DEPARTMENT OF HEALTH AND HUMAN SERVICES

FOOD AND DRUG ADMINISTRATION

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PUBLIC HEARING ON

FDA REGULATION OF OVER-THE-COUNTER

DRUG PRODUCTS

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Thursday, June 29, 2000

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The public hearing was held in the Ballroom, Gaithersburg Holiday Inn,
Two Montgomery Village Avenue, Gaithersburg, Maryland, at 8:30 a.m., Dr.
Robert J. DeLap, Director of ODE V, presiding.

FDA PANEL PRESENT:

JANET WOODCOCK, M.D., Director, CDER

RUSSELL CAMPBELL, Office of the Commissioner

DAVID FOX, J.D., Office of the Commissioner

DIANNE MURPHY, M.D., Acting Deputy Director,

Office of Review Management

ROBERT TEMPLE, MN.D., Associate Director for

Medical Policy; Director, ODE I

JOHN JENKINS, M.D., Director, ODE II

FLORENCE HOUN, M.D., Director, ODE III

ROBERT J. DeLAP, M.D., Director ODE V

CHARLES GANLEY, M.D., Ph.D., Director, Division

of Over-the-Counter Drug Products

FDA PANEL PRESENT (Continued):

GARY CHIKAMI, M.D., Director, Division of

Anti-infective Drug Products

LOUIS CANTILENA, M.D., Ph.D., Acting Chair,

Nonprescription Drugs Advisory Committee

SANDRA TITUS, Ph.D., Executive Secretary,

Nonprescription Drugs Advisory Committee

NONPRESCRIPTION DRUGS ADVISORY COMMITTEE MEMBERS PRESENT:

RICHARD A. NEILL, M.D.

EDWARD KRENSELOK, Pharm.D.

EDWIN GILLIAM, Ph.D.

JULIE JOHNSON, Pharm.D.

Y.W. FRANCIS LAM, Pharm.D.

DONALD UDEN, Pharm.D.

HENRY WILLIAMS, M.D.

SPEAKERS PRESENT:

JEFFREY L. ANDERSON, M.D.

BRUCE PHILIP BARNETT, M.D., J.D.

LINDA BORSCHULE

CATHY BROWN

JUDIE BROWN

ELIZABETH A. CAVENDISH

JEROME D. COHEN, M.D., FACC

SUSAN COLEMAN

OLGA FAIRFAX

EDWARD FROHLICH, M.D., FACC

SPEAKERS PRESENT (Continued):

ROSALIE M. GROSS, M.Ed.

STEPHEN J. HELLEBUSCH, Ph.D.

JOSEPH C. HOWARD, JR., M.DIV.

SUZANNE HUGHES, R.N.

RANDY P. JUHL, Ph.D.

GRETCHEN F. KIDDER

ALLAN KORN, M.D.

MARISSA MAGNETTE

THOMAS R. MOENCH, M.D.

KIRSTEN MOORE

ELIZABETH RAYMOND, M.D.

LORIE G. RICE, M.P.H.

ROBERT C. SEIDMAN, Pharm.D., M.P.H.

SUSAN SHELLABARGER

TARA SHOCHET, M.P.H.

JACK E. STOVER

KEVIN J. WHALEY, Ph.D.

RUDOLPH M. WIDMARK, M.D., Ph.D.

BEVERLY WINIKOFF, M.D., M.P.H.

C-O-N-T-E-N-T-S

[PAGE]{.underline}

Introductions 5

Judie Brown, American Life League, Inc. 8

Cathy Brown, Why Life 12

Father Joseph C. Howard, Jr., M.Div., American

Bioethics Advisory Commission 19

Olga Fairfax 22

Kirsten Moore, Project Director, Reproductive

Health Technologies Project 26

Jack E. Stover, Chief Operating and Financial

Officer, Gynetics, Inc. 32

Tara Shochet, M.P.H., Deputy Director, American

Society for Emergency Contraception 40

Beverly Winikoff, M.D., M.P.H., Population

Council 47

Elizabeth A. Cavendish, Legal Director, NARRAL 54

Elizabeth Raymond, M.D., Family Health

International 60

Rosalie Gross 65

Suzanne Hughes, R.N., President Elect, Lipid

Nurse Task Force 74

Jerome D. Cohen, M.D., FACC, Saint Louis

University 80

Jeffrey L. Anderson, M.D., Chief, Division of

Cardiology, University of Utah School of

Medicine, Merck Research Laboratories 106

Edward Frohlich, M.D., FACC, American College

of Cardiology 127

Lorie G. Rice, M.P.H., USCSF School of

Pharmacy, Bristol Myers Squibb 143

C-O-N-T-E-N-T-S (Continued)

[PAGE]{.underline}

Bruce Philip Barnett, M.D., Heeger and Barnett,

L.L.P., accompanied by Mr. Calabio 51

Gretchen F. Kidder, Alliance for Microbicide

Development 164

Thomas R. Moench, M.D., Medical Director,

ReProtect, L.L.C. 173

Kevin J. Whaley, Ph.D., Director, EPIcyte

Pharmaceutical, Inc. 181

Robert C. Seidman, Pharm.D., M.P.H., Vice

President, Pharmacy, Blue Cross of

California/Well Point Health Networks 190

Linda Borschuk, Patient Advocate 212

Stephen J. Hellebusch, Ph.D., Q2 Marketing

Research, Inc. 221

Susan Shellabarger, Hill Top Research 229

Marissa Magnette, Allergy and Asthma Network

and Mothers of Asthmatics, Inc. 237

Allan Korn, M.D., Blue Cross/Blue Shield

Association 241

Randy P. Juhl, Ph.D., Consumer Healthcare

Products Association 253

Susan L. Coleman, NCI Consulting 270

Rudolph M. Widmark, M.D., Ph.D. 282

Closing Remarks, Robert DeLap, M.D. 283

P-R-O-C-E-E-D-I-N-G-S

(8:39 a.m.)

DR. DeLAP: Well, good morning, and welcome to the second day of our open
public hearing on the over-the-counter drug products.

I\'m Dr. Robert DeLap, and I\'m serving as the moderator, and I\'m just
going to show a couple of the slides that I showed yesterday morning
since our audience may have changed somewhat between yesterday and
today.

The underlying reason for this hearing is described on this slide. In
light of the continuously changing health care environment, including
the growing self-care movement, the agency continues to examine its
overall philosophy and approach to regulating OTC drug products.

FDA is soliciting information from and the views of interested persons,
including health professional groups, scientists, industry and consumers
on the agency\'s regulation of OTC drug products.

And the scope of the hearing, as described in the [Federal
Register]{.underline} notice that published in April included questions
in several different areas, again, with the intent of our getting a good
overall view of people\'s views on the OTC marketplace.

Criteria for OTC availability of drug products, what kinds of products
should and shouldn\'t be in the OTC marketplace, how we insure that we
communicate with consumers about the products that are in the
marketplace, how people can select the best treatment for themselves;
are there options for other ways of marketing OTC products; and our role
in switches of products from the prescription only environment to the
OTC marketplace.

And then finally, again, this is the format for an open public hearing.
The hearings are transcribed. Speakers may use their time as they wish
consistent with an orderly hearing.

If a person is not present at the scheduled time for their presentation,
an attempt will be made to provide time at the end of the hearing.

Persons serving on the panel may ask questions of speakers. Persons in
the audience may not interrupt or question speakers.

Persons in the audience may request time to speak at the end of the
scheduled presentations, and again, if people are interested in being
added at the end, they really need to tell us by noon today so that we
can plan the last session.

With that, I think I would like the people on the panel to just briefly
introduce themselves again since, again, our audience may have changed
since yesterday.

So, Dr. Titus, we will begin with you.

DR. TITUS: I\'m Sandy Titus, and I\'m the Executive Secretary for the
Nonprescription Drugs Advisory Committee.

DR. GANLEY: Charlie Ganley. I\'m the Director of the Division of
Over-the-Counter Drugs.

DR. CANTILENA: Yes. I\'m Lou Cantilena, head of clinical pharmacology at
Uniformed Services University and a member of the NDAC Advisory
Committee.

MR. FOX: Dave Fox. I\'m an Associate Chief Counsel in the Office of the
Chief Counsel of the Food and Drug Administration.

DR. CHIKAMI: I\'m Gary Chikami. I\'m the Director of the Division of
Anti-infective Drug Products.

DR. MURPHY: Dianne Murphy, Acting Deputy Director for Office of Review
Management.

DR. WOODCOCK: I\'m Janet Woodcock. I\'m Director of the Center for Drug
Evaluation and Research.

DR. HOUN: Florence Houn, Office Director for Drug Evaluation III.

DR. JENKINS: I\'m John Jenkins. I\'m the Director of the Office of Drug
Evaluation II.

MR. CAMPBELL: I\'m Russell Campbell, Senior Consumer Affairs Specialist.

DR. DeLAP: And, again, if we could have the invited guests in the first
row over here also briefly introduce themselves.

(Whereupon, the invited guests introduced themselves.)

DR. DeLAP: Thank you.

Then we\'ll proceed directly to our agenda. The first speaker on the
agenda is Judy Brown of the National Life League.

MS. JUDIE BROWN: Ladies and gentlemen of the panel, I am Judie Brown,
President of American Life League, and due to the limited time and
because you all have copies of my testimony I will selectively read from
it points that I wish to emphasize this morning.

My first point is from the study of the record with the Food and Drug
Administration and the relationship that the FDA has had with the birth
control pill, which is my purpose for being here this morning, it is
clear that the Food and Drug Administration has worked very diligently
to collaborate with pharmaceutical companies and the population control
idealogues for the purpose of constructing new definitions for
pregnancy, personhood, and abortion.

Additionally, from the beginning the FDA has turned a blind eye to the
potential for serious health hazards dangers of the pill did and does
pose to women of all child bearing ages.

It is certainly true that the composition of the pill has changed over
the past 40 years, but the health hazards for women remain and are very,
very real. Most recently, within the last two weeks, the
[Lancet]{.underline} medical journal published a study by the New
Zealand Ministry of Health indicating that over the past ten years 20
women have died of pulmonary embolism. The research suggests that for
every 10,000 women who take oral contraceptives, one a year will die,
and the study suggests that the risk is twice as high for women who are
taking third generation pills.

In other words, the pill is a potentially dangerous chemical compound
for women, and it is deadly for human beings starting their lives in
utero, which brings me to the next point of concern regarding the
honesty in labeling requirements of the Food and Drug Administration.

When it comes to the birth control pill, it is clear there are no such
requirements. Human embryology teaches beyond a reasonable doubt that a
human being begins at conception/fertilization when the sperm and the
egg unite. This new, individual human being, who is also known as a
person, is not his mother, is not his father, but is a distinctly
different human being with his own unique DNA.

This is evidenced in scientific studies, human embryology textbooks, and
it is a fully documented, irrefutable fact. It is not a matter of
belief.

That being the case, one would have expected the FDA to explain in
detail that the birth control pill may chemically abort the person whose
life begins at conception. A warning should be posted on all birth
control package inserts from the very first such insert. None has been
in evidence even though women have a right to know in plain English that
the pill they are about to ingest may kill a baby whose life has already
begun.

The political definition of pregnancy as a process alleged to begin at
implantation, which is actually five to seven days after it actually has
begun, has affected the FDA\'s attitudes regarding these various drugs
and devices, and I think is the reason why there is no warning that the
birth control pill may kill a human being whose life has begun at
conception, not at implantation.

I am here to call on the Food and Drug Administration to do three
things.

First of all, belatedly require that all birth control pills carry a
warning regarding the potential the pill has to kill an embryonic human
being.

Second, emphasize the risks in a way that promotes greater discussion
between the physician and his or her patient prior to the first
prescription ever being written.

And please do not consider the birth control pill as an over-the-counter
drug.

Thank you.

DR. DeLAP: Thank you very much.

Questions from the panel?

DR. MURPHY: The second request about promoting further discussion, would
you like to make some comment on that?

MS. JUDIE BROWN: Yes. Over the course of the last 27 years that I have
been involved in the work that I do in the pro life movement, I must
have given, well, thousands of talks. During the course of every one of
those talks I talk about the way the birth control pill works and its
potential for killing a child whose life begins at fertilization.

And I cannot tell you how many women I\'ve met who never knew that the
birth control pill they\'ve been ingesting has potentially had the
opportunity to and does kill children, and I think that physicians owe
it to their patients to explain that a human being\'s life, if that
human being exists, can be destroyed by the chemical action of this
pill.

DR. DeLAP: Other questions?

(No response.)

DR. DeLAP: If not, we\'ll proceed to the second speaker, Cathy Brown,
Why Life?

MS. CATHY BROWN: Good morning. My name is Cathy Brown, and I speak to
you today as the Director of Why Life?, a youth outreach program of the
American Life League.

I\'m speaking today on behalf of over 30,000 members of Generation X and
Y with whom we communicate monthly and who have been personally affected
by the contraceptive culture that we live in.

In the 1930s only one in seven marriages ended in divorce. By the 1960s
when birth control was legalized and accepted by Americans nationwide,
divorce rates jumped to one in four, and at that time there were only
two common STDs both of which were curable. Today teens are threatened
by over 35 common sexually transmitted diseases, some of them carrying
hundreds of strains. HPV carries 100 different strains and is not
curable.

In addition, my generation and those younger have now only a 50 percent
chance of being in a marriage that lasts until death do us part. I think
this is due largely, in part, to the contraceptive mentality that is
pervaded our society.

Considering these devastating facts and the future of our nation, I
would encourage the FDA to take a serious look at who will be most
affected if the pill becomes available over the counter. Maybe it will
be the 12 year old girl whose father is molesting her. Now he can be
fairly certain that he\'ll never get caught. He can buy her birth
control with no questions asked, no gynecological exam for her, no one
to ask her why she wants to take the pill at such a young age.

Or maybe the 16 year old who wants to sleep with her boyfriend after the
prom. She can pick up the pills when she goes to get her make-up, no
questions asked. She won\'t read the instructions or the insert in the
package. Teens rarely do. She won\'t take them properly because there
was no doctor present to tell her that they\'re not effective unless
you\'ve been taking them for at least one month.

At 16 her chances of becoming a mother just increased drastically, or
maybe it will be the 14 year old who has never talked to anyone about
sex. She thinks the pill prevents disease, as many teens do, and again,
she won\'t bother to read the package insert either. Rarely do adults
even read package inserts for over-the-counter drugs. So what can we
expect of a teen?

Soon after she may develop chlamydia, which could render her sterile if
left untreated, and since she didn\'t have to go to a doctor to get the
pill, why would she even think of going to one for the slight symptoms
that chlamydia can cause?

The pill already comes to teens at a very high risk. Even when regulated
and monitored by a physician, side effects occur. With the use that is
both unregulated and unmonitored, teens stand to suffer even greater
risks.

No long term studies have been done on the safety of the pill,
especially in young women. Risks range from minor side effects like
weight gain and acne to life threatening conditions, including strokes,
blood clots, and breast cancer.

For the past three years I\'ve been talking with teens who are using
oral contraceptives through correspondence and E-mail at work and by
volunteering my time with young women who are pregnant and unmarried.
Overwhelmingly they are misinformed about the birth control pill, and as
stated earlier, for the most part they are completely unaware that the
pill has the probability of killing an unborn child.

Overwhelmingly they wish that someone would have told them that
abstinence was a viable option, and overwhelmingly the only time they
ever talk seriously to anyone about the pill is when they go to the
doctor to request prescriptions or when their contraception fails and
they end up in need of a free pregnancy test at a local center.

Our young people are misinformed daily by their peers, teachers, and the
media. Talking to and being examined by a doctor before taking the pill
drastically increases a teen\'s chances of being properly informed. This
type of information is essential for the continued health and well-being
of our nation\'s youth.

Let us also not forget that the birth control pill, if it becomes an
over-the-counter pill, unplanned pregnancies will increase dramatically
as young women blindly take the pill with little to no regularity.

History has proven that contraception does not decrease the rate of
unplanned pregnancies, even when monitored by a physician. According to
the U.S. Center for Health Studies, out of wedlock births jumped
dramatically from 202,000 in 1957 to 1.3 million in \'94.

Can you imagine then what the increase will look like when doctors are
removed from being in a position to explain how to properly take the
pills?

An increase in unplanned pregnancies will inevitably increase the number
of abortions that are performed on teens and young adults. It should be
obvious why providers of abortion want to see the pill become an
over-the-counter drug.

Over-the-counter birth control pill sales equals an increase in cash for
the distributors of the pill as more and more young women will be
attracted to the idea of being able to buy contraception without seeing
a doctor, and failure to use the pill correctly equals an increase in
unplanned pregnancies, which equals an increase in the number of
abortions performed. This formula translates into a plethora of cash for
abortion providers.

On behalf of young women across the nation who will be negatively
affected if the pill is available over the counter, I plead with the
FDA. Young women deserve to be protected, and they deserve to be
informed. Given what we know about the behavior patterns of teens and
the risks associated with the pill, it would be a grave mistake to offer
the birth control pill over the counter.

Thank you.

DR. DeLAP: Thank you.

Do we have questions?

DR. MURPHY: Sort of the same sort of question. What do you think would
help understanding as far as communication to these young ladies?

MS. CATHY BROWN: Excuse me? Could you ask the question one more time?

DR. MURPHY: You feel that the young women are not getting the message as
to how to effectively use to prevent pregnancy. What would be your
recommendation? What sort of communication do you think would help them
understand?

MS. CATHY BROWN: Well, I think that communication needs to come
primarily from their parents. I think that parents need to be educated.
Parents need to know how to discuss abstinence with their teenagers,
with young people, and then and only then are we going to see a decrease
in rates of unplanned pregnancies and in rates of promiscuity among
teenagers.

DR. MURPHY: So by that answer you don\'t think there\'s anything we
could tell young women to help them use the birth control pill
appropriately? Because your statement was if they don\'t use it
appropriately, they will get pregnant.

MS. CATHY BROWN: I\'m saying that if it\'s over \-- they do not use it
correctly now and it\'s not over the counter. When it becomes over the
counter, they\'re even less likely to use it correctly, which translates
into an increase in abortions and an increase in pregnancy.

I think that they need to be informed about how the pill works, that it
is an abortive agent, that it does come at huge risks to them. I would
like to see the pill not offered at all to young people because it is a
danger to them. It is a danger to their future children.

And I think, again, that communication about abstinence needs to come
from the parents and communication about the dangers of the pill needs
to come from the parents as well.

DR. DeLAP: Other questions?

(No response.)

DR. DeLAP: If not, thank you very much, and we\'ll move to Father Joseph
Howard, the American Bioethics Advisory Commission.

FATHER HOWARD: Good morning. I serve as the Executive Director of the
American Bioethics Advisory Commission, which is a division of American
Life League in Stafford, Virginia. We have no financial association with
any pharmaceutical companies manufacturing oral contraceptives.

I speak to you today regarding the possibility of oral contraceptives
being made available over the counter, not requiring a prescription by a
physician.

Because of serious side effects and complications which are associated
with the use of oral contraceptives, it is essential that physicians
maintain control of who has accessibility to them. It is imperative that
they not be made available over the counter, or from a scientific
perspective alone, it\'s clearly empirically the best interests of women
that these oral contraceptives remain available by prescription so that
physicians can monitor and follow their patients accordingly.

It is well known, I\'m sure, to each of you the risks that are
associated of increased serious conditions including disorders, vascular
problems such as myocardial infarction, thromboembolism, cerebral
vascular disease, hepatic neoplasia, ocular lesions, gall bladder
disease, carbohydrate and lipid metabolic effects, hypertension,
headache, bleeding irregularities.

The risk of morbidity and mortality, as you well know, increases
significantly in the presence of underlying risk factors such as
hypertension, hyperlipidemia, obesity, and diabetes.

While it is true that many of these physiologic effects that are bad and
associated with the use of oral contraceptives containing higher
formulations of estrogens and progesterones have changed, the long term
effects of ones containing lower formulations of estrogen and
progesterones remain to be determined.

One grave concern that exists if they were to be made over the counter
would be significant increases in STDs, particular HIV. Large numbers of
high school and college students continue to engage in risky sexual
behaviors not realizing or accepting the fact that they are candidates
at this time in our country to contract diseases that can have
devastating consequences on their lives.

Having taught high school and college biology, physiology, philosophy,
and theology for the past ten years, I am acutely aware that these young
people would be very likely significantly affected if something such as
oral contraceptives were to be made over the counter because so many of
them remain unaware, in denial, that these consequences could occur to
them in their lives.

It is common for these young people today in our own country to be
unaware that HIV is spreading most rapidly at this time in our country
in the high school/college age heterosexual population. We must not
allow this to happen, to have our youth exposed to such risk, because
they are the future leaders of our country. We must do what is ethically
appropriate to protect them and help them as they prepare themselves to
assume leadership in our great country.

Making oral contraceptives available over the country would contribute
to the detriment of our youth and subsequently our country. It would be
an unjust practice, especially not only in regards to our youth, but to
women in general.

So in closing, I would strongly urge the FDA to not make oral
contraceptives available over the country in America.

Thank you.

DR. DeLAP: Questions?

(No response.)

DR. DeLAP: Well, thank you very much, and we\'ll continue with Rosalie
Gross.

Okay. Then we\'ll continue with Olga Fairfax.

MS. FAIRFAX: I\'m one of the many victims of the pill. When I got
married in 1965, there was not one woman I knew who was not on the pill.
I used it for a year. I was never able to get pregnant afterwards when I
wanted to. It masked infertility, and frankly, I think it actually
prevented fertility.

Now we know that there are many dangers, risks, and hazards to the
so-called contraceptive pill. I say \"so-called\" because the lower
dosages allow break-through ovulation and conception.

Because the lining of the womb has been altered, a tiny new human being
is often sloughed off in a early abortion.

Also, the pill can cause serious threats to a woman\'s life and health.
I read that when the first dangers of the pill taking were announced at
a medical convention in the early \'70s, at the very first break many
male doctors races out of the room to the bank of telephones in the hall
to call their wives and tell them to stop taking the pill. Unfortunately
many of them continued to prescribe it for their patients.

Just read the insert on the pill. It\'s enough to scare the wits out of
you and to scare you from taking it. The doctor who prescribed the pill
for me did just a very cursory, five-minute examination, cursory family
history, if any, and never even mentioned the side effects or the
dangers, and every three months I just got the prescription renewed
without a pelvic exam.

And I hope today at age 59 that my only child, an adopted daughter,
learns from me never ever, ever to take the pill.

From the [Washington Times]{.underline}, May 16th, \"This Evil Creation.
This week the birth control pill turned 40 with supporters celebrating
its cosmetic advantages and the so-called freedom it has given women.
They should have been draping themselves in black and painting poison
labels on the pills\' containers, in mourning for the terrible damage
done to the individual women and to society by this evil creation. The
dangers are nearly too numerous to list. Simply read the back of the
insert where you can find the catalogue of possible side effects,
including death.\"

But that\'s just the beginning. Four new studies have definitely linked
the pill to increased chances of breast cancer, and we are beginning to
see evidence that prolonged use of the use might affect the uterine
lining, making future pregnancies difficult or problematic.

And all of that doesn\'t address the most serious issue of all, the
damage that the pill as the flag bearer of the contraceptive mentality
has done to our culture and our families. We\'re celebrating 40 years of
promiscuity, increased abortion, increased child abuse, increased
divorce. Our television programs have become so unwatchable because of
their unrelenting sexual context. Our young girls are trained to be
sexual toys. Their bodies are used like playgrounds.

Just the other day my husband was driving with my 12 year old in the
back with her 12 year old girlfriend listening to DC-101, and there was
an ad for condoms. The two girls in the back were giggling, and I
thought, \"What\'s going to happen when over the counter the pill
becomes advertised on our radio programs aimed at our teenagers?
They\'ll be giggling, won\'t they?\"

The last thing I\'d like to say is the new danger alert about the pill.
This came out in the \'70s. The pill has been called the ultimate
pleasure drug. We\'re all against drugs, their illicit use, dangers, and
so forth, but isn\'t the pill the ultimate pleasure drug? Is the pill
the miracle of our age or is it killing women?

Dr. Sidney Wolfe calls the pill a health threat. It may be the leading
cause of death, other than suicide and car accidents. There\'s already
evidence suggesting the link between pill and cancer. If this is the
case, it could be the most serious, most serious consequence of the
pill.

In Dr. Wolfe\'s opinion, many women who are now taking the pill would
not be if they were fully informed about the dangers and the
alternatives.

And I liked what Cathy Brown said the best. As a Generation X
representative, the promiscuity. Why not abstinence? Why not purity? Why
not chastity? This is what certainly I\'m trying to do with my own 12
year old, to instill the values in her so that as with the Norplant now,
if a girl has it in her arm, the fellows know that she\'s ready for sex.

So I would beg you, I would beg you, every one of you, please, please,
for my daughter, for your daughters, for your granddaughters, please
don\'t even think of putting the pill over the counter.

Thank you very much.

If there are any questions.

DR. DeLAP: Questions from the panel?

(No response.)

MS. FAIRFAX: Okay. Thank you.

DR. DeLAP: If not, I\'d like to thank you for your comments, and I know
this is a lot of work in preparation, and we appreciate your coming and
sharing your comments with us.

Okay. We\'ll move on then for the next session, which is on emergency
contraceptives, and our first speaker is Kirsten Moore, Project Director
for Reproductive Health Technologies Project.

MS. MOORE: Good morning. My name is Kirsten Moore, and I direct the
Reproductive Health Technologies Project.

The project is a nonprofit advocacy organization that works to increase
the options that women and men have in this country to prevent unwanted
pregnancy and to prevent sexually transmitted disease. We also work to
improve access to those options. We do not receive any funding from
pharmaceutical companies.

For eight years the project has considered emergency contraception one
of the highest health priorities for women in the U.S. As you all know,
if taken within 72 hours, this pill can dramatically reduce the risk of
unintended pregnancy, and if it were more available, it could
dramatically reduce the rates of unintended pregnancy country-wide.

Recent clinical evidence from the World Health Organization tells us
that this pill is more effective the sooner it\'s taken, and for this
reason, the project is strongly in favor of moving emergency
contraception, these safe, simple, effective pills, over the counter.

In the interest of time and because a number of my colleagues are going
to enumerate some of the scientific and medical literature or elaborate
on some of those facts, I\'m going to skip over some of the reasons why,
that we\'ve elaborated for why this meets the FDA standard of safety and
efficacy for an OTC product, but suffice it to say I think it really
does reach that standard.

I would like to make two quick points through related to safety or the
public health concerns that you posed in your petition, in your call for
response, and the first is that as you posed the question whether making
drugs available over the counter would increase the possibility of risk
taking behavior, and when it comes to emergency contraception, I want
you to know that that is not borne out by the facts.

Women use this drug as effectively and safely and as responsibly as they
use any other drug. A study in Scotland shows that when they were given
it in advance they were more likely to use it, but they weren\'t more
likely to use it repeatedly. They had a lower pregnancy rate, and they
were not less likely to use an ongoing method when they had it in
advance rather than having to go and get a prescription filled from a
clinician.

Secondly, although not related to the safety and efficacy of ECPs
themselves, it is true that some women who have had unprotected
intercourse will also be at risk for sexually transmitted disease. The
manufacturers of the current dedicated products, Prevent and Plan B,
have included a voluntary label notice on their packaging that alerts
women to that risk and encourages them to seek STD screening if they
think they\'re at risk, and we would hope that a similar kind of warning
or notice would appear on an OTC product labeling.

The most compelling reason for moving EPCs over the counter is to
improve access. The project operates the national toll free emergency
contraception hot line, 1-88-NOT 2 LATE, and the hot line provides basic
information about emergency contraception. It also gives callers the
names and telephone numbers of five providers nearest them who agree to
prescribe emergency contraception.

Although I do want to point out that if you\'re calling from Arkansas,
Mississippi, North Dakota, for example, there are fewer than five
providers listed in those states on our hot line.

Callers can also leave messages for us on the hot line, and usually
these are thank you\'s for the information, thank you for letting me
know this option is available, but I\'d like to share a few comments
that are germane to today\'s hearing.

\"I had no luck in reaching a doctor who could give me a prescription
for emergency contraception. Please call me right away because I need
this resource.\" This was from a young woman in the 215 area code on May
26th, 2000.

\"I\'m calling from Los Angeles, California. I\'ve had a completely
fruitless attempt to try and get Plan B. Of course, I need it today.\"
Again, a young woman calling in the 323 area code on June 6th of this
year.

Unfortunately these women are not alone. Our own evaluation of the hot
line shows that women even under the best of circumstances, women who
know they want ECPs, who place calls to a self-identified pool of
providers during regular business hours will often have difficulty
getting a prescription.

I just want you to imagine the frustration or even panic of a woman
who\'s trying to make those calls during a week night or during a
Saturday of a long weekend, or imagine the panic or frustration of a
woman who gets a prescription and then goes to get it filled, but is
told by a pharmacist that she won\'t fill the prescription because it\'s
against her religious conviction or because her company has made a,
quote, business decision to not stock the product.

These women aren\'t simply inconvenienced. Despite their best efforts,
they\'re now facing the risk of an unwanted pregnancy.

Finally, while the women\'s health community is strongly united in their
assessment of the safety, efficacy, and net public health benefits of
emergency contraception, we do have one concern, and that is insurance
and access.

There will be women who can\'t afford an OTC product, and for this
reason, we encourage the FDA to consider making \--

(Ms. Moore is escorted to a chair.)

DR. DeLAP: Well, I\'m comfortable that the people who have attended our
last speaker will be able to take of any issues there may be there. I
hope there\'s no significant problem there, but we\'ll proceed with our
next speaker, Jack Stover for Gynetics, Incorporated.

DR. MURPHY: Why don\'t we just take a five-minute break just in the room
till we get \--

DR. DeLAP: Yeah, I think in fairness to the next speaker, perhaps we\'ll
just take a five-minute break in the room.

DR. MURPHY: She\'s okay. We got everybody back and we\'ve got a report.
That\'s what we want.

DR. DeLAP: We got everybody back. Okay.

DR. MURPHY: That\'s what we needed, to make sure she\'s okay.

DR. DeLAP: Okay, all right. I think then, Mr. Stover, please proceed.

MR. STOVER: Thank you.

Good morning. My name is Jack Stover, and I am Chief Operating and
Financial Officer for Gynetics, Inc., headquartered in Belle Mead, New
Jersey.

I want to thank the FDA for allowing Gynetics to share our views on the
questions and issues compiled in the [Federal Register]{.underline}
announcement of this meeting.

As you may know, Gynetics is a private company that was started in 1995.
Our first pharmaceutical product, PREVEN emergency contraceptive kit,
was first approved by the FDA in early September 1998.

When we obtained approval, we shortly thereafter launched PREVEN.

In addition to PREVEN, Gynetics also has Alleve and ogestral (phonetic)
based emergency contraceptive and several new oral contraceptive regimes
in development and distributes a disposable medical device as well.

However, we would like to limit our discussions and remarks today to
emergency contraceptives and the consideration of taking ECs over the
country.

Experts estimate that as many as 1.7 million of the over three million
unintended pregnancies occurring each year in the U.S. could potentially
be prevented by use of emergency contraceptive pills, according to a
study completed by Dr. Trussell (phonetic) published in [Family Planning
Perspectives]{.underline} in 1992.

Additionally, research studies and experience have shown that ECs are
generally a safe and effective method of preventing pregnancy as a
back-up method to regular contraception and can generally be used by
women without the direct supervision of a health care provider.

The biggest challenge we face today in expanding the use of emergency
contraception is, one, lack of awareness; two, timing and accessibility;
and, three, confusion around the off-label usage of the product.

