from a fixed position OTC version of

oral appliances, their willingness to pursue a more

professional and therapeutic version of an oral

appliance will most likely be tempered.

            Data regarding safety and efficacy of oral

appliances utilized in this OTC manner, preferably

performed by entities devoid of a profit motive or

other conflicts of interest, would be required prior

to an OTC intended use decision.  Data to this effect

is currently lacking.  The long‑term impact of oral

appliance therapy on TMJ function within the body of

scientific literature also is currently lacking.

            Adequate device labeling would require

complete descriptions of the symptoms, causes, and

consequences of obstructive sleep apnea; the need for

appropriate medical evaluation for OSA, including the

differentiation of primary snoring from OSA and the

relationship of snoring to OSA; and an overview of the

mechanisms of oral appliances.

            Consumers would need to be warned that

treating their snoring may not eliminate OSA, even

without other symptoms being present, resulting in

silent apnea.  Patients should be advised to contact

their health care providers for any suspicion of OSA

or if the devices are unsuccessful in eliminating

snoring.

            Consumers would also need to be warned of

the following serious potential adverse events, as

mentioned by a previous speaker.  True, there are OTC

appliances available to the public for treatment of

tooth grinding or bruxism, but these appliances are

not being asked to do what an advancement appliance is

doing and do not bear the same type of forces being

brought to bear for patients with OSA.  Considering

these forces, the potential for adverse effects is

greatly magnified compared to these bruxism or mouth

guard appliances.

            In conclusion, the ADSM strongly opposes

making oral appliances available for OTC use.  Oral

appliances can be effective therapy for snoring and

OSA, particularly in mild to moderate, severe OSA.

However, the difficulty in differentiating between OSA

and snoring, the need for clinical evaluation and

physiologic testing and the potential for significant

complications listed above, particularly in lieu of

clinical data showing safety and effectiveness in an

OTC model, make it essential that oral appliances be

provided under the direction and care of medical and

dental personnel trained in the management of patients

with sleep disorders.

            CHAIRPERSON GULYA:  Thank you, Dr. Moore.

            Any questions from the panel for Dr.

Moore?

            (No response.)

            CHAIRPERSON GULYA:  No.  Okay.  Thank you.

            Dr. Thornton?

            DR. K. THORNTON:  Thank you.  I'm Dr.

Keith Thornton.  I'm in the private practice of

dentistry in Dallas, Texas.  I am the owner of Airway

Management, Incorporated, which makes the TAP oral

appliance.

            I also have a number of other inventions.

I am now part of the visiting faculty at Baylor

College of Dentistry Department of Orthodontics.  I

have taught there in treating temporomandibular

disorders and have taught at Pankey Institute the last

30 years.  I am a consultant to Wilford Hall and to

the Army in oral appliances and have worked for a

number of people, including the Academy of Dental

Sleep Medicine.

            My issue today really is to come and say

as a practitioner, I have treated probably 300

patients a year for the last ten years.  And I have

given some pictures to you of the morbidity that is

caused by these devices.  The device that I have

developed can move the jaw beyond maximum protrusion

in what we call passive stretch position, must beyond.

            If you look at the publication by Jeff

Pancer and the editorial afterwards, it says now that

we can treat severe sleep apnea ‑‑ and that is what we

are treating.  That is who I treat.  I treat the

people that are non‑compliant severe sleep apneics.

            In that picture, as you see, the patient

was a 95‑year‑old patient that is in Class I occlusion

when I started treating him in '93.  By '97, he was

seven millimeters forward of that position.  And that

was a permanent position.

            He stopped wearing the appliance in about

'99 to 2000.  And he has not worn the appliance since.

He has no sleep apnea, and it is almost like I did

orthomatic surgery on him.

            I have seen that in about four and a half

percent of my cases.  It is a frightening thing when

we see that.  I have decided not to take my device and

make it even a non‑custom appliance because I do not

feel that it needs to be in the hands of anybody that

is a non‑dentist.  And I am talking about physicians,

anybody else that is a non‑dentist, even a

professional.  So my determination as a company is to

keep it within the dental profession.

            As far as the warnings and labeling, we

have just finished going through our booklets on

clinician instructions and made a lot of changes,

including in our packets, some really significant

things that I think are important.

            One of these you will see in the next

pictures over are pictures of what we call our

exercise bite tabs.  They go into every one of our

boxes.  And it's one of the things that when I teach

dentists ‑‑ and I have taught at all of the meetings.

            I said the most critical thing that you do

every morning is get the mandible back in the right

position and teach the patient so that they can feel

their back teeth every morning.  If they don't do that

within three weeks, I've seen it where they cannot get

their teeth back into centric occlusion where they

can't get their back teeth together.

            We are now working with the head of the

Orthodontic Department and looking at doing dog

studies in effecting what we are really doing with

this jaw joint and how it functions.  It can cause

very significant morbidities.  As a practitioner and

as a manufacturer, I don't think it is ethical for me

to come out with something that is any less than a

device that is made by dentists.

            Thank you.

            CHAIRPERSON GULYA:  Thank you very much,

Dr. Thornton.

            Do we have any questions for Dr. Thornton?

            (No response.)

            CHAIRPERSON GULYA:  Thank you.  And,

lastly, we will have Mr. George Dungan.

            MR. DUNGAN:  Thanks very much for the

opportunity to participate today.  Respironics is a

leading manufacturer of sleep and respiratory

products.  I'm the manager of clinical affairs, and

I'm here in that capacity.

            Our focus at this meeting concerns two

important opportunities to improve patient care;

specifically, over‑the‑counter treatment of snoring

with appropriately tested and effectively used oral

appliances and over‑the‑counter use of screening tools

for sleep apnea.  As you have heard, sleep disordered

breathing affects millions of Americans and is largely

under‑diagnosed and under‑treated.

            Obstructive sleep apnea affects at least

18 million Americans, with up to 80 percent

undiagnosed currently.  At the other end of the sleep

disordered breathing spectrum, snoring is a noxious

condition that often prompts some intervention or at

least accommodation by sufferers.

            Many OTC treatments are promoted for the

treating of snoring, although none have proved

clinical evidence as to their overwhelming efficacy.

On the other hand, efficacy has been established by

the many prescription devices that have been cleared

by the FDA to treat snoring.  Many of these are oral

appliances, the safety and efficacy of which have been

demonstrated through clinical trials over the past ten

years.

            OTC clearance for oral appliances to treat

snoring focuses on two questions:  first, whether the

treatment of snoring would prevent a user from seeking

treatment for a potentially more serious condition,

such as OSA; and, second, whether a user can

successfully choose, fit, and treat the snoring on

their own.  Both of these risks are mitigated through

education and labeling.

            The ability of adequate instructions in

labeling to permit the safe and effective use of OTC

products has been demonstrated by the numerous

clearances associated with other OTC medications and

devices.  These products show that consumers can

readily understand when a medication or device is

right for them, how to properly use the product, and

when to seek medical assistance.

            The same model can be applied to an OTC

oral appliance.  Such devices will need to include

specific warnings and educational information for

determining proper fit and use of the appliance.

            Further, labeling and instructions should

help users identify obstructive sleep apnea.  The

instructions should direct patients to seek medical

attention if they currently have symptoms of OSA, if

their condition does not improve, or if they

experience discomfort or side effects from use of the

device.  We believe that any OTC device must also

include a clear directive to the patient to include

the appropriate clinician as a partner, even in their

self‑treatment.

            FDA clearance of an OTC oral appliance

should be supported by adequate clinical data,

demonstrating the safety, efficacy, and useability of

the device.  These data would need to be submitted to

the FDA for review prior to clearance and should

address the following:  compliance with FDA guidance

on oral appliances; studies of long‑term effects of

continuous use of the device; demonstrated therapeutic

efficacy; and, finally, demonstrated useability.

            An important consideration for the use of

OTC appliances is the adequate identification of the

likelihood of obstructive sleep apnea.  Thus, OTC

screening for OSA is tied to these appliances.

Patients pay a key role in their own transition for

personal awareness to diagnoses.  To help aid in that

transition, we feel that tools raising awareness can

help patients overcome that barrier.

            The availability of at‑home OTC screening

devices for OSA will enable patients to move more

readily towards appropriate diagnosis and treatment by

a clinician.  Failing to substantially address OTC

screening may, in fact, perpetuate significant

under‑diagnosis of OSA.