We at Gynetics feel that making ECs available in a controlled manner
over the counter would help us effectively deal with these challenges.

Because of the sporadic use of ECs whereby many women may only use the
product once in their lifetime, it creates many unique challenges to
increasing awareness, cost effectively. However, unless we are able to
raise the broad based awareness of emergency contraception, it will
never be as effective as it could be.

The problems of awareness are only enhanced by several key issues.

One, private practitioners who generally do not discuss EC with patients
and, as a matter of fact, may not talk about contraception in general.
Often times, as the previous speaker indicated, women find that they
need ECs on a Friday or Saturday night. Availability of a medical
practitioner and access to a pharmacy who actually has the product on
hand is very difficult, to say the least, especially within a 72 hour
window, even though PREVEN is available in nine out of ten of the
largest drug store chains and most large distributors.

As we know, ECs are more effective when taken as soon as possible after
a conceptive failure. Many pharmacies still operate under the conscious
clauses, and therefore, are but another obstacle for women obtaining EC.
Surveys on the EC hot line have confirmed that access is a problem.
Almost one quarter of all calls failed to obtain access to EC.

Family planning clinics that are publicly funded generally do a very
good job of communicating about EC to their patients, but may close,
move, or are only open on a part-time basis and, therefore, pose yet
another barrier.

And of course, the confusion with the \"morning after\" pill exists as
well.

We at Gynetics believe that the availability of emergency contraception
over the counter could certainly expand public awareness of ECs by way
of the customary high levels and volumes of consumer advertising.
Independent studies and evaluations that we have participated in say ECs
in the United States could be a \$100 million a year product with the
proper level of support and advertising.

Additionally, such advertising will, of course, emphasize that ECs are
not as effective as regular birth control methods, nor will ECs protect
against HIV, STDs, and therefore, ECs should only be used as a back-up
method.

Going over the counter with ECs will cause a significant increase in
awareness alone, improve availability and the ease of access, and
further reduce the unintended pregnancies, as well as abortions.

With 24 hour pharmacies, grocery stores, and convenience stores
proliferating much of the country, availability of ECs and awareness of
ECs would simply be significantly expanded.

Emergency contraceptives are widely recognized as being, quote, low risk
drugs. I have heard physicians say that cigarettes should require
prescriptions, not ECs.

ECs are also indicated through self-diagnosis like headaches. A woman
knows if she has experienced unprotected sex within the 72 hours. There
are, as we know, significant risk factors, such as smoking, obesity, and
a family history of blood clots. However, these risks are now widely
known since the same risk factors have existed with regular oral
contraceptives since their introduction.

However, the medical risks of a full term pregnancy for a woman with
these risks factors is probably greater than if she did take ECs.

As we all know, the off-label use of oral contraceptives being cut up
with handwritten instructions and often no expiration dating and other
procedures continues to a great extent today even with two FDA approved
ECs available. This surely must confuse the consumer even more and
certainly acts as a disincentive to legitimate pharmaceutical companies
who must spend millions of dollars to obtain FDA approval of their
products only to find other drugs being used off label.

In summary, we at Gynetics believe that a well planned and controlled
expansion of ECs as OTC products, as an example, initially with a good
deal of control about them, such as age restrictions, et cetera, makes
good sense. With OTC status, ECs could be properly marketed and expand
awareness and availability significantly from the low levels that we
experience today.

Additionally, the need for off label use and all other variations of
concoctions to provide ECs should be significantly reduced with broad
based but controlled availability over the counter.

Thank you.

DR. DeLAP: Thank you. Questions?

DR. KWEDER: I just have one question. You commented that for many women
they\'ll only have a prescription or use an EC, you know, once in a
lifetime. What\'s the other end of that range? Do you have any data on
frequency of use, say, for women in a year\'s time, frequency of use?

MR. STOVER: No, I don\'t. Our experience though in the short time we\'ve
been marketing the product is that it is clearly not being used as a
regular oral contraceptive. That\'s for sure, and we from a marketing
perspective as we evaluate this, we see it being used perhaps up to
three times in a woman\'s life.

DR. DeLAP: Dr. Temple.

DR. TEMPLE: Maybe that last comment is the answer to the question I was
going to ask. One would have thought that anyone knowledgeable about the
existence of such contraception and at least the potential to use it
might get a prescription for it ahead of the actual need for use, but I
guess what you might be saying is that it\'s so uncommon that many
people who use ordinary methods simply wouldn\'t expect to have to need
this and discover only after the event that they needed it.

But I guess my question to you is wouldn\'t people knowledgeable about
this just get a prescription ahead of time and keep it.

MR. STOVER: The answer is that depending upon the physician, to date we
have seen most physicians push back on that. There are certain areas of
the country, for instance, southeast Pennsylvania, the area that we
operate in or near where we operate in, that does a great deal of
advanced prescribing. We think that is a very proactive way of dealing
with the issue. However, it\'s not widely accepted.

DR. GANLEY: Could you explain what you mean by a controlled manner of
distribution over the country since I\'m not clear what mechanism
you\'re referring to that currently would exist to allow that?

MR. STOVER: As some examples of what we are potentially talking about,
as opposed to having it on the shelf and available for anybody to buy,
have it what we would consider to be not necessarily behind the counter,
but in the controlled manner, such as you need to present some sort of
identification and age notification to acquire it. I might even consider
it to be kind of a caged drug where the pharmacist or whoever maintains
the store and has responsibility for the store, is required to, you
know, obtain certain information about the individual.

DR. DeLAP: Okay. If there are no other questions, thank you very much.

MR. STOVER: Thank you.

DR. DeLAP: And we\'ll continue with American Society for Emergency
Contraception, Tara Shochet.

MS. SHOCHET: Good morning. I\'m Tara Shochet from the American Society
for Emergency Contraception. I\'m here to tell you why emergency
contraceptives should be sold over the counter.

They\'re best known for the treatment of rape victims, but any woman
suffering a contraceptive accident might benefit from taking them if she
acts quickly.

Emergency contraceptives hold the potential to cut unwanted pregnancies
and abortions in America by 50 percent and to save up to \$1 billion
each year in health care costs.

Emergency contraception is the clearest example of a misclassified
prescription drug in America today. You already know that emergency
contraceptive pills were deemed safe and effective by the FDA in a
published statement in 1997.

More recently, in the past two years, the FDA approved two brands of
specifically packaged pills to be marketed for emergency use, PREVEN in
1998 and Plan B in 1999.

The World Health Organization considers both of these to be essential
drugs and declares them to have no contraindications.

In addition, it is now clear that emergency contraceptives work better
the sooner they are taken.

The WHO published a study last year in the [Lancet]{.underline} showing
dramatic improvements in effectiveness when women were able to start
their therapy within 12 hours of unprotected sex rather than waiting
until the traditional limit of 72 hours. Indeed, the risk of pregnancy
is eight times as high when treatment is started close to the 72 hour
mark as compared to when it is started in the first 12 hours following
unprotected sex.

Every hour lost tracking down a doctor and waiting for a prescription
boosts a woman\'s risk of unwanted pregnancy.

Now, a prescription requirement might be justified even if it slows down
the woman\'s effort to start treatment, but it would be justified only
if it serves an important purpose. The American Society for Emergency
Contraception has examined the evidence and sees no significant purpose
at all.

For the rest of my testimony today, I\'ll review the reasons people
might think prescription status generally helps to safeguard women. Then
I\'ll explain why we think each does not hold in the case of emergency
contraception. First I\'ll cover medical reasons. Then I\'ll turn to
social reasons.

Finally, I will mention what is happening in Europe and in some special
cases here in the States where emergency contraceptives are sold
directly in pharmacies.

What are the medical reasons to keep a pill on prescription status? Do
women need help diagnosing their need for emergency contraception?

Not at all. If women didn\'t think they needed the therapy, they\'d
never make a doctor\'s appointment for a prescription in the first
place. The doctor does not need to do a physical exam, and as with
aspirin or decongestant, there\'s little harm done if the woman takes
the pills when she doesn\'t actually need them.

According to the World Health Organization, there are no women on earth
who should absolutely avoid the drug. All women take the same dose and
same brands. So they don\'t need help there.

Is the therapy difficult to administer? No. It\'s just a few simple
pills.

Are the pills addictive and would an overdose be dangerous? No and no.
We need to remember that oral contraceptives and, by extension,
emergency contraceptives are among the safest and best studied drugs in
the history of medicine.

Could there be compelling social reasons to limit emergency
contraceptives to prescription status? Perhaps it\'s not the job of the
FDA to consider this in the first place, but let\'s examine the evidence
anyway.

Some opponents of women\'s reproductive rights might allege that women
will abuse emergency contraceptives if they\'re available without the
clinician as gatekeeper. It\'s not clear how this abuse could occur
unless women microwaved the pills perhaps or backed over them with a
pick-up truck.

But if people are worried that women who have easier access to ECs will
throw away their more effective contraceptives and rush out to have
unprotected sex just for the chance to use emergency contraception, they
can rest easy. Women will use emergency contraceptives as responsibly as
they do any other medication.

Looking to Washington State where women have been able to get emergency
contraceptives directly from pharmacies since 1998, there is no evidence
of abuse, and in a study recently published in the [New England
Journal]{.underline} researchers in Scotland told what happened when
they actually gave women emergency contraceptives ahead of time to keep
on hand in case of need. These women did not substitute the emergency
contraceptives for their regular methods, and the pregnancy rate was
lower than that in the control group.

Indeed, based on this and other evidence, the British Medicines Control
Agency is currently reclassifying emergency contraceptives so that they
will be available directly from pharmacies. British pharmacists and the
British Medical Association support this move, as does the Royal College
of Obstetricians and Gynecologists.

In France, emergency contraceptives are available today directly from
pharmacists without a doctor\'s prescription. It\'s time American women
had the came access to emergency contraception as European women do.
These pills are safe, simple, and effective, and they work best when
they are started without delay.

When responsible adults get a medically unnecessary runaround when they
are trying to prevent an unwanted pregnancy after a contraceptive
accident, something is wrong. Requiring a prescription for using
emergency contraception is as foolish as requiring prescriptions for
using fire extinguishers.

Thank you.

DR. DeLAP: Dr. Houn.

DR. HOUN: I have the same question as we posed to the Gynetics Chief
Financial Operating Officer in that if the study in Scotland told that
women who were given emergency contraceptives ahead of time in the case
of need showed advantages, in your current experience, are women asking
for it ahead of time? Is that something that education needs to be done?
Are you also encountering that prescribers are unwilling to give it
ahead of time?

MS. SHOCHET: The problem seems to be at this point that women aren\'t
asking and doctors aren\'t telling. So it\'s kind of like everyone is
waiting for the other person to speak up first.

One thing that was mentioned also is that, you know, wouldn\'t it be
great if we give out prescriptions ahead of time? Unfortunately that\'s
not happening widespread, and you still come up with the problem of a
pharmacist who might be unwilling to prescribe.

DR. HOUN: So is your organization working on educating women that this
is something that they should be pushing for?

MS. SHOCHET: Pushing for in terms of over the counter or \--

DR. HOUN: In terms of having it on hand prior.

MS. SHOCHET: Definitely. The best way to do it is to either go to the
store directly and get it the minute you need it and the second best
would be to have a prescription ahead of time and to have it in your
medicine cabinet.

DR. KWEDER: Can you clarify for me? Did you say that it already is \--
the EC is available over the counter in Washington State? Was that what
you said?

MS. SHOCHET: In Washington State there is an agreement that the
pharmacists have set up what they call collaborative agreements with
doctors that under prescribing authorities from the doctors, they are
able to directly give out to women.

DR. KWEDER: Do you have any information from that experience that would
profile the average user? Who is she? You know, what\'s the age range?
How old are the majority of the users?

MS. SHOCHET: Unfortunately I don\'t have statistics on that.

DR. KWEDER: Okay.

DR. DeLAP: Thank you very much, and we\'ll continue.

MR. FOX: Bob.

DR. DeLAP: Oh, we have one.

MR. FOX: Would you favor an age restriction on the availability to
obtain it over the counter or \--

MS. SHOCHET: Absolutely not.

MR. FOX: No age restriction?

MS. SHOCHET: No restriction on age.

DR. DeLAP: Okay. Well, thank you very much.

And we\'ll continue with Beverly Winikoff for Population Council.

DR. WINIKOFF: Good morning. My name is Beverly Winikoff. I\'m a Public
Health physician, and I\'m Program Director of Reproductive Health at
the Population Council in New York, a nonprofit research and technical
assistance organization that works internationally as well as
domestically on problems of population, reproductive health, and
technology development.

As such, the council has participated in the development of over half a
dozen FDA approved drugs and devices and has additional pending
applications with the FDA at this time. Our institutional and
professional experience in developing product for use in fertility
regulation and other aspects of reproductive health has provided the
opportunity for us to think carefully about the criteria involved in
classifying drugs for safe and effective over-the-counter use.

Prescription status is reserved for products that are not safe for use,
except under the supervision of a licensed practitioner. I would like to
discuss seven criteria that seem particularly important in designating a
product as appropriate for nonprescription, over-the-counter
availability, and then I\'ll apply each of these criteria to hormonal
contraceptives to make the case that these products should be available
over the counter probably generally, but at least for certain
indications and under certain conditions.

A drug that\'s sold without prescription should meet the following
criteria. It should be nonaddictive. It should have an indication for
use that\'s self-diagnosable; have a recommended regimen that is easy to
comprehend and to execute; have a low likelihood of substantial
incorrect use; have low potential for harm in the case of incorrect use;
have mild side effects that are also largely self-diagnosable; and be
more effective if obtained quickly.

All oral contraceptives generally meet all of these tests. First, the
drugs themselves are nonaddictive when used either as ongoing
contraception or for the indication of emergency contraception in the
event of unprotected intercourse.

Second, the indication is quintessentially self-diagnosable. A women,
and few others actually, knows that she\'s had unprotected intercourse
in the case of emergency contraception or desires to delay or avoid
pregnancy in the case of ongoing contraception.

Third, the regimens are easy. All the regimens for ongoing
contraceptions involve taking one pill a day, sometimes continuously,
and sometimes with a break of seven days.

Emergency contraception regimens involved taking two doses of pills,
either one or two pills for each dose, 12 hours apart and then stopping.

It\'s hardly likely that American women who can prepare a TV dinner or
operate a Walkman radio would have trouble following directions such as
these. A label appropriate for all patients, and having passed
appropriate label comprehension studies, would be easy to prepare for
such a regimen.

Fourth, it\'s unlikely to use these pills incorrectly. In other words,
it\'s unlikely that a woman would take an entire pack of pills with her
afternoon tea in the thought that these would more effectively prevent
pregnancy than following the package directions. The most common error,
in fact, would be to forget to take a pill, but this just reduces the
possible efficacy of the method and does not cause medical problems.

In fact, there is not even any evidence that getting a pill through a
prescription for such an indication would reduce the likelihood for
forgetting to take one.

Fifth, there\'s low potential for harm if these medicines are used
incorrectly. Even if a woman were to take more pills than directed,
there\'s virtually no recorded toxicity from overdosage. It\'s
impossible to commit suicide these pills, for example, or to abort or
damage a fetus if a women takes them if she\'s already pregnant. And the
potential for harm relates merely to the lack of efficacy as above if
contraceptives are taken sporadically or to a potential loss of efficacy
if a second dose of emergency contraception is not taken.

Six, side effects are mostly mild for these medications. Serious effects
are exceedingly rare, and most side effects such as breast tenderness,
headache, et cetera, are self-diagnosable by the woman. She can then
elect to discontinue treatment to seek medical advice about how to
manage the side effects, or to continue despite some personal
discomfort.

Perhaps the most important aspect of all these medications, given their
exceptional safety profile is that in every case efficacy is time
dependent. For a woman who wishes to avoid an unwanted pregnancy after
unprotected sex, the evidence is absolutely clear that the single most
important message is to take emergency contraception as soon as
possible. Anything that delays access to the pills decreases the
efficacy of treatment.

Prescription status would delay access for every woman who wanted to
take these pills unless she already had them in her medicine cabinet.
There is no question that over-the-counter status would allow a woman a
more effective remedy for a problem that she can diagnose and for which
there are essentially no contraindications.

In some respects it is, frankly, illogical to make such a medication
dependent on a visit or even a phone call to an open doctor\'s office
before a woman can have access to pills. Similarly, in the case of
ongoing contraception, women want effective protection as soon as
possible after they\'ve decided to use it, and while it may be
reasonable to expect a woman to wait to begin pills once she has started
them, many women may face a situation of needing a refill before being
able to get to a clinician.

It\'s also illogical to require a woman to get a prescription to replace
a lost or destroyed pack of pills during a month in which she is taking
that medication. At the very least, women who are pill users should be
able to reorder, replenish, and resupply themselves without needing
additional medical prescription. In fact, it is probably reasonable to
allow ongoing oral contraception to be purchased over the counter by
some women, while it remains a prescription item for those who choose to
seek medical counsel before embarking on such a regimen.

With respect to oral contraceptives, the FDA must face an important
reality. Making these drugs more accessible more immediately also makes
them more effective. American women deserve and, indeed, require easy
over-the-counter access to these important adjuncts to health,
self-care, and peace of mind.

Thanks very much.

DR. DeLAP: Thank you.

Question? Dr. Cantilena.

DR. CANTILENA: Right. If I can just ask you to comment on sort of the
issue with the ongoing over-the-counter contraception, with regard to
drug-drug interactions, have you thought about what possible, you know,
negative outcomes in terms of, you know, failed contraception would
result from some fairly well known drug-drug interactions?

DR. WINIKOFF: Well, I think I\'ve thought about it. I think that
probably it\'s not a reason to withhold this change in status. There are
labeling issues, and there\'s also the fact that it\'s not clear that
prescription status protects very well against this problem. Many
practitioners are not able to counsel effectively on this as well.

And as I understand, its evidenced in some of the more common ones is
equivocal. So I think that there\'s room for guidance in labeling on
this.

DR. DeLAP: Thank you very much.

The next speaker is Elizabeth Cavendish for NARRAL.

MS. CAVENDISH: Hi. I\'m Elizabeth Cavendish. I\'m Legal Director of
NARRAL and Vice President of the NARRAL Foundation. NARRAL stands for
the National Abortion and Reproductive Rights Action League.

Thank you so much for holding this hearing. I\'m delighted to submit
testimony on behalf of NARRAL, a 504(c)(4) grassroots national advocacy
organization of over 200,000 members with an affiliate state network and
the NARRAL Foundation, its 501(c)(3) educational counterpart.

NARRAL and the NARRAL Foundation are committed to insuring women\'s
access to the full range of reproductive health options, including
preventing unintended pregnancy, bearing healthy children, and choosing
legal abortion.

We believe that increasing accept to ECPs is the single more promising
avenue for reducing unintended pregnancy and the need for abortion, and
we argue that ECPs should be available over the counter.

ECPs, as you know, are ordinary birth control pills that significantly
decrease a woman\'s chance of becoming pregnant when administered within
72 hours of unprotected sex. Estimates show that increased use of ECPs
could reduce the number of unintended pregnancies and abortions by half
annually.

In recent years the FDA has approved two types of ECPs, the PREVEN
emergency contraception kit and Plan B, both of which are available by
prescription.

Currently ECPs can be difficult to obtain in a timely manner because
women must obtain a prescription to use them. For example, a woman faced
with a broken condom on a Friday night whose doctor\'s office is closed
over the weekend might have to wait till the following Monday, three
days later, to obtain a prescription for ECPs if her physician won\'t
prescribe over the phone on the weekend.

Women in rural areas may have to travel great distances to reach the
nearest doctor or clinic, making a prescription within 72 hours of
unprotected sex difficult, if not impossible, to obtain.

Even under less extreme circumstances, obtaining a prescription for ECPs
can be problematic as you\'ve heard from other witnesses today. A recent
study of the EC hot line, 1-88 NOT 2 LATE, a 24-hour automated phone
line that provides the names and telephone numbers of clinicians who
prescribe ECPs in the caller\'s geographic area found that even when
calls to clinicians were made during business hours, only three out of
four attempts to obtain ECPs resulted in appointments or telephone
prescriptions within 72 hours.

Because ECPs are more effective the earlier they are used and most
effective within the first 12 hours of unprotected sex, the obstacles
associated with obtaining a prescription for ECPs pose a serious threat
to women\'s health. Because ECPs are safe, effective, and easily
administered, they are suitable for nonprescription, over-the-counter
availability.

Making ECPs available over the counter would eliminate an unnecessary
barrier to women\'s access to this important contraceptive option.

You\'re all very familiar with your own criteria for over-the-counter
drugs, but to be approved by the FDA for over-the-counter distribution,
a drug must meet certain criteria. It must be safe and effective. Taking
the drug must be safe enough that medical supervision and, thus, a
prescription is not necessary to preserve public health due to the
drug\'s toxicity, its potential for harmful side effects, or its method
of use, and the drug must be simple enough to use that instructions on
the drug\'s packaging are sufficient to insure safe and correct
self-medication.

Dr. Winikoff just went over those criteria. I think she demonstrated
amply that the criteria are met here. So, again, NARRAL reiterates that
ECPs meet these criteria for nonprescription status and can be safely
marketed over the counter.

Oral contraceptives, the same drugs found in ECPs have been studied for
three decades. They\'ve been studied more extensively and have been
found safer than most drugs in medicine. No serious medical consequences
from an overdose of oral contraceptives has been reported.

ECPs are 75 to 89 percent effective when a specific dose is taken within
72 hours of unprotected sex and a second dose is taken 12 hours after
the first dose.

The most common side effects of ECPs are nausea and vomiting. Other side
effects include dizziness, fatigue, and headache. Long term side effects
are unlikely, and all of the side effects of ECPs are less dangerous
than either pregnancy or childbirth.

They\'re easy to self-administer as others have said, and
nonprescription access to ECPs does not discourage ongoing contraceptive
use.

Better access to ECPs will improve women\'s health, and for that reason
NARRAL is strongly committed to seeing them go over the counter. We
believe that increasing women\'s contraceptive options, better access to
ECPs will give women greater control over their reproductive lives.

To just sum up here, I see my time is out. If women simply saw them in
pharmacies, awareness of ECPs would increase tremendously. One of the
biggest barriers to use is lack of awareness. This could make a crucial
difference to millions of women, and making ECPs available over the
counter would help to remove this barrier to access and help improve
women\'s health and, in fact, their reproductive rights.

Thank you.

DR. DeLAP: Thank you.

Questions? Discussion?

DR. KWEDER: I have one, Bob.

The same question that was asked of one of the previous speakers. Would
you have \-- do you have any perceptions on how access would be limited
appropriately or inappropriately by a third class of distribution, say,
pharmacists, through a pharmacist still without a doctor\'s
prescription?

MS. CAVENDISH: Right. Well, we favor them completely over the counter.
As I said, if people saw them on counters with other regularly used
products, that would increase awareness, and that\'s a huge barrier. The
estimates differ on what percentage of people are even aware of them,
but only one percent of women have used them so far, and almost nobody
knows really about the regimen.

There\'s tremendous misunderstanding. People think they\'re illegal in
this country, and so we\'d like them to be on the shelves, but if
pharmacists simply could provide them, as happens in Washington State
now through the project mentioned earlier, that\'s still a big
improvement if it eliminates the need to go to a doctor\'s office.

So even behind the counter status, if I gather that\'s what your
question is about, like in Canada, would be a big improvement, but we\'d
prefer them actually on the shelves.

DR. DeLAP: Okay. Well, thank you very much \--

MS. CAVENDISH: Thank you.

DR. DeLAP: \-- for your participation.

And our next speak for Family Health International is Dr. Elizabeth
Raymond.

DR. RAYMOND: Good morning. My name is Elizabeth Raymond. I\'m an
gynecologist. I\'m Associate Medical Director at Family Health
International, where I do research on contraception, and I also see
patients at the Planned Parenthood Clinic in Raleigh, North Carolina.

Family Health International has had a contract with Women\'s Capital
Corporation to assist with preparation of their new drug application for
Plan B emergency contraceptive pills.

I\'m here today to tell you why emergency contraceptive pills should be
made available over the country. Emergency contraceptive pills are
basically high does birth control pills that a woman can take after
unprotected sex to prevent pregnancy. If taken within three days after
intercourse, these pills reduce the chance of pregnancy by 75 percent or
more depending on the particular hormonal regimen in the pills.

Recent data have shown that the efficacy of emergency contraceptive
pills is significantly greater the sooner the pills are taken after sex.
In a study from the World Health Organization, the pregnancy rate was
approximately eight times higher, eight times higher if the woman waited
three day safer sex to take the pills than if she took them within the
first 12 hours.

This is quite a remarkable finding. Women really must use this treatment
right away in order to get maximal benefit from it. Hours count. This
need for speed is the most compelling reason why emergency contraceptive
pills should be made available over the counter.

A prescription requirement which usually involves an actual visit to a
doctor or other practitioner will inevitably delay the onset of
treatment. If women can buy the pills directly from pharmacies, they can
get them immediately whenever they need them. Making emergency
contraceptive pills over the counter may be the only practical way to
insure that women have immediate access to this treatment.

The other reason that emergency contraceptive pills should be sold over
the counter is that there is no medical reason for the prescription
requirement. A woman certainly doesn\'t need a doctor to diagnose the
fact that she\'s had unprotected sex or to help her take the pills.

The treatment is also very safe. The most recently approved regimen
which is marketed now under the brand name Plan B has only three
contraindications listed on the FDA approved label: allergy to the
product, undiagnosed abnormal vaginal bleeding, and ongoing pregnancy.

The first of these, allergy, is extremely rare, and if allergy were a
rationale for keep a drug prescription, then no drug could be available
over the counter.

The second contraindication, abnormal vaginal bleeding, frankly,
doesn\'t make sense from a medical point of view. I can think of no
particular reason why a woman with abnormal vaginal bleeding should not
use this treatment. Other expert organizations, such as the World Health
Organization and Planned Parenthood Federation of America, do not
consider vaginal bleeding as a contraindication to this treatment, and
in any case, a woman knows whether or not she has abnormal bleeding.

Finally, advice not to use during pregnancy can be found on the label of
many drugs currently sold over the counter. In the case of emergency
contraceptive pills, pregnancy is a contraindication not because the
treatment is dangerous for pregnant women or for their pregnancies. The
FDA itself has declared that the treatment does not harm pregnancies.

Rather, it\'s listed because the treatment is ineffective in women who
are already pregnant. If ECPs were made available over the country,
undoubtedly some pregnant women would end up taking them, but no adverse
consequences are expected to result from this.

Of course, emergency contraceptive pills, like all drugs, have some side
effects, such as nausea and breast tenderness, but some 10,000 women
have used emergency contraceptive pills in monitored studies and many
more in clinical settings. No serious or life threatening consequences
have ever been attributed to emergency contraceptive pills.

Judging from 40 years of experience with regular birth control pills,
the chance of serious adverse effects from taking the hormones in
emergency contraceptive pills for only one day is probably so small as
to be unmeasurable.

Furthermore, whether emergency contraceptive pills are distributed by
prescription or over the country will not affect either the incidence or
the severity of any side effects that do occur. With some drugs, a
doctor may be able to screen out women who will have side effects or
treat them differently, but this is not possible with ECPs. Certainly
emergency contraceptive pills are much safer than many other drugs that
are currently available over the counter.

Unwanted pregnancy is a huge public health problem in this country, and
it\'s a huge problem also for a woman who has one. Emergency
contraceptive pills have the potential to cut in half the number of
unintended pregnancies and also to half the number of resulting
abortions if women could obtain them and take them promptly.

Requiring emergency contraceptive pills to be distributed only by
prescription restricts access and is medically unnecessary. In the
interest of the public, the FDA should act swiftly to correct this
situation.

Thank you.

DR. DeLAP: Thank you.

Comments? Questions?

DR. MURPHY: This morning we\'ve been talking about where the
effectiveness and the success. Would having this therapy over the
counter affect the results where the therapy fails, or outcome or
safety? In other words, the emergency use failed. The woman is pregnant.

DR. RAYMOND: No drug is 100 percent effective, and this treatment, like
all treatments, sometimes will fail, and some women will become
pregnant. Eventually a woman who becomes pregnant will figure that out,
and she will seek appropriate or seek treatment when she discovers that
she\'s pregnant, and that\'s not affected by whether the drug is over
the counter or prescribed for her.

DR. DeLAP: Thank you very much.

And at this point we had one speaker who was out of the room at the time
of her scheduled talk, and we\'ll add her here at the end of this
session. Rosalie Gross.

MS. GROSS: Good morning, ladies and gentlemen seated on the Federal Drug
Administration panel, and good morning, Mr. and Mrs. America seated
today in the audience.

Thank you for the opportunity to address you with my deep and heartfelt
concern for the physical and mental health and the educational and
socioeconomic well-being of minor female students located in the middle
and high schools not only in my city and state, but also all across
America.

My name is Rosalie Marie Gross. I have a Master\'s degree in education
from Millersville University of Pennsylvania. I am Pennsylvania
certified elementary and secondary teacher with 15 years of teaching
experience gained mostly in middle schools and in high schools.

In addressing the issue of whether or not birth control pills should be
made available on an over-the-counter basis, I intend to confine my
comments to a selected segment of society with which I have dealt
extensively on a daily routine basis in schools where I have taught and
continue to teach.

Therefore, on behalf of minor female middle and high school students
between the ages of 12 and 18, I beg you, I beseech you, I implore you
not to allow birth control pills to be sold in drug stores over the
counter. This would be physically harmful, psychologically damaging,
educationally destructive, and socioeconomically deleterious to these
girls.

Here are the compelling reasons why. Over-the-counter birth control
pills will only make graver and more serious the physical and mental
risks ranging from serious or fatal to minor or trivial, which are
already inherent in their usage. A list of the common side effects of
these potent artificial steroids which might befall minor teenage girls
include heart attacks, blood clots, high blood pressure, strokes,
migraines, weight gain or loss, and if a female is nulliparous, that is,
a female that has never conceived a child, and most of our minor
teenagers are of that category, then that female has a 45 percent chance
of developing an aggressive form of breast cancer and a 40 percent
chance of developing an aggressive form of cervical cancer some time in
her life.

Should the birth control pill act as an abortifacient instead of a
contraceptive, which it often does, causing an interruption in
pregnancy, the teenage girls\' chance of getting breast cancer rises to
50 percent.

Now, folks, we all know the sale of cigarettes to minors is prohibited.
Why? Mainly because of their carcinogenic risks. Now, why on earth would
the sale of birth control pills over the counter be permitted when these
have far greater health risks and far greater carcinogenic risks than
cigarettes?

Also, the use of birth control pills by minor teenage girls does not in
any way prevent them from contracting one of the 30 different kinds of
known sexually transmitted diseases, including chlamydia, genital
herpes, HPV, and HIV.

Alarmingly, sexually transmitted diseases are spreading at a rapidly
increasing rate among teenagers. One statistic that I have seen reported
that one out of five sexually active teenagers was coming down with some
sort of a sexually transmitted disease.

Over-the-counter birth control pills will cause grave and serious
psychological and emotion problems for minor teenage girls. The more
teenager girls are given birth control pills, the more they will engage
in sexual activity because they labor under the false assumption that
these pills will keep them from getting pregnant.

The more they engage in sexual activity, the greater is their chance of
getting pregnant since the failure rate of birth control pills among
teenagers is quite high. One statistic sets the failure rate at one out
of six for teenagers due to the fact that most teenagers are not very
good about following pill usage directions.

I can tell you they\'re not very good at following any directions,
period.

The greater the failure rate of birth control pills, the higher the
number of pregnancies and the higher the number of abortions. The
driving force behind this cascade of sequential events is called frail
human nature.

While minor teenage girls are not children, they are not adults either.
During their highly formulative in between years, they need all of the
love and guidance they can get from their parents and their teachers,
who should be teaching them abstinence and helping them to practice this
100 percent, fool proof method of avoiding pregnancy and abortion, and
they should not be handing them birth control pills and encouraging
their sexual activity with all its concomitant problems.

The practice of abstinence would allow our teenage girls to gradually
evolve into young women. The practice of abstinence would protect them
from being suddenly thrust into the adult world, from being suddenly
laden with the adult responsibilities of motherhood and child rearing,
or worse yet, from being heavily burdened with the guilt and suffering
that comes from having destroyed one\'s innocent, helpless baby while
still a dependent preborn in the womb.

Over-the-counter birth control pills will prove to be as educationally
destructive for minor teenage girls as are their prescriptive
counterparts, if not more so. To begin with, minor teenage girls should
not be engaged in sexual activity of any kind. While physically able to
perform the sex act, they are in no way mentally or emotionally ready to
handle the multi-faceted aspects of this act, the physical consequences
of pregnancy, nor the psychological consequences of intimacy.

These same minor teenage girls should be focusing on their school work,
on learning communication arts, mathematics, science or social studies
instead of thinking about sex or daydreaming about their male sexual
partners.

They should be worrying about the grades they will be receiving in their
subjects or about the dresses they will be wearing to the school dance,
not about whether or not they are pregnant or whether or not they have a
sexually transmitted disease.

The birth control pill, whether prescriptive or over the country, is
truly the archenemy of education. The extensive use of this pill and the
large number of female high school dropouts is intricately connected.
Because of the birth control pill and its high rate of failure among
teenage girls, the majority of pregnant teenagers either drop out of
school shortly before the birth of their baby or shortly thereafter.

Too often these teenagers, because of their motherhood and child rearing
responsibility, find they have little in common with their carefree and
fun loving classmates. Too often these teenagers drop out of school
because they find they can no longer be students and tend to their
studies and at the same time be mothers and tend to their babies.

What\'s wrong with the schools today? Everyone asks this question. Most
teachers know the answer. I think I do. In a nutshell, it\'s a lack of
discipline on the part of students and a lack of involvement on the part
of the parents.

Birth control pills destroys both of these concepts. Minor teenage girls
are not animals in heat, incapable of exercising willpower, unable to
control their sexual urges, incapable of disciplining themselves to
refrain from certain deleterious actions.

All teachers know that if high standards, such as abstinence, are set
for adolescents, they will achieve them and vice versa for low
standards. If adults believe in youth, that they can be their best,
youth will give their best. If adults believe that youth can be noble
and disciplined, they will rise to the occasion.

While educators are trying to get parents involved in the lives of their
children and what they are doing, over-the-counter birth control pills
will undermine these efforts, causing minor teenagers to literally sneak
behind their parents\' backs.

The majority of these teenagers will buy and ingest these pills without
the knowledge or consent of their parents, as they now do with their
prescriptive counterparts. This is truly an infringement of the
authority and the rights parents have over their children.

They have the right to know what their children are doing, if they are
engaged in sexual activity. They have the right to know what medications
their children are ingesting. After all, should a minor teenage girl
suffer dire consequences as a result of using birth control pills, her
parents will be the first to be called on the carpet. They will be asked
to suffer all of the heartaches and hardships involved, to pay all of
the necessary doctor bills and hospital costs and maybe even to care for
their grandchild from infancy to maturity.

Over-the-counter birth control pills will prove to be socioeconomically
deleterious to minor teenage girls. Given the high failure rate of these
pills and the resultant pregnancies, a minor teenage girl who becomes a
single parent will find herself at a definite financial disadvantage,
especially if she as a result of her pregnancy and childbirth has
dropped out of high school.

If so, such a single parent without a high school diploma is doomed to
work in low paying jobs and doomed to struggle financially throughout
the life of her child. Climbing the socioeconomic ladder, though not
impossible, will nonetheless be for the majority of minor teenage girls
who became single mothers in high school a most difficult proposition.

Finally, let me beg you, ladies and gentlemen of the FDA panel, beseech
you and implore you on behalf of minor teenage girls everywhere in
America not to make birth control pills available on an over-the-counter
basis.

In closing I would like to reiterate the words of Christa McAuliffe,
killed in the 1986 tragic explosion of the spaceship
[Challenger]{.underline}, who said, \"I touched the future. I teach.\"

I would like to challenge all of you on the FDA panel to do the right
thing by minor teenage girls. I would like to say to you you touch the
future. You decide.

Thank you.

DR. DeLAP: Thank you.

Do we have questions or comments?

(No response.)

DR. DeLAP: Well, thank you very much.

We\'ll proceed then to Suzanne Hughes, Lipid Nurse Task Force.

MS. HUGHES: Good morning. My name is Suzanne Hughes. I\'m a registered
nurse in the Section of Preventive Cardiology at the Cleveland Clinic
Foundation, but I\'m here today on behalf of the Preventive
Cardiovascular Nurses Association, formerly the Lipid Nurse Task Force,
and I\'d like to thank you for allowing our organization this forum.

We are a national organization of professional nurses dedicates to the
primary and secondary prevention of coronary heart disease, vascular
disease and stroke. Our mission is achieved through professional and
public education, through increasing consumer awareness of the
importance of cardiovascular risk reduction, and through advocacy of the
need for nursing involvement in the care of persons and families at risk
for coronary heart disease and stroke.

We are supported by the dues of our membership, which is over 1,500
strong, and by our Pharmaceutical Round Table. My presence, time, and
travel here today has not been underwritten by any of these
organizations.

It\'s estimated that 98 million Americans have blood cholesterol levels
of 200 milligrams per deciliter and over. This represents 52 percent of
our adult population.

In numerous well designed clinical trials over the past ten years
involving hundreds and thousands of American adults, cholesterol
lowering through the use of HMG CoA reductase inhibitors has been found
to be remarkably safe and effective. The results of these trials
demonstrated substantial reductions in morbidity as well as mortality.

The benefit to quality of life and to the reduction in cost of
hospitalizations for coronary disease and stroke is also enormous. These
benefits are seen across the adult age span, as well as across genders.

What is also clear is that millions of Americans with modestly elevated
cholesterol are not being identified and/or treated. The need for an
effective treatment for elevated cholesterol and the availability of
this very safe and effective group of medications compels us to
seriously consider the great public health benefit of allowing this
class of medications to be made available over the counter.

We strongly support the concept of over-the-counter availability of an
HMG CoA reductase inhibitor based upon the satisfaction of the following
criteria.

Number one, that research demonstrates that the population who chooses
to use this product is comprised of appropriate candidates for OTC lipid
lowering therapy with regard to age, medical history, and baseline lipid
levels.

Number two, that research shows that those who elected to use the
product follow the instructions on the label with regard to dosage and
frequency.

And, number three, that research shows that those who elect to use the
product consult with their health care providers regarding its use and
for clinical follow-up.

The Board of Directors of the PCNA strongly recommends that the FDA
consider the benefits of bringing HMG CoA reductase inhibitors over the
counter in order to reduce the burden of cardiovascular disease and
stroke that affects one in two adult Americans.

Thank you.

DR. DeLAP: Thank you.

Dr. Woodcock.

DR. WOODCOCK: Thank you.

I read your entire written testimony, and one of the things that is very
challenging about this area, I think, and these proposals is that the
proposal to move certain products over the counter based on widespread
under treatment of the population for known life saving or morbidity
preventing interventions is based on the failure of our current health
care system or inability to effectively deliver these medications to
people who need them, right?

And it does arise; the question arises: is this the \-- this is a
default. This is a less than ideal perhaps solution to the problem of
the inability of the health care system to deal with this problem in the
traditional manner, and I\'d just like you to perhaps expand on that
analysis more.

I mean in some ways this proposal asks to take the health care provider
out of the equation because that system of health care provision is
failing to deliver the health benefits to the population, and one has to
wonder is this the optimal approach that our society should take.

MS. HUGHES: So if I understand your question, the health care industry
or the health care provider industry is thus far failing to treat
optimally in both primary and second prevention. So is the solution to
go to over-the-counter treatment?

I think our position on this is that over-the-counter treatment is a
small portion of a proposed solution to that problem. Certainly we do
not advocate over-the-counter adoption of these products in the
secondary prevention group or in persons with extremely high levels of
cholesterol or in the diabetic population. So this would be in a certain
subset of the population, healthy American adults, with a total
cholesterol between 200 and 240.

In my personal experience, we\'ve seen extremely compulsive compliance,
if you will, with patients taking all the over-the-counter products and
very spotty compliance with things recommended by physicians. So I think
the behavior of American consumers is changing with regard to certainly
our patients desiring to get their information and seeking health care
outside of the realm of what is recommended by their physician or by
their non-physician practitioner.

So this is only a partial solution in response to that observation.

Yes?

DR. TEMPLE: The population you describe ‑- at least you can correct me
if this is wrong \-- under current guidance is not a group for which
drug therapy is recommended. That is, they\'re healthy. They\'re not
particularly filled with risk factors, and they haven\'t had prior
evidence of coronary artery disease, and current labeling doesn\'t
particularly urge that use.

Now, I know Dr. Anderson later is going to describe data that suggest
that that group could benefit from therapy. I take it your view is that
that\'s now well established enough so that this population, the 200 to
240 range, at least making some assumptions about their HDL, ought now
to be treated and that current guidance ought to be modified. Is that -‑

MS. HUGHES: No suggestion that we throw out the current NCEP adult
treatment panel guidelines at all. Considering that a total cholesterol
level of 240 probably translates to an LDL cholesterol of somewhere
around 180, if we\'re looking at the population with greater than two
risk factors for coronary heart disease, I think we are getting into the
range at which pharmacologic therapy might be entertained.

DR. TEMPLE: But to some extent you\'re talking about having it available
for people who won\'t necessarily know all those things.

MS. HUGHES: That\'s correct, although the research that I\'ve seen so
far did indicate that those who took advantage of these types of
products in a simulated over-the-counter trial were those people who
tended to have health seeking behaviors. So they tended to be a healthy,
more well educated population.

DR. TEMPLE: But just to be clear, you\'re still suggesting it for the
population that would now have treatment recommended for it under
current guidelines?

MS. HUGHES: Absolutely.

Thank you.

DR. DeLAP: Thank you.

We\'ll change the sequence slightly at this point and we\'ll hear from
Dr. Jerome Cohen.

DR. COHEN: Thank you very much, Mr. Chairman, ladies and gentlemen.

Thank you for changing the sequence, and I want to thank the agency for
holding these public hearings in the first place because it\'s something
I\'ve been interested in for many years.

I do serve as a consultant to Bristol Myers and have done as such for
about five years.

In addition, I\'ve done research in the lipid lowering field with every
approved statin drug, and so therefore have had research funding from
Pfizer, Warner Lambert, and \-- thank you \-- Merck, as well as Bayer
and Ovartis.

I speak to you today, however, as someone who has a lifelong background
in my medical career in preventive medicine and in public health and in
preventive cardiology. My background and training is as a clinical
cardiologist, and I\'m a past president of the local affiliate of the
Missouri Heart Association.

As an old professor, I use an old technology of slides. I have no
prepared notes, and so if we can get that in focus, that would be great.
I\'m absolutely amazed. I think over the last two days this is the first
time slides have been used.

Let me begin at the beginning as to why we\'re all here interested in
this particular topic, and that is we\'re talking about a number one
killer, and that is cardiovascular disease, and among cardiovascular
disease is coronary heart disease. It\'s an equal opportunity killer.

About half the people in this country, more than a million deaths every
years are from cardiovascular disease, and this despite the great
advances of the last 20 years or so.

We\'ve seen advances in the coronary care we never dreamed of. So we
have thrombolytic drugs. We have drugs that can slow heart rates and
reduce myocardial oxygen demand and improve ischemia.

We have the ability to defibrillate, and the approach now has taken a
secondary prevention emphasis, and so what have we seen spread
throughout this country in terms of trying to prevent this number one
killer? We\'ve seen defibrillators grow. Airports, National, Dulles,
probably in stadiums and ballparks around this country, and soon to be
on airplanes, and probably one day because of the high risk character of
some of these people in the room, we\'ll have them right here in the
back of the room.

(Laughter.)

DR. COHEN: I would submit to you, and think about this, that this is not
the way that we should be approaching prevention in terms of coronary
heart disease.

And so what we have begun to understand over the last several decades is
that the fundamental disease process is atherosclerosis, and that\'s
what we need to be thinking and teaching about, is atherosclerosis and
can we prevent it or can we change the natural history of this disease?

The modifiable risk factors have been known for years since the
Framingham began in 1948, and amongst them the most dominating is the
cholesterol level and specifically the LDL, a surrogate for which we use
the total cholesterol from the large trials that I\'ll tell you about.

And I was involved and still am involved in the multiple risk factor
intervention trial with regard to what we\'ve been able to show as risk
factors. It is shown on this slide, and I hope you can see this because
what it shows is 360,000 people who have been followed now up to 20
years, and want you can see in the left curve is a strong, continuous,
graded relationship between total cholesterol and death rates from
coronary heart disease.

There is no risk level above which it doesn\'t continue to climb as
cholesterol goes up or below which it doesn\'t continue to decline as
the rates drop, and so that\'s reflected in the right-hand side of the
curve, which shows a relative risk fixed at 1.0 for levels of 200.

But let us examine risk of 300. It\'s four times higher. When I began
medical school, in fact, 300 was often called normal, and we\'ve seen it
drop to 280 and 250. Two, fifty offers twice the risk as 200, but let us
look at 200, which is now considered so-called desirable.

Do you want a level of 200? The answer, I would hope, when you know the
data is no, an ideal level which I would define as optimal levels of
cholesterol is shown there at 150 milligrams per deciliter, which
minimizes your risk for death from vascular disease, and we\'re moving
in that direction. Make no mistake about it. The wheels of progress are
moving. The wheels of progress, however, move slowly.

Let us examine what we know from the MRFIT data with respect to where
people come from who have heart attacks in terms of their cholesterol
levels, and what I want you to focus on there is the levels between 200
and 240.

Shown in the orange is the distribution of the population cholesterol
levels, and what you can see is the preponderance of cholesterol levels
from which coronary disease eventually arises is in this so-called mild
elevation of cholesterol range.

That\'s where the action is. That\'s where the majority of people are.
That\'s the group that\'s often dismissed by physicians and say, \"Well,
our cholesterol is a little high, 210, 220.\" It\'s almost normal; it\'s
almost average.

Well, the average person in this country dies from coronary heart
disease, and so you don\'t want to have an average level. You want to
have an optimal level. Remember that if nothing more.

So now what is the rationale for OTC treatment? Let us examine where we
are.

We know that the current guidelines define an ideal level that\'s less
than the 200 total and less than 130 as desirable levels, and I showed
you the epidemiologic data from a huge database, each of those points
representing 20,000 people, saying that this is just an arbitrary cut
point. Two hundred is an easy number. Is there anything better about 200
versus 201 or 199? It\'s a continuous risk.

But for reasons of definition, we have defined it in that way from the
NCEP guidelines, which were written, the current ones, in 1992 and
published in 1993. Now the Healthy People 2010 takes a stance in this
regard, moving forward from Healthy People 2000 and saying, \"We would
like to have 75 percent of Americans have a total cholesterol below
200.\"

Currently the average, the mean cholesterol in the United States is
about 206, and more than half of our population has a cholesterol above
200 milligrams per deciliter, above the currently defined desirable
levels.

We know that elevated blood cholesterol is significantly under treated
despite widespread knowledge of it. Less than four percent in some
studies who are eligible for primary prevention are actually being
treated and actually below what we would consider their ideal goal.

And despite the knowledge about statin therapies that we\'ve been grow
in the last six years and the growth of the sale of statins, the growth
rate has slowed. There are data to support that.

And this data has shown a disappointment to me because despite our best
efforts in academia and in government and by the pharmaceutical
industry, the message isn\'t getting out there, and that\'s partly
reflected in Dr. Janet Woodcock\'s question. Is this the answer? I\'ll
come to hopefully answer that question as well.

We also know something important is happening out there. Let us not lose
sight of where we are. There\'s a growing interest in self-care and
self-treatment, not necessarily self-diagnosis, but self-treatment in
collaboration oftentimes with health care providers.

And so an OTC approach can be a complementary one. There is no single
answer to this problem, this huge public health problem. It\'s a
multi-faceted approach, and the FDA has to be part, I think, of the
solution to this approach.

So who are we targeting OTC therapy for with regard to lipid lowering?
We are targeting it to patients who have been told to lower their
cholesterol level. It\'s too high. You try diet. You try exercise. You
try lifestyle approaches, and we know oftentimes it doesn\'t work or
even despite the best efforts of our patients, they don\'t succeed or
they don\'t reach the desirable levels.

And so these are people whose cholesterol levels are between 200 and
240, whose LDLs are above the desirable range of 130, again, an
arbitrary cut point. We don\'t want to have our level at 129.

Generally healthy people, importantly so. No evidence of cardiovascular
disease, coronary disease, or diabetes that puts them in this special
high risk group. We would not target specifically that population.

And these are people who are likely to reach their goal with only a
modest to moderate reduction in their cholesterol levels, and so that\'s
who I would personally target our information to with regard to
availability of an OTC product.

Now, what do we need to assure ourselves that this is a reasonable
approach? The one theme that was common throughout yesterday was [primam
non nocere]{.underline}, safety, safety, safety. I liken it to my
friends who are in the real estate business. It\'s location, location,
location. Well, it\'s safety, safety, safety.

And we need to assure ourselves that this highest level is met by any
proposed OTC product. So the safety profile has to be expanded for use
in less supervised environments, using a compound that has come from
clinical trial data to be shown to be safe, as well as effective.

And in my estimation, the best way to look at safety is to have a
numerator, to have a denominator, and to have a comparison group that in
the earlier trials relate to placebo control. Then we can put it into a
perspective of is this something unusual. Is there something happening
out there?

And if there are such databases, they should be examined carefully to
give us the answer to whether or not there is harm out there.

We would like a product that has no abuse potential, that has no serious
sequelae if taken in overdose quantities, and it\'s safe if taken
inadvertently during pregnancy.

We heard those issues arise earlier in these meetings.

We would like a product that is free of drug-drug interactions for
oftentimes these people are taking other ingredients.

No biochemical monitoring is needed for safety, and adequate and
appropriate efficacy has been shown in the appropriate OTC population.

Let us turn our attention to consumer use trials. This was brought up
yesterday. We need to have information about the consumer with respect
to availability of OTC lipid lowering. Can they read and understand the
label? Absolutely that is a must.

Can the defined population use the product in accordance with the
labeling? The behavior, that is also a must.

Compliance in an OTC environment will result in predictable and
consistent safety and efficacy profiles from what we expect from the
clinical trial data, as well as the experiential use over many years of
some of these products.

The physician-patient maintained relationship, that is, that it
shouldn\'t detract from the medical system, and in fact, if anything,
there is data to suggest it would take people into the system on a net.

Adverse consequences of inappropriate use would be minimal, and
cholesterol lowering, which is what the approval would be sought for,
not reduction in events; cholesterol lowering as we would translate it
from the epidemiologic database, would then translate into a benefit
that would far outweigh the potential risks.

In summary, let me say that coronary heart disease remains our number
one killer and has been such since 1917. Coronary disease and
atherosclerosis are preventable. You\'ve got to believe that.

Despite our current efforts, adoption of effective strategies for
getting populations controlled has not been very effective, and adoption
has been low. Consumers are interested in nonprescription options.
They\'ve already spoken with their wallets. One estimate I\'ve heard is
around \$400 million are being spent for these kinds of products
currently, many of them not of proven safety and of no proven efficacy.

The OTC population can be defined. Issues surrounding the OTC
availability of cholesterol lowering can be identified in testing and
appropriately designed studies, and that OTC availability of a safe,
well characterized compound would complement the existing efforts toward
reducing cardiovascular risk.

Finally, in closing, Mr. Chairman, let me just hold up newspapers that
were published two days ago. One is the headlines of the White House
conference on the genome research, remarkable achievement and one of the
great scientific achievements, I think, of all time.

At the same day, in the [USA Today]{.underline} on the back page cover
story is \"Drug Makers Prescribe Move in Terms of OTCness,\" and I found
it ironic that these two articles were juxtaposed in a way because the
attention went to the White House, and the genome and the DNA, a great
story to be sure, but when you examine the issue of atherosclerosis and
lifestyle nd how we can prevent it and change the natural history, to my
way of thinking what we do in this room today and in the near future
will better determine the future prevention of cardiovascular disease in
the near term at least in my medical career than anything else that
comes out of the genome research.

Thank you very much.

DR. DeLAP: Thank you, Dr. Cohen.

Questions?

DR. GILLIAM: I understand there\'s going to be new NCEP guidelines
coming out. Do you have any indication of what they will be?

And the second question is: if these were to come over the counter then
you\'re saying that there shouldn\'t be any worry about monitoring liver
function tests and that kind of thing?

DR. COHEN: There are two questions. One is NCEP guidelines, which I
mentioned were published in \'93. New guidelines are currently being
written. I\'m not on the committee. However, they are due out early next
year, I am told now, and perhaps in the spring. There was hope they
would come out this year, and I do not know. I\'ve heard rumors probably
as most of us have about what it will consist of, but I\'m not prepared
to comment on that in this hearing.

In terms of its availability I think was the second part of your
question, in terms of the liver function we would want a compound
ideally that has very little evidence of liver damage and a widespread
utilization pattern that would indicate such in hopefully controlled
clinical trials. I think if we have those data ideally then in hand, we
can look at evidence, real evidence, with respect to numerators,
denominators and comparative groups and make a determination whether
there is a risk, and if that risk is great or if it potentially
outweighs the potential good with respect to cholesterol reduction.

DR. DeLAP: Dr. Templer.

DR. TEMPLE: The group, if I understood you, that you\'d be targeting for
the over-the-counter availability with low doses are people who don\'t
have established coronary artery disease and are in the 200 to 240
neighborhood.

DR. COHEN: Correct.

DR. TEMPLE: That\'s correct, I think. I have a number of questions.

Some of those people probably have HDL levels that would make them at
very low risk. Is it important that those people not be treated or is
that not something to worry about very much?

DR. COHEN: I would hope that future drugs that go OTC would involve the
strategy of including the physician in the mix. This is not to exclude
the physician out of the loop and directions would say, \"Consult with
your physician to see if this is the right product for you,\" and if the
HDL is high enough to sufficiently offset a higher than desirable LDL
level, perhaps treatment wouldn\'t be indicated.

So I think the intent here is to have the consumer look at a product
that\'s available and make a decision hopefully in consultation with the
medical care provider about whether this product is appropriate or not.

DR. TEMPLE: Not top ut words in your mouth though, I think you\'re also
saying if that didn\'t occur, the risks would be pretty low and you
could tolerate that. Some people \--

DR. COHEN: Yeah, you could put those words in my mouth.

DR. TEMPLE: Okay.

DR. COHEN: I think the risk of harm with respect to inappropriate use is
really small relative to the benefit, and as I indicated to you, and
this is an important point, that the risk continues to decline. So if
you take it and your level is 199 and you end up with a cholesterol
level, a total let us say of 160, in fact, the epidemiologic database
would suggest you\'ve done yourself good.

DR. TEMPLE: Actually that\'s the area of my next question.

DR. COHEN: I wanted to set you up for that.

DR. TEMPLE: Okay. I think, if I understand it, you\'re making two
arguments. One is that implicitly we should believe the epidemiology is
pertinent to treatment because as we test each level of patient over
260, 200, people with heart disease and so on, it seems to keep
confirming more or less the epidemiology.

So you don\'t have reservations about treating the lower populations
that appear to be at risk epidemiologically, and I understand that
argument.

What data would you cite, however, if you felt some obligation to cite
it, that we know that those levels in the 200-240 range provide benefit
to people, apart from the epidemiology?

I don\'t dismiss that, but \--

DR. COHEN: Well, there are trials on primary prevention that include
people in the lower end of this distribution, and perhaps Dr. Anderson
will be commenting further on that. I don\'t know, but there are
clinical trial data that would suggest continuation of the benefit down
into that range.

In addition, let me importantly say this to the committee, that you
can\'t look at a single study or a single bit of data. You\'ve got to
step back and look at the totality of the evidence, from the animal
experimental data with regard to atherosclerosis, from the epidemiology
data which I showed you which has really never led us astray when it\'s
been large trials like MRFIT and Framingham, and from the limited
clinical trial data.

And when you take a step back, I think a good scientist couldn\'t help
put say that the preponderance of evidence suggests that benefit will be
done in the absence of endpoint data which I think we agree probably
won\'t be done.

DR. TEMPLE: Last question. Are you at all concerned that patients who
start their lipid lowering program on their own without being revved up
by the physician community won\'t treat it as a lifelong need the way
someone who was part of the medical system would?

DR. COHEN: I am. I think that\'s a concern, and really as someone who\'s
interested in preventing disease, what we need to develop are programs
to keep people on therapy.

One of the problems is that people stop therapy or don\'t recognize the
lifelong need here and that they shouldn\'t go off of diets or try to
make every attempt at lifestyle, and so I think ideally these kinds of
programs should be in place.

The National Lipid Nurses Association and other groups, the Heart
Association have worked hard to work in the public domain, and industry
is doing a lot as well, and so I think together we can try to educate
the population about the importance of maintaining lifestyle and
importance of maintaining medical therapy in terms of drugs, if that is
what\'s recommended.

DR. DeLAP: Dr. Kweder.

DR. KWEDER: To follow up on that just a little bit, when you envision an
OTC version of these agents, are you envisioning sort of a one size fits
all regimen?

DR. COHEN: Well, I\'ve personally been involved in research that\'s
looked at various doses of the statins, and what\'s being proposed or
perhaps might be proposed are low dose statins which would, in fact, as
I mentioned in one of the points, get people down to levels that would
be considered desirable because these are people who are modestly
elevated range, but at risk importantly.

And let me say that this has often been considered the most dangerous
cholesterol levels in America, this 200. Why? Because when it\'s higher,
your doctor says, \"Your cholesterol is too high. We\'re going to treat
you.\"

And this is the level that\'s ignored and with low dose of many of the
therapies that are available today, we can see those people come down to
within the range that we want to see, and the guidelines for the Healthy
People 2010 clearly state we\'d like to get three-quarters of the
American public below that.

And I think this is one took that we might have to help us do that.

DR. DeLAP: Dave Fox.

MR. FOX: I\'m just having trouble understanding one thing. It\'s
probably I\'m not knowledgeable in this area. To what extent is your
risk-benefit analysis premised on making sure that only the target
population avail itself of the OTC therapy?

DR. COHEN: I think what we\'re concerned about there is risk rather than
benefit because I don\'t know who\'s using it in terms of that size of
the population, but if it\'s inappropriately used, let us say, by women
who are pregnant, by people who have unknown liver disease that isn\'t
known by them, but if they were to see a doctor, their enzymes may be up
and they haven\'t seen the physician. We would like to have some data if
we were to go OTC with respect to considerations of products that would,
in fact, give us confidence that we\'re probably not going to do harm.
Harm is very unlike, and that the benefit thereby would be achieved by
getting somebody whose cholesterol, let us say, is 190 total down to
150.

Again, that\'s in the range below which was recommended, but you\'re
setting up a scenario of inappropriate use.

MR. FOX: Well, I\'m trying to project out the implications for people
who have a much more serious condition, but it\'s still asymptomatic,
that they would try to self-treat.

DR. COHEN: Yeah. Can you give me an example? I mean, I\'m not quite sure
\--

MR. FOX: Well, somebody who has multiple risk factors and hasn\'t even
checked their cholesterol.

DR. COHEN: Okay. You have to look at the system as it exists today. I\'m
a clinician. I see patients every day, and so what we have is a system
whereby people either come in and see us and we define their risks for
them or they don\'t, and hopefully when they see this package on the
shelf it will say, \"See your physician if this product is right for
you.\"

If they don\'t and they take it anyway, I would submit to you, in my own
estimation, and I\'m speaking now not from science, but from my best
guess, that they will benefit from having a lower lipid therapy, a lower
lipid level in the context of the other risk factors, let us say,
hypertension and smoking, than they would had they not bought the drug.

But hopefully, when they see that package, it will drive them into their
physician who will then say to him or her, you know, \"This product is
right,\" or not right. \"You\'re multiple risk. You need to be on a
higher dose,\" or whatever.

DR. DeLAP: Dr. Ganley.

DR. GANLEY: Yeah, I guess the question that I have then is if the
individuals with the higher cholesterols are inadequately treated now,
why aren\'t you gearing the OTC population to that population? Why do
you even need a physician involved?

If you\'re able to explain some benefit to this population that has less
of a risk, why can\'t you do that on a label for people that have a
greater risk and, you know, develop a paradigm for treating them? Why
are you limiting it to that?

DR. COHEN: Theoretically that could be done, but I think that\'s a group
that we would say really has a higher risk by definition of whatever we
want it stated as, a diabetic, let\'s say, or somebody with heart
disease.

Those patients should be clearly within the confined medical care
system, and so with the warning says, \"Do not use this product if you
have that high risk\" whatever it is, diabetes, heart disease.

Then, in fact, hopefully you will not purchase this product or you will
discuss the potential purpose of it with your provider.

DR. GANLEY: But why? If physicians aren\'t adequately treating it now,
why shouldn\'t the message get out there to the people most affected?

DR. COHEN: Well, it gets to the one size fits all question. Okay? And
the definition of 200 to 240, I think we can get the majority of them
below the ideal level with low dose therapy that might be proposed,
whereas if you\'re saying the levels are much higher, then you can\'t
really get there very often in the face of low dose therapy.

DR. GANLEY: But I guess if you go along with that philosophy, then
someone that would get from 240 to 230 would obtain some benefit. Well,
wouldn\'t it be better to get them under 200? It\'s the same titration
type argument.

DR. COHEN: I agree.

DR. GANLEY: So why? You know, that goes back to the question. If you\'re
going to treat this population, why are you limiting it to a population
with the lowest risk?

DR. COHEN: This is the target population really, and it\'s not limited
necessary, and you could purchase it if it were available if you are
that high risk individual, and in my opinion, you would do some benefit
even though you may not get down to the levels that NCEP defines as
normal. You would, in fact, get your levels, let us say, 15 to 20
percent lower, and that I think would translate into a lower risk at
least on a population basis.

DR. DeLAP: Dr. Jenkins.

DR. JENKINS: I guess following up on what Dr. Ganley just asked you
about, I\'m confused here about the OTCness of this product because you
see to be suggesting that the only thing that would change really
optimally in the care setting is that patients would buy this over the
counter, but they would still see their physician for their risk
assessment. They would still see their physician for their follow-up. So
the only thing you\'re proposing to change is how they buy the drug; is
that correct?

DR. COHEN: Basically so. We would like to have this as an option.

DR. JENKINS: That\'s an atypical OTC drug. I mean there are some drugs
out there now that say if you\'ve been previously diagnosed by a
physician and have used this drug before, you can use it again without
seeing your physician or consult your physician before using the drug.

But one that simply changes the marketing from prescription to OTC, but
still says you need the physician to use it optimally, that would be a
very atypical product.

DR. COHEN: Well, I\'m not familiar with everything that\'s available
OTC, but it may fall into what we\'ve got, an atypical problem here, and
that problem is a mass killer of coronary disease, and we\'ve got to
address it in ways that aren\'t being met at the present time, and that
includes bringing people into the system who may not be currently
treated, and that as I see it is really a very important step in terms
of the availability OTC to solve this problem.