            Such OTC devices for use in the home by

untrained patients would need to meet several

requirements.  First, the device must have the

appropriate level of sensitivity to identify sleep

apnea while maintaining a low rate of false negatives.

Manufacturers should provide the FDA with clinical

data comparing the results of the OTC use in the home

to the results of subsequent formal diagnostic

procedures.

            Second, user validation studies should be

submitted to the FDA, demonstrating that the patient

can properly determine that the device is appropriate

for their signs and symptoms; use the device;

understand the labeling; and, finally, understand the

results.

            We feel very strongly that any OSA

screening device should deliver unambiguous results,

results that are not subject to interpretation such

that a patient would definitively know whether to seek

further medical assistance for their OSA.

            CHAIRPERSON GULYA:  You need to be

wrapping up.

            MR. DUNGAN:  In summary, Respironics

believes that the OTC availability of oral appliances

for snoring and, finally, oral screening aids is

extremely important to reach a large at‑risk

under‑served population.  When supported by proper

data, these two types of products can offer

significant benefits to patient management.

            Thank you.

            CHAIRPERSON GULYA:  Thank you, Mr. Dungan.

            Any questions for Mr. Dungan?

            (No response.)

            CHAIRPERSON GULYA:  Okay.  Well, with

that, our open public hearing session draws to a

close.  I thank our public speakers for the

information they have taken the time and trouble to

bring to the panel.  I would like to turn to Sally

first to see if she has any announcements or anything

for the panel.

            EXECUTIVE SECRETARY S. THORNTON:  I don't

think so, not at this time, except to say that there

will be a second open public hearing session this

afternoon of a half‑hour duration.  And we do have one

speaker at that time.

            CHAIRPERSON GULYA:  Well, with that, the

panel has already had a pretty busy morning.  I

propose we take about a 15‑minute break and plan on

being back here at 10:30.  Thank you.

            (Whereupon, the foregoing matter went off

            the record at 10:17 a.m. and went back on

            the record at 10:35 a.m.)

            CHAIRPERSON GULYA:  We now have two panel

presentations, the first of which will be by Dr. David

Terris.  Dr. Terris?

            DR. TERRIS:  Thank you.

                 PANEL PRESENTATIONS

            DR. TERRIS:  Good morning.  It's an honor

to have the opportunity to address this distinguished

group about several issues.  I was asked to take sort

of an evidence‑based approach to answering multiple

issues.  I want to start by thanking Kenny Pang, who

is our sleep surgery fellow with the Medical College

of Georgia, who helped with a lot of the background

research.

            So there were three specific issues I was

asked to focus on.  The first lends itself last to an

evidence‑based approach, which is simply a defined

occurrence of standard of care for diagnosing sleep

apnea; secondly, to consider the issue we have heard

about already, which is, are patients capable of

diagnosing themselves with having sleep apnea based on

a series of signs and symptoms; and, then, finally, a

related issue, which is, can they, therefore, monitor

the effectiveness of treatment utilizing those same

signs and symptoms and how does that correlate with

objective measures of success?

            I actually think it is quite important to

spend just a few minutes talking about the importance

of the diagnosis and treatment of sleep apnea.  We

have heard a little bit about this.

            The cardiovascular impact we know from the

sleep heart health study now, quite definitely, the

impact of sleep apnea, the neurovascular risks, and

the risks for motor vehicle accidents.  This is an

older study but quite clearly shows the impact of

sleep apnea on mortality.  This is from 1988, patients

with an apnea index of more than 20 or less than 20

over time untreated, you can see what happens

independent of other comorbidities.  This is the

mortality, the cumulative survival on the y‑axis.

            The sleep heart health study is a very

important study put on by Susan Redline and her

colleagues at Wisconsin.  There has been a series of

publications related to this study of over 6,000

subjects enrolled.  All underwent ambulatory

polysomnography.  And the most important finding was

a very strong correlation of sleep disorders with

cardiovascular disease independent of other risk

factors.

            We know about driving while sleeping.

It's a terrible problem.  National Highway

Transportation Safety Administration estimates over

50,000 accidents, with 1,500 deaths, due to sleep

drivers.  Again, this is something we are all familiar

with.

            Something else most people are aware of is

the Exxon Valdez crisis, but what many people don't

know is that ten years after the catastrophe, it was

determined that this was caused by a sleep captain of

that ship who probably had an underlying sleep

disorder, so very significant ramifications.

            The scope of the problem, we know that the

society is becoming more obese, resulting in increased

prevalence of sleep disorders and, therefore,

proliferation of products to treat this problem.

            This simply represents this advancing

creep of obesity in society.  Of course, coming from

Georgia, I am particularly concerned about the dark

green because that is more obesity.  They are most

closely associated with the prevalence of sleep apnea.

            Not everybody thinks this is a problem,

however.

            (Laughter.)

            DR. TERRIS:  Well, again, proliferation of

a number of different products.  The snore pills,

which come in a regular or allergy‑type modification;

the snore sprays, which are typically emollients that

lubricate the upper airway; and one that we're going

to consider I guess today, which is nasal strips, the

Breathe Right strip.  We have heard a little bit about

that.  It's important to make sure it's placed

accurately and depending on the nasal architecture,

make sure you have enough of them.

            (Laughter.)

            DR. TERRIS:  Oral appliances I'm going to

just skip through this.  There's a number of different

products available, which have different ways that

they're manufactured.

            Okay.  So getting to the issue of

polysomnography, this was first described in the

1950s, popularized by Dement of Stanford in the 1960s

and really is considered the gold standard today.  And

this is what we're talking about.  Level I attended

polysomnography has a series of monitors that are

placed:  an EEG monitor to confirm that the patient is

in sleep; EOGs to test for REM sleep; EKG monitor,

self‑explanatory; EMG to evaluate for periodic leg

movements, snoring sounds, nasal and oral air flow;

and then plethysmography for chest and abdominal

movements, as well as pulse oximetry and positional

monitors.

            I have some personal experience with this

particular modality, having had a sleep study myself

about ten years ago, prior to having some minor

snoring surgery.

            This is what it felt like the day after

the study.  This is now sleep like you would at home

after being hooked up to these monitors.  So it's a

quite involved process.

            This is the information that is obtained

from the sleep study.  So we know that the patient is

asleep.  We see increasing respiratory effort but no

air flow in this patient having an apnea.  Therefore,

they have a corresponding drop in their oxygen

saturation.

            Therefore, the brain has a choice to make.

It wants to stay asleep, but it also need oxygen.  So

ultimately it usually makes the right choice and

awakens so that the muscles surrounding the throat

regain tone and you reestablish air flow.  And,

therefore, the oxygen saturation can go back up to

normal.

            So this is standard polysomnography.  And

that's in an attended in‑hospital study.  Ambulatory

polysomnography, which you have heard a little bit

about, typically involves at least four channels

looking at pulse rate, oximetry, some type of measure

of air flow, and then abdominal or chest movement.

            This is I think a very good way of

diagnosing sleep apnea.  Again, this is the modality

that was utilized in the sleep heart health study.

However, the ASDA has come out with a position

statement in 1994 that ambulatory monitoring is no

substitute for attended Level I polysomnography with

the exception of rare circumstances, patient can't get

to a lab or there is some contraindication to an

attended in‑house study.

            There are a series of screening devices

that are being investigated.  Pulse oximetry has been

utilized quite frequently.  There are a number of

studies examining this particular modality with

sensitivity ranging from 23 percent to 90 percent.

That is part of the reason why this is really

considered to be a non‑realizable technique for

diagnosing sleep apnea.

            A couple of more promising techniques.

The Watch PAT device is a finger‑mounted optic

pneumatic sensor.  It actually detects obstructive

events from the sympathetic events that are caused by

the obstruction.  There has been some promising

correlation with full polysomnography and then another

device.

            Then let me just give full disclosure.  I

have no financial interest in the company that makes

SleepStrip, but I am about to start a study looking at

this as a screening device.  So this is an upper lip

adhesive device that has flow sensors and oximetry

and, again, some promising early data that we are

going to try and evaluate.

            So issue number one was an easy one for

me:  the standard of care for diagnosis of sleep

apnea.  It's polysomnography.  I am quite certain that

Dr. Epstein and his colleagues would agree with that

from the sleep medicine world.