We\'ve got a huge problem. Together we\'ve got to do this. I heard
yesterday a plea to the FDA panel and the agency as a whole to approach
this as an open mind with regard to what can be done and what should be
done, with the important safeguard of safety, safety, safety and
efficacy, and then looking at the potential in terms of benefit-risk
ratio.

DR. DeLAP: Yes, Dr. Temple.

DR. TEMPLE: I thought you were actually saying that while you think
optimal therapy would involve continued participation of the physician,
you think things would be better off even if that didn\'t occur, even
whether it\'s a high risk person, moderate risk person. You still think
that you\'d be better off even if you didn\'t behave optimally. Isn\'t
that \--

DR. COHEN: Bob, if you moved the whole distribution of the cholesterol
to the left, it would really make things better.

DR. TEMPLE: Well \--

DR. COHEN: So if the population were taking it as a whole or if people
were taking it inadvertently, then I think that we\'d be better off on
the average, yes.

DR. TEMPLE: I\'m trying to follow up on Dr. Jenkins\' question. Your
answer was that, yes, you really did want it to be part of the usual
system.

DR. COHEN: Yes, absolutely.

DR. TEMPLE: So he had asked quite properly, well, what\'s changed. I
thought you accepted his answer too quickly because I really think you
mean that even if they don\'t do it right, they\'d be better off. I
mean, I think that\'s sort of the fundamental argument.

DR. COHEN: I think that\'s what I said or at least I hope that\'s what I
said. I mean, the risk of doing it wrong is relatively small with regard
to the benefit, and that\'s what we need to assure ourselves of in the
long run.

DR. DeLAP: Okay. Well, we need to move on.

DR. COHEN: Thank you for all the questions.

DR. DeLAP: And I\'m sure we\'ll continue to have some discussion on
these same points with the next speakers. Thank you.

We\'ll move then to Dr. Jeffrey Anderson, University of Utah.

DR. ANDERSON: Members of FDA, ladies and gentlemen, good morning. I
thank you for the opportunity to address the potential of OTC
availability of cholesterol lowering medications, and I also wish to
address the committee as an advocate for the review of this new
application.

I do so as a physician with a long history of interest in broad research
and clinical experience in pharmaceutical therapies. I also have been
exposed to industry\'s role in drug development and respect the value of
ethical pharmaceuticals, and I understand the special responsibilities
of regulatory agencies, having served on the FDA\'s Cardiorenal Advisory
Committee.

I do wish to disclose that my participation today was suggested by Merck
& Company, and they are sponsoring my trip. However, the views I express
are my own.

As Dr. Cohen has very nicely described, cardiovascular disease is our
leading cause of death and disability. Almost a million Americans die of
it each year. Perhaps surprisingly slightly more women than men are
affected, although women develop it about ten years later.

Coronary heart disease of heart diseases is the single most important
cause of death, claiming almost a half million lives annually. Over a
million suffer myocardial infarction or heart attack annually, and 12
million are alive with a history of a heart attack or angina pectoris,
perhaps an equal number with undiagnosed disease.

Heart disease also is our leading cause of disability. Medicare spends
\$11 billion each year on coronary heart disease.

As we\'ve already heard, high blood cholesterol is a major and well
established risk factor for coronary heart disease, and even average
levels of cholesterol and its low density or bad lipoprotein fraction
are associated with increased risk when accompanied by low levels of
high density or so-called good lipoprotein cholesterol.

I would also like to emphasize that almost 60 percent of the U.S.
population, the majority, have undesirable levels of total cholesterol,
LDL and HDL, or clinical heart disease, and half of these, about 30
percent, have cholesterol levels in the range of 200 to 240 milligrams
per deciliter, a range that is average or only slightly elevated, and I
count myself in that category, by the way.

Yet the Framingham study suggests that at least a third of all coronary
events occur in this range. These are people who are not eligible for
treatment by their physicians under current guidelines.

Full recognition of the importance of lowering serum cholesterol for
risk reduction has been long in coming. I recall my excitement as a
first year Harvard medical student reading a landmark study in the [New
England Journal of Medicine]{.underline} in 1967 by Drs. Frederickson,
Levy and Lees describing how fats are transported and lipoproteins and
classifying the hyperlipoproteinemias into five distinct types.

I pursued my interest at that time with a student fellowship in their
laboratories and clinics as a third year medical student in 1971 and
shared in the excitement of those years.

Well, here we are, almost three decades later. Unfortunately the early
experience with lipid lowering was not particularly promising. Available
drugs were only modestly effective, poorly tolerated, and some actually
increased the risk of adverse events, for example D-thyroxin or estrogen
therapy in men.

Diet also fell short. Adherence was difficult, and inherited metabolic
factors were found to be more important then diet in determining
cholesterol levels.

I recall a particularly cynical article in the [New England Journal of
Medicine]{.underline} in 1977 entitled \"Diet Heart: End of an Era.\" So
cholesterol lowering at that point had hit rock bottom.

But then in the 1980s a new approach emerged, a blockade of cholesterol
synthesis at the key step of HMG-CoA reductase, and drugs that inhibit
this synthetic enzyme became known as statins.

I was an investigator in EXCEL, a major study published in 1991 of the
first marketed statin, Lovastatin, in 8,000 patients. The excellent
tolerance, safety, and cholesterol lowering ability of Lovastatin were
impressive, but what remained to be shown was whether this reduction
could, in fact, translate into a reduction in adverse events, heart
attacks, and improved survival.

This beneficial potential of the statins has now been well demonstrated
in a series of singularly successful and self-reinforcing studies
published in just the last six years. These began with populations at
highest secondary risk and then proceeded and concluded with those at
average to slightly elevated to primary risk.

In each of these studies the benefit of statins was shown. The first of
these, the Scandinavian Simvastatin survival study, published in 1994,
tested Simvastatin in patients after a myocardial infarction. SSSS
demonstrates substantial survival benefits in these patients who had
also high cholesterol levels.

Deaths were reduced by 30 percent, coronary deaths 42 percent, any
coronary event 34 percent.

The care and lipid trials with Pravastatin extended benefits to the
majority of patients after MI and many with average cholesterol levels.

The West of Scotland study, or WOSCOPS, next showed that statin therapy
could prevent a first heart attack in subjects with very high levels of
cholesterol.

And most recently, in 1998, the Air Force, Texas coronary
atherosclerosis prevention study, extended the demonstration of benefit
in primary prevention to those with average cholesterol levels and no
evident heart disease.

Among 6,600 participants, Lovastatin reduced fatal and non-fatal heart
attacks, unstable angina, and sudden death by 37 percent. It also
indicated beneficial potential and safety in subjects resembling those
who would be candidates for OTC statin therapy.

Well, given that background, what then is the next step in primary risk
reduction through cholesterol lowering? I believe the next logical step
is to review and, if appropriate, then approve the statins for
appropriate OTC use.

Today the public is better informed and more interested than ever in
personal risk factor reduction. At the same time and sadly, funding for
programs within our traditional health care system is diminishing. There
is a growing gap between primary preventive efforts and public concern
about risk factors.

The consumer already has moved to fill this gap, even if ill advised,
through self-medication with so-called nutriceuticals. I\'m told that 65
million Americans or one-quarter of all adults are concerned about their
cholesterol levels, and of these one-half already use a nutriceutical,
such as Vitamin E, garlic, niacin, and herbal preparation, for example.

Though often relatively ineffective in cholesterol lowering and largely
unsupported by randomized trials, these products form the fastest
growing segment of the health product market, with \$12 billion spent
last year.

Patients in my own practice regularly list self-selected health
supplements in their medical histories. One of these, red yeast rice,
contains Lovastatin in doses that approximately the proposed OTC dose
and is available to the public and has generated a good deal of
interest.

We in the health care community should recognize this entrenched and
growth public health movement towards self-medication for risk reduction
and respond constructively.

In considering OTC statins for primary prevention, four questions come
to mind. First, what is the advantage of this approach?

These products derive from good manufacturing processes, insuring
reliable dosing and purity, are backed by clinical trials, should be and
would be, I hope, marketed in a regulated and in educational
environment, are safe. For example, the adverse effect rate, event rate,
with a dose of 20 milligrams of Lovastatin, twice the proposed OTC dose,
is no greater than placebo, and a further public health advantage of
expanded statin use is that each individual who lowers his or her risk
contributes to the general health of our nation.

Second, why should we move ahead now? Now is the appropriate time
because of the convergence of evidence, feasibility and interest.
Evidence for benefit and safety of long-term statins in this average to
slightly elevated cholesterol primary prevention population is now
available from the AFCAPS/TexCAPS study. Easy, reliable, automated
approaches to cholesterol testing to guide therapy also are now
available directly to the public.

Finally, the public already has shown substantial interest in pursuing
OTC approaches to coronary risk reduction, as I\'ve mentioned.

Third, what should be the target population? The greatest unmet need and
demand lies in the population with average to mildly elevated
cholesterol levels. These levels of 200 to 240 generally do not meet
guidelines for drug therapy, although that is under review, as we\'ve
heard, and yet over a third of total coronary events occur in this
range.

There is now evidence for benefit and safety of statins in this cohort.
So the question is: why should we limit the choice and access of
interested responsible individuals within this group to unproven,
relatively unregulated nutriceuticals?

And finally, fourth, how will this affect the physician-patient
relationship? The answer is, I believe and would hope, that it should
enhance it. The patient encounter with an ethically formulated, marketed
product can educate and triage. Patients whose cholesterol levels place
them at high risk and those with concomitant diseases or interacting
medications would be instructed not to self-medicate, but to see their
physicians.

A proper OTC initiative would also increase awareness of the use of drug
therapy as an adjunct to diet and exercise in a primary prevention and
open a new dialogue among physicians, other health care providers, and
the public.

This population targeted for OTC use otherwise is unlikely to be treated
or covered by current insurance plans.

Finally, the educational encounter could reassure those at lowest risk
who should continue with healthy life styles.

In conclusion, I believe that OTC cholesterol lowering with low dose
statins is a rational treatment option that health care consumers should
have the reasonable right to choose. I urge the FDA to consider and
carefully review applications for OTC statin use by subjects at moderate
coronary risk who choose to practice improved primary prevention.

Thank you for your attention.

DR. DeLAP: Thank you.

Dr. Jenkins.

DR. JENKINS: Yeah, thanks for that.

I\'d like to follow up on a question that Dr. Temple asked Dr. Cohen
earlier, and that\'s what\'s the evidence of benefit in this patient
population that you\'re referring to for your target population. You\'re
targeting total cholesterol, 200 to 240, and you\'re citing primarily
the AFCAPS trial. Other than the epidemiologic data, that\'s the primary
clinical trial that may show some benefit from a cardiovascular
standpoint for this group.

And yet that study specifically recruited people with low HDL
cholesterol. So do you think that HDL cholesterol should be part of the
OTC paradigm? Should we only be targeting patients in this group who
have low HDL cholesterol? And if so, how would you accomplish that in
the OTC setting?

DR. ANDERSON: Well, I think that\'s a very good question, and I think
that one could go either way, choose simplicity. That is, the majority
in the range of 200 to 240, in fact, would meet those guidelines or, in
fact, measure HDL cholesterol which would require a more sophisticated
approach, but can be done with current technology. It can measure HDL.

In my own practice, I prefer to also look at HDL. I would just add
though that the entry criteria for AFCAPS/TexCAPS with respect to HDL
were not very strict. I believe it was less than 50, which is very
common.

So I think that that would deserve more discussion and should have full
review, that question, simplicity versus a more exact stratification and
triage.

DR. DeLAP: Dr. Temple.

DR. TEMPLE: Not to name names, but some statins have problems with
interactions, and in the OTC setting presumably strict avoidance of
antifungal agents and things like that might be harder to communicate
than others.

Is that a worry? How worried would you be at the low doses that you\'re
talking about?

DR. ANDERSON: Well, I think that that\'s important and should be
obviously stressed in any approach. I mean I think that this should be
different than perhaps some other OTC medication. It should be like
joining a program where there\'s adequate educational material and
there\'s interaction with pharmacists and with physicians and other
health care personnel along the way.

But I think at this does, at least my read is that these are safe
medications. Lovastatin, for example, has been out there for 13 years,
and there is a wide margin of safety in terms of the dose that can be
taken and tolerated, and what would be given in this program.

So that should clearly be addressed. I agree with Dr. Cohen that safety
is a key issue. I do believe it can be addressed.

DR. MURPHY: Let me follow up on that. Is it fair that you\'re saying
that you believe that the population that wants to self-medicate will
continue to seek other approaches, and that that risk is higher than the
proposed OTC for the statins that you\'re \-- for the reasons that
you\'ve stated about manufacturing, et cetera? But is that sort of a
summary of what you\'re saying?

DR. ANDERSON: By other approaches, nutriceuticals and so on?

DR. MURPHY: Right.

DR. ANDERSON: Well, I think the group that is into risk reduction, is
into self-medication will, my view is, will be better served more
safely, more reliably by low dose statins which, as I mentioned,
actually can be taken in a nutriceutical formulation right now without
any assurance of safety, of dosing reliability, or of purity.

Hopefully though this will also encourage people who otherwise would not
take anything because of those concerns into doing that because they
would be assured that the product they\'re taking has been tested, is
pure, and that they can take a reliable dose, and also would have access
to educational materials and interaction with other health care
personnel in guiding treatment of their high cholesterols.

So I think it would expand beyond those who are currently in that
setting, but certainly would deal more effectively with the group, the
large group, the growing group, that is taking a number of products OTC.

DR. DeLAP: Mr. Campbell.

MR. CAMPBELL: Are you suggesting that such products should be behind the
pharmacy for pharmacy, that you had to go to a pharmacist to use them,
or is it purely over the counter? Because you mentioned educational
materials.

DR. ANDERSON: I really didn\'t come prepared to propose a specific
guideline. I think there needs to be more interaction certainly in terms
of educational materials and other programs perhaps with a pharmacist
than with other OTC products because it is a chronic product, but I
think that that should be a focus of discussion.

I have seen a number of proposals, some of which included that format;
others have not, that I think are reasonable to consider.

DR. DeLAP: Dr. Jenkins.

DR. JENKINS: I\'d like to get your views also on the issue of
compliance. We know that this would be in many cases lifelong therapy,
and now you\'re targeting people who have a lower risk of cardiovascular
disease and, therefore, may need to take the drug five, ten, 15, 20
years to get an individual benefit to that patient.

We know that in the prescription setting with doctors involved and
nurses involved, compliance with these chronic therapies is very, very
pool. So what\'s your thoughts about how can we actually derive a
benefit for the individual patient given compliance in the OTC setting
for a chronic medication like that? Do you think that\'s actually going
to happen?

DR. ANDERSON: Well, the first thing I would say is that the medications
are incredibly well tolerated. So I don\'t think that adverse effects is
going to be a factor in terms of limiting compliance. I think it\'s a
matter of individual motivation and choice, and the people that I think
will self-select to take this chronically are those who are motivated,
who really are worried about risk factors. We\'ll follow them along and
will track them, who also exercise, will be on a good diet, and so
forth.

So it\'s true that some will start out and fall by the wayside, as they
lose motivation, but it\'s for those who really want to affect their
primary risk who will be ignored by their current physicians in their
current environment or don\'t feel that it\'s appropriate to use up
health care dollars for that that will take it long term and will
benefit.

DR. JENKINS: As a follow-up to that, do you have any concerns about
patients who might with this available over the counter misuse it so
that they can continue to eat their unhealthy diet, not to name names.

(Laughter.)

DR. JENKINS: And continue not to exercise appropriately? Do you see that
as a concern and how much of a concern?

DR. ANDERSON: I don\'t have data on that. I think that likely those will
be the ones who will be in for the short term and try it for a few
months and then go back to their previous lifestyles, but this should be
an adjunct along with other measures, although I must say of the three
thing, it\'s probably going to have the greatest impact on LDL.

You know, a lot of people get discouraged because exercise doesn\'t do
much. They try diets and it only works partly.

DR. DeLAP: It\'s hard to get a question in edgewise here at this point.
I\'d like to ask one question, and I think I know what you\'d say to
this, but I just want to be sure. Clearly, as we\'ve looked at different
kinds of cholesterol lowering agents over the years, not all cholesterol
lowering is created equal. Some products may lower cholesterol, but not
give you the same benefit, say, as the statins seem to be giving.

Now, within the class of statins, given how difficult it is to do real
outcome studies and confirm what the treatment outcomes are, within the
class of the statins, do you think that we should be regarding them as a
class in the sense that if you have a drug in that class and it provides
a certain level of cholesterol lowering, then we know what that
translates to in terms of benefit based on a study that was actually
done with a different drug in that class?

DR. ANDERSON: This is a very difficult question to answer, you know.
Sort of speaking as a former panel member, regulator, obviously one is
most confident using the specific agent in the specific dose in the
specific population, and there one can, you know, pretty much rely on
the result, and there\'s less confidence the further one steps away in
terms of chemicals, doses, and population, and I think the same would
apply here.

You know, I personally believe that among at least the two or three
statins that had been used in broad clinical trials, the data are quite
consistent, and I think that there certainly is a class effect, but
there certainly are ancillary drug properties that may add or detract
from that effect. I don\'t think all statins are exactly equal, and
other have editorialized about this.

So I think this will be a difficult question to deal with. It should be
carefully and thoroughly reviewed, but I don\'t know that I have an
answer to give you today.

DR. DeLAP: Dr. Jenkins.

DR. JENKINS: I just wanted to clarify one point. In reading through your
statement, there\'s a lot of references to public health and societal
benefits. Can you clarify is your enthusiasm for the OTC availability of
these products directed towards the individual patients who would use
them or are you more enthusiastic from an overall societal lowering of
cardiovascular risk and mortality?

DR. ANDERSON: Well, I think both of them certainly add to the
enthusiasm. As I mentioned, there\'s sort of a convergence of win-wins
here that suggest that this is a good step to take. I suspect that my
enthusiasm would be almost equally applied to both of those with
particular emphasis on individual choice though in this particular
situation. I think later, as we get more information as we perhaps can
fund more therapies for broader groups of people that it might have
greater impact on public health.

DR. DeLAP: Dave Fox.

MR. FOX: Are there any comparisons that can be drawn between the way we
have regulated low dose aspirin, which is now \-- I mean the entity is
available over the counter, but the indication for stroke and recurrent
heart attack, second heart attack is supposed to be done through
intervention of the physician, by professional use only.

I\'m just wondering if there\'s any comparison that can be drawn there.

DR. ANDERSON: I\'m not sure how far we can take that. Aspirin obviously
is very easy to get any way. So this would be a little different in this
case, and by the way, I think the evidence for primary prevention there
is still controversial. That is, it does reduce heart attacks, but
there\'s a concern that it doesn\'t offset morality as well.

So I personally recommend aspirin for secondary prevention on a routine
basis, but not necessarily for primary prevention. So I think that there
probably are some limited comparisons, that is, it\'s a chronically used
medication. You have to be concerned about safety, as well as efficacy,
but there are also some major differences.

DR. DeLAP: I think we \--

MR. FOX: Differences in the sense that there you think on balance you do
need the intervention of a physician, and with the cholesterol lowering
on balance you think the risk-benefit points the other way. You could
tolerate not having the necessary step of a physician intervening.

DR. ANDERSON: Well, I think I\'m not sure if that\'s exactly the
difference that I was thinking of specifically. Certainly interaction
with health care personnel, physicians and pharmacists and other
providers, I think is to be recommended in all of these settings, and
certainly that should be encouraged in this setting as well, but I think
physicians, we simply don\'t have the manpower or potential within our
current medical care system to handle 60 percent of Americans in this
system, and so that\'s the limitation.

DR. DeLAP: Well, I think we could continue this discussion for quite a
while. Dr. Ganley, do you have something very quick? Because I think we
will need to move on.

DR. GANLEY: Yeah. I just want to provide or ask the same question I
asked Dr. Cohen about, you know, it\'s obvious at higher cholesterol
levels in people with previous risk, they derive the most benefit, which
would be easy to quantitate on a label. Yet you don\'t want to include
that population as the OTC population. I\'m not sure why that is.

DR. ANDERSON: Well, I think I\'d have to sort of reiterate Dr. Cohen\'s
response, and that is \-- and it does seem pyridoxic clearly on
reflection \-- is that those patients in the highest risk need to, in
general be on higher doses. They need to be titrated. There is greater
need, therefore, to be concerned about side effects which are dose
related with, for example, liver function abnormalities, myopathies, and
so forth, and that\'s the reason to triage them into the medical system.

So what we should do is try to get those patients into the medical
system, and that\'s the win-win in terms of physician-patient
relationship, is to use that as the first approach.

Now, obviously they can take it out of label or use it out of label, if
you will, and they\'ll probably benefit more by it than if they didn\'t
do anything. So I think that\'s the other side of it.

DR. DeLAP: Okay. Well, thank you very much.

I think at this point in time we\'re way overdue for a break, and I
think we\'ll have a 15-minute break, but we will start precisely 15
minutes from now because we\'re a little behind.

(Whereupon, the foregoing matter went off the record at 11:13 a.m. and
went back on the record at 11:32 a.m.)

DR. DeLAP: Our next speaker is Dr. Edward Frohlich, representing the
American College of Cardiology.

Dr. Frohlich.

DR. FROHLICH: Thank you very much, and I apologize that I have come out
of sequence if those of you have the score cards are keeping score, but
my name is Dr. Edward Frohlich, and I\'m pleased to speak today on
behalf of the American College of Cardiology, or as I will refer to it,
the ACC.

I\'m a fellow of the ACC, as well as a member and Master of the American
College of Physicians. I\'ve also served as a member on the Board of
Trustees of ACC, and I might say parenthetically on the first
Cardiovascular Renal Advisory Committee of this group.

I am currently the Alton Ochsner Distinguished Scientist of the Alton
Ochsner Medical Foundation and the Ochsner Clinic in New Orleans, and
I\'m Editor-in-Chief of Hypertension, an official scientific journal of
the American Heart Association.

The ACC appreciates this opportunity to offer its comments regarding the
Food and Drug Administration\'s approach to regulating over-the-counter
or OTC drug products. The ACC is a 25,000 member nonprofit professional
medical society and teaching institution that represents over 90 percent
of the nation\'s cardiovascular physicians.

Our interest in the FDA\'s regulation of OTC drug products grows out of
a primary responsibility as cardiovascular physicians to insure that
patients have the best care available to them, care that is safe,
effective, appropriate, and comprehensive.

And our testimony today is provided with that responsibility clearly in
our minds. We are advocates for good drug therapy because we know that
when appropriately utilized, they can substantially improve patient
outcomes.

Within that framework we propose guidelines for the FDA to consider when
evaluating applications for OTC status. We find that the FDA\'s current
regulatory approach insures that \"consumers have easy access to certain
drugs that can be used safely for conditions that consumers can
self-treat without the help of health care practitioners,\" and is the
correct approach to regulating OTC drug products.

The ACC has developed a set of guidelines that we believe are
appropriate for FDA application and are all cardiovascular OTC drug
products globally as considered today. We believe that our guidelines
are fully consistent with the FDA\'s regulations, and the following
summarizes areas of general agreement between the ACC and the FDA.

First, low side effect profile. Like the FDA\'s regulations, we believe
that drugs made available for OTC use should have a, quote, low
incidence of side effects. We add that where side effects exist in an
OTC drug, they should be of the type which can be monitored without
physician assistance or testing.

For example, nonsteroidal anti-inflammatory drugs typically can cause
stomach upset prior to gastric ulceration.

We further believe that side effects which can only be detected by
laboratory tests or physician monitoring compromise consumer safety by
going undetected until they become severe enough or life threatening.
Thus, drugs with such side effects should not be available OTC.

Second, low potential for harm due to abuse. The FDA regulations state
that an OTC drug should have \"a low potential for harm which may result
from abuse under conditions of widespread availability.\" We agree with
that potential for harm if abused and should below.

We would add, however, that drugs which have a great potential for abuse
should not be available OTC, even if the harm from abuse is not great.
Such a drug would not be a good OTC candidate because it would not be
used according to \"adequate directions for use and warnings against
unsafe use,\" and hence would not provide the type of relief claimed.

As an example of an abuse of an OTC drug might be for fraudulent
purposes. It is conceivable that certain drugs may be taken over a short
duration to achieve a clinical endpoint in order to mask a clinical
condition. For example, the individual where FAA or Federal Aviation
Administration licensure or insurance approval is required.

Anti-hypertensive agents, for example, may lower blood pressure rapidly,
allowing a person with hypertension to appear normotensive for an FAA
exam or an insurance exam or even pre-employment exam. Such fraud has
cost or can cost the immediate incident, and these costs may be also
with the higher insurance premiums for all or a danger to public safety
in the case of the pilot who is not on regular treatment program yet
passes an examination.

Third, clinically significant relief. FDA\'s regulations define
\"effectiveness\" as \"a reasonable expectation that in a significant
portion of the target population, the pharmacological effect of the drug
will provide clinically significant relief of the type claimed.\"

Since OTC drugs are usually available in the lowest possible therapeutic
dose, those doses which are subtherapeutic should not be made for OTC
use. This is especially true for drugs that do not produce symptoms, or
if a drug\'s claimed relief requires laboratory tests or some other
technical intervention, consumers may believe that they are relieved
when, in fact, they are not.

Thus, the following is an important guideline that the American College
of Cardiology would add to FDA regulations, and that is the existence of
symptoms.

The prescription of drugs which the FDA has thus far changed to OTC drug
status are used to relieve consumers\' symptoms. For example, the
nonsteroidal anti-inflammatory drugs alleviate pain, and when the
consumer uses an over-the-counter NSAID, he or she knows when it\'s
effective on the basis of the pain that is relieved.

Likewise, H2 blockers are used to relieve heartburn, and their
effectiveness is known to the consumer based on symptom relief.

The ACC believes that the relief of symptoms should be an important
requirement for OTC product. If, on the other hand, a currently
available OTC drug does not relieve a symptom, the consumer is more
likely to seek the advice of a health care professional for providing
the relief.

However, if relief requires a laboratory test, the consumer does not
know whether he or she, in fact, are relieved. This is especially
important for cardiovascular drugs which often can treat conditions
which no associated symptoms with which a consumer can assess the
drug\'s efficacy.

The risk of subtherapeutic dosage or suboptimal therapeutic endpoints is
increased when a drug requires monitoring to assess effectiveness. High
risk consumers and those with established disease are particularly
vulnerable, and we believe that the management of these patients should
always be supervised by a physician.

It is, therefore, of vital importance that if drugs used for treating
such silent conditions are made available OTC, important information
must be provided regarding all risk factors and their management. We
propose that medical specialty societies participate in the preparation
of guidelines for patients who would use OTC drugs. Such guidelines are
appropriately developed by physicians with input from patients and can
include information on when the taking of an OTC drug may or may not be
benefit under supervision of the physician.

Risks will increase if OTC drugs are taken without appropriate
monitoring and consumer access may actually be hampered when drugs that
are available OTC are no longer covered by health plans.

We also believe that drugs that do not relieve symptoms but instead
require some other intervention to assist the effectiveness do not
qualify for OTC basis based on the Congress\' mandate that drugs
requiring \"collateral measures necessary to their use\" be available by
prescription only. Laboratory determinations and professional
supervision for follow-up constitutes such \"collateral measures,\"
making drugs requiring such monitoring unacceptable for OTC use.

So in conclusion, we understand that the FDA is considering changing its
criteria for OTC status and considering drugs which are to treat silent
conditions, as well as conditions which are chronic and often
multi-factorial in nature.

We understand that OTC status may increase access to certain drugs which
are safe and, therefore, reach populations which have not benefitted
heretofore. We applaud such efforts to increase such access to
appropriate drugs and therapies.

However, we also believe that the FDA must carefully consider OTC status
for drugs which treat those conditions described above. Coronary artery
disease is an excellent example of a chronic disease that is
multi-factorial and often without symptoms until well advanced.
Physicians treating such patients address all risk factors and institute
and monitor therapies beyond pharmacological interventions.

Physicians advise on life style changes, including diets, smoking,
exercise, other interventions, as well as monitoring the responses to
such therapies that we talked about. In such cases, such lifestyle
changes eliminate the need for pharmacological therapy and have benefits
beyond the specific condition where they\'re instituted.

These collateral benefits should also be taken into account when an OTC
switch is considered for drugs treating conditions such as these.

The ACC neither recommends nor opposes OTC status for any particular
drug with this testimony. We believe that such switches should be based
on sound evidence that benefit consumers. We strongly believe that
consumer education is of paramount importance with any new drug class
that becomes available OTC, and we look forward to working further with
the FTC as it continues to review its regulatory framework for
over-the-counter drugs.

And I should be happy to answer any questions at this time, sir.

DR. DeLAP: Thank you, Dr. Frohlich.

Questions? Dr. Cantilena.

DR. CANTILENA: Yeah, just a question about your comment on the
guidelines for the patients. Can you tell me what you\'re referring to
in terms of are the guidelines going to be something that would be for a
specific, you know, product or, you know, disease?

And also, how would those guidelines be distributed, you know, like in
the actual package or at the physician\'s office or in the pharmacy?

DR. FROHLICH: It\'s a good question. The guidelines are already
available by FDA. We have gone through each and every guideline step by
step as presented by the FDA, but we added the one issue as it concerns
symptoms because we felt this was important, but it is well known, and
this is what we based our response to you and your committee today,
based on those guidelines that exist adding one additional caveat.

DR. CANTILENA: I was actually, you know, referring to the guidelines for
patients who would use over-the-counter drugs.

DR. FROHLICH: This is what I\'m referring to, yes, sir.

DR. CANTILENA: Okay, okay. I misunderstood what you were saying before.
Thank you.

MR. FOX: Several of the speakers have noted prominently the presence and
availability, popularity of dietary supplements, and patients or
consumers are seeking those out. To what extent, if at all, do you think
that affects the paradigm when looking at Rx versus OTC, the extent to
which we should as a policy matter start to consider the availability of
dietary supplements?

DR. FROHLICH: Well, let me speak from my point of view as a practicing
physician and not as an individual representing ACC. We haven\'t made
any position on nutriceuticals or the like.

It does confuse the problem. There have been recent reviews in journals,
such as the [New England Journal]{.underline}, in the past month or two
that talks about the number of nutriceuticals that are available and how
they can interfere by drug-drug interactions and the potential.

Because FDA does not have the mandate to go over that each of these
improve efficacy, it\'s very difficult for the FDA to follow this. This
is an issue that is of great concern when we know a number of patients
with cardiovascular disease, for example, are taking anticoagulants, and
there are a number of nutriceuticals that can affect prothrombin times
and so forth.

So I think this is an important issue that you\'re going to have to
face, Bob, with your group and to see how this can be addressed as you
go into the consideration of a wide spectrum of other drugs. We are
looking more globally at all cardiovascular drugs than any one single
class of agents.

DR. DeLAP: Yes, Dr. Woodcock.

DR. WOODCOCK: Yes. You make the point that asymptomatic conditions would
be more difficult for a consumer to recognize and treat, and you make
the point that the ideal clinician intervention would be counseling on
diet, exercise, cessation of smoking, and reduction of risk factors, as
well as potential pharmacologic interventions.

One of the \--

DR. FROHLICH: In addition.

DR. WOODCOCK: Pardon me?

DR. FROHLICH: In addition to.

DR. WOODCOCK: In addition, yeah.

One of the issues that we\'re discussing, however, is the fact that that
is widely failing to happen even in the clinician interaction with
patients, and that is widely acknowledged and documented.

DR. FROHLICH: I missed what your \"it\" is.