            The second issue was the possibility of

patients self‑diagnosing sleep apnea.  First of all ‑‑

and this would be related to the signs and symptoms of

sleep apnea.  So let's make sure we know what those

are.  Snoring, excessive daytime somnolence, and

witnessed apneas are the three mainstays.  There are

a number of other symptoms that patients can present

with, including morning headaches, irritability,

neurocognitive deficits, including memory impairments,

impotence, and nocturia, particularly in children.

            In addition to those signs and symptoms,

there are other so‑called risk factors for developing

sleep apnea, so advancing age, gender.  Being male is

not a good thing.  Body mass index.  So that's the

weight of the patient and then neck circumference.  So

we know that these are associated with the development

of sleep apnea.

            So looking individually at the three

primary symptoms, snoring to start with, there is

quite a strong correlation of snoring with sleep

apnea, but you can see it's as low as 72 percent, as

high as 87 percent in a number of studies that have

looked at this as a specific symptom of sleep apnea.

            Probably the best way for evaluating

excessive daytime somnolence in an easy fashion is the

Epworth Sleepiness Scale.  It's the most commonly

utilized tool for assessing sleepiness.  But even

this, 41 percent only of 440 snorers with an elevated

Epworth scale score have sleep apnea, 61 percent in

another study, so, again, not a very good predictor of

the likelihood of having sleep apnea.

            What about witnessed apneas, which is

another common finding more commonly seen in patients

with sleep apnea but, again, not a one‑to‑one

correlation?  So armed with some of this information,

a number of investigators have attempted to develop

models for predicting sleep apnea, again based on

either symptoms and/or some of the other risk factors

that I mentioned.

            This was one study of 410 patients with a

relatively complex algorithm.  And you can see only a

46 percent positive predictive value in diagnosing

sleep apnea.

            Another study with slightly better data,

427 patients, again, acknowledging snoring, witnessed

apneas, gasping, age, gender, BMI, found only a 60

percent sensitivity in diagnosing sleep apnea.

            And then the larger study of 744 patients,

somewhat better results, a more complex scoring

system, but you can see 86 percent sensitivity, 77

percent specificity, 89 percent positive predictive

value.

            So based on this evidence‑based review, I

would say one cannot reliably predict the presence of

sleep apnea without performing some type of

polysomnography.

            And then the final issue is, again, a

related issue.  Can we determine the effectiveness of

treatment by evaluating signs and symptoms of sleep

apnea?  I'm just going to show three of many studies

that would suggest that that we can't do that.

            So this was an earlier study from Shiro

Fujita, who did a lot of the early work with surgical

interventions with sleep apnea.  This was on

palatopharyngoplasty.  He was one of the first to

recognize that even in his group of 31 patients, even

patients who had improvement in their sleepiness may

not have improvement in their polysomnographic

evidence of sleep apnea, so creating what was referred

to earlier as the so‑called silent sleep apneic.

            Nelson Powell in Palo Alto has done a lot

of work with radiofrequency ablation of the palates.

In this study of 22 patients, they showed no change in

the polysomnographic parameters in their patients, but

the snoring improved by 77 percent and the sleepiness

improved in 39 percent.  So, again, the patients are

going to feel better, but they may not be better.

            And then our own data looking at hyoid

myotomy, genioglossus advancement, and palatal frontal

plasty, 32 patients, again, we have very good

improvement in the sleep but not as good as we got in

the snoring and the sleepiness.  So that's one reason

why these patients do need to be followed up

post‑surgically and reevaluated with polysomnography

after any surgical intervention.

            So, to finish off, improvements in the

signs and symptoms of sleep apnea often occur in the

absence of objective evidence of improvement in sleep

apnea.

            Thank you.

            CHAIRPERSON GULYA:  Thank you very much,

Dr. Terris.

            Do any of the panelists have questions for

Dr. Terris?  I think we will have an opportunity to

readdress some of these issues when we go into our

deliberations over the questions as well.  Yes?

            DR. ROSENTHAL:  Dr. Terris?

            CHAIRPERSON GULYA:  Could you please give

your name?

            DR. ROSENTHAL:  Rosenthal, Division

Director.  That was an excellent presentation.  Can

you tell us something about the longitudinal nature of

this condition?  Do people progress from mild to

moderate to severe over time?

            DR. TERRIS:  Yes, it gets worse over time

for a lot of different reasons, primarily related to

increasing weight and laxity of tissue.  So it's one

of those progressive diseases, chronic diseases, over

time.

            CHAIRPERSON GULYA:  Yes?

            MEMBER ZUNIGA:  John Zuniga.  Related to

that same question, is there a percentage of patients

that go from mild to severe and vice versa without

treatment?

            DR. TERRIS:  I'm not aware of a single

patient that went from severe to mild without

treatment depending on how you define treatment.  I

just saw a patient in the office the other day who had

a gastric bypass, which I consider treatment for sleep

apnea, and lost a couple of hundred pounds and went

from an RDI of 90 to an RDI of 3.  So if you include

that as treatment, then no, I have never heard of that

ever happening.  But to go from mild disease to severe

disease, yes, it happens with regularity.

            CHAIRPERSON GULYA:  Yes, Dr. Woodson?

            DR. WOODSON:  Gayle Woodson.  Now, you

have patients who say they feel better but are not

better.  If you have someone who does feel better and

he's functioning better, then there's a disconnect

between the functional results of it and the

objective.

            Now, have you looked at like sleep onset

time because that is one objective measure of whether

or not they're really less sleepy, rather than just

saying they're less sleepy because they don't want

another operation?

            DR. TERRIS:  Yes.  Well, the problem is

it's not ‑‑

            CHAIRPERSON GULYA:  Please identify

yourself for the transcriptionist.  They're trying to

‑‑

            DR. TERRIS:  That was Gayle Woodson.  I'm

Dave Terris.

            EXECUTIVE SECRETARY S. THORNTON:  Yes.  I

think once around for everybody clearly into the

microphone will be enough for the transcriptionist.

Correct?

            CHAIRPERSON GULYA:  Okay.

            EXECUTIVE SECRETARY S. THORNTON:  Thank

you.

            DR. TERRIS:  The problem is that it's kind

of like hypertension or diabetes.  I mean, if you ask

a patient with hypertension, "Do you feel badly," they

say, "No.  I feel fine."  But, nevertheless, this is

a chronic disease that is taking its ‑‑ exacting its

toll over years.  So to me, yes, there are better ways

or good ways to carefully document if the sleepiness

has gotten better.

            On the other hand, even if the sleepiness

is better, they can still have the cardiovascular

ramifications of the obstructive events occurring

frequently during the night.

            DR. WOODSON:  Yes.  But isn't the evidence

for the cardiovascular kind of epidemiologic and a lot

of it is snorers have more strokes?  There's not that

much good prospective data about people documented to

having sleep apnea and the results.

            So specifically somebody who objectively

in a lot of ways is not better.  Is there a

possibility he might not be having as much sequelae?

I mean, we don't have the data to say that, really.

I mean, it just makes sense compared to hypertension,

but we don't really have that data, right?

            DR. TERRIS:  I'm trying to think if that

specific study has been done.  And if anybody else on

the panel is aware of it, please speak out.

            DR. LI:  Kasey Li from Stanford.  I just

want to make a couple of comments.  One, the

improvement that you see in some of these studies,

none of them are from placebo‑controlled.  So they're

short‑term studies.

            So, one, you have to look at the

possibility of placebo effect on improvement of

symptoms.  That's number one.  Number two, a lot of

times you see short‑term improvement in a matter of

three to six months in terms of functional

improvement.  They have relapse.  And even though they

may have some improvement, that doesn't mean that they

have resolution of the disease.  So the improvement in

snoring doesn't really reflect, as you see in the

literature, an improvement or resolution of sleep

apnea.

            There are a lot of epidemiology studies,

two large studies from Wisconsin Cohort as well as the

National Heart Lung study looking at specifically and

demonstrating that sleep apnea is an independent risk

factor, I think, for cardiovascular disease.

            So I think that the evidence is fairly

profound sleep apnea by itself significant affects the

well‑being of the patient.

            CHAIRPERSON GULYA:  Thank you, Dr. Li.

Okay.

            DR. TERRIS:  I certainly would agree with

all of those comments.  I guess it still doesn't get

at Gail's question of if the patient feels better and

their sleepiness is better, even if they have

polysomnographic evidence of sleep apnea, is their

risk of cardiovascular disease diminished?

            Again, I don't know whether that study has

been done, but I can't imagine that that would be the

case.  That's the only way.  I would say that.

            CHAIRPERSON GULYA:  Okay.  Well, thank you

very much.  We will now hear from Dr. Demko.

            DR. DEMKO:  Thank you.

            My name is Gail Demko.  I am a dentist in

private practice.  And my practice has been limited to

treatment of patients with obstructive sleep apnea

since 1997.  What I am going to talk about today is

oral appliance side effects and how I use that in

patient selection, appliance selection because there

is no question about it.  Of all of the patients that

are referred to me, I treat fewer than 75 percent of

them.  And I am going to go fast.

            What I want you to worry about is what

everybody else has been talking about, symptom

responders.  This is from Anette Fransson's Ph.D.

thesis in Sweden, where patients who are given oral

appliances and were subjectively better when tested

polysomnographically, it was found out that they were

not better.  So even though the patients felt fine,

they weren't.

            The majority of the appliances on the

market are mandibular repositioning devices.  Their

job is to bring the jaw forward and keep it closed.

Those two movements open the airway, both

retroglossally and behind the soft palate.

            What I worry about is the more you open

that mandible, the more it is going to be in a

rotational mode.  The more it rotates where the

genioglossus attaches at the anterior portion of the

mandible, the more it is going to rotate backwards and

close the airway.

            So one of the things in choosing an

appliance, one has to look at how much do you have to

open that patient to get an effect?  This is a typical

ceph on a patient of mine with and without an oral

appliance.  The more you open him, the more you are

going to have to bring him forward, which is basically

what this person is saying.

            So there are short‑term changes with

appliance use.  There are long‑term changes.

Short‑term many times is just self‑resolving.  The

excessive salivation occurs when a patient can close

around an appliance because it is small enough.

            Other patients will complain of dry mouth

because they cannot close.  But the bulk of the

appliance is so big that they have lip incompetency

and now are mouth breathing, which is basically what

I don't want a patient to do because nasal breathing

makes the appliance work better.

            Pain in individual teeth happens almost

always in patients who have teeth with very sharp

edges, very crooked teeth.  It can be that the model

that I sent to the laboratory was worn in shipping,

the impression was distorted, or that when the patient

took a boil and bite appliance home, if they got them

over the Web, which they can illegally from England

and Canada, that if there is contact with the edge of

that tooth and the hard outer shell of the boil and

bite, there will be pain.  Very simple.  Adjust the

appliance.

            Pain in the anterior teeth that the

patient is clenching, clenching forces can often

intrude teeth.  Again, I want to make sure that that

patient has contact all the way around on the arch, at

least in a tripod configuration.

            The mobility of the anterior teeth is

extremely common from the forces of the mandible being

forward by virtue of the appliance pulling it forward,

the muscles pulling it back.  I will always go in and

adjust an appliance on the facial aspect of the upper

anteriors and the lingual aspect of the mandibular and

take those forces off the teeth.  It doesn't stop them

from moving, but it stops them from being mobile.

            Posterior open bite in the morning.  There

are always arguments about why this happens, but

Fernanda de Almeida has done MRI studies where as that

mandible is moved down and forward out of the socket,

you actually will get edema in the joint space.  Some

theorize it's shortening of the internal lateral

pterygoid, but that couldn't happen as quickly as this

fluid buildup is.  And within two to three weeks,

patients will have evidence of a posterior open bite,

where their anterior teeth are the only things that

contact because the fluid is holding the condyle down

and forward.

            I have patients who will chew bubble gum,

just clench, but I tell them that that fluid needs to

be gone in 15 minutes after they get up in the morning

or there are going to be problems later on.  It

doesn't prevent problems later on, but it seems to

minimize them.

            Patients who have joint pain bilaterally

I find that predominantly it is excessive mandibular

advancement, which for some patients may be anything,

but it's beyond the ability of the joint structures to

tolerate.  In some cases just setting the appliance

back further is fine and takes care of the problem.

In some places, they will have to discontinue care.

            If they have unilateral pain, it seems

more often it is an eccentricity so that the mandible

is off to one side.  Once you line up their midlines

or however they are naturally because patients can

deviate as they open and close their mandible, you

want to match that movement with your appliance, that

just moving the appliance one way or the other will

solve that problem.

            There are allergic reactions, people who

are nickel‑allergic, latex‑allergic, and methyl

methacrylate.  All three of those things are in

various appliances, and patients do need to be warned

about that.

            Things that worry me:  long‑term changes.

These long‑term changes do not normally become obvious

for a year.  Anything that happens within six months

of wearing an appliance seems to be self‑resolving if

the appliance use is discontinued.  After that, all

bets are off.  These changes are permanent.

            So in this case, I have gotten patients

who have developed all sorts of fibromas from hitting

the edges of appliances.  What I did with this, the

patient had to go to the oral surgeon, have the

fibromas removed.  We redesigned the appliance so

there was no more irritation of soft tissues.

            Hard tissues changes are related to

incomplete coverage of the dental arch ‑‑ we argue

about this at all meetings ‑‑ and related pressures on

the dental arch because these appliances are basically

functional orthodontic appliances.  The big deal is

that transceptal fibers, which sit in the roots around

the teeth, are the fibers that kick off orthodontic

movement.

            And once they are activated, they transmit

forces around the arch, even away from where the force

is originally brought.  And they will continue to act

24 hours a day with or without forces being brought.

            So you will have with incomplete coverage

block movement of teeth.  So this is just showing that

I could take a model where the floss could go between

those last two teeth.  Open contacts are fairly small

in most instances, solve that by redesigning the

appliance or changing it to make sure that the back

molars are hooked around to now when you move the

teeth, you move all of them, as opposed to leaving two

behind.

            We know that there is anterior tooth

movement.  Rich's article, Rose's article, Marklund's

article, all of them will tell you anterior tooth

movement.  The forces brought on those teeth take the

maxillary teeth, make them more upright, take the

mandibular teeth, and actually move them towards the

lip.

            What I will see over periods of time is

opening interdental spaces.  And this is a combination

of effect, but it is from those transceptal fibers.

The only way to put these patients back where they

started if that's possible would be orthodontics.

However, with so many of these, the posterior teeth

extrude into position.  And now they are locked

forever in that bite.

            Again, the fluid build‑up is a short‑term

change that can lead to long‑term changes because as

the condyle is held out of the fossa, the space that

that creates, the posterior teeth will extrude and

either keep it so the patient ‑‑ this is a physician.

He is so happy with this appliance, he refuses to give

it up.

            Again, I don't see this type of movement

as often as other people do because I am really riding

patients hard.  He has had spacing in his teeth.  He

has had advanced modal, almost a quarter of an inch,

in his mouth.

            This is a patient that used to be an

anterior grinder and wear his teeth.  And now he can't

even touch his front teeth anymore.  This is a patient

who was wearing an appliance, had mandibular

advancement.  They put her in orthodontics.  She had

a bridge on the upper that wouldn't move.  They put a

lingual wire on the bottom so those teeth wouldn't

move.  And after her orthodontics, she had a lovely

anterior open bite.

            So there is a disagreement now among us as

to do materials of the appliance, do thermal active

acrylic appliances, Klearway, PM Positioner, or others

that you will heat up every night to put them in, move

teeth more than hard acrylics?  There is no published

data that appears definitive on that.

            Does moving the patient's mandible forward

seem to matter?  Big deal.  The statistical studies

show us that 75 percent advancement within the

patient's individual physiologic range seems to be the

most effective position.  However, that really means

as statistics look only at large groups, that my

patients have been successful anywhere between moving

them 50 to 125 percent of their normal range.

            So statistics tell us anybody who can't

move his jaw six millimeters, an appliance is not

going to be effective that moves the jaw forward.  And

patients' ranges will vary from 4 to 18 millimeters.

The further you move them, the more likely there are

side effects.

            Chris Robertson is looking at statistics

again, not individual cases, on how many patients

move.  The permanent movement of teeth begins between

6 and 12 months, and it continues past 30.  He's up

now to two more years of data.  It is not published.

He keeps the same original cohort and crunches

different things and publishes lots of articles.

            This is a patient who bought her appliance

online from overseas.  The same thing happens to these

boil and bite appliances as happens with the

prescription appliances that in this country are

available from dentists.