DR. WOODCOCK: For example, there\'s an article in the [Washington
Post]{.underline} yesterday or recently about and it included the fact
that very few clinicians are counseling smoking cessation. So the
reality is this isn\'t happening. That\'s why we\'re having this
discussion, I think, is that patients are not receiving or consumers are
not receiving the proper counseling advice and even consideration of
pharmacologic interventions even though they may be attending a
physician.

DR. FROHLICH: You raise a very important point. I, again, have to speak
as an individual. I personally believe that there has been a tremendous
impact on consumer education on this. Not enough people have stopped
smoking. Not enough people are losing weight in this country, for
example. We don\'t have very good behavioral modification techniques
available, as you know, to us medically.

Nevertheless, if you look at the decrease in smoking in this country, we
have come a long way, baby, as they say in their ads for women who
smoke.

I think, for example, we need to apply better and continuous educational
methods. Coming from an institution that started the relationship of
smoking and lung cancer advised by Alton Ochsner many years ago, I can
tell you that we have, in fact, decreased the amount of smokers.

We need to do better. The number of smokers and the number of people
smoking in this room is markedly different than it would have been 25
years ago, 30 years ago. So we have done this, and physicians must do
this with their patients. There\'s no excuse not to. It\'s just a
question of continuous education, and you know the public media is such
that they have a disease of the year that grabs them.

Back in the \'70s we had hypertension, which was very exciting. Then in
the \'80s we had cholesterols. Now it\'s maybe breast screening and
cancer, but the issues here have to be \-- all of them have to be \--
addressed continuously, and I couldn\'t agree with you more.

DR. DeLAP: Yes, Dr. Temple.

DR. TEMPLE: Ed, you draw a sort of bright line between treating symptoms
and treating signs, I guess you could say, and one of the reasons is
that a patient can\'t assess whether his sign has improved without some
external help.

However, in two conspicuous areas, cholesterol and blood pressure, you
can go to your Giant Supermarket and get your latest blood pressure. I
don\'t know how accurate those are, but you can do it, and there are or
will be simple tests of cholesterol available.

So a person who was taking an over-the-counter drug in order to modify
those signs would, if they were interested in the first place, be able
to see how they were doing, if they bothered. Does that affect your view
of the bright line?

The other I saw had the same question. I thought what David Fox was
asking was \-- that\'s the question over there \-- was whether the fact
that people are treating their blood pressure with garlic makes you more
inclined to think that maybe they should have something that would work.

(Laughter.)

DR. FROHLICH: Well, again, I agree with you, and as you know, the
announcement of this meeting that caught the attention of the American
College of Cardiology was to address more globally all of the
cardiovascular drug therapies and not any one specific. I know you\'re
going to be talking at least next month about the issue of cholesterol.
So, again, I would have to be thrown to my own point of view because our
leadership has not addressed any one class of drugs.

But, yes, I think there has to be monitoring by the patient reliably,
and as you know, in the hypertension area patients have been taking home
blood pressures for many years and doing a good job of this, but not
necessarily people taking home blood pressures and treating themselves
with effective anti-hypertensive therapy. This has to be worked out very
clearly, particularly with a much more potentially dangerous class of
drugs.

The statins is another issue, and again, I have been searching my mind
how patients can do this. Perhaps they can work out with health care
providers copies of laboratory tests that can be sent to their physician
and they can continue on. Perhaps the companies might even provide
tear-offs from labels that after five purchases of four or five months
of treatment they can have a copy of a laboratory test done when they
submit five labels for a laboratory examination. A copy would go to the
patient, a copy to the physician.

We have to be just as innovative in this look as you are in looking at
over-the-counter innovation, and i think both of these have to mesh
together and still follow your mandate from Congress.

DR. DeLAP: Well, I think that that\'s \--

DR. FROHLICH: Have I answered your question, Bob?

DR. TEMPLE: Well, except about whether you\'re influenced by the fact
that people are self-treating these very things. I mean you talked about
the potential for interactions, which is certainly a legitimate worry. I
think the question was whether the world as we know it, in which people
are using a variety of substances to treat these very things, should
influence us.

DR. FROHLICH: Yeah. My personal experience as a person treating
hypertensive patients now for 40 years, I don\'t have the problem
necessarily of the nutriceuticals and blood pressure. They soon become
available is not very effective.

On the other hand, I don\'t know what happens with these other drugs. I
have not seen enough patients that will treat themselves with statins,
although, you know, statins are available outside the United States. I
don\'t know how many people are using them over the counter.

DR. DeLAP: Okay. Thank you very much.

DR. FROHLICH: Thank you.

DR. DeLAP: And I apologize for how far behind we\'re getting here to the
upcoming speakers, but I think this discussion is very useful to the
agency.

Our next speaker is Lorie Rice from the UCSF School of Pharmacy.

MS. RICE: Thank you for the opportunity to speak with you today.

My name is Lorie Rice, and I\'m here to convey my perspective of key
issues in the consideration of cholesterol lowering drugs for OTC
status.

It\'s been a while since the last time I participated in an FDA hearing,
and I can tell you now it\'s much easier to participate on the other
side of the microphone.

Before I begin, I want to disclose that I serve as a consultant to
Bristol Myers Squibb. My full-time job is the Associate Dean of External
Affairs and assistant clinical professor at the University of
California, San Francisco, School of Pharmacy. I teach pharmacy law and
ethics.

My comments today, however, are my own, neither those of Bristol Myers
Squibb, nor UCSF.

I served as a consumer representative on the initial NDAC for four
years. It was both an honor and a marvelous learning experience.
Representing consumer interests, however, was not a new experience for
me. In California, I served as the Executive Officer of the State Board
of Pharmacy for seven years, and then I served as a consumer
representative on the State Board of Behavioral Sciences.

In May I was appointed by the governor to serve on the State Medical
Board, again, as a consumer representative. I take these
responsibilities with utmost seriousness.

This is an excellent time to be a consumer representative. Consumers
themselves are becoming more vocal and more engaged, and you\'ve heard
this several times this morning.

This is particularly true in the area of health care or self-care. The
reasons for consumer involvements actually come as no surprise. First,
the rise of managed care has, to a large extent, depersonalized health
care and made it challenging for patients to get quick responses to
their health care needs.

Also, every day consumers find more products and more information at
their fingertips or at the click of their mouse. Many adults rely on
multiple sources for their health information, such as television,
magazines, and journals.

The explosive use of the Internet has also provided a readily accessible
method of disseminating and retrieving information on everything from
herbal cures for hair loss to the molecular structure of
antidepressants.

It is no wonder then that consumers are making personal decisions about
their health care after gathering information from a variety of sources,
some that are reputable and some that are not. The simple fact is that
consumers are seizing these opportunities in involvement. All
indications are that this trend is unstoppable.

For example, consumer use and interest in alternative medicine is at an
all time high. A recent survey in JAMA found that 42 percent of
Americans used some form of alternative therapy in 1997 at a cost of
nearly \$30 billion in unreimbursed expenses.

Between 1990 and 1997, patient visits to primary care physicians
remained constant, but their decision to visit complementary and
alternative medical practitioners increased by almost 50 percent. This
same study noted that almost one in five adults taking prescription
medicine also was taking herbal products and/or high dose vitamins.

Consumer pursue these options because they perceive them to be effective
and because they are congruent with their values and beliefs about
health. In recognition of the consumer demand for information and newer
and better ways to participate in their own care, the University of
California, San Francisco, has recently established the Center for
Responsible Self-Care.

We are all familiar with and appreciative of the options now afforded
the consumer with the many switches over the last several years of
prescription drugs to the nonprescription category. When I was a
committee member, we evaluated data on safety and efficacy and weighed
the benefit-risks for products proposed for OTC status to fill unmet
needs. Some of these expanded the definition of OTCness.

As a result, the consumer has been given even more choices for self-care
remedies, and these to our benefit have all met the standards required
by the FDA.

Today and in July, it will be up to you as well to help consumers as
they continue their efforts to help themselves. Along with many others,
I look forward to your next meeting when you will have a unique and,
indeed, historic opportunity to consider case by case whether an
approved cholesterol lowering drug should be made more accessible to an
eagerly awaiting consumer population.

During those deliberations, there are specific issues which I would ask
you to give your special consideration. These are the points that I
would be thinking about if I were sitting on the other side of the
table. I was educated on these points during my tenure on the NDAC, and
in fact, the committee\'s diligent application of these criteria were
critical for each and every OTC switch.

First, please remember again that consumers do want to be involved in
their own health care, and once they decide to do so, they will begin to
try a variety of options. They should be given this chance with products
that clearly demonstrate predictable safety and efficacy.

Second, it is imperative that labeling directions provide all the
information a consumer needs in order to decide whether the product is
appropriate and certainly when and how to initiate and continue
administration.

I think that you can feel confident if you are provided with data
reflecting a high level of label comprehension in a study of a broad
based population.

Third and equally as important, you must be assured that consumers can
not only read and understand the directions for use, but they will also
follow the label message. This must be illustrated by consumer use
trials.

Fourth, especially in cases such as cholesterol lowering drugs, you must
be convinced that the doctor-patient dialogue is maintained. A sponsor
must present research that provides convincing evidence of minimal
interference in that relationship.

Lastly, please be prepared to consider the related and significant
benefits that a switch could afford the target population. This was
always an important issue for me. Examples include the facilitation of
entrance into the health care system, the enhancement of the
doctor-patient relationship, and the full array of otherwise unavailable
education and support programs which increase health education for the
individual and the population at large.

If, upon reflection, a candidate meets these criteria in a data driven
matter, you should be persuaded that that drug is, indeed, suitable for
OTC availability as a contribution and a complement to their total
health care.

Thank you.

DR. DeLAP: Thank you.

Questions?

(No response.)

MS. RICE: Thank you.

DR. DeLAP: Thank you very much.

Our last speaker for this session then is Dr. Bruce Barnett and Mr.
Calabio.

DR. BARNETT: Thank you very much for this opportunity, esteemed panel.

Mr. Calabio and I will not stand here together to distract you for the
entirety, but I did want you to meet Mr. Calabio.

My name is Bruce Barnett. I\'m a physician. I\'ve been a physician for
nearly 25 years, and most recently I\'ve become an attorney. I
specialize in medically related legal issues.

I have traveled from Los Angeles to be here today, along with John Paul
Calabio, to put a face on the difficulties associated with the drugs
we\'re talking about, the statins, so that you have this much data also
to consider.

Mr. Calabio is going to sit down right in front so that he\'s available
for questions, and I\'ll continue now to help bring this data to your
attention.

Elnoisa Calabio, the wife, mother, a registered nurse. Her face is in
the materials that we presented to you today, along with my CV, by the
way, and a written and brief statement about the issues that I want to
address.

Mrs. Calabio died as a result of taking a statin, and her death, which
occurred in October of 1999, was attributed to statin by the physicians
who took care of her, attributed to the statin by an independent medical
examiner who looked at her record thereafter.

She started taking the statin in July of 1999 upon the recommendation of
her physician. I will repeat this later on, but her cholesterol level at
that point, while elevated, did not meet the national guidelines for
statin treatment.

This was not the first death from statins that is reported in the
literature, nor is it the first death from a particular kind of disease
that caused her death. She died from the complication known as
interstitial pulmonary fibrosis.

Shortly before her death, Ms. Calabio said to her family members,
knowing that it was the drug that made her ill, \"Do what you can,\" she
said, \"that other people should not have to die as I or become ill from
the drug.\" She died, again, in the fall of 1999.

And, again, in the literature I\'ve attached to the materials I\'ve
submitted the kind of death she had experienced had been reported in the
literature since 1995.

I expect that the reports in the literature underestimate the side
effect which I described. For reasons best known to the FDA, best known
to the manufacturers of the drug, and this drug in particular \-- and,
again, I respect the spirit of these hearings to not name names, but
obviously the specific drug involved here will be important. As was
said, all statins are not created equal, and I give you the literature,
and I give you the information on this drug in the package.

But for reasons best known to the FDA and the drug manufacturer, the
deaths and the illnesses from pulmonary complications attributed by
scientists to this particular drug do not appear in any of the PDR
literature, that is, the material sent to doctors; has not appeared
since they\'ve been put together; do not appear today, as you can see in
the literature I\'ve given you, and in 1999 or the year 2000 PDR
material, nor do they appear in advertisements which are promoted to the
public through the [Wall Street Journal]{.underline} and others.

The Calabio familiar and I feel the following points are very important.
Number one, Mrs. Calabio had an LDL of 158 when she started her
treatment with this drug. As we know, the guidelines say that 158
already is an improvement on the actual target goal for a woman like her
with only one risk factor. Her target goal was 160, and at 158 she
didn\'t need the drug.

Mrs. Calabio\'s cholesterol level, which was admittedly elevated at the
time she took it, was what alarmed her doctor, I\'m sure, was not check
again after a period of exercise and diet, but instead she went right to
this drug.

Why did she take it? She took the drug because neither she nor her
doctor presumed or believed that any severe harm could come from it.
They didn\'t even see the remote possibility of death.

There is this common misperception also that was played out here. She
was started on 40 milligrams of the drug. After all, if 20 milligrams
will lower your cholesterol and we want to have the lowest possible
cholesterol, then, hey, 40 milligrams must be better.

Number two, the advertising promotions, I think as we see in this case,
in many cases, if not universally, have all but drowned out or
obliterated the fine print warnings that had been placed by the
manufacturers and endorsed by the FDA. Health care professionals far and
wide just don\'t see the statins as being dangerous or appreciate.

Really, if you think about it scientifically, the profound pharmacologic
effect these drugs are having to completely reorient the way our body
metabolizes the food substances and creates cholesterol.

Third, this widespread misunderstanding of the potential toxicity, as
I\'ve mentioned, leads to a higher than necessary dose, and I believe
this is a real risk when we have an OTC consideration. We have a hard
enough time controlling how many pills people will take of their aspirin
or Advil or Tylenol \-- excuse me for naming names \-- but we would
certainly have the same problem here.

Again, if 20 milligrams helped, 40 milligrams is better.

Fourth, as you\'ll see from the materials I\'ve given you, Mrs. Calabio
did not stop her medication immediately when the very first signs of
toxicity appeared in her case. The physicians treating her also did not
jump on her case with the extreme level of aggressiveness that would
have been merited and possibly would have saved her life, in part,
because there\'s this complacency abounding.

But I think, in part, what we\'ve heard today and perhaps well grounded
in data, but this complacency cannot mean that on an individual case a
person can\'t be fatally affected by this drug, and this complacency has
left the doctors unprepared to aggressively treat the side effects. This
is, of course, a grave concern to safety.

Number five, and last in my points, is simply this and is why Mr.
Calabio, John Paul Calabio, son of Mrs. Calabio, wanted to be here
today. As far as that family is concerned, statin was a 100 percent
failure. As far as that family is concerned, statin had no risk-benefit
ratio for her and her case, and I don\'t think this is just an
individual case where you just say it\'s an anecdotal allergic reaction.

The literature will show that it\'s not an allergic idiopathic result.
It\'s an expected complication of a drug used in a large population with
the program that could have indicated the need for aggressive treatment
and immediate cessation therapy, but those opportunities were lost
because the publicity driving this drug, again, obliterates a scientific
analysis and a full participation of doctors at the level they need to
be.

Let me conclude by pointing out personally as a physician that I have
long felt that patients rely far too heavily on expensive, complex, and
potentially toxic medications instead of using common sense and instead
of using good health habits. Making the statins over the counter,
particularly as regards certain statins that the panel will determine
are pharmacologically different, potentially more hazardous than others,
sends the wrong message to our society that there is a pill for every
ill. You can smoke, but you can take care of it with a statin. You can
eat at these nameless restaurants \-- don\'t name names \-- but you can
take care of it with a statin pill.

It\'s interesting how we all come from our educational backgrounds and
arrive at the end with a slightly different perspective. Dr. Anderson,
who graduated from Harvard Medical School, four years, I think before I
did, although we haven\'t checked our ages, has come up with a very
different perspective. He has been enthusiastic about the pharmacologic
measures that have improved our lives.

From the same school I was taught be very cynical about new drug
developments. Be very cynical about what the manufacturers of these
drugs have to say about the performance of the drug because you\'re the
scientist, and the panel here being physicians, as scientists
themselves, will be making the decision.

I want to very lastly say that by way of the materials in that packet,
my address, my name is there. This is a very short period of time, I
think, for the panel to get all of the answers you necessarily want. I
don\'t want to put you under pressure to ask me all of the questions you
want to ask me if you have any or Mr. Calabio right now because I know
we\'re over schedule.

I am very happy to augment my record, augment our report, and just be of
help to any of the panel members or the panel generally at any time in
the future.

Thank you.

Any questions for me or for Mr. Calabio, please, we\'ll entertain them.

DR. DeLAP: Well, I think we\'re all very sorry for the experience that
Mr. Calabio and his family have gone through.

Do we have comments or questions from the family \-- from the panel? Dr.
Kweder.

DR. KWEDER: I have a question. Certainly you\'ve provided a fair amount
of literature to support that this particular event is out there and has
occurred to other people. I think maybe it\'s fair to say it\'s not a
common event. To the individuals who are affected, that\'s no
consolation at all.

DR. BARNETT: Well \--

DR. KWEDER: There are other medications on the over-the-counter market
that also have serious outcomes in small numbers of people. I can think
of some, for example, some of the decongestants, and we could probably
name many.

Do you think that all of those should not be over the counter, as well?

DR. BARNETT: No. I think that one of the better examples of this is
acetaminophen, which caused Reyes Syndrome in children, and that
certainly caused probably a death rate and an instance \-- I\'m sorry
\-- aspirin. Excuse me. Name, very important. Embarrass my professors
from the past if I \-- aspirin. Thank you.

And aspirin is far from coming off the market, but what did happen was
as soon as the incidence became appreciated, that the warnings were far
and wide, and the opportunity for physicians to intervene immediately
upon notice of any inkling of this effect was present.

I fear that an OTC product like the statins, if not accompanied by a
sufficiently well balanced warning against the overt engagement of
publicity and public persona to support it, in absence of that balance
people won\'t be prepared to take the precautions when they are amongst
the very few who will get ill, and I think that\'s mostly our warning
here today.

Because it is quite possible that Mrs. Calabio would be alive today if
she had stopped the pill and acted more aggressively for this disease
that she had the moment that she had her side effect, and I really
believe that she and her physicians, as the record will indicate, just
didn\'t know it was coming.

And I think \-- does that answer your question?

DR. DeLAP: I think, again, it\'s our expectation that products in the
over-the-counter marketplace should be quite, quite safe and should
provide a benefit that balances risks that there may be.

Of course, there aren\'t products that have no risks, and as long as we
have an OTC marketplace, we have to try and make sure that the products
that are there are as safe as they can possibly be, and that the risks
that are attendant with their use are well communicated so, as you
expressed, people can do a good job of managing and minimizing the
potential for harm.

Are there \-- Dr. Temple.

DR. TEMPLE: Yeah. I just had one question. Obviously I hadn\'t looked at
the cases you had before. Most of them appear to be single cases, and
not many of them say that the relationship to the use of the drug was
not obviously.

Is there any epidemiologic back-up of this? Just as an example, it\'s
been possible to show the relationship of certain weight loss products
to pulmonary fibrosis using epidemiologic methods. Of course, the risk
there was relatively large. Anything like that here?

DR. BARNETT: What you\'ve got is the results of my search using Medline
and other library resources. I\'ve got more material coming from the FDA
through the Freedom of Information Act as to other reports, but none of
them come to an epidemiologically significant report that the particular
complication here of the pulmonary fibrosis is actually a public health
issue, which is why it is kind of I hope \-- I get the indulgence of the
committee and they\'ve had me here \-- that it\'s important to put this
kind of different perspective.

Everything has been epidemiological so far. I don\'t claim this is an
epidemiological event. It may be in the aggregate a few lives lost are
better than thousands of lives if that\'s what a certain drug leads us
to. I haven\'t got \--

DR. TEMPLE: No, I was wondering about the causality of the relationship.
There are events that happen in the population without benefit of
therapy, and so I was wondering how good the evidence was that it was
causal.

DR. BARNETT: As to that, in terms of statistically, because we\'ve had
this question, for example, on breast implants, can you statistically
connect the connective tissue disease. I don\'t have that information
that there is that connection, that the incidence here isn\'t, in fact,
the same as the population at large.

However, the articles that I\'ve submitted, if you read them critically,
do indicate there are indicia there which to the authors make it
unmistakable in their minds that the statin was the direct cause of the
syndrome. But I don\'t have anything to help you with the particular
question.

DR. GILLIAM: Zocor is not one of the drugs that we will be considering
for over-the-counter status, and it is far more potent than the ones
that we are considering. Do you have any indication that these ones that
we will be considering would have the same side effect profile or would
have less of a chance of causing these problems?

DR. BARNETT: Well, I concentrated my research on Simvastatin. However,
the fluvastatin also, which I understand is a chemical which is
nonorganically derived \-- it\'s a produced chemical \-- had a similar
event occur, and across the board, all of the statins \-- the answer to
your question is, yes, I suspect that there\'s a problem will emerge
over time if people use doses which are high and don\'t pay attention to
the side effects because all of the statins do report what they call a
lupus-like syndrome.

And the phenomenon here of the pulmonary fibrosis is a variant in the
extreme manifestation within the pulmonary tree of a lupus-like syndrome
amongst those people who end up with that lupus-like syndrome. So I
would predict that over time if enough people use this drug, there will
be a sufficient number of people getting pulmonary problems as well as
lupus-type problems to raise alarms and, I think, to be of some concern.

DR. DeLAP: Well, thank you very much.

That concludes our session on the cardiology and cardiovascular drug
class issues, and now we have a session on antimicrobials and antibiotic
issues, and the first speaker is Kathleen Young for the Alliance for the
Prudent Use of Antibiotics.

Is there someone here from the Alliance for the Prudent Use of
Antibiotics?

(No response.)

DR. DeLAP: If not, we\'ll proceed to Gretchen Kidder, Alliance for
Microbicide Development.

MS. KIDDER: Hi. I\'m speaking here today on behalf of the Alliance for
Microbicide Development. The alliance is a coalition of most of the
major researchers and organizations involved in the development of
microbicides, topical genital application being designed to help prevent
sexually transmitted infections, STIs, very importantly including HIV.

It comprises developers from \--

PARTICIPANT: We can\'t hear you.

MS. KIDDER: You can\'t hear me? Okay. Is this better?

It comprises developers from 34 biopharmaceutical companies, scientists
from 26 nonprofit research institutions, and representatives of 20
health research and advocacy groups. The alliance is maintained with
support from private philanthropies and accepts no federal funding.

The mission of the alliance is to accelerate the development and
availability of microbicides for the millions of individuals globally
who could benefit from them. The women of the world lead that list of
potential beneficiaries for two primary reasons. The first is the
feminization of the AIDS epidemic.

In the United States, women constitute the fastest growing group of
those newly infected with HIV, and worldwide almost half of the almost
14,000 adults infected daily with HIV are women, with over 90 percent of
those new infections being spread through unprotected heterosexual
intercourse.

The second reason is that the currently most effective protection
against HIV and most other STIs is the male condom. Yet since many men
resist condom use, it is infrequent or irregular in many partnerships,
and especially problematic where proven fertility is important or where
couples want children despite their infectious status, as is often the
case in developing countries.

Negotiating condom use or refusing unsafe sex may be particularly
difficult in primary relationship partnerships where trust becomes an
issue and in relationships where women are at risk of violence or
abandonment.

We are talking about a population of many millions and a need that is
relentless and immediate so that speed is of the essence in the
development processes and in terms of practical availability once a
produce has proved safe and efficacious in appropriately designed
clinical trials. The assumption in much of the microbicide development
and advocacy community has been that microbicides based on ingredients
used mucosally for many years and generally recognized as safe, GRAS,
but which represent roughly one quarter of the microbicides currently in
development might reasonably be expected to go to market as
over-the-counter products.

This view in no way excluded recognition that products dependent on
totally new chemical entities, NCEs, would probably and appropriately
require at least initial launch as prescription products, nor did this
view imply any willingness to sacrifice safety for speed.

However, the possibility that all microbicides might require initial
prescription introduction has raised concerns about what that might mean
for market readiness and the various dimensions of availability,
importantly including cost, provider barriers, and physical access.

Because these hearings offer a proper venue for commentary and in order
to present the perspectives of the microbicide community in a
responsible way, this issue was discussed at the May 13th through 14th
meeting of the alliance and was further addressed in a subsequent poll
of those alliance participants who are developing products.

The following paragraphs present the results of those activities.

Consumer utilization of microbicides. There was consensus without
exception that across the board and unrelenting prescription
classification would hinder access and, therefore, microbicide
utilization in a number of ways, and that the public health and
individual human cost could be substantial.

In very practical terms, women in general could well find it more
difficult to purchase microbicides on an as needed basis for routine
prevention if they were not able to do so in an open marketplace,
unconstrained by provider dependents.

The shared view was that product costs to consumers would inevitably be
higher under prescription labeling added to which would be provider
fees. The observation was made that sexual relations are not in
themselves a disease requiring provider intervention, but rather
decisions made by individuals on their own time.

The related comment was made that condoms are available over the counter
for individual decisions by men without requiring the intervention of a
learned intermediary by which token microbicides should be available
over the counter for individual decisions by women.

Particular concern was expressed on behalf of women at risk. Such women
are often disadvantaged by poverty, their position and social
structures, and age, and might well be intimidated by those conditions
and contained by possible stigma from seeking microbicides dispensed
only by physicians or public health system providers.

Several respondents did note that there would also be market interest
were prescription microbicides also to be available, partly deriving
from the character of the product itself, partly deriving from the
associated endorsement by the medical community, partly deriving from a
potential higher price.

Market intentions. Of 12 companies actively developing products, most of
whom who have advanced beyond the preclinical phases, four are planning
on over-the-counter introduction. Four foresee a prescription
introduction followed by transition to over-the-counter status. One
anticipates prescription classification, and two are unsure or
undecided.

The issue of transition from prescription to over-the-counter status
emerged as pivotal and is addressed below. Respondents were asked what
the effect of determination to make all microbicides prescription
products would have on their current plans and what effect such a
determination might have on a prospective partner.

Because the overwhelming majority of those individuals and companies
that are developing microbicides will be inevitably dependent on some
kind of partnership to take their products forward, this consideration
is not small. Of 12 developers, eight had either anticipated at least
initial prescription status or felt that they could adjust to such a
determination even if not anticipated, noting that while the objective
of reducing the spread of HIV compels them to continue, the requirement
for a prescription classification would impose serious cost constraints
and time line extensions.

However, of that group, five noted that the issue of status could make a
difference to a prospective partner. One company felt that it would have
to withdraw from the field altogether if initial OTC classification
could not be anticipated, while four who might have to consider
withdrawal would be able to stay in the field if there were a standard
procedure for switching their product from prescription to OTC in a
relatively brief period.

One creative proposal that emerged in the course of alliance discussions
is the notion of developing a formal post introduction, post market
consumer reporting system that could gather the kind of information the
FDA would require for the transition from prescription to
over-the-counter status.

This remains a germ of an idea that has already attracted interest as a
subject worthy of pursuit and a topic for discussion with the agency
itself.

The final question in the poll asked if opposing criteria for regulatory
decisions about status would be helpful. The sense of the responses was
that attempting to establish such criteria in any fine grained way is
premature. Although there was some agreement that microbicides based on
currently marketed, over-the-counter or GRAS active ingredients or
products based on components with long term safety records could
reasonably be considered for initial over-the-counter classification,
the point was made that some new chemical entities might prove to have a
better toxicity profile than some older molecules and should not be
disqualified from the outset simply because they were new.

From a richly textured discussion, however, two bottom lines emerged.
The first was that determination about initial status should be made on
a case-by-case basis.

The second was that any rigid, a priori decision about launch status for
microbicides of the drug category should be assiduously avoided.

In conclusion, these opinions are based on a small sample, but the
constituency represented and the weight of opinion within that
constituency are not trivial. The core message from the microbicide
community is an appeal to the Food and Drug Administration for careful,
but flexible and expeditious consideration of the merit and potential
value of each microbicide against a background of urgent need among the
very many who have no other protection from prospective death and
disability.

Thank you.

DR. DeLAP: Thank you.

Comments? Questions?

Dr. Chikami.

DR. CHIKAMI: In your discussions with the people you polled or in your
alliance, did you all consider the possible approach for those products
which may already be over the counter, for example, for other
indications, the approach of professional labeling for the microbicide
indications and how that might impact their view of developing products
in this area?

MS. KIDDER: I don\'t believe so, but we will.

DR. CHIKAMI: The other issue, I think, that you\'re appropriately
pointed out, in fact, the products in this area represent are quite
heterogeneous. Some of them, in fact, may be already on the market for
other indications. Some of the development is involved in developing new
chemical entities for which there may be little, if any, clinical
experience.

And I guess one of the issues relates to not only their safety profiles,
but their effectiveness. Microbicides is a broad term, and in fact, the
intention is to prevent a number of sexually transmitted infections,
bacterial and viral and quite a diverse nature of viral infections.

And your views in regard to the appropriateness of these products for
the OTC market, if in fact they may not be able to or their
effectiveness against these very sexually transmitted infections, in
fact, might not be uniform, for example, and how that might be
appropriately communicated to the consumer.

MS. KIDDER: I\'m not exactly sure, and I don\'t believe that I should be
the person answering, but I would like to relay that question to our
participants and get their feedback on that and add it to our written
follow-up if that would be okay.

Thank you.

DR. DeLAP: Thank you.

Our next speaker is Dr. Thomas Moench from ReProtect, L.L.C.

DR. MOENCH: Thank you, Dr. DeLap.

I\'m Thomas Moench, the Medical Director and a part owner of ReProtect,
L.L.C.

ReProtect is a small pharmaceutical company developing a spermicidal
microbicide gel intended to protect women against pregnancy, HIV, and
other sexually transmitted diseases.

We thank the FDA for establishing the Microbicide Working Group to
streamline the process of microbicide review. However, like other
members of the microbicide development community, we were surprised and
concerned when FDA staff announced in January at the preclinical
microbicide workshop that all new microbicide-spermicide products might
be classified as prescription drugs.

Our product, Buffer Gel, is made entirely of components that have been
used mucosally for decades and are classified as GRAS, that is,
generally recognized as safe. Buffer Gel maintains a protective vaginal
acidity by maintaining a safe and effective concentration of protons in
the vagina, and the buffering agent in Buffer Gel is Carbopol, a gel
forming polymer that is used simply as an excipient in over 120
currently marketed pharmaceutical products, including at least nine
products that are used vaginally.

Phase I studies show that unlike most existing spermicides based on
detergents, intensive use of Buffer Gel does not disrupt
cervical-vaginal epithelium. In this important respect, Buffer Gel
appears to be safer than detergent based spermicides that have long been
available OTC.

Unlike antibiotics discussed yesterday by Dr. Sparling, Buffer Gel has a
low potential to encourage pathogen resistance since it simply maintains
the naturally occurring vaginal acidity.

Other sponsors are developing microbicide products that have a similarly
high expectation of safety. We believe that Buffer Gel and other
microbicides based on low toxicity, nonabsorbable agents should be
considered for direct approval for OTC use after adequate preclinical
and clinical testing and with appropriate post marketing surveillance.

We believe that the public health impact of vaginal microbicides would
be severely limited if they were restricted to Rx status since a woman
is much less likely to use a microbicide if she must visit a physician
to get a prescription. This is especially true for the very women who
would most benefit from microbicides, the poor, the disadvantaged, and
the young.

Many women will be too embarrassed or too intimidated to obtain safer
sex products from a physician. Sexually transmitted diseases and AIDS
remain highly stigmatized in our society, and when a woman asks a doctor
for a safer sex product, she may feel that she is telling her physician
that she intends to engage in high risk sex. Women may wish to avoid
such a conversation.