            What I don't like to see is anything that

does not completely cover the mandibular teeth

completely.  When you have these lingual flanges, the

forces on those lower anterior teeth will actually

avulse the teeth, even if they were healthy to start

with.

            What you want to be aware of is that there

is a significant decrease measured in the overjet and

overbite.  And in a Pantin study, only two of nine

patients who had total lack of contact on their

posterior teeth even noticed this.  Again, in Pantin,

fewer than half of his patients with occlusal changes

were aware that their teeth didn't hit like they used

to because these changes are so subtle.

            Tongue retaining devices are also on the

market.  There are very few of them.  They are not

without problems.  The majority of practitioners don't

use them because they're relatively tricky and

difficult to spit, but that will change as people come

up with better ideas and better mousetraps.

            A tongue retaining device that was

explained earlier moves the tongue bodily forward and

forces nasal breathing in most cases.  That is not

true with some of the other designs.  They are less

effective than mandibular repositioners.  And all

studies done on their efficacy back in the 1980s with

Ros Cartwright looked at also changing weight and

position of sleep.  Therefore, they never studied the

TRD all by itself, nor did they break those out.

            Again, short‑term side effects and

long‑term side effects.  It's going to cause excessive

salivation, irrigation on the tip of the tongue from

the suction.  Simple.  You teach the patient not to

put quite so much suction on the tip of their tongue.

Irritation from the edge of the appliance, wherever it

hits in the mouth, if it hits the Stenson's duct,

where patients have salivary flow or down in the

underneath of their tongue, you're going to get scar

buildup, that appliance needs to be reshaped or

replaced.

            Tongue lengthening.  People never thought

of this.  I only picked it up because one of my

patients is Hispanic and she is a Spanish teacher.

After three years of using her tongue retaining

device, she could no longer speak Spanish.  She

couldn't roll her R's.  She had to go into speech

therapy for two months to be able to go back to work.

She's still wearing her tongue retaining device, and

it's three times even longer than that.  Now it's got

52 millimeters.  But with speech therapy, she can take

care of that.

            So if you put suction on soft tissue, it's

going to move.  Her teeth have also extruded in the

past because the position that these appliances keep

the anterior teeth open, it means that if there is not

complete coverage of those teeth in back holding them

in position, they are going to move.

            Every patient of mine who goes into a

tongue retaining device for more than six weeks

because it takes at least that long before they can

even learn to tolerate it gets retainers.  And since

this patient has been in retainers, the last two years

her teeth have not moved, but her bite is still

permanently there.  It is probably that that change

came from the fluid buildup in the joint because once

you move the patient, open the anderum sizably, more

than a centimeter, there is going to be fluid buildup

in the joint.

            So how do I use all of this to help me

decide what patient I am going to treat and what

appliance.  I am going to do the typical looking at

decayed, missing, and filled.  Do I have enough teeth

to hold onto the appliance?  The forces these

appliances put on teeth are phenomenal and their

periodontal status.  I don't want to be doing

extractions.  That is a job for an oral surgeon.  That

is basically straightforward dental evaluation.

            This is the evaluation that really makes

a difference as to how I am going to choose oral

appliance choice.  When I am going to look, I am going

to look at the oropharyngeal opening.  Is it wide

open?  I want that patient.  Is it looking like this?

I want them to go see a surgeon first.  If it looks

like this, they're getting a tongue retaining device

because I can't see anything back there.  I may as

well get that tongue that's as big as Cleveland out of

the way.  If I see this, I am going to make sure that

that is not consistently what they are doing before I

send them back to their physician.

            When I look at their anterior open bite,

I want to know how these teeth are because the more I

open that anterior segment, the more likely it is that

I am going to rotate that condyle out of the fossal.

            If their bite is like this, I have to open

them 11 millimeters to get them past their front teeth

in the first place.  Then I have to have room for the

appliance or I'm going to be rotating that condyle way

out of the fossal, and I'm going to end up with a

little bit more problem.

            The catch is with the anterior open bites,

those patients, every time you put a millimeter of

material between their molars, it corresponds to a

three‑millimeter opening in the anterior.  So if I am

putting in a boil and bite appliance on that patient

that is going to open the posterior six millimeters,

I'm going to be opening them about 18 in front, going

to get into a lot of trouble.  So, again, I need to

know where their teeth are because I can decide which

appliance I am going to use.

            I want to look at tooth damage.  This

patient is a severe gastroesophageal reflex patient

because of his sleep apnea, lo and behold.  And when

he is sleeping at night, that acid comes up in his

mouth, eats his teeth away.  And his teeth are so

short, the appliance doesn't hold on.  He's in a

tongue retaining device at this point.

            This patient was sent right off to the

maxillofacial surgeon because I wasn't going to put an

appliance in a mouth that looked like that when she is

in the full bite.  This patient is a severe bruxer.

He's been eating his teeth away for years.  He breaks

his appliance routinely, about on a monthly basis.  I

finally taught him how to realign his own tap in this

case, and he has been happy ever since.

            This patient has periodontal problems,

missing teeth.  Put that patient in a tongue

stabilizer.

            Patients I don't touch.  I don't touch

this patient.  This is a hypoplastic maxilla.  I am

moving the mandible forward against the maxilla as my

anchor.  If the maxilla is too far back, it doesn't

matter how far I move that mandible.  It's not going

to be far enough.  Don't treat steep mandibular jaws.

            This patient up here doesn't look it

because she doesn't have your typical long lower face.

She has a 50‑degree angle on her mandible.  So that

any appliance I put in her mouth will automatically

rotate her mandible almost directly back.  And I will

simply lower and exacerbate her blockage.

            Patients that are in cross‑bite, either

unilateral or bilateral, where I've got a jaw size

discrepancy, I will do my best to bring those patients

forward, but it would be really nice if their palates

could be split because if the palate is narrow, the

nasal passages are narrow, and I really like to have

free nasal breathing with my appliances.

            So for a mandibular repositioning device,

I want to treat retrognathic patients.  If they come

in looking like Prince Charles with his money, that

would be nice.  Thin patients, young patients.  The

older the patient is, you get over 65, appliances

don't work as well.  When you're sagging on the

outside, you're sagging on the inside.  It's really

hard to get the appliances to work.

            Female patients, Marklund, new study shows

an odds ratio of over 12 for just being female with

the success of an oral appliance.  I want a healthy

dentition.  I want a protrusive range of more than

seven millimeters.  And I would like to have a

moderate anterior overbite, which their teeth do

overlap.

            With a tongue retaining device, again, the

correlates with success are normal weight, that they

are worse in a supine position, ‑‑ therefore, they get

better if you put them in a lateral position ‑‑

macroglossia, definitely not tongue‑tied, and normal

soft palate length.

            Going to fail with obesity.  Retrognathic

patients do not do well with tongue retaining devices

because the real problem is jaw size, short lingual

frenum, tongue‑tied, severe sleep apnea, no positional

changes.  And, no matter what, it's less effective

than a mandibular repositioner.

            So selection of the appliance depends on

the patient's dental health, on their jaw size, the

severity of disease, age, and lifestyle because I'm

not going to give somebody an appliance that looks

really clunky if that person is really worried about

his Saturday night date.

            Looking at occlusal schemes, I am looking

at their bruxism and whether they have acid reflex.

TMJ history, it turns out I have very little problem

with patients who have a history of TMJ.  I always

give it to people who have never had it before.  The

people who had it before seem to get better.

Mandibular repositioners are one of the number one

appliances used for treating locked jaws.

            So fabrication requires that I measure how

much advancement can I get with a George gauge.  I

like using adjustable appliances to limit the amount

of joint problems I am going to have.  If I take an

impression, I always worry about aspiration of that

material.  I want complete coverage of the dentition

and have an impression that doesn't distort, doesn't

have bubbles, or voids.  With a tongue retaining

device, I'll do anything to prevent tooth extrusion.

            George gauges are fitted in the mouth,

like this, so the teeth come all the way together.

They do have a bite for top and bottom.  The patient

can pull his mandible all the way back without tooth

contact, push it all the way out.  And on this handle,

here is a millimeter scale that will give you about 18

vectors of movement all put into one nice little

package.  It's not as accurate as we would like, but

it's great.  It's all we've got.