The argument might be made that hormonal contraceptives are widely used
despite Rx classification and hence Rx status is not a severe barrier.
This is an inappropriate analogy when applied to microbicides. Women
understand and accept that they are at risk of pregnancy, and being a
fertile woman carries no stigma.

In contrast, a woman who seeks to obtain a microbicide that\'s available
only Rx must overcome a powerful stigma. She must reveal to others that
she may be concerned she is having sex with an unsafe partner.

We recognize that the Rx only status may enhance detection of certain
adverse events of new products that were not detected during clinical
trials. We believe this might be an appropriate basis for Rx
classification of some of the new microbicides now being developed, but
we believe that in its deliberations on OTC versus Rx status of vaginal
microbicides, the FDA should consider not only the benefit of detecting
those rare adverse events in users of the new product, but also the risk
to public health if access to these products is limited by an Rx hurdle.

We ask the panel to consider the probable impact on public health if
condoms were available only by prescription. Recall that condom sales
increased substantially with the simple change of placing them on
accessible displays rather than keeping them out of sight, behind the
pharmacist\'s counter where they must be asked for.

This marketing experience shows that even the most minor barrier to
access significantly limited the use of condoms. We believe that an Rx
hurdle placed in the way of microbicides would much more dramatically
limit their use by women.

We urge the panel to proceed on a case-by-case basis with microbicides
and not to establish a categorical guideline that new
microbicides/spermicides must initially be classified as prescription
drugs.

Some new microbicides are composed of nontoxic ingredients with long
track records of safe mucosal applications. Categorically imposing an Rx
hurdle would risk the loss of major public health benefits, especially
for those women most in need of vaginal products for safer sex.

Thank you for the opportunity to speak.

DR. DeLAP: Thank you.

Comments? Questions?

I have one question. When you described making products available with
appropriate post marketing surveillance, what ideas might you have about
appropriate post marketing surveillance?

DR. MOENCH: Well, I think the goal would be to detect adverse reactions
that were rare enough that they weren\'t observed in clinical trials,
and the kind of surveillance that could be envisioned would be either
manufacturers or an organization like the Alliance for Microbicide
Development, creating a registry for reporting of such events, possibly
even having an 800 telephone number on all products so that women would
be sort of actively encouraged to report events.

DR. DeLAP: Dr. Ganley.

DR. GANLEY: Yeah, I guess one of the concerns has less to do with
providing or the safety is what is the efficacy of these products, and
we heard yesterday that you have to gear labeling down to a seventh
grade education. So how can you adequately explain to a consumer that
this treats certain sexually transmitted diseases or sexually
transmitted diseases. It\'s not an absolute preventive, or should the
requirement be that it\'s an absolute preventive?

I think that\'s really one of the main concerns as opposed to the
necessary safety issues, but how do you provide this information, and
what criteria should be used to say that something is effective?

I think the Rx \-- one of the advantages of an Rx product are that
there\'s an intermediary there to actually explain to a consumer, you
know, what the down side is regarding effectiveness. So how do you
overcome that?

DR. MOENCH: Well, I think it is an important question, and labeling of
these kind of products is difficult and will require lots of thought and
back and forth between the sponsors and the agency.

I wouldn\'t want to overestimate the difficulty of explaining to people
that something can give them partial protection. I think in all of our
lives we know that. We wear seat belts. We have air bags. You might
worry that gives people a false sense of security and encourages bad
driving habits. Maybe that\'s true, but the benefits outweigh the risks
of some misunderstanding some of the time.

So I do believe that consumers understand that there can be products
that give them partial protection. In fact, I think most people in daily
life know that that\'s the rule rather than the exception.

I do think it\'s going to bear emphasis on labeling, but I believe that
that concept can be gotten across to consumers.

DR. GANLEY: Should there be certain diseases that we are more concerned
about, for example, the transmission of HIV which could lead to a fatal
outcome as opposed to other sexually transmitted disease which may have
a morbidity, but not necessarily mortality associated with it?

DR. MOENCH: I think that\'s true, and I don\'t think that the labeling
will have to do a lot to do that. When you look at the public\'s fears,
it already lines up in those kind of ways. So I think it is true that a
higher priority is placed by consumers and product developers, and I
would assume the agency for protecting against a disease like HIV.

DR. GANLEY: But getting to HIV, if you were able to share that there\'s
a 50 percent reduction in transmission, there\'s still going to be a
certain percentage of people out there that will develop an infection
despite using the product, and I guess it gets back to how do you label
that geared towards a seventh grade education.

DR. MOENCH: I think people with a seventh grade reading comprehension
can understand the concept that this gives a 50 percent protection.

DR. DeLAP: Thank you very much.

Our next speaker is Dr. Kevin Whaley for EPIcyte Pharmaceutical.

DR. WHALEY: Can you hear me all right?

I\'d like to thank the FDA for allowing me to speak to you today. My
name is Kevin Whaley. I am representing EPIcyte Pharmaceutical. I\'m
also a member of ReProtect, the previous speaker, and I\'m also a
participant in the Alliance for Microbicide Development.

My purpose in requesting an opportunity to speak to the panel is that I
wanted to give the panel sort of a view of the spectrum of products that
we\'re expecting that are coming out of the microbicide field. The
Alliance for Microbicide Development has a range of products, and I
think the products that were presented by Dr. Moench represent some
products that, a class of products that actually may reasonably be
considered to go OTC.

On the other hand, we have some things that are in the Alliance for
Microbicide Development that are being considered, but are new chemical
entities, but on the other hand, I would like to make the case that they
may be considered for OTC or at least fast track switch.

I\'m going to be using the products that we developing as sort of a case
study. I think Buffer Gel is one example of one that might be considered
for OTC application very early on, but I\'m also very interested in
giving you a view of what we believe may occur in terms of new chemical
entities.

The molecules that I\'ll be talking about are antibodies. Antibodies I
think the agency has a lot of experience with. They are being regulated
primarily as therapeutics, but we believe that because of some new
breakthroughs in the field, we believe that antibodies will be a
relatively new area for prevention transmission, and I think we have to
give great consideration to technology that prevents the transmission of
infectious diseases.

Ninety percent of all infections begin on a mucosal surface, and mucosal
antibodies help prevent mucosal infections.

In terms of the comments about efficacy, I think there\'s been some data
in animal studies that have shown that antibodies on mucosal surfaces do
prevent disease, whether or not they\'re a virus or a bacteria or fungus
or a parasite.

There are very few clinical trials, however, that have randomized double
blind prospective clinical trials that have looked at this, but
nonetheless, the prevention of transmission has been relatively
impressive. It\'s enough to encourage us to continue to pursue this as a
strategy.

We also feel fairly confident and because the agency has previously
evaluated antibodies, and there are a large number of antibody products.
We know a lot about the mechanism of action, and primarily on mucosal
surfaces, it\'s agglutination, blocking of adhesion, and mucophylic
trapping. It\'s a noninflammatory response, doesn\'t require most other
components of the immune system.

Why this technology has not previously been used in the prevention of
disease \-- you will have to remember that the immune system was
developed to protect us from disease \-- is because we have not
previously had the technology to produce them at low cost and high
capacity such as is required for OTC products.

That was recently done in 1995 where we were able to produce antibodies,
human antibodies, and particularly secretory antibodies that go on
mucosal surfaces in plants for low cost and large capacity production.
These are very specific molecules, and we think they\'re very desirable
from the point of view of microbicides.

So the plantibodies that we\'re talking about are going to be used as
mucosal protectants. The plantibodies are human antibodies produced in
plants at low cost and large capacity. They are purified from plants and
formulated as pharmaceuticals, particularly, say, for example, for
microbicides, and plantibodies will supplement and mimic the prevention
that we already see with mucosal antibodies.

There\'s only been one clinical trial aimed at plantibody. That was
recently reported in [Nature Medicine]{.underline}. It was to treat
Strep. mutans, an ecological imbalance, and where we had six
applications over 20 days, and the endpoint was to prevent
recolonization.

The actual clinical efficacy was actually quite traumatic. The
recolonization was prevented in four of four patients. There were no
adverse side effects, and there were no serum antiplantibody responses.
Admittedly this is very small numbers, and obviously large numbers of
clinical trials need to be done with plantibodies, but our experience
with antibodies and now beginning with plantibodies I think is very
encouraging.

From EPIcyte\'s point of view, our first generation of products are
going to be a lubricant that prevents sexual transmission of HSV2. We
are developing a microbicide that prevents horizontal and vertical
transmission of HIV.

We\'re also working not only on the genital-urinary tract, but also on
the respiratory tract and for the gastrointestinal tract. We would like
to see prevention, technology that prevents transmission much more
widely used.

But I would like to spend the remaining amount of time that I have on
the opportunities that we see in the microbicide field, the vaginal
microbicides.

We\'re primarily driven by the fact that in 1999, 15.4 million people in
the United States acquired a new sexually transmitted disease, and it\'s
a causative factor for infertility, pregnancy complications, cervical
cancer, and infant mortality.

We\'re also driven by the fact that there\'s been a failure of
imagination on the part of the scientific community in thinking about
prevention of transmission of infectious diseases. Vaccines have clearly
been thought about as a technology, but for all of the sexually
transmitted diseases we do not have a vaccine against any of the
sexually transmitted pathogens.

Also, the cures, at least for the viruses, are not \-- we do not have
tremendous therapeutic endpoints, and we are starting to see some drug
resistance with some of these products.

In terms of some of the points that have been made about acceptability
and efficacy, we\'re very enthusiastic about antibodies because that\'s
their physiological role and because they are not absorbed as Dr. Moench
mentioned about Buffer Gel, but also the fact that they\'re not really
metabolized. They\'re not metabolized, and they\'re not broken down in a
significant way on mucosal surfaces.

That allows us to have a residence time that is dependent upon the
mucous turnover time, and that allows one to think about products that
have 18 to 24 hours\' worth of protection. If one takes this half
residence half time of an antibody, which was done in a study recently
in reported in the Microbicides 2000 meeting, one can model what this
might do in terms of acceptability.

If a woman were using this on a day-to-day basis and failed to use it on
the fourth day, she still would have a significant level of antibodies
in there, assuming we gave, because these are potent molecules, several
half times of the molecule. We would still have protection on the second
and perhaps even the third day. This is conjecture on our part, but this
is preliminary data that is very intriguing to us.

From a regulatory point of view, because we\'ve had a failure of
imagination in the scientific community on thinking about mucosal
protectants, we also do not want the regulatory entities to have a
failure of imagination to think about how these products will be
regulated.

The first generation will be similar to things that have already been
regulated, that is, there will be single antibodies against a single
pathogen, but eventually we think the most promising mucosal protectants
at least for antibodies will be multiple targets and with multiple
antibodies.

I\'ve used mucosal antibodies strictly as a case study. The Alliance for
Microbicide Development does have a range of products. There are some
that might be considered to go directly over the counter. We have some
new chemical entities. I would like to think that we will continue to
\-- there\'s been a lot of discussion about a case-by-case basis. I
would like to see that open even for new chemical entities if we involve
the OTC regulatory people very early on in our process.

But talking generically about mucosal protectants, I think we need more
technology in this category. Individuals are exposed to a range of
mucosal pathogens on a daily basis. The strategy and technologies for
preventing transmission of infectious diseases at mucosal surfaces is
very limited, and because accessibility is important for personal
protection, we believe that accessibility is a key issue, and we would
like to see these things available as widely as we possibly can.

Thank you very much.

DR. DeLAP: Thank you.

Questions?

(No response.)

DR. WHALEY: Thank you.

DR. DeLAP: I think you covered things very well. Thank you.

Before we break, has Kathleen Young from Alliance for Prudent Use of
Antibiotics returned?

Otherwise we\'re at our lunch break. It is currently ten minutes to one
o\'clock, and we\'ll try and reconvene here at 1:30, 40 minutes for
lunch, 1:30.

Thank you.

(Whereupon, at 12:53 p.m., the meeting was recessed for lunch to
reconvene at 1:30 p.m., the same day.)

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

(1:44 p.m.)

DR. DeLAP: We\'re going to slightly change the sequence for Session 7
for the allergy and asthma drug issues, and under the revised plan, the
first speaker will be Dr. Robert Seidman, Vice President, Pharmacy, Blue
Cross of California.

DR. SEIDMAN: Thank you.

My name is Dr. Robert Seidman, and I am Vice President of Pharmacy for
Well Point Health Networks based in Thousand Oaks, California.

Well Point Health Networks is one of the nation\'s largest publicly
traded managed care companies serving the health care needs of over 7.5
million medical and approximately 31 million specialty members
nationally.

Given our limited time today, I would like to take the opportunity to
respond to the questions outlined by the FDA in the April 27th, 2000
[Federal Register]{.underline} notice of this hearing.

Can you hear all right in the back?

In responding to these questions, I want to focus on the documented
safety and effectiveness of the prescription nonsedating antihistamines
Claritin and Alegra and the minimally sedating antihistamine Zertec.

Through our prescription drug benefits, Well Point Health Networks
currently provides access to these drugs at a copayment paid by the
member.

There are three criteria that the FDA should consider in rendering
decisions on over-the-counter availability of drug products: ease of
self-diagnosis; ease of compliance with the treatment regimen; and drug
safety.

In applying these three criteria to the second generation antihistamines
referenced above, we have found that the average lay person can easily
self-diagnose allergic rhinitis and treat the condition with relative
issue.

This self-diagnosis and treatment is performed by millions of Americans
daily with the current complement of over-the-counter antihistamines
available.

The third criteria, safety, is also satisfied since hundreds of
randomized controlled studies in the peer reviewed medical literature
clearly show that these agents are safer than the currently available
over-the-counter antihistamine alternatives.

To support our claim of second generation antihistamine safety, we have
also contracted with the University of Southern California School of
Pharmacy to perform a meta analysis on all peer reviewed articles on
antihistamines.

Our preliminary analysis of 84 peer reviewed articles clearly shows that
the second generation antihistamines, Claritin, Alegra, and Zertec, are
safer than those antihistamines that are currently available without a
prescription.

The complete results of this analysis will be provided to the FDA as an
amendment to our existing petition to convert these drugs to
over-the-counter status.

The majority of Americans seek to self-medicate with over-the-counter
drugs, and it is incumbent upon the FDA to insure access through OTC
status of drugs that have documented safety, efficacy, and ease of use.

Regarding the treatment of chronic conditions, two interests must be
balanced: potential harm of self-treatment versus the value of early
diagnosis of a debilitating chronic disease.

It would also be beneficial for a portion of close to the \$2 billion
that are currently being allocated to direct-to-consumer advertising to
be redirected to efforts to help patients with the early diagnosis and
treatment of disease states where our current medical interventions have
been inefficient in improving the lives of Americans.

Diseases such as diabetes, asthma and hypertension are particularly
amendable to greater health education. Drugs like antibiotics should not
be available OTC because the current system of medical management has
not succeeded in stemming the inappropriate prescribing of antibiotics
and the resultant danger of increase in antimicrobial resistance.

Again, I want to focus on the safety and efficacy of the second
generation antihistamines and not venture into the other more
complicated classes of drugs. The second generation antihistamines
clearly meet the criteria utilized by the FDA in determining whether a
drug should be available over the country.

Consequently, they can be used as a model for other classes of drugs.
When the marketplace, through direct-to-consumer advertising, converts a
drug into a virtual over-the-counter drug, consumers can easily
understand the benefits and risks of these products.

There is documented evidence demonstrating that DTC advertising of
second generation antihistamines has increase physician office visits to
request prescriptions for these drugs, and that physicians are
uncomfortable declining these requests.

As a result of this phenomenon, second generation antihistamines are
virtual OTC drugs today. Even today we have examples of OTC and
prescription versions of drugs in the same milligram and delivery
system. So the issue of co-existing products is not new or novel.

Again, with a second generation antihistamines, there is no clinical
controversy about converting these drugs to OTC status. When
prescription drugs do go OTC, which I hope the second generation
antihistamines will shortly do, the first drug converted is not
necessarily the gold standard, although it would be difficult to imagine
drugs safer and more efficacious than the currently available second
generation antihistamines.

Personal consumer experience will determine which is the better drug.
The question here is whether the pharmaceutical manufacturer has sole
discretionary power to decide what is in the best interest of society.
It is my belief that this important decision making process should be
vested in the clinical merits of these drugs and supported by the FDA.

The current structure for marketing OTC products in the United States is
flawed. Currently no safe and effective drug has ever gone OTC without
the pharmaceutical industry initiating the request for that conversion.
In areas where controversy is nonexistent, as in the second generation
antihistamines, the FDA should be proactive in providing easier access
to these drugs. Maintaining Claritin, Alegra and Zertec as prescription
drugs deprives the majority of patients ready access to the highest
quality pharmaceutical care and trivializes the patient-physician
relationship.

When there is no toxicity associated with a drug and a layperson can
easily diagnose and treat a condition or disease, the FDA should take an
activist role in converting those identified prescription drugs to OTC
status.

As I indicated in our petition to the FDA, patients are seeking greater
ownership of their health care and often prefer to self-medicate when
feasible.

Of all the therapeutic classes of drug available, the discrepancy and
safety between the current antihistamines available OTC compared to
prescription second generation antihistamines is most pronounced. The
health care system should not be burdened with the increased cost and
patient inconvenience associated with these drugs remaining prescription
only.

The millions of allergy sufferers should have unimpeded access to these
drugs as they do in Canada and in Europe. I request that the FDA review
our petition and expedite the conversion of prescription Claritin,
Alegra, and Zertec to OTC medication status.

At this time I would also like to present to the committee samples of
these drugs from Canada and a receipt from the pharmacy showing the cost
effectiveness of these agents and the labeling that is available in
Canada.

Thank you.

DR. DeLAP: Thank you.

Can we keep these?

DR. SEIDMAN: Those are for personal use or getting you arrested.

(Laughter.)

DR. DeLAP: Just to start, how much experience do you think is enough
with a new drug before it is contemplated for OTC use? I mean, clearly
we can say that when a new drug becomes available and there\'s not much
experience with it, there may not be many safety reports, but that may
just be that there isn\'t much experience and the drug may turn out to
have some safety problems when we have more experience.

So how much experience or how do you think we should be measuring the
amount of experience people have to have with a new drug before we can
conclude that we know as much as we need to know to think about bringing
it over the counter?

DR. SEIDMAN: My initial comment is that from our personal experience we
are covering over 800,000 prescriptions of these agents a year, going
back to when they were initially FDA approved. For this specific
situation, I am personally comfortable with the amount of dosages that
have been consumed by Americans.

Additionally, looking at the Canadian and European experience, there\'s
a wealth of information on the safety and efficacy of these particular
agents. I do appreciate the question as to when an FDA approved
prescription drug is found to be safer than the already commercially
available OTC products. What is the appropriate time frame to be
determined?

And I would really be, you know, more comfortable deferring that
decision to the clinicians within the FDA to who are reviewing basically
similar data that we are reviewing today in the peer reviewed
literature.

DR. DeLAP: Dr. Cantilena.

DR. CANTILENA: I just have a couple of questions. One with regard to
access from your subscribers, if these drugs were over the counter,
would they have a copay, you know, situation in terms of, you know, the
over-the-counter status? Would it cost the subscriber any more money to
use them over the counter?

DR. SEIDMAN: The sole intent of our petition was to increase access to
health care, and in all of the financial modeling that we have done in
comparing these products\' costs in the United States, in Europe, and in
Australia, in U.S. dollars, and specifically in referencing the visual
aids that I have presented to the committee, one month\'s supply of
Claritin in Canada in U.S. dollars is 11, \$11 per patient, per month.

In managed care plans, the average brand copay probably ranges from ten
to \$20 per month per prescription. We do not believe that there will be
an additional out-of-pocket cost for these agents when they are
converted to OTC status because of the competition in the marketplace
between the three pharmaceutical manufacturers.

I believe that the cost effectiveness of converting these drugs to
over-the-counter status can really be answered in three ways. First,
unfortunately, there are millions of people in the United States, unlike
those who are in the room today, who do not have any health insurance,
who are paying totally out of pocket for their office visit to see their
physician. They are paying totally out of pocket at 50 to \$60 per month
for these prescriptions.

For those people who are uninsured, having these products available at
\$11 per month is in their best interest.

We also have a tremendous number of people who are uninsured who would
like to be insured, and removing these products from the prescription
drug product gives health plans greater flexibility in pricing, in
creating these products to make them more affordable.

And thirdly, removing these products from prescription status allows us
to focus our energies on those therapeutic classes of drugs that really
do require the analysis and the care management to insure that we obtain
appropriate outcomes in our patients with diabetes, hypertension, et
cetera.

DR. CANTILENA: So in follow up, if \-- I think I hear you saying that
it\'s a wash from the subscriber point of view in terms of cost, and in
terms of from the, you know, perspective of the health care network is
that, you know, financially advantageous to have it OTC versus
prescription other than allowing you to focus your efforts on these
other, you know, disease categories.

DR. SEIDMAN: We currently are experiencing a crisis in health care, and
that is prescription drug costs are increasing at 15 to 20 percent per
year. Some employer groups that have a larger retiree population are now
spending 25 percent of their total health care dollars on prescription
drugs.

Retaining these products as prescription is inherently inefficient.
Moving them to over the counter status will free health plans and
provide greater access to consumers to these agents.

DR. DeLAP: Dr. Temple.

DR. TEMPLE: Not that this is something we necessarily think about, but
nothing would actually stop you from continuing to pay for it even if it
were over the counter if you wanted to. Plans pay for insulin, for
example. At least many do. So that would be up for discussion, and
people would yell and scream until a decision was made.

DR. SEIDMAN: We have a responsibility to be responsive to the needs of
the marketplace. We are already involved in pilot programs in which we
are sampling some of the over-the-counter antihistamines amongst medical
groups. Kaiser has a similar program.

The question of what the coverage options will be is open to discussion.
We know currently the way that these products are delivered is
inherently inefficient to the health care system and required
modification.

DR. DeLAP: Could you clarify what you meant by sampling some of the
currently available OTC products to physicians?

DR. SEIDMAN: Many medical groups, as a way to modify the current cost
burden of the second generation antihistamines, have relationships with
some of the over-the-counter antihistamine manufacturers, to use them as
initial therapy, step care therapy before moving to a second generation
\-- excuse me \-- antihistamine.

I would be much more comfortable sampling Claritin, Alegra and Zertec in
their over-the-counter form to members who present with an initial
diagnosis.

DR. GILLIAM: My experience in Arizona has been that once these
medication become over the counter, that HMOs then do not pay for them
anymore because they are over the counter, unless they\'re like, for
example, in our state Medicaid agency access, they will pay for some
over-the-counter medications in indigent populations. However, for the
most part once drugs become over the counter, HMOs don\'t pay for them
anymore.

DR. SEIDMAN: I think that it\'s important for us to look at the
opportunities that the conversion of these products from prescription to
over the counter present, the decrease in cost burden both to the
individual without health insurance and the health plan, and I think
that you will see flexibility and creativity on the part of the health
plan to meet the needs of their members.

If the average out-of-pocket cost is \$10 for these agents and the copay
is \$10, then we feel it is better for the patient to have an
out-of-pocket cost associated with that. As a member of the panel said,
it would be a wash.

We will be looking at this as we go forward, and we will be flexible in
how we present solutions.

DR. DeLAP: Dr. Jenkins.

DR. JENKINS: A couple of quick questions. In your statement you talked
about a meta analysis that you had commissioned to be done where you
concluded that the second generation antihistamines were safer. Can you
talk a little bit more about how did you reach that conclusion?

When you say \"safer,\" what adverse effects were you looking at in
particular?

DR. SEIDMAN: Is Jack Kern in the audience? Jack, could you stand up,
please?

Jack Kern is our principal investigator for the study.

DR. KERN: The question with regard to how the meta analysis was set up
to look at this, I think the first part that\'s important is trying to
eliminate bias is the whole purpose of the meta analysis. So you look at
the universe, the literature that\'s available, focus on a patient
population that\'s uniform which has to do with rhinitis seasonal and
parenteral rhinitis, and then focus in on side effects that are measured
in a common fashion among enough articles that you can begin to combine
together, and that\'s what was done, and we were looking primarily at
sedation.

And we also looked at all other side effects, and in the sedation
profile it\'s clearly shown that the second generation antihistamines
are safer than the first, by far, and then when you begin to look even
at other literature talking about performance associations with these
drugs, having to do with their ability to go to school, having the
ability to do work, fly an airplane, drive a car, second generation
antihistamines are clearly safer than the first generation.

Adverse drug reactions, talking about the combination with alcohol, once
again the second generation antihistamines are clearly safer than the
first.

DR. JENKINS: Okay. As a follow-up to that, one of the reasons we heard
yesterday, reasons why FDA should not initiate over-the-counter switches
and, rather, that should be the sponsor\'s responsibility, is that the
sponsors know the drug the best. They have access to all the data that
they\'ve generated on the clinical trial.

And I\'m wondering if, Dr. Seidman, you could comment now that you\'ve
done this meta analysis, if you have any comments about that
perspective, that only the sponsor knows enough about the drug to make
that decision.

DR. SEIDMAN: Well, I think Jack could comment on this as well. We
believe that the same peer reviewed articles that we are reviewing are
the same articles that are in your files for the prescription approval
that you granted to these agents a number of years ago.

DR. KERN: I\'d like to also add that with regard to that issue as far as
new information coming out, it\'s available to the public. It\'s not
proprietary. If it\'s proprietary, that makes you concerned about bias.
Why isn\'t it public information?

Also, large databases that are from like the Compass database that has
four states in the United States that look at from an epidemiology point
of view, look at this type of outcomes with these drugs. So I don\'t
think we\'re necessarily hamstrung that we don\'t have good information
post marketing of these drugs. I think we actually do.

DR. DeLAP: Dr. Uden, do you?

DR. UDEN: Where do the second generation antihistamines fall in terms of
number of prescriptions in your organization or rank as numbers of
prescriptions, and how many dollars does your organization spend on
these annually?

DR. SEIDMAN: Ranked by therapeutic class, ranked by dollar, the second
generation antihistamines are probably fifth or sixth in the continuum
of therapeutic classes.

In terms of costs incurred to a health care system, whether it\'s Well
Point Health Networks or another, for our five million lives, we are
currently spending a combination between pharmacy and office visits of
\$84 million a year.

DR. WOODCOCK: Yeah, I asked this yesterday. What is the split between
the toll of office visits, paper processing and everything, and actual
out-of-pocket costs for the drugs from your pocket?

DR. SEIDMAN: I\'m sorry. I don\'t think I understand.

DR. WOODCOCK: The split, how much of that is office visit and how much
is paying for the drug?

DR. SEIDMAN: It\'s interest. It\'s 50-50.

DR. WOODCOCK: Thank you.

DR. DeLAP: Dr. Kweder.

DR. KWEDER: Just in follow up to Dr. Jenkins\' question about available
data to assess safety, do you have any information from the evaluations
that you\'ve done that would suggest that there are safety issues unique
to the U.S. population that don\'t apply to Canada or any of the other
countries where these are available over the counter that might be why
the sponsors are so reluctant to submit for OTC status?

DR. KERN: I would say not. I would say that the population we\'re
looking at, the rhinitis population, is very similar from one country to
the other. They\'re not different.

DR. MURPHY: Sort of following up on that, what about looking at your
database as comparing a U.S. population, use of other drugs? Because we
do see this in other trials where U.S. population uses other drugs where
some of the other countries don\'t. We tend to self-medicate more.

Do you have any information on adverse events where other drug use may
play a role?

DR. KERN: No, I don\'t think so, no. Do you want to comment?

DR. SEIDMAN: I was just going to comment on the contention for QT
elongation and the interaction with some of the agents that have been
seen with the earlier second generation antihistamines which are no
longer available.

No interactions have been found with the current armamentarium of second
generation antihistamines.

DR. KERN: I think as a follow-up, of interest there was an excellent
epidemiology study as a follow-up having to do with this cardiac
arrythmia, and it\'s been shown and the actual conclusion of the article
by these authors is that it raises a health concern with regard to the
first generation antihistamines that are currently available in the
United States primarily having to do with diphenhydramine, that the
incidence of these serious adverse effects are much more common with
diphenhydramine than they are with the second generation antihistamines.

DR. DeLAP: Dr. Jenkins.

DR. JENKINS: One more question. The packaging of the Canadian products
are unique in the sense that they have to have English in one side and
French on the other. So that severely limits the space that\'s available
to convey information to the patient. Did you look at the packaging and
were you satisfied that the information that was on the packaging was
adequate to allow patients to safely and effectively use these drugs,
despite the fact that only half of the packaging was in English?

DR. SEIDMAN: We did not spend a lot of time looking at the English and
French packaging from Canada. We felt that the Food and Drug
Administration would be responsible in initiating specific labeling for
these products in the United States.

And I do want everyone on the panel to know that those drugs are
prescription in the United States of America, and if you plan on taking
any of them, you do need a prescription today.

(Laughter.)

DR. LAM: Just a quick question. One of your arguments is that there\'s
not so much differential in the cost. Therefore, there should be a
consideration in terms of switching it from prescription to OTC. How do
we know that when it is approved for OTC status that the consumer would
not be paying two times, three times, or four times what they\'re paying
now?

DR. SEIDMAN: We can only use the experience that we have from previous
conversions of prescription only to over-the-counter medications. In our
review of some of the medications that have gone over the country since
1997 currently in comparison and looking at the average wholesale price
of these products per unit when they were prescription only in 1997 to
the average wholesale price per unit today when they\'re OTC, the cost
decrease was absolutely precipitous. The cost today is an absolute
fraction of what these products cost when they were prescription only.

Also, when we look at the financial modeling in Canada where these three
products are available over the counter and they compete aggressively
within the Canadian market for market share, there\'s couponing,
there\'s discounting, and the cost per member really comes out to be
between ten and \$15 per month, which is very similar to a managed care
copay today and much less than an individual who does not have insurance
today would pay for a comparable prescription.

DR. DeLAP: Dr. Jenkins.

DR. JENKINS: I promise this will be the last one. To some degree, to
play the devil\'s advocate here, one of the strengths of what we\'re
doing here is discussing what\'s available in the Canadian marketplace
with regard to these products, and I\'m wondering if you could comment
on your perspective and thoughts about the fact that you\'re using that
as part of your rationale for these products, but until very recently
Hismanol and Seldane were also available over the counter in Canada, and
we know that those two products were associated with serious and life
threatening adverse events and actually were taken off the market in the
U.S. for that reason.

DR. SEIDMAN: I have to apologize. There\'s tape down here that I think
the contestants or the presenters are being stuck to.

The issue here has to be looked at clinically. I\'m co-chair of the Well
Point Health Network\'s pharmacy and therapeutics committee. We reviewed
Seldane and Hismanol, and those products were removed from formulary as
soon as those adverse reactions were presented in the literature.

In our review of the current literature on the three commercially
available prescription nonsedating antihistamines and Dr. Kern\'s
review, we have shown clinically that there are at a maximum zero side
effects or, as the commercial states, similar to those of a sugar pill
or side effects that are far less than any of the commercially
available, over-the-counter antihistamines that are available today, and
we believe that it is in society\'s best interest that all Americans
have ready and easy access to these products.

Thank you.

DR. DeLAP: Thank you.

Our next speaker then will be Linda Borschuk, consumer advocate and past
board member of Asthma and Allergy Foundation.

MS. BORSCHUK: Thank you.

My name is Linda Borschuk. I am an advocate for families with asthma and
allergies, and I\'m a past board member of the Asthma and Allergy
Foundation of America, Maryland, Greater D.C. Chapter, having served
from 1991 through 2000.

Today I represent no organization, nor do I have any financial
association with any company whose product or issue is being considered
by the FDA panel members.

In fact, on the surface my position on this issue would seem to harm me
financially as a consumer of a significant number of prescription drugs.

I have struggled with asthma and allergic disease all my life and am the
mother of three children whose allergies and severe asthma have greatly
impacted our lives. All of my children developed asthma and allergies as
infants. Zach is now 15, Adrian is 13, and Sam is nine.

It has been through are turbulent journey toward health that I became an
advocate for other who didn\'t have access to the same resources. I have
learned first hand that no two people have the same combination or
degree of symptoms, triggers, or response to medications.

Asthma and allergies are serious. They are chronic, and they can be life
threatening. In our family, we all have asthma and allergies. My primary
triggers are dust, pollen, cockroach, mold, animals, latex, and foods.

Zach has a severe allergy to dogs, horses, and ragweed.

Adrian has reactions to tree pollen.

And Sam has as his triggers GE reflux, chronic sinusitis, and multiple
life threatening food allergies.

Viral infections trigger my asthma, and I usually need antibiotics, such
as the course I am currently taking in response to yet another
respiratory infection.

Adrian can sometimes fight off viral infections by just increasing her
meds. for a few weeks. But if Zach or Sam get a viral infection or are
exposed to one of their allergens, it almost always results in missed
school time, antibiotics, and oral steroids.

To maintain optimal control, we all take medication on a daily basis,
but none of us is on the same regimen. Zach is on a high dose of inhaled
steroids in rotor disk form, and I am on a low dose of the aerosol
version.

But Sam needs a different inhaled steroid altogether because he has a
life threatening allergy to milk, and the rotor disk version contains
lactose, a milk derivative.

Zach responds best to dry aerosol nasal spray. Adrian and I benefit most
from a once a day liquid nasal spray.

I need an anti-cholinergic inhaler twice daily. My boys only need an
anti-cholinergic when they\'re sick and using the nebulizer.

Zach, Adrian and I have recurrent sinusitis due to viral and bacterial
infections and allergic reactions. This always requires a phone call to
the doctor, an adjustment of our daily medications, and the addition of
other medications, such as antibiotics, decongestants, and oral steroids
for a few weeks.

Sam has chronic sinusitis and has been on twice daily antibiotics since
he was three weeks old, and every winter brings a change in these
medications as he develops resistance.

We have all been to the emergency room in years past due to asthma or
anaphylactic allergic reactions, but Sam has had it the hardest. From
the time he was one and a half until he was seven, he spent an average
of three and a half months of every year in the hospital, his stays
ranging from a few days to six weeks, with many of those stays beginning
in the pediatric intensive care unit.

Not one of us has been to the emergency room or been hospitalized for
asthma or allergic reaction in over three years. We\'ve avoided these
expensive hospital encounters because we are well educated about our
illnesses and well managed on our medications.

To achieve this level of management, two critical factors must be in
place. First, there must be an ongoing relationship between the patient
and the physician that allows effective two-way communication and give
and take.

I remember many times when Sam was in the midst of his worst
exacerbations calling his pulmonologist and saying, \"He doesn\'t seem
right. I don\'t feel comfortable managing him at home. I think he should
be admitted.\"

After discussion about the progression of Sam\'s symptoms, his doctor
and I agreed he should be admitted. I didn\'t have to prove anything
because there was an established level of trust. After all, our goal was
the same, a health child on the least possible medications.

Secondly, the patient must truly understand their illness so that
informed decisions about proper medical care can be made jointly by the
patient and the physician.

This was never clearer than in 1994, the last time Sam was in intensive
care. He was in respiratory failure. We were out of options for what
medications could be added, and we were looking at experimental
medications. Our outlook was pretty bleak.

The decision was made to stop all food and drink and feed him
intravenously for a period of time in the hopes that food allergy was
the trigger. Fortunately it was the right decision.

I hadn\'t been properly educated on the intricacies of food allergy
avoidance, and it was discovered that he was being triggered through
cross-contamination. I had no idea that a few molecules of milk protein
could kill my child, but that\'s what almost happened.

Proper education could have prevented this situation. I could not manage
my family\'s asthma and allergies without these key factors, working to
support and guide our medical decisions. Had these relationships not
been in place, Sam would not have lived past infancy, nor would Adrian
be able to sing in the Peabody Children\'s Chorus or Zach compete in
running cross country for his school.

Every year we meet with our allergist to evaluate the past year, discuss
new medications that have become available, alternate dosing schedules,
such as is there a medication that lasts longer so that my kids don\'t
have to take medicine at school, and revise the plan for the coming
year.

And every time there is an exacerbation of their asthma or an allergic
reaction, I talk to their doctor. We work as a team, and we reap the
benefits of a healthy and more normal life.

I believe that asthma and allergy medication should remain under
prescriptive care because they are serious drugs that help manage
chronic illnesses in conjunction with proper education and the support
and guidance of a physician, a physician who knows the patients and
their symptoms and triggers and who can educate them on avoidance
techniques and prescribe effective medications with the fewest side
effects tailored to that individual\'s needs.

In conjunction with this, I feel it important to mention the financial
burden proper asthma and allergy management places on a family. Our
pharmacy bill is extraordinarily high because we have a health plan and
pharmacy benefit which are not tailored to meet the demands of chronic
diseases such as asthma.

But most people have insurance that covers their prescription
medications, except for a small copay. If we had insurance that only
charged \$10 per prescription, we would have pharmacy bills of over
\$600 a month.

Asthma and allergies are hereditary, and it is not unusual for a family
of five to have four members with these chronic illnesses. If the
average salary is considered, it is tough to come up with an extra \$600
a month for medicine, but inconceivable for a family to pay double or
triple that amount just because the medications went over the counter
and their insurance companies stopped covering the cost.

It is almost certain that emergency room visits, hospitalizations, and
deaths from asthma and allergies would increase dramatically, costing
insurance companies more in the long run.

The Breathmobile in Los Angeles has proven that regular visits with
physicians can improve the management of the patient\'s asthma and
allergies and dramatically reduce emergency room visits and lost school
days.

Research on asthma and allergies has come a long way in just the past 15
years, but there is important work that still needs to be done.
Physicians are still not following the asthma guidelines created by the
National Institutes of Health ten years ago, and the allergy report, the
defining resource on how to treat allergic disease has just been
created.

Far too many physicians are just waking up to the fact that 50 million
Americans have allergic disease and less than half of them see a doctor;
that asthma has increased 75 percent between 1980 and 1995; and that
more than 5,000 people with asthma and allergies die unnecessarily every
year.

Now is not the time to expect the public to attempt to manage a chronic
illness that physicians are just beginning to understand.

Thank you.

DR. DeLAP: Thank you.

Questions? Dr. Jenkins.

DR. JENKINS: Thank you for those comments.

You included in your conclusions \-- you lumped allergy and asthma
medications together. I\'m wondering if we could split those out for a
moment and ask you your thought about the allergy medications that we
just talked about in the previous presentation, the nonsedating
antihistamines, and also as you know, a couple of years ago the
Chromelin nasal preparation was switched to over-the-counter status.

Do you think that that\'s a problem? Do you see the antihistamines and
the agents such as Chromelin being a problem or would you separate those
out?

MS. BORSCHUK: I like to lump them together because the majority of
people with asthma have allergies anyway. I think they are serious
diseases. You need to see a doctor, and I don\'t think that it\'s right
to make them over the counter just because so many people have
allergies. Let\'s just give them the medication; there\'s so many
people, instead of fixing the health care system itself.

DR. DeLAP: Well, if there are no other questions, thank you very much.

MS. BORSCHUK: Thank you.

DR. DeLAP: We will have a speaker for the Allergy and Asthma Network,
but that will be in a few minutes from now. So we\'ll proceed in the
meantime to the next speaker on the schedule, Dr. Stephen Hellebusch,
representing Q2 Marketing Research on label comprehension issues.

DR. HELLEBUSCH: Thank you for the opportunity to speak.

By way of introduction, I am Dr. Steve Hellebusch, president of Q2
Marketing Research, Inc. I have a Ph.D. in experimental psychology and
20-plus years of experience in consumer research. I\'m not being
compensated to be here.

I\'m here because I\'m very interested in the topic of Rx OTC switch and
in the use of consumer behavioral research to help answer some of the
questions surrounding switches. I\'ve conducted label comprehension
studies since 1989, and I\'ve seen the procedure evolve.

I was somewhat surprised by the tonality of the questions that the FDA
asked concerning consumer understanding, and they struck me as
challenging the usefulness of consumer research. I would like to provide
some assurances.

I would like to make three points concerning label comprehension testing
specifically. It is a valid method of psychological testing. Many of us
would not be here if psychological testing in the form of GREs or some
other standardized test had not assured an educational institution of
our comprehension level.

Label comprehension testing is iterative. Typically more than one study
is conducted to make certain the label is the best it can be. Label
comprehension testing and, indeed, consumer research is a useful tool
for making switch decisions based on data. Sound scientific decisions
are driven by fact.

Validity in psychological testing is defined as the degree to which the
test actually measures what it purports to measure. There are three
specific categories of validity.

Content validity refers to the nature of the subject. In the case of
label comprehension testing, it is the communication objectives for the
label.

Construct validity refers to comprehension, the psychological construct
being measured. I, however, prefer to think of this as making certain
the test is constructed in an unbiased fashion to achieve this
measurement.

Criterion related validity determines whether the test measurement is
related to an independent measure of whatever the test is designed to
measure. In label comprehension testing, it is very useful to have a
control or comparator to be able to relate the results to the real world
somehow.

An example is a label comprehension test designed with the objective of
determining whether users of a certain prescription drug understood that
they were not to use the switch product without consulting a doctor.

Content validity is demonstrated by the fact that a clear communication
objective was established for the study.

Construct validity was demonstrated in this case by asking unbiased,
open ended questions to determine target consumers\' comprehension of
this point.

Criterion related validity is established by testing the same warning as
found on an existing OTC product. The results of this test showed that
the target population had a high intent to heed the warning that was
tested in both the switch candidates\' labeling and in the existing
products labeling. There was no difference between the two. It was known
that the existing product did not have difficulties with the issue,
giving confidence that the switch candidate would not experience
difficulties.

This switch candidate is now an approved OTC product and has experienced
no problems. The consumer label comprehension study provided valuable
data for this OTC decision.

Label development is an iterative process. I was involved in the
Nicorette and Nicoderm switches. They\'ve come back again, as well as
the approval of Rogaine 5%, better known as Rogaine Extra Strength for
Men.

For the smoking cessation products, we conducted eight different label
comprehension tests. For Rogaine Extra Strength for Men, we conducted
five. As we learned more, we tried other ways to communicate to find the
best way.

This process has evolved and improved over time. For example, today if a
manufacturer approaches us with a label developed internally, we
recommend beginning with qualitative research to identify and fix any
glaring misunderstandings before any large sample label comprehension
testing occurs.

The iterative process of OTC label development is a key aspect and makes
these studies useful in switch decisions.

It is a very useful tool, but don\'t expect a perfect score. In my small
example here \-- excuse me. Label comprehensive testing has shown itself
to be a useful and valid tool in all three cases that I\'ve referred to,
helping the manufacturer and FDA to make sound decisions based on data.

But expectations need to be set appropriately. There will always be a
small percentage of consumers who are either so uninvolved with the
research that they\'re inattentive or that they\'re not taking it
seriously.

In my little example here, six percent changed their age. My
interpretation is that the four percent who stayed within a year were
just a little confused. The two percent that changed their age by more
than a year are an indicator of the percentage who are not taking the
testing seriously.

This type of data fit well with the points Dr. Solar made yesterday that
the switch candidates need not have an expectation of 100 percent and
the target population having 100 percent benefit. The judgment has to be
made in some relevant terms.

In summation, label comprehension testing is a form of psychological
testing that\'s a valid scientific tool. It\'s evolved into an iterative
procedure that improves labeling and development, and it\'s become
essential to the switch process.

As I mentioned, I\'m a researcher. I am not a regulatory affairs
professional. I always thought that everyone involved in switches was
trying to do the best thing for the public health, and I wonder why
wouldn\'t all involved welcome any discipline that would provide another
means of learning about the public.

Label comprehension testing and consumer research in general has been
and can be very useful in making sound judgments.

Thank you.

DR. DeLAP: Thank you.

I don\'t think I\'d want to leave the impression that we don\'t value
label comprehension studies. We do. I think our concern is that the
information that is to be conveyed is getting to be increasingly complex
with some of these newer proposed switches, and we need to make sure
that we\'re getting the information that we need.

Dr. Woodcock.

DR. WOODCOCK: Well, I think that\'s what label comprehension studies are
designed to find out, whether or not information such as incomplete
treatment of sexually transmitted \-- prevention of sexually transmitted
diseases, for example, is a concept that can be grasped by a consumer.

DR. HELLEBUSCH: Very much.

DR. WOODCOCK: My question for you is how much data are there that the
information that is gained from label comprehension studies \-- what
correlation is there with actual behavioral changes in consumers and how
much is known about that?

DR. HELLEBUSCH: Not a lot that I\'m familiar with, to be honest with
you. My best indicator there is my use of some sort of comparator, some
way to relate it back to the real world, and it is reasoning by analogy,
saying if it worked in this instance, certainly it ought to work in this
instance.

DR. WOODCOCK: From the field of behavioral science though there must be
more general understanding of this. Of course, just because people
understand instructions doesn\'t mean they follow them.

DR. HELLEBUSCH: Well, that\'s certainly correct.

DR. WOODCOCK: But it\'s so specific that you\'re unable to really
extrapolate into the OTC world?

DR. HELLEBUSCH: I am unable, yes.

DR. DeLAP: Dr. Cantilena.

DR. CANTILENA: I guess just sort of in follow up to that, you know, what
do you think would be an approximation of sort of the drop-off in the
study setting where you have the results of a label comprehension study
with a relatively, you know, for example, high level of comprehension,
and then you do an actual use study? You know, what in your experience
is sort of an approximation of the drop-off, if you will, from the
comprehension study into the actual use, they follow the directions?

DR. HELLEBUSCH: I haven\'t been involved in enough where I was able to
follow that all the way through to be honest. The example I\'m most
familiar with is Nicorette and Nicoderm where that actual issue was
explored as to what were the reasons for the drop-off, and of course,
you can always come back and do research to address the issue. Again,
consumer research may be the only thing necessary in that case, but it
can be addressed.

DR. DeLAP: Dr. Kweder.

DR. KWEDER: Do you have any experience in your company with doing
labeling comprehension studies using languages on populations other than
English speaking?

DR. HELLEBUSCH: No, we have not.

DR. DeLAP: Very well. Thank you.

DR. HELLEBUSCH: Thank you.

DR. DeLAP: And we\'ll proceed then to Susan Shellabarger, Hill Top
Research.

MS. SHELLABARGER: Good afternoon. I\'m Susan Shellabarger, and I\'m the
Senior Director of Business Development for OTC products for Hill Top
Research.

I\'m very pleased that the FDA is holding this important meeting today
on OTC drug products, and I want to thank them for allowing me time to
share my comments on the validity of consumer behavioral research.

I\'m representing myself, and I\'m not receiving any financial
compensation for being here today.

As most everybody in this room will agree, the past few years of Rx to
OTC switching have been quite a learning process not only for our
sponsor companies, but also for the FDA.

We\'ve learned that study design and analytical methods can be developed
to meet specific needs and answer specific questions.

We\'ve also learned that with each new Rx to OTC switch effort new ideas
emerge, especially as they relate to testing consumer understanding and
behavior regarding OTC products.

I believe one of the most important learnings is that company sponsors
and FDA have to have open, interactive discussions and mutually agree
upon the research required and the general study designs, and these
discussions should be specific to each and every switch consideration.

As part of the dialogue between companies, sponsor, and FDA, there
should be consideration given to existing knowledge about the parent Rx
product, such as adverse events, drug interactions, and product use
issues, as well as to issues identified regarding the proposed OTC use
of the product, such as product labeling, misuse, and abuse.

Over the past few years, many company sponsors have used studies that
have become unique to the Rx to OTC switch process. These studies fall
into two categories: label comprehension studies and actual use studies
or sometimes called \"all comer\" or naturalistic studies.

Label comprehension studies have proven to be useful tools for
evaluating the general consumer\'s ability to read and understand a
product label, as well as gaining insight to the consumer\'s behavioral
intent regarding use of a new product.

Actual use studies strive to reach the next level of a consumer\'s
actual behavior regarding their purchase and use of the product without
any additional influence from a health care professional.

Many clinical scientists tend to categorize these studies as just market
research or just consumer research, and therefore assume that they are
not scientifically valid. I believe just the opposite is true.

These studies are very scientific in their design, in their
implementation, and in their management and analysis of the data.
Consequently, they have become an essential basis for switches today.

In fact, the \"all comers\" approach to subject recruiting and
enrollment provides a very representative sample of the user population
in these studies, much more so than what is routinely practiced in your
Phase III or Phase II Rx trial, where there are extensive
inclusion/exclusion criteria which can bias the study population.

I think we all agree that Rx to OTC switches are and should continue to
be a very important strategic direction for both manufacturers of health
care products, as well as for general public health. Decisions have been
made in the last to the detriment of this strategy based upon subjective
ideas or hypotheses and without regard to existing data. This shouldn\'t
happen.

Most all ideas, concerns, and hypotheses can be tested. Usable, reliable
data can be obtained through well designed and well implemented studies
that are scientifically valid. Any component of a product label can be
tested for comprehensive, and most consumer behaviors can be tested
through label comprehension and actual use studies.

I\'d like to share an example of a label decision based upon subjective
information. The very first H2 blockers introduced into the OTC
marketplace had efficacy data in their package insert provided in the
form of bar graphs. While most of us in this room have had the education
necessary to interpret bar graph information, my supposition was that
this would not be the case for the general population.

As a result, we designed a study to investigate consumer comprehension
of such H2 blocker heartburn efficacy data under four different
experimental label conditions, and copies of this paper, which was
published in the [DIA Journal]{.underline} in \'97 have been included in
my presentation packet.

We had 440 people from the general population look at four different
labels. The first was a control label that contained no efficacy
information at all. The second label provided efficacy data in text
format. The third label used a bar graph format, and the fourth label
used a bar graph format that was enhanced with text data.

The results of this simple study may not be very surprising, but they
illustrate the need to be wary of subjective bias when defining elements
of OTC labeling. We found that, in fact, consumers cannot accurately
estimate product efficacy if no data is presented. More than 80 percent
were incorrect in their estimates.

On the other hand, a majority of people, over 60 percent, when given
efficacy data can comprehend the effectiveness of that drug.

In presenting efficacy data, even minor differences in format can affect
comprehension as seen between the graph and the graph-plus, which is the
graph enhanced with text.

In this particular study, text presentation of efficacy data had an
advantage over graphical presentation, and although not shown on this
particular graph, we determined that only 46 percent of the subjects had
an accurate understanding of the concept of placebo. If that is going to
be one of your efficacy endpoints, measurement of your active versus
placebo, this doesn\'t bode well for trying to understand efficacy
information on the part of the consumer.

I\'d like to conclude my remarks by restating three points this
afternoon. Rx to OTC switches are strategically important not only for
the manufacturers, but also for the general public\'s health. The Rx to
OTC switch research process has been validated, but still should be
considered on a case-by-case basis.

Label comprehension and actual use studies, when well designed and
implemented, are scientifically valid and have proven to be useful tools
in the evaluation of the Rx to OTC switch process.

OTC product labeling much of the time acts as the learned intermediary
for consumers. We\'ve heard this time and time and time over the last
day and a half.

Therefore, decisions about product labeling should be driven by data
obtained through well designed and implemented studies and not through
untested, subjective views.

Thank you very much for allowing me time on today\'s docket to present
my views.

DR. DeLAP: Thank you.

Comments? Questions? Dr. Cantilena.

DR. CANTILENA: Yeah, I guess I sort of run the risk of being somewhat
defensive since I may have been involved in the bad example that you
cited here.

(Laughter.)

DR. CANTILENA: So I\'ll try not to sound defensive, although Dr. Juhl
certainly had a larger role than I did.

(Laughter.)

MS. SHELLABARGER: That\'s why I wanted to go first.

DR. CANTILENA: But, I guess, you know, just to follow up on that, have
you done any further, you know, work to look at what sorts of, you know,
displays for efficacy are the most helpful, other than, you know, what
you just, you know, went over?

I mean, you know, this is an issue that comes up and sort of, you know,
the motive for a lot of us is to, you know, fully inform the consumer,
including the possibility of, you know, comparative efficacy and those
kinds of things.

So have you looked at, you know, other sorts of, you know, displays or
other sorts of formats for information, you know, thus far?

MS. SHELLABARGER: I personally have not. There may be others who have,
but I have not.

DR. DeLAP: Dr. Kweder.

DR. KWEDER: Similarly, have you done any work that\'s looked at formats
for providing safety information?

MS. SHELLABARGER: No.

DR. KWEDER: And as a follow-up, to ask you the same question I asked the
previous speaker, do you have any experience in doing these types of
studies in non-English speaking populations?

MS. SHELLABARGER: No. Most all of them that I\'m aware of are done in
English.

DR. KWEDER: Why do you think that is?

MS. SHELLABARGER: It\'s the primary language in the United States.

DR. DeLAP: Well, if there are no other questions, we\'ll continue. Thank
you very much.

At this point I believe we have a representative now from the Allergy
and Asthma Network, Mothers of Asthmatics, Marissa Magnette.

MS. MAGNETTE: Good afternoon. My name is Marissa Magnette, and I\'m
speaking on behalf of Nancy Sander, President of the nonprofit, patient
education organization Allergy and Asthma Network, Mothers of
Asthmatics, Incorporated, based in Fairfax, Virginia.

I am here on behalf of our membership, families affected by allergies
and asthma. AANMA opposed OTC status of asthma medications for the
following reasons.

Fifteen people die of asthma every day. Asthma is a serious, potentially
life threatening condition that requires careful individualized
treatment and monitoring by skilled primary and specialty care
physicians. While the incidence of asthma is projected to double by the
year 2020, there is no explanation nor plan for halting it.

In 1996, when FDA was considering OTC status for albuterol and Chromalin
sodium, AANMA posed that question to our members: is this a good thing?
An overwhelming majority said no. They valued the importance of
physician monitoring and strategic planning to reduce or eliminate
suffering. They said OTC status would eliminate prescription copay, and
their solution: change their medication to a different prescription.

Their fears were not unfounded. For example, in 1996, OTC Primatine Mist
cost more than twice the most expensive, long acting, prescription
bronchodilator on the market, Seravin, and one puff of Primatine Mist
lasted 20 minutes as compared to two puffs of Seravin lasting 12 hours.

By the way, our members asked FDA to remove Primatine Mist from the OTC
market.

Asthma, whether mild, moderate, or severe, has the potential to drown
its victims in their own mucous and inflammatory cells. Therefore,
before asthma is not an OTC disease, please restrict treatment options
to those prescribed by our physicians.

In the case of allergies, however, we do have considerable patient
experience with existing OTC antihistamines, nasal sprays, and eyedrops.
Today\'s OTC antihistamines are predictable, but they can cause
drowsiness, as can other cough and cold preparations sold OTC.

Though it may seem on the surface that placing nonsedating prescription
antihistamines on the OTC market is a rather seamless idea, AANMA sees
conflicts and concerns. An estimated 85 percent of patients with asthma
also have allergies. Allergies range in severity from mild to moderate
and severe. When children suffer with allergic rhinitis and sinusitis,
allergic conjunctivitis and associated chronic cough, they don\'t have
the choice of seeing a physician or selecting their own treatment from
the broad range of available OTC products. Most OTC purchase decisions
are made reading the back of the box or asking a store clerk for advice.

The child becomes the at home experiment as parents leave the stores
arms laden with anyone\'s guess of what will work.

Poorly managed allergies in childhood are a precursor to developing
asthma. Chronic allergic rhinitis and sinusitis, for example, can leave
to malformed teeth and facial bones. Chronic ear infection, secondary to
allergies, can cause temporary hearing loss resulting in learning
difficulties later in a child\'s life.

Many third world countries sell all medications directly over the
counter to anyone who can pay for them. However, convenience and
accessibility has never eliminated or reduced morbidity or mortality of
allergic diseases. Availability of a medication never insures it will be
used correctly or for the proper length of time.

We process nearly 100 inquiries a day from patients and families. In 15
years, not one has requested OTC status for asthma or allergy
medications.

In the State of Oregon, allergy patients must now pay for amino therapy,
a treatment that must be administered in the physician\'s office up to
eight times a month. At ten to \$15 each, the patient increasingly bears
the burden of trying to breathe.

OTC status of these medications will not make their lives easier. The
patient and physician relationship is the most cost effective and
efficient means of delivering medical treatment in our country. Please
do not dilute the importance of physician interaction in our asthma and
allergy care by reducing these diseases to OTC status. Please do not
increase our out-of-pocket health care costs to manage our very costly
disease by approving OTC status for allergy and asthma medications.

Thank you.

DR. DeLAP: Thank you.

Questions?

(No response.)

DR. DeLAP: It appears you\'ve made a clear case and there are no
questions. Thank you very much.

Well, we\'ll move on then to Session 9, process issues, and the first
speaker for this session is Dr. Allan Korn, Senior Vice President, Blue
Cross/Blue Shield Association.

DR. KORN: Good afternoon. I am Dr. Allan Korn, Senior Vice President and
the Chief Medical Officer of Blue Cross and Blue Shield Association.

We represent the 47 independent Blue Cross and Blue Shield plans in the
United States that provide health care coverage today to over 74 million
Americans.

Blue Cross and Blue Shield plans do have extensive experience in
providing prescription drug coverage through the variety of our
products.

Thank you very much for the opportunity to appear before the Food and
Drug Administration at today\'s hearing and to share our views with you
with respect to over-the-counter drug products.

Although the [Federal Register]{.underline} notice announcing today\'s
hearing lists several areas that the FDA will examine as it reviews its
approach to regulating over-the-counter drug products, I will focus my
remarks on the process for the designation of drugs as over the counter.

Specifically, I would like to address the following two questions posed
in the [Federal Register]{.underline} notice for today\'s meeting.
First, under what circumstances should the Food and Drug Administration
actively propose over-the-counter marketing for a drug in the absence of
support from the drug\'s sponsor?

And, secondly, should the Food and Drug Administration be more active in
initiating switches of prescription products to over-the-counter status?

As I\'ll soon explain, we recommend that the FDA adopt the fundamental
policy that a drug should be designated as prescription only where it is
not safe and effective for the drug to be designated over the counter.

Since 1951, the Durham-Humphrey amendment to the Federal Food, Drug, and
Cosmetic Act has required that all drugs safe enough to be sold over the
counter be designated as such. The law states that drugs that should
require a prescription only if \"toxicity or other potentially harmful
effect\" make it necessary for a licensed practitioner to supervise the
patient.

Despite the fairly broad statutory criteria for designating a drug as an
over-the-counter product, the conditions under which a drug has been
switched have been, as we know, fairly limited. My written statement
includes a more detailed overview of the current processes governing the
OTC designation, but I won\'t waste your time this afternoon presenting
them to you orally.

Let me jump to my recommendations. First, Blue Cross/Blue Shield
Association recommends that the Food and Drug Administration adopt a
fundamental policy that a drug should be designated as prescription only
where it is not safe and effective for the drug to be designated as over
the counter.

In order to achieve this objective, we recommend that the FDA engage in
a deliberate process, a structured process for switching drugs from
prescription to over-the-counter status where such designation is safe
and effective for the consumer.

One suggestion for approaching this process would be to being by
reviewing drugs that are over the counter or in a comparable third class
of drugs in other industrialized nations with meaningful requirements
for the safety and efficacy and effectiveness of such drugs.

The Food and Drug Administration should begin its review with drugs for
which a drug manufacturer has made representations to other governments,
the European Community, Canada, Australia, and elsewhere, that a drug is
safe and effective for over-the-counter use in that market.

This sort of comprehensive review has a precedent in the
over-the-counter drug review process. However, this review should not be
a one time effort, but we believe an ongoing and continuous activity
within the Food and Drug Administration.

Another basis for review should be individually initiated petitions that
are supported by credible information meeting switch criteria. Many
parties, other than manufacturers, have an interest in the switch
process. These parties should be allowed to participate in the FDA\'s
scientific and clinical evaluation of drugs potentially eligible for a
switch.

We do not believe that the designation of a drug should be purely an
economic decision made by the manufacturer of the drug perhaps for its
own self-interest. A proactive review process, such as discussed, will
go a long way to assuring that clinical criteria are paramount in
determining whether a drug is appropriately classified.

Such a process undoubtedly would require additional resources. We do
believe that such resources would serve the public very well.

Consumers benefit when drugs are appropriately switched to
over-the-counter status. Consumers are knowledgeable about their health
care and the value of access to over-the-counter products.
Self-treatment offers consumers convenience. A physician\'s visit is
often not necessary just to obtain a prescription.

There is also evidence that when a drug moves from prescription to
over-the-counter status, prices quickly move into line with what
consumers can afford.

A competitive market drives down costs. For example, we all know that a
75 milligram tablet may have a cost of 28 cents when purchased in a
Target store in Minneapolis in February of this year, while the average
wholesale price for the prescription, 150 milligram strength, was
\$1.77, corrected for dose, a 300 percent difference.

Whether or not designation results in coverage by a third party payer
should not be a consideration for the Food and Drug Administration. The
designation of whether a drug is prescription versus over the counter
has important consequences for the portion of the health care insurance
dollar that will be available for breakthrough therapies and life saving
prescription drugs yet to be introduced that do require the supervision
of a health care professional.

A more proactive approach for the designation of drugs as over the
counter will result in a wiser use of these ever scarcer health care
insurance premium dollars.

A recent study sponsored by the Prescription Health Value Coalition, a
broad based coalition of consumer groups, unions, health plans,
employers, clinicians, and advocates, of which, by the way, Blue
Cross/Blue Shield Association is a member, and conducted by Brandeis
University shows that prescription drug costs for a continually insured
population of individuals grew at an annual rate, age adjusted, of 24.8
percent each year from 1996 through 1999.

Another study sponsored by the association and conducted by the
University of Maryland shows that the drug pipeline is full and that
new, high cost drugs will make up to 40 percent of drug costs in the
near future. To the extent that they are breakthrough and life saving
drugs, insurance coverage should be available if physician supervision
is required.

These studies raise the question of whether because of rapidly
increasing prescription drug costs employers can afford to keep offering
the coverage. There is also the question of whether employees will be
able to afford their share of premiums, copayments, and deductibles.

When health plans\' costs increase, employers ever more now are tending
to shift cost increases to their employees, and the rapid increase in
prescription drug costs are likely to make drugs a focus of ever
increasing cost sharing.

Revision of the over-the-counter designation process so that only drugs
that truly need physician supervision are designated as prescription
drugs and thus covered by health plans is critical to assuring that
coverage is and will be available and affordable for all of us and for
all of the employees who sponsor health plans.

In conclusion, the Blue Cross and Blue Shield Association recommends
that the FDA adopt a fundamental policy that a drug should be designated
as prescription only when it is not safe and effective for the drug to
be designated as over the counter.

In order to achieve this objective, Blue Cross/Blue Shield Association
recommends that the Food and Drug Administration engage in a deliberate
and ongoing process for switching drugs from prescription to
over-the-counter status where such designation is safe and effective for
the consumer.

This policy would be best carried out through a two part approach.
First, the adoption of a policy of proactive and continuing review of
prescription drugs to identify those that are appropriate based on
clinical and safety evaluations for over-the-counter designation.

And, second, consideration of switch petitions from parties other than
manufacturers.