            And then a bite registration is taken at

the position where I think they are not going to get

TMJ pain, which is if they come in with preexisting

TMJ problems, I put them 50 percent forward.

Otherwise it's 60 percent.

            So when patients are treating themselves,

first of all, they're not going to have an idea what

kind of periodontal condition that they have because

they don't go to the dentist anyway when they have got

problems.  And now with all of this big push on

periodontal disease causing heart disease, you don't

see a huge influx of patients into the office saying,

"Stop my heart disease.  I need my gums cleaned."

            You have all of the parafunctions that

patients are not aware of.  Clenching really bugs me

more than anything else.  Bruxism you can see.

Clenching is strictly by report.  I look at the

occlusal clasp, the proper fit of the appliance, their

denial of side effects, just as they deny they have

obstructive sleep apnea.  All appliances do the same

thing.  There has never been any study that shows that

one is less damaging than any others.  It is

unpredictable who is going to have problems with tooth

movement when and how far.

            One thing we have noticed is that

pregnancy makes it worse, that I've had patients where

there was no jaw repositioning, no tooth movement, and

they got pregnant.  When joints start letting go, they

let go.  And within two months, she had moved over a

quarter inch.

            So, in conclusion, there is no way to

predict who will be successful with oral appliances.

Statistics run just about 62 percent of unselected

patients who are successful patients who get worse are

the ones with steep mandibular angles, patients who

gain weight during study times.

            We can't predict all of the people who

actually do get worse.  There is no way to predict who

will have unwanted side effects.  Patients are not

aware of these dental changes.  The patients with

symptom relief may still have serious disease.  And

there are very few diseases maintaining written

publishable data banks.  Alan Lowe does because he is

university‑based.  He says 75 percent of his patients

have dental changes at 5 years.

            Glenn Clark used to be at UCLA, is now at

USC.  He says 50 percent at 5 years.  However, Alan's

work is clinical.  He actually sees the patient.  This

was by questionnaire.  So knowing that patients don't

notice that they have dental changes, it could be very

high.

            Christ Robertson did not look at the

number.  He simply looked at overall statistics.  And

Marie Marklund is starting putting together all of her

5‑year data now on over 800 patients.

            Any questions?

            CHAIRPERSON GULYA:  Thank you very much.

Do any of the panelists have any questions?  Yes?

            DR. STERN:  While I understand that there

are a lot of dental changes, how serious are these

dental changes as far as the repercussions other than

cosmetic repercussion, as in facial appearance doesn't

look so good and the bite is not so good?  How serious

would that be to the patient if they come in and they

have these changes?  Does it really affect them other

than, you know, appearance‑wise?

            DR. DEMKO:  Right.  Basically what I look

for with patients is the patient I showed you with the

great morbidity, where his mandible came forward, he

is a physician.  When he disappeared, wore his

appliance, kind of jerry‑rigged it himself for five

years, when he came back and he looked like this and

I really went through the ceiling because dentists

worry in microns, not in millimeters, he looked at me,

and he said, "I'm a physician.  The side effects of

what I do kill patients.  All you did was move my

jaw."  For him, who was a severe sleep apneic and it

totally controlled his disease, he was willing to put

up with that.

            What I try to do with patients is the

minute I see something changing where I think it's

going to be permanent, I sit down and talk to the

patient and try to get them to go back on CPAP.  If

they refuse, then I always send a letter to their

dentist saying that "This patient's occlusion is

changing."  I have never had a patient complain of

anything other than cosmetic changes.  They don't have

any difficulty with function.  They manage just fine,

just as do edentulous patients who don't wear

dentures.

            CHAIRPERSON GULYA:  Okay.  Dr. Suzuki?

            MEMBER SUZUKI:  Jon Suzuki, Dental.  Have

you ever had to resort to either major or minor

occlusal adjustment involving enamoplasty when the

teeth migrate or super‑erupt?  You didn't mention

that.

            DR. DEMKO:  I actually send them back to

their own dentist.  Because all I do is sleep

dentistry, I don't want any general dentist thinking

that I am stepping on his toes.  So I will send them

back, explaining what I think should be done.  But I

don't do that.  I will send them to the orthodontist.

I will send them back to a general dentist.

            But yes, enamoplasty is very important,

especially when you have got a super eruption, mild

super eruption, of molars.  That's what's locking them

in place if I can get rid of that.

            One of the things I do with oral

appliances is when the anterior teeth start moving,

you can actually put dots of acrylic.  Maxillary teeth

tend to labiovert.  Mandibular teeth lingualize.  You

can put dots of plastic and push the teeth back into

position using an appliance that is thick enough, you

can use it as an orthodontic appliance, put the teeth

back.  You just can't if they start splitting out.

            CHAIRPERSON GULYA:  Okay.  Dr. Terris?

            DR. TERRIS:  Gail, I enjoyed your

presentation.  It was very informative.  One thing I

hope you can clarify for me, I would have thought that

in terms of the safety of the appliances, one could

make the argument, "Well, the patient can self‑treat."

And if they're having some of these problems, they can

just stop or seek help.

            It sounded like from what you said that

some of the changes that can start while they're

self‑treating can become permanent essentially.  Is

that true?

            DR. DEMKO:  Right.  It's between 6 and 12

months is where we start seeing changes that will

become permanent.

            DR. TERRIS:  Thanks.  Okay.

            CHAIRPERSON GULYA:  Dr. Zuniga?

            MEMBER ZUNIGA:  John Zuniga.  Do you have

any MRI data to collaborate or support the theory that

there is, in fact, edema in the temporomandibular

joint?

            DR. DEMKO:  The only study done was

published by Fernanda de Almeida.  That was published

two years ago.  She looked at only eight patients.

They were looking at how far out of the fossa was the

appliance moving them related to the kind of pain and

compliance of that patient.  She did pick up that

there was some proliferation of posterior fibers.

There was definite edema.  But that was the only

change they picked up.

            There are no studies that I know of done

long‑term, certainly not published, looking at MRI

data as to whether we get changes, permanent changes,

in the socket, in the joint.

            CHAIRPERSON GULYA:  All right.  Dr. Li?

            DR. LI:  Gail, a couple of issues.  One,

can you comment on the difference in terms of

retention of the appliance between the boil and bite

type versus a custom type?  That's the first question.

The second question is in terms of objective testing

after the delivery of the appliance and on follow‑up?

            DR. DEMKO:  Okay.  The boil and bites are

very rarely as retentive as the custom fabricated

because the custom fabricated locks into better

positioning.  Boil and bites when they're heated up,

you bite down into them.  They don't come back in and

hug the neck of the tooth.  So you're not going to

have a lot of undercut and retention there.

            The other appliances, then they're custom

fabricated.  You can put clips on them, clasps.  You

have other ways of making additional retention on

those.  And there's a lot that even I get back from

the laboratory and have to paint on more plastic to

lock in, especially on bruxors or people who have lost

over 20 percent of their tooth bite.  So that

retention is very different between boil and bites and

the custom fabricated.

            As for objective testing, I will do

preliminary testing using something like a SleepStrip

or an oximeter on a patient to make sure that the

appliance is titrated out to where that says

everything is fine.  Then they go back for full

polysome because it's hard to try and get patients to

do that.  They don't want to go through another sleep

study.

            I will not give them the results of the

test for my Better SleepStrip or whatever, but

routinely I'm finding that they're not far enough

forward.  I just had a patient come back with a

SleepStrip of 3, which means he's having more than 25

events an hour.  If anything, that is probably under

recording.  I want that patient to move his appliance

further forward and go back for full polysome.

            CHAIRPERSON GULYA:  I think this will be

the last question before we start deliberating.

            MEMBER ZUNIGA:  Thank you.  John Zuniga

once again.  What is the cost difference between the

boil and bite and the hard acrylic process?

            DR. DEMKO:  Do you mean my cost or ‑‑

            MEMBER ZUNIGA:  General.

            DR. DEMKO:  ‑‑ or the patient is going to

be doing this?  The lab fees run up to, maximum is,

$600 that I have seen for lab fees.  That is for the

silencer, the boil and bites.  They can get them from

England for $30.

            MEMBER ZUNIGA:  And the patient who cannot

afford the larger cost, will you use the boil and

bite?  Do you have any personal outcomes that you can

share with us?

            DR. DEMKO:  I very rarely use boil and

bites because they are so bulky and so poorly

retentive that patients do not stay with them.  They

will if they get it fit right, if they are very lucky.

But because of arch sizes, where some patients have

extremely wide arches and others don't, the boil and

bites don't fit everybody.  It's very hard to find

them.  Unless you're looking at a white female, small

white male, it's hard to find boil and bites to fit.

            CHAIRPERSON GULYA:  Okay.  Well, I would

like to thank Dr. Terris and Dr. Demko for some highly

illuminating presentations.  They certainly brought

into focus some of the issues and also complemented

the materials provided by FDA staff.

                 PANEL DELIBERATIONS

            CHAIRPERSON GULYA:  According to my math,

which is always suspect, ‑‑ so I am willing to stand

and listen to corrections ‑‑ I think we have about 75

minutes now to start going through some of these

questions.

            And I am reminded a little bit of the

labors of Hercules.  I will remember to thank the FDA

for giving us such a nice task to keep us busy.

            That having been said, in all seriousness,

I would like to see us try and tackle question number

1.  I think looking at it at one big clump, it seems

insurmountable.  But I think if we break it down to

the little bits, we can kind of chip away at it.  And

hopefully if we chip away at it, we might even get it

done by lunch, by 12:30.

            What I propose we do is in a roundtable

fashion so that every panel member has an opportunity

to speak his or her mind, I would like to go through

each device and have each panelist discuss their

risk‑benefit analysis with respect to the different

indications.

            So, for example, for the tongue retaining

device, if we could just go through the risks and

benefits of snoring and then through the different

stages of obstructive sleep apnea.

            And I think if we keep in mind that we

probably have about 10‑15 minutes for each device and

note that probably some devices will require a little

bit more time, some devices probably a little bit less

time, I think we can kind of in our own heads kind of

adjust how much verbiage we give to each one of these.

            So let me see now.  Why don't we start

with Mr. Crompton.

            MR. CROMPTON:  Yes.  This is Mike

Crompton.  I'm going to limit my discussion to the ENT

devices and then defer to my colleague here for the

dental devices.

            I think based on the presentations we

heard this morning, the risk profile for the ENT

devices is obviously less of an issue compared to the

dental devices.  However, the definitional aspects are

something that I think I need clarification on and

industry as well in terms of these classifications for

obstructive sleep apnea, primarily the differentiation

between moderate and severe.  So we would look to the

panel, the clinicians here, to offer some guidance on

that.

            Also, we are going to defer and wait for

Dr. Mann's presentation on the mandibular support

devices, which he alluded to he was going to discuss

that because that, frankly, could be a device that

could be of some value OTC for the OSA indication as

well.

            So I think those are the general comments

we have on the devices at this point.

            CHAIRPERSON GULYA:  Okay.  It sounds like

your name was called.

            DR. MANN:  I just wanted to point out that

we are not going to have any further discussions of

the mandibular support devices, that we just brought

that up because we have received queries from industry

as to what would be necessary in terms of clinical

data to support an indication for obstructive sleep

apnea or snoring with those devices.  We have not

received any 510(k)'s for those to date, but based on

the queries, we thought it was reasonable to at least

raise it as a possible device that we may be seeing at

some point in the future.

            MR. CROMPTON:  Okay.  That clarified that,

then.

            CHAIRPERSON GULYA:  Okay.  Thank you.  Mr.

Schechter?

            MR. SCHECHTER:  This is Dan Schechter.  I

had some consultations with various members of

industry.  The comments that I have received are

somewhat mixed, but I think I would encourage the

panel to consider if there are perhaps a subset of

these devices, even within one of these three dental

device categories that would be suitable for OTC use.

            I think it is probably generally

recognized that there are devices, professional

devices, that simply are too complex or too active in

terms of their activity in the mouth to be used over

the counter.  But, on the other hand, there are

devices that might lend themselves more easily to OTC

use.  I would encourage the panel to try and find that

subset here today.

            CHAIRPERSON GULYA:  Let's just try and

look at the tongue retaining device in terms of the

risk‑benefit analysis for snoring and obstructive

sleep apnea.  I think we can just focus on that for

now and maybe just pass if you feel you do not wish to

comment on that.  Ms. Howe?

            MS. HOWE:  I appreciate the opportunity to

represent consumers to both the Dental and the ENT

Panels and hope that in reviewing the tongue retaining

device and other devices, that we look at the safety

and the efficacy but also access to care, that we're

talking about a large group of people if we do look at

snoring, a large population, who will not readily go

to their dentist or their medical professional for

treatment.  And they're seeking some form of treatment

resolution to their problem and also some education

about it.

            I would like to refer back to the

individual who spoke about the opportunity that an

over‑the‑counter product might give people to learn

more about what is snoring and, in fact, help in the

screening process of OSA.

            In referring to one product or the other,

I certainly have to defer to the specialists here, who

can talk more about the manufacturers' products that

they're using or placement, fit, and adjustment

abilities for an over‑the‑counter product.  But,

again, hopefully everybody will take into

consideration access to care for people who would not

normally be going to see a professional for their

snoring problem.

            CHAIRPERSON GULYA:  Thank you.

            Dr. Stern?

            DR. STERN:  I'm sorry.  Could you please

‑‑

            CHAIRPERSON GULYA:  Sure.  We're looking

at the tongue retaining device, question number 1,

looking at the risks versus the benefits of allowing

it to be marketed as a device for snoring, obstructive

sleep apnea.  What are your thoughts?

            DR. STERN:  That's a tough question, I

think, because it seems like it has to be a product

that has to be fit a certain way.  Consumers have to

be educated regarding putting their tongue in and

retaining it and the side effects and things like

that.

            As far as snoring, we need to make sure

that there are some sort of screens that tell me,

"Okay.  I'm snoring" and then have a partner or

somebody that is going to be able to listen to what is

going on, a family member.  You need another person

involved somehow or a tape‑recording device to find

out exactly what is going on, "Why am I having this

problem?"  It seems like it's a multifactorial thing

here.

            It seems to me also that the lack of

public awareness is a significant issue with regard to

this.  Even myself as a physician, I was not aware

that this was something that would be an option to

recommend to patients.

            So I think lack of public awareness is a

significant issue here.  And I am not convinced that

if there is something that is going to be made over

the counter, then are there enough documented studies?

            It seems like most of these things have a

fairly small number of patients.  And so if it is

going to be made over the counter, I would recommend

that it probably be recommended that it be tried over

the counter and then see what studies have been done

to show that this is a modifiable appliance that can

be even used and that patients are able to understand

the impact and the significance and the indication for

being able to be used and that it is understood that

this is recommended only for snoring and maybe not for

obstructive sleep apnea and that the risks and the

benefits and alternatives are also explained in lay

language and whether or not this would be a product

that would be easy to use.  It's just something you

just put it in your mouth and then stick your tongue

in here.  And this is what you do, and it's used for

a certain amount of time.  Is this something that's

going to be easy to use, easy to adjust?  And I'm not

sure that I am convinced that that is the case yet at

this time.

            CHAIRPERSON GULYA:  Thank you very much.

Dr. Zero?

            MEMBER ZERO:  Domenick Zero, Dental

Products Panel.  I will give a qualified response in

that I am not an expert in this area, and I am

learning a lot about it.  It is a very fascinating

area.

            This may apply to all of these devices

that are under consideration.  The first issue is

diagnosis.  I don't understand how a patient or an

individual can make an appropriate diagnosis as to the

condition they have, the severity of that condition,

and then following from that the appropriate treatment

decisions to manage that condition.  I just don't.  In

something as complicated as this and something as

serious as this, I don't see how an individual can

make that decision from an over‑the‑counter product.

            The other issue is monitoring.  It is

obvious that there are a number of untoward effects

that can occur that can be at least controlled and

modified if a professional is involved, a dental

professional is involved with that use of the device.

I don't see how an individual can properly monitor the

symptoms, the changes that could occur in their mouth

over time and do that in a way that would prevent a

serious complication.

            So with that, I see the risk‑benefit to be

really on the side of too much risk and not enough

benefit.

            CHAIRPERSON GULYA:  Thank you very much.

            Dr. Li?

            DR. LI:  I concur in terms of the

diagnosis.  I see approximately 30 new sleep patients

a week.  And I perform sleep studies on all of them.

Even for well‑trained physicians in terms of

specializing sleep, I'm often surprised at the

severity of the disease with their objective testing.

            So I think it would be in error to approve

an OTC device that "treats" sleep apnea without a

physician evaluation and to really look into the

severity of the problem.  That's number one.

            In terms of a tongue retaining device, my

understanding of the literature is that the result is

actually fairly mixed.  And that goes along with some

other devices as well.  So in terms of efficacy, I

think before even approving that as an OTC device, we

will have to look at the effectiveness of the device.

            CHAIRPERSON GULYA:  Could you please

address the issue of snoring?  I just heard about OSA.

            DR. LI:  I think in terms of, well, the

first issue, I think for the layman, you need to

separate the issue between snoring and sleep apnea.

In terms of snoring, I think it's reasonable for a

tongue retaining device to probably be approved for

snoring, but in terms of fabrication, the

effectiveness, I think it would be a pretty

challenging issue for the manufacturer to make it

effective for snoring improvement.

            CHAIRPERSON GULYA:  Okay.  Thank you.

            Dr. Jenkins?

            MEMBER JENKINS:  I would think in terms of

snoring that the risk‑benefit ratio would be better in

that it can control that and if the changes in

dentition are monitored, then it could possibly be,

you know, that caveat needs to be into labeling that

they need to have monitoring and possible changes in

their dentition.

            However, in obstructive sleep apnea, since

we as physicians have trouble making this diagnosis,

to have a patient make this diagnosis and use it as an

across‑the‑counter device on their own, that I think

would be very difficult.  And the risk‑benefit ratio

would be very negative.

            CHAIRPERSON GULYA:  Thank you.

            Dr. Suzuki?

            MEMBER SUZUKI:  Jon Suzuki, Dental

Products.  I guess one of my major questions would be

if the tongue retaining devices were, in fact, OTC,

would it increase at all the risk for either

aspiration or partial obstruction of airway?  I don't

believe I have heard data representing either side.

            CHAIRPERSON GULYA:  From my read of the

literature we were provided, I would have concerns of

providing this as an OTC device, certainly for the

OSA, for reasons that have been already suggested in

terms of the difficulty of even us making diagnoses

with sophisticated equipment.

            For snoring, again, I am not convinced

that there is data showing sufficient efficacy.  So

that would be I would have concerns on all fronts

regarding the tongue retaining device.

            Dr. Zuniga?

            MEMBER ZUNIGA:  John Zuniga.  I'm coming

from the point of view of that of a person with

clinical experience with patients, but from listening

to what has been presented here ‑‑

            EXECUTIVE SECRETARY S. THORNTON:  Excuse

me, Dr. Zuniga.  Could you please speak into the

microphone a little bit more?

            MEMBER ZUNIGA:  I'm sorry.  From reviewing

what I have heard today and the provided information,

I think it is quite clear that the tongue devices for

OSA do not provide the benefit versus the risks that

it can ensue.  And, similarly for snoring, the

information is minimal for efficacy.  So I think that

for both cases, the risks are higher than the

benefits.

            CHAIRPERSON GULYA:  Thank you.

            DR. MAIR:  Eric Mair, San Antonio.  In

typical vice presidential debate fashion, I think I

want to answer one other question first from the

industry.

            (Laughter.)

            DR. MAIR:  The question was, what is the

difference ‑‑ I mean, this is important ‑‑ between

mild, moderate, and severe apnea and how that effects

because we really need to know what those definitions

are.

            The AASM has come out with these

definitions.  And mild is between 5 to 15 apnea or

hypopnea events per hour.  Moderate is 15 to 30.  And

severe is greater than 30.  It's important to know

those are more than just numbers.  There's no adequate

prospective study that has validated the severity

criteria for any of this.  And the reason for the

severity criteria is based on some data from the

Wisconsin Sleep Cohort that showed an increased risk

of hypertension with an AHI of approximately 30.

            So to distinguish mild to moderate apnea

is a very difficult thing to do.  And it's not based

on really good science.  To throw another wrench into

everything, too, we talk about ‑‑ in all of the

studies that we have presented so far today have

mentioned that the gold standard is the polysomnogram.

We do everything based on the polysomnogram.  I think

that we know now that the gold standard is a little

bit tarnished.

            Some of the studies that we have been

doing and many others have been doing, too, have

looked at the variance of reader to reader of

polysomnogram and the night‑to‑night variation.  These

can be greater than 30 percent in multiple studies,

including ours.

            What this means is that one question asked

I think by John is, what happens if someone has severe

apnea?  Can they have mild apnea afterwards?  I think

David's answer was only after some sort of therapy,

not necessarily so.  It's so dependent on the study

itself, where it's done, how it's read.  There are

some problems in this area.

            Back to the question at hand, tongue

retaining devices I strongly feel should not be over

the counter, mostly for reasons that there are

different manufacturers of these, that for the patient

to squeeze the tongue and give negative pressure on

the tongue so that there's going to be venous

congestion of that area, we're concerned about airway

edema, airway problems if these things intermittently

fall off in the middle of the night if there is too

much negative pressure on these things.  They could

cause some significant tongue edema, which from a

surgeon's point of view, from ENT, that's one of the

problems that we deal with.  We could see this

definitely over the counter.  And just on tongue we're

talking about right now.

            Let me pass it on to the next vice

presidential candidate.

            CHAIRPERSON GULYA:  Dr. Orloff?

            DR. ORLOFF:  Thank you.  Lisa Orloff.

Just sort of an extension of what you just said, Eric,

if there is such variation in the interpretation of

polysomnography or variation from one night to the

next, I guess we have to look at whether our follow‑up

polysomnograms after treatment are really reflecting

an improvement or a lack of improvement adequately

with any of these devices.

            Specifically addressing the tongue

retaining device and snoring, not sleep apnea but

snoring, from what I have heard today and from what I

have read, I have gotten the impression that the

tongue retaining device is the least favorable oral

appliance relative to the mandibular repositioning

device.  And I'm not sure about comparison directly

with the palatal lifting device.

            My fear if the tongue retaining device

were to be over‑the‑counter ‑‑ and I think we'll be

discussing the other devices more next ‑‑ are likely

to not be supported for obstructive sleep apnea use by

this panel, that more patients would be selecting the

one product that is available over‑the‑counter, being

the tongue retaining device, when it is actually

appropriate for what sounds like the smallest subset

of patients with snoring.  So I would oppose having it

be available over the counter.

            CHAIRPERSON GULYA:  Thank you.

            Dr. Woodson?

            DR. WOODSON:  Yes.  Gayle Woodson.  I'm

pretty much in concurrence with everybody who has

talked so far in terms of what is the best thing in

terms of an ideal world where everybody can go to the

doctor and get their sleep study and know these

things.

            I think we live in a world where not

everybody in the country has health insurance.  Even

those who have health insurance, many times their

health insurance doesn't cover the cost of a sleep

study or maybe it will pay for it if you get the sleep

study and it turns out you have sleep apnea, it will

pay for the study, but if not, it's out of your own

pocket.  So there are definite economic things we have

to think about.

            So when we treat patients, even in our

office, with snoring, sometimes we go ahead and treat

snoring because there are not the resources to do the

sleep apnea testing.

            So if you think about that the major risk

of a lot of these snoring treatments is that 25

percent of them could have sleep apnea, well, that may

be just a ‑‑ otherwise, if we're dooming everybody to

continue suffering with snoring without trying

anything else, if we deny all snoring treatments

because they should have sleep testing, I don't think

I have enough evidence in here to tell me whether

tongue retaining devices help snoring.  I think there

are some patients that it probably would work with and

some that it wouldn't.

            I think, rather than saying a blanket "No,

no tongue retaining device should be over the counter"

or "Yes, they all should," I think that they would

have to be on an individual basis of looking at the

data for each device and having real clear labeling,

telling people if somebody knows you stop breathing,

although with the labeling, the warnings, the caveats.

            I think we have to be careful about

blocking people from being able to try something that

doesn't have a lot of down side risk from the

appliance itself.

            CHAIRPERSON GULYA:  Dr. Terris?

            DR. TERRIS:  In response to Eric Mair's

comments, I was going to suggest that I could be Dick

Cheney and maybe you would be John Edwards when, in

fact, it doesn't work because we totally agree.

            And so your criticism of polysomnography

is one of my favorite topics to talk about.  I didn't

discuss that in my 12‑minute presentation that I was

allocated this morning, but yes, the so‑called gold

standard is the best