Blue Cross/Blue Shield Association believes that the approach
recommended herein will empower consumers to safely self-treat with
over-the-counter drugs at affordable prices, and we further applaud the
Food and Drug Administration for addressing this critical health care
issue, and we support you in this endeavor.

Thank you very much.

DR. DeLAP: Thank you.

Questions? Comments? Dr. Kweder.

DR. KWEDER: I want to just go back to your main point about considering
drugs for OTC unless they have a specific reason they need to be Rx. Are
you suggesting that while drugs are in the development process we
exploring that with sponsors, pharmaceutical sponsors?

DR. KORN: Yes.

DR. DeLAP: Dave Fox.

MR. FOX: I take it you believe that the agency should follow your
recommendation of designating a product or allowing a product to be
marketed OTC unless otherwise required, even if the sponsor of the drug
is in disagreement with that position.

DR. KORN: Yes.

MR. FOX: And yesterday we heard testimony that it\'s in the public
interest for the sponsor of a drug to initiate the switch, and that the
sponsor and only the sponsor is in the best position to decide whether a
switch should be initiated.

What\'s your view of that testimony?

DR. KORN: My view is that only the Food and Drug Administration is in
the position of making that decision. When a sponsor implies that only
they are in a position to make that decision, it suggests to me as a
physician that they know something about safety and/or efficacy that
they have failed to share with you. If that is the case, we have a far
different issue on the table than legend to over-the-counter status.

The Food and Drug Administration has done an outstanding job over the
years with few exceptions of protecting the American public from the
dangers of chemicals and the benefits of drugs, and knowing the
difference, I think, is what the FDA is about.

Manufacturers are granted, I think, extensive protections to nurture the
development that we all hope and pray for in terms of new drugs and
breakthrough therapies, but there comes a time when we reach a plateau
of safety and efficacy that we need to look at whether or not we need to
move on, and that is a decision that I firmly believe as a Blue Cross
and Blue Shield Association, a decision that rests in the hands of the
Food and Drug Administration.

DR. DeLAP: Dr. Temple.

DR. TEMPLE: Yesterday in talking about similar things Dr. Wolfe
suggested that at least ten years was needed before one could be
reasonably assured that a drug didn\'t have unexpected, nasty things. I
don\'t think we\'ve necessarily thought that ten years is necessary, but
there certainly is a belief that at least for systemically absorbed and
administered drugs, some period of time is needed; a period of time as
marketed under a prescription legend is needed.

We\'re all moderately conscious of the fact that we were all thinking of
terfenadine as a likely over-the-counter drug that we thought maybe
needed three years before it was ripe. So it declared its unripeness at
about three years.

Were you implying that that\'s an unnecessary concern or do you think
that part of determining whether something is ripe for over-the-counter
use safe enough might in many cases at least require a certain period of
marketing experience?

DR. KORN: I\'m sorry I can\'t see you.

It\'s certainly a fair question, and the answer is, you know, we\'ve
never really tested that. There\'s really only today an on and an off
switch. It\'s sort of a binomial process, and I would say that along the
way if we\'re truly to work together, I mean, those who give us the
money that we use to pay the bills, our premium payers, et cetera, those
of us who actually consume the products and derive benefit, and then
those of you who regulate the market perhaps should revisit that.

You know, is there a continuum that we need to consider here in terms of
drugs when they\'re designed for self-diagnosed illnesses when they
appear relatively safe during the development process? Should there be a
two or a three or a five-year interim process that does not now exist?

We would commit to exploring that with you, to using whatever data
resources we might have, and to helping develop the kind of a policy
that would help make the broadest array of products affordable and
available to the largest number of American citizens that we possibly
could.

DR. TEMPLE: Development typically would expose somewhere between 1,500
to several thousand patients, not that that couldn\'t change if one
wanted to, and it\'s fairly common for important changes in labeling to
occur. I think our current estimate was something like 30 percent.
That\'s down from previously because we\'re all so much better at this
than we used to be, but that\'s still a lot.

Does that factor into your view on this?

DR. KORN: Sure, and that\'s why I\'m suggesting that there ought to be
some continuum here that you might, in your wisdom, perhaps construct
that would enable us to deal with those issues in a way that\'s
respectful of what we want our pharmaceutical industry to continue to
do, but equally respectful of the resources that we devote to
pharmaceuticals so that we are certain to have what we need for those
truly breakthrough therapies that do require intense physician
supervision.

DR. DeLAP: Well, thank you very much.

And we\'ll proceed to Dr. Juhl.

I just wanted to mention one other thing. We had a few requests to speak
at the open session at the end, but only a few. So I think what our plan
is going to be, we\'ll continue directly into that after Dr. Juhl\'s
comments rather than taking a break just so we can finish expeditiously.

So I\'ll turn it over then to Dr. Juhl from the University of
Pittsburgh.

DR. JUHL: Thank you.

I appreciate the opportunity to speak to you, and I also appreciate your
endurance.

(Laughter.)

DR. JUHL: There are hardly any heads down on the table. That\'s a good
sign.

Afternoon. I\'m Randy Juhl, Dean of the School of Pharmacy at the
University of Pittsburgh, and I also serve as the Associate Vice
Chancellor for Research Conduct and Compliance.

I\'m here today courtesy of the Consumer Health Care Products
Association, who paid for my air fare. In the interest of full
disclosure, I serve as a consultant for a variety of consumer products
manufacturers about their OTC drug products.

On the other side of the fence, I served as the chair of the
Nonprescription Drug Advisory Committee from its inception in 1992 to
the completion of my term in \'96, and I\'m currently chair of the
FDA\'s Advisory Committee on Pharmacy Compounding.

I\'d like to address three topics today in my brief time: first, the
role of the FDA in self-care; second, a little bit about the tasks of
the advisory committee; and, third, some issues that have arisen during
the past day or so that I wished I would have had the opportunity to
comment on.

First of all, it\'s evident to all that self-care is a major trend that
will only increase in coming years. There are several factors that are
catalyzing the popularity of self-care or wellness or fitness or
whatever euphemism you prefer. I\'ll discuss two of those factors.

First of all, because of a change in our societal values and an enhanced
access to information, consumers desire and in some cases demand to take
a more active role in their health and wellness. This can be observed
simply by viewing the marketplace.

Health spas, rowing machines, sports medicine, heart health diets,
exercise videos, Diet Coke, reduced fat food, meditation, dietary
supplement purveyors of all types, the Thigh Master, functional foods,
therapeutic magnets, skim milk, Lean Cuisine, running shoes, relaxation
therapy, fat burners, Yoga, mall walkers, bike paths, climbing walls,
Geng Shui, Fun Run, Stairmaster, personal trainers, and stress
management, and the list goes on. These are terms you didn\'t hear about
20 years ago.

Now, these products and activities have efficacy ranging from none to
questionable to pretty good when used appropriately. And it should be
noted that even though we all continue to be fat, sleep deprived, have
high cholesterol levels, and on the verge of road rage \--

(Laughter.)

DR. JUHL: \-- we continue to make the sellers of these products and
services very rich. I see no end to our search for variations on the
Fountain of Youth theme.

In addition, secondly, the consumers, in addition to their preference
for self-determination, they or we \-- I guess we all are involved or
are being dragged sometimes kicking and screaming into self-reliance by
our health care financing system. We have become so technologically
proficient that we cannot afford to provide everything that we can do to
everybody, and that has recently come to include meaningful visits with
our physicians.

The health care system really only has time for sick people. If you\'re
trying to prevent yourself from becoming sick, you\'re pretty much on
your own.

Now, although this is a different view of the world than I and most of
you grew up with, it\'s not all that bad. As I mentioned before, many
consumers have both the desire and the sophistication to care for
themselves at a higher level.

Now, what does all of this have to do with the FDA, and specifically
nonprescription drugs? Well, if you\'re expecting a plea to start
switching drugs as fast as you possibly can, I will disappoint you.
Rather, I\'d like to take the perspective that was hinted at by your
questions to consider a different role, a broader role for the FDA and
self care.

Now, the medical community, and I include myself in this, is commonly
viewed as being out of touch with the public when it comes to self-care.
In fact, we sometimes deride and ridicule products and services whether
they are dietary, herbal, spiritual or the like, and even I can\'t let
the opportunity to pass to say that there is much to deride in the
marketplace.

Now, in addition, patients have access to a flood of information about
health, and we sometimes resent it because the information that their
sources provide is not of the same quality that we can provide, if we
had the time.

But rather than serving as a partner and discussing and choosing
strategies that are likely to be more helpful for consumers, we are seen
by the public as being decidedly unhelpful in this venue. A recent
study, for example, showed that patients frequently withhold information
from their physician about consumption of dietary supplements and other
alternative medicine.

Now, the FDA, although further ahead than the majority of the medical
community, could do more to assist the public in making good decisions
regarding self-care, specifically in the area of nonprescription drugs,
and I will emphasize for the record that OTC drugs constitute the most
evidence based modality available to consumers in the self-care arena.

I believe the agency should take a more active role in self-care. You
might consider adding a line to your mission statement from those
well-known pharmacologists Simon and Garfunkle. \"We\'d like to know a
little bit about you\" for our files.

(Laughter.)

DR. JUHL: \"We\'d like to help you learn to help yourself.\"

I think the essence that comes through in that is what I would like to
see happen. I\'d like to encourage you to continue to actively consider
self-care solutions for consumers, especially in new categories, and by
the way, you\'re doing that today, and I\'m deeply appreciative of that.

I think individual companies are more than capable of assembling Rx to
OTC switch development programs for specific drug products. However,
there really isn\'t a good methodology for establishing new categories,
and we we\'ve struggled with that.

Now, in the distant past, the agency held advisory committee hearings on
new categories prior to consideration of an NDA: asthma drugs, nicotine
replacement products, recurrent genital herpes, daily requirements for
analgesic products were some of those topics.

This approach has not been used as commonly in the past few years and
might be a better mechanism to openly discuss the barriers to providing
consumers additional self-care options, whether the new options
encounter some of the things we\'ve heard in the past two days in
continence, BPH, emergency contraception, and others.

And what I\'d like to see is the agency using a lot of your creativity,
which I know you folks have, in proactively helping self-care to become
a more viable option for consumers.

I alluded to the advisory committee and would like to address some
comments to members of the advisory committee that are remaining. I
thoroughly enjoyed my time on the Nonprescription Drug Advisory
Committee.

However, it also caused me great intestinal distress. Everyone on the
committee then, as now, struggled conscientiously with questions that we
were asked to consider. The issues were not easy. \"If they were easy,
we wouldn\'t need you,\" the office director told us on several
occasions.

My experience in this regard is not different from what you currently
experience. However, most of you have never had the experience of seeing
a drug product that you reviewed actually appear on pharmacy shelves.

During the years of 1995 to \'97, there was a flourish of Rx to OTC
switches. I\'ve included a list of those switch products in your
handout, and as you can see, the agency and NDAC was very busy during
those years, meeting sometimes four and five times a year.

There were several new categories established in that time period, and
for each of those new categories, and in fact, all throughout the
history of switch, predictions of doom were not in short supply. Renal
failure and GI bleeds would be rampant from OTC nonsteroidals.
Nonprescription H2 receptor antagonists would lead to mass GI cancers,
not to mention all of the drug interactions. Consumers would be using
Rogaine in all kinds of inappropriate ways, which would delay treatment
for various scalp cancers. Dogs would die, and kids would be hooked on
OTC nicotine replacement products and other potential horror stories.

I\'m not suggesting that these sky is falling prophecies were trivial.
They were very helpful in the discussion, but in the end, the data and
the common sense didn\'t support the predicted worst case scenarios.

And time has shown that the public has acted responsibly in using these
products similar to the ways that would have been predicted from the
actual use studies that were presented during those time periods some
five, six, seven years ago.

I should also note for the purpose of balance our committee also
recommended that several products not become OTC for various reasons.

Now, for the past several years, I\'ve been able to walk into any
pharmacy in the country and see nicotine replacement products on the
shelves, and even though I wish we knew how to use them better, and I
think there\'s more we have to learn, I know that there are several
hundred thousand smokers every year that attempt to quit to smoke or
attempt to quit, and many are successful.

In fact, the number of quit attempts aided by OTC nicotine replacement
products has increased fourfold in comparison to when the products were
on prescription, and I have to tell you as corny as it sounds, it gives
me a great sense of satisfaction to see that, knowing that our committee
had a role to play in that process.

And of course, I\'m also grateful that the dogs aren\'t dying from
eating the used patches and the teenagers aren\'t becoming addicted by
the thousands, although I wouldn\'t mind my neighbor\'s dog getting a
hold of some of those.

(Laughter.)

DR. JUHL: Now, in the coming months you\'re going to have the
opportunity to hear some interesting proposals regarding Rx to OTC
switches, and there is always a churning of extraneous issues that occur
beneath the surface. There\'s the economic issues that the sponsor has.
Physician specialist self-interest rears its ugly head. There can
sometimes be longstanding disagreements between experts who become
personally antagonistic with each other, and special interest groups,
such as those that you\'ve heard today.

However, I think that adhering to the agency\'s principle of a
case-by-case data driven consideration of the proposal, including the
label comprehension and actual use studies, seems to work quite well in
my opinion, and as I said, the experience that I had on the committee
was very rewarding, and I do have to say I miss it.

I\'d like to in the remaining seven seconds that I have comment on a
couple of the issues that come up frequently to date. The first one has
to do with the third or alternative class of drugs. Being a pharmacist
and a Dean of Pharmacy, I have some views on that and would like to take
a second to do that.

I\'ve often posed the question to the agency whether you need to
regulate from the real or the ideal, and I face the same issue now. From
the ideal, yeah, everybody ought to talk to a pharmacist before they
take anything because we know we can do a better job in educating
consumers to make right choices and to purchase and to take the drug and
make right choices about how they monitor their therapy as well.

However, when we get to the realities of things, our profession has not
generated a public health case to say that a third or alternative class
of drugs would be good, and I think this has to be a case-by-case data
driven decision, too, and we haven\'t come up with that data.

And from a real practicality, there\'s a tremendous shortage of
pharmacists these days. They all go out making more money than faculty.
It\'s a good deal for students, but their ability to care for patients
the way we\'ve taught them is not very good. Just the production of
getting through the prescription part of the job is quite in and of
itself overwhelming.

Now we\'re going to say that we\'re going to have a third class of drugs
and pharmacists who receive about a dollar an hour or a dollar a minute
\-- the dean gets a dollar an hour \--

(Laughter.)

DR. JUHL: \-- how long is it that they need to spend with a consumer to
properly explain what we need to have done? I think we really need to
stick with a system that we have in terms of making the labeling work,
and if it isn\'t going to work, well, then it shouldn\'t be on
prescription.

Now, there are some innovative ways. I was impressed today with the
reports from the folks from Washington with emergency contraception and
the way they have set that up. Without a change in the laws, they\'ve
used their state practice acts to find a way that worked on a
case-by-case basis for that particular kind of therapy.

So I think using collaborative care agreements, pharmacists and
physicians get together and do many of these kinds of things. In fact,
if the issue with the nonsedating antihistamines really is access and
safety, I\'m sure that our colleagues at the insurance company in
California could set up collaborative care agreements between physicians
and pharmacists so that any of the subscribers who want a nonsedating
antihistamine can just go into the pharmacy and pick it up whenever they
want. So I think that would be a way that that could happen without a
change in the law.

On the other hand, if the issue with that particular problem is
economic, and I shudder to think that it is, but if it is economic,
well, then that creates quite a set of different problems for the FDA,
and if I was sitting on the advisory committee I\'d really not like to
have to make a decision based upon an insurance company telling the drug
company their prices are too high and the drug company telling the
insurance company, \"Well, if your insurance was cheaper, they could
afford that and they could get our products.\"

That would be a hard decision for me to have to make in terms of
scientific advisory committee, anyway. I think really what we\'re
dealing with, and not to trivialize either of the arguments because I
think they\'re both valid, is more of a public policy issue and would
need to be addressed in the entire context of the drug approval process.

I\'ll give you an example that\'s a personal one. One of our faculty at
Pitt. and his wife, bless their souls, adopted some kinds from Eastern
Europe, and the little girl, a bright eyed little girl who already knows
English better than my kids who are 24 and 21 \--

(Laughter.)

DR. JUHL: \-- they found out she was positive for Hepatitis C, and this
was quite crushing to them.

Well, I know that one company that makes a nonsedating antihistamine
also works in the Hepatitis C area, and if I was going to vote where the
extra money should go, I\'d want it to go into the research project that
is dealing with Hepatitis C, and that\'s just an example.

But what unfortunately the agency has to do is, rather than look at
these things in isolation, you\'ve got to look at the whole thing. A
problem like this is very much like a water bed. If you press down on
this side, what\'s going to pop up somewhere else?

And I think in order to determine the right outcome from that, it
probably needs to be done in a public policy level, not on an individual
drug level, letting somebody suggest it during the drug development
process.

I will conclude my comments and be happy to entertain questions.

DR. DeLAP: Thank you, Dr. Juhl. It\'s always a pleasure to hear from
you.

Do we have comments or questions?

DR. MURPHY: Dr. Juhl, the last two days we\'ve heard health care system
has failed, becoming not able to provide some of the care patients need,
at least in the way of time. We just heard others and you say maybe the
third system people proposed involving the pharmacist may not be \--
would be ideal, but may not be idealistic.

But you mentioned a system in which the pharmacy dispensed the product
and to get to the issue of follow-up of adverse events. Do you see a
role that the pharmacist, if they dispense that product without a
prescription I\'m talking about here, would be able to be involved in
any adverse event data collection? I mean again thinking beyond what we
have available now.

DR. JUHL: I think there is a great opportunity for the collection of
that kind of information in the pharmacy, but it would require
collaboration between the pharmacy, the pharmacist, and whether it\'s an
HMO insurance company or an employer.

To collect that kind of information, I think it would be exceptionally
valuable, especially when we\'re thinking about switch or when you\'re
thinking about drugs of choice. So I think those kinds of things can be
done.

There are some examples of that happening now using community pharmacies
for outcome studies. In fact, using the hand held that the patients seem
to really like, to enter a lot of the information that they\'re
searching for. This happened to be a study on cholesterol lowering. So I
think that\'s a wonderful opportunity where people come back in every
month because they can\'t get more than 34 days\' supply. We have the
opportunity to provide information, and patients actually think of that
as a service as opposed to an imposition; that somebody actually asked
them to put some information about how they\'re doing.

DR. DeLAP: Do you have any further comments about the practicality of
the possible new class of drugs that has been raised on several
occasions? I heard some comments about whether it was something that
pharmacists could accomplish in the course of their duties, given how
busy they are.

DR. JUHL: Yeah. I mean, I know we are capable of doing that if we had
enough pharmacists to do it, but I don\'t believe that we do, nor do I
see an economic system that would reimburse the pharmacist. I mean,
that\'s the problem alleged with the prescription, that they cost too
much.

Well, there would be costs in providing that kind of information at that
level. Now, you could, I guess, switch it so that someone just had to go
into the pharmacy to buy something and they would just wave at the
pharmacist as they went past, which would get rid of the cost, but it
really wouldn\'t do anything in terms of public health.

DR. DeLAP: I think that\'s one of my concerns, is we don\'t want to go
down a path just because it looks useful unless it really makes a
difference for the consumer.

Other questions or comments?

(No response.)

DR. DeLAP: If not, thank you very much, Dr. Juhl.

DR. JUHL: Thank you.

DR. DeLAP: And we\'ll then proceed with our requests to speak at the
open public hearing.

DR. TITUS: Before more of you leave, we just wanted to remind you that
the dockets would have the information, and you\'ve been asking us when,
and July 10th is what Dockets has told us the material from these two
days will be posted, and I would guess that the transcript would be
mounted the following week. It\'s usually a little bit longer than two
weeks before the transcript gets up there. So July 10th.

DR. DeLAP: The first person that we\'ll ask to speak for our Section 10
is Susan Coleman, whose affiliation is NCI Consulting.

MS. COLEMAN: I am Susan Levine Coleman, president of NCI Consulting. We
are a consulting firm that works with the pharmaceutical and OTC drug
industries.

We have, just for perspective, worked on the majority of the switches
that have occurred in the last ten years, and unfortunately also a
majority of those that haven\'t occurred in the last ten years.

And I\'ve watched with interest the discussion over the last two days,
and I wanted to come back to this fundamental question of what should
FDA\'s role be in regulating OTCs.

I\'ve seen an interesting dichotomy emerge in the questions. On the one
hand, we\'ve got sort of the traditional agency role of protecting the
consumer. So we had questions about labeling and multiple languages and
how much do consumers want to know and need to know, and can they choose
among various products?

We had questions about safety assessment and putting it in the context
of current Rx practice and so on. We had questions about the removal of
OTCs if the risk-benefit changes because of the availability of new OTC
therapies.

Okay. So those are what I would characterize as the traditional domain
of FDA questions in the area of OTCs and OTC switch, but we also had
another area which I haven\'t seen much emerging in discussion of
OTCness, which is this issue of ought FDA embrace a role of promoting
public health.

Now, yes, we had that little sidebar conversation whether FDA had as its
mandate public health, and my personal opinion is that\'s nonsense. If
you\'re going to do risk-benefit analyses, you know, you are in the
public health business and that\'s part of the charge. So, yes, public
health is what you\'ve done, and typically it\'s been characterized as
protecting public health.

But now the issue is ought you to make the step as part of your charge,
part of your mandate to move to promoting switch. So we\'ve had the
questions: ought FDA be initiating switch? And in what circumstances?

And we even had the suggestion if we have a real public health benefit
that we can well characterize, ought FDA to provide incentives to
encourage manufacturers to move those products over the counter earlier
so that we can get the benefit of that public health benefit rather than
just waiting for patent expiration.

Now, as I look back on, you know, sort of this change, this new approach
to thinking about ought FDA\'s mandate really be now to promoting public
health, you know, it seems to me it\'s rather consistent with the
changes we\'ve seen in FDA over the last five years on the Rx side,
perhaps in response to FDAMA, perhaps in response to the activist
community of recognizing there is a role of getting life saving
therapies, you know, out there as fast as is safely possible.

But up till now that hasn\'t spilled over into the OTC context, and so
now the question is should it.

My view is that if FDA doesn\'t take on this role, it\'s not going to
happen. And the reason is, you know, we do a lot of work for our
pharmaceutical clients with medical directors and pharmacy directors and
PBNs in the managed care world, and I can\'t tell you the number of
times we have heard the comment that the typical managed care patient is
in that organization, in that institution, HMO, for two years, three
years, and then they\'re out to the next plan.

And the managed care organization cannot afford in investing in benefits
that are going to accrue in ten years. They\'ve go to have the results
now in things that are going to materially affect that patient in the
near term, and that\'s where they put their limited resources, in those
conditions where they can make a difference right now.

So as we think about, well, is it possible that lower dose cholesterol
therapy might actually yield a public health benefit and all of these
prevention therapies that we\'ve talked about today, could it make a
difference?

It\'s not going to be coming from managed care that that change is going
to occur. I think what we see is the industry \-- I mean we have worked
in virtually every single category \-- the industry is interested in
making good therapies available over the counter. We continue to get
some push back from FDA on those really \-- even in the most benign
situations on those protecting consumer issues, and we still have to, of
course, deal with that, but I believe the proposal for collaboration and
working at identifying where public health can be served, I think,
industry will work with FDA in coming up to solutions so that we can get
better therapies out there that will serve the public interest.

One final point on the third class since I have a couple more seconds,
which is that we\'ve done the analysis in multiple categories looking at
whether third class could actually address what the issues are in any
particular class, and time and time again it ends up, you know, in
theory seeming nice, but in practice really not addressing what those
fundamental issues are.

That is not to say that there\'s not some alternate midway, something
that could be developed that could actually facilitate making those
therapies available while giving the assurance that products could be
handled safely, and I think there\'s infinite creativity on the industry
side and a willingness to work with FDA to come up with some of those
new systems, new ways of getting products to consumers that really could
address that need to protect the consumer while delivering the public
health benefit.

Thank you.

DR. DeLAP: Thank you very much.

Comments or questions? Dr. Kweder.

DR. KWEDER: Just a question on your last point about a possible third
class. Are you saying that you think that it would be preferable to work
out solutions on a case-by-case or drug class or drug-by-drug basis
rather than an overall systems approach?

MS. COLEMAN: Yes. I think, you know, each drug is different, and maybe
it can be done class-wide if they\'re similar enough, but every time
we\'ve looked at it, I mean, you look at the issue of emergency
contraception versus hypertension versus cholesterol lowering, what you
would want the pharmacist, for example, to do is different in each case,
and sometimes they may be equipped to do it, and in other cases they are
really not.

And in many, many cases when you really start thinking it through, all
the pharmacist would be doing would be asking the questions that might
otherwise appear on the label or be in advertising that could cause a
person to think that pharmacy isn\'t really set up to, you know, take
blood and do the analysis and so on.

I think another point, and it goes back to something that the fellow
from Kaiser Permanente made, a point he made yesterday, which was we
have had, he said, in 1990 25 to 30 percent of people had Rx coverage.
Today 75 percent of people have Rx coverage. We have overwhelmed the
pharmacist system right now in terms of the number of people who are now
able, you know \-- it\'s wonderful \-- able to get prescription
coverage, but we similarly haven\'t increased the number of pharmacists
available.

So I think, you know, to Dr. Juhl\'s point, that system is overburdened
to be able to handle it, but I do think there are ways, other things we
could do. If we understand what the issues are we want to get protection
on or assurance on, then we can case by case or category by category
devise solutions, and some of those solutions, like the pharmacy, you
know, cooperative use right now, some of those systems might actually be
available to us now.

DR. DeLAP: Dr. Ganley.

DR. GANLEY: Yeah. Could you just give me your view of whether we \-- I
got a sense that we should be proactive from your comments. Is that an
accurate \--

MS. COLEMAN: Yes, although I noticed in various comments today that
one\'s definition of proactive \-- there\'s a spectrum there, but, yes,
I would generally agree with proactive.

DR. GANLEY: Well, you know, we have these two issues. One is the non or
less sedating, I\'m going to characterize it, less sedating
antihistamines and the cholesterol lowering agents where we have two
different driving forces, and if we had a public health \-- overall
public health viewpoint in mind where the ultimate goal was to improve
access to these products to improve public health in general, then we
should be more proactive in forcing switches.

MS. COLEMAN: Well, it\'s interesting.

DR. GANLEY: Without a sponsor supporting that necessarily.

MS. COLEMAN: Okay. I\'ve been following switch for about 20 years. So I
remember Metapaternal (phonetic), which was the one instance where FDA
tried to force switch, and it\'s interesting because in some ways it was
quite analogous to the situation we\'ve got right now with nonsedating
antihistamines.

We had with Metapaternal a clearly safer product as Rx. FDA made the
decision that because it was significantly safer than the current OTC
product, it ought to be made available in an existing OTC category.

My personal opinion is that that was a right decision based on the
public health facts, but the reality and the politics of this situation
was that there was major push-back from primarily the medical community
and pharmacists, and Congress got into the act, and that decision was
reversed.

Now, so we have one model. I would call that a slightly adversarial
model of promoting public health.

We have another model, and it is the example of actually the Rx approval
of emergency contraception. Here was a category with emergency
contraception, a category that industry hadn\'t stepped up to the plate
on. Industry wasn\'t do anything. FDA made it clear that FDA felt that
this was a need that needed to be addressed.

And by making the marketplace aware that FDA was receptive, all of a
sudden the market took its course and very quickly, even though the big
companies didn\'t step in, the small ones stepped in and introduced
products that we talked about earlier today.

So then the question becomes, okay, both methods work with some
tradeoffs, and the issue is what is the best method to achieve this
public health endpoint. I would argue that the industry, the people who
are still after all these hours sitting in this room, are interested in
making this happen, and that the way to get this accomplished is through
collaboration; that if FDA opens the door and will, you know, work with
industry and help us, you know, define what needs to be done \-- and,
boy, the message is loud and clear that you want Claritin switched. The
industry has heard that message, I can guarantee you \-- I think that
the market will respond and that the need to actually go out there and
force something to happen I think will actually be longer than the
collaborative approach in achieving the desired endpoint.

DR. MURPHY: Bob, it\'s the end of the day. So let me ask something \--

DR. DeLAP: Okay.

DR. MURPHY: \-- really different. Of all the systems that we\'ve been
talking about, they\'ve involved people, and we keep talking about
technology, but in an effort to both have the patient answer questions
or be given queries and to collect follow-up data, has your consulting
group or any other consulting group looked at a system that involves a
machine, like our banks give us money, only you go to the pharmacist and
the pharmacist is filled with whatever the drug is, and you would answer
questions and put in information that would give you the drug for 30
days, and you would come back and fill in?

Has anybody looked at anything like that?

MS. COLEMAN: I can tell you that the industry has looked at infinite
variations on the theme, and you may well in the next advisory committee
next month begin to hear some of those variations on the theme.

I think the challenge so far has been that those kind of methods, you
know, one can clearly logic one\'s way into seeing how an educated
consumer, an English speaking consumer, a fairly knowledgeable consumer
can be looped into those kinds of systems and do those things.

It is harder in terms of creating systems that can be broadly effective,
that can, you know, pull in all the consumers that could really benefit
from a public health standpoint and make it equally easy and so on to
use. So some have used devices and Internet systems. Some have used
promotional incentives and other ways to give a month trial and then you
can\'t get the rest free unless you come back and get the test.

So, yes, I think you can be assured that there\'s a lot of good, hard
work trying to come up addressing this very same issue, which is how can
we be sure that they\'re being used safely. How can we be sure that the
people who are going to benefit are the ones who are using it and not
the people that we don\'t want to use it?

So I think there\'s a lot going on in that area.

DR. DeLAP: Okay. If there are no further questions, thank you very much.

And we have one other participant for this part of the meeting. Dr.
Widmark.

DR. WIDMARK: Well, as a former FDA medical officer, presently retired
\-- I\'ve not yet mentally retired \-- I wanted to congratulate you for
organizing this meeting. I believe it\'s fantastic that we had listened
to the exchange of ideas and proposals.

It\'s funny that what I wanted to say was preempted by Dr. Juhl in his
\-- and I can\'t even compete with his way of delivery, and if you think
he\'s not even a physician \-- but what bothers me and should be
considered by you is the existence often in the marketplace of the
phytoceuticals.

They are sold in health stores as dietary substances, and they contain
sometimes active drugs that cause drug interactions with prescription
drugs or OTC drugs, and they are not regulated. And I wonder if there is
any move to start regulating these types of active drugs.

That was all. Thank you.

DR. DeLAP: Well, that\'s something that we could have another meeting
on, I think.

(Laughter.)

DR. DeLAP: Are there any questions or comments that people have in
response to Dr. Widmark\'s comments? Dr. Woodcock.

DR. WOODCOCK: Well, I just will say that the Center for Foods, which is
responsible for looking at implementing the DSHEA, the act, the
congressional statute that established a framework for marketing of
dietary supplements like these, is undertaking a program of implementing
the statute.

And we published, as you know, a rule telling what claims could be put
on these products in distinguishing structure function claims from drug
claims, and we\'re in the process still of implementing that, and the
food center is looking into good manufacturing practice regulations for
dietary supplements to insure uniform manufacture.

DR. DeLAP: If there are no other comments, I\'ll just take two minutes
at the podium, Dr. Titus, for some closing remarks.

I wanted to take this opportunity to thank the people that had worked so
hard to organize this meeting. One person, Patricia De Santis put a
tremendous amount of work into scheduling and working out the logistics
here and couldn\'t be with us today.

Obviously Dr. Titus and her colleagues, Kathleen Reedy and other people
in the advisors and consultants staff, have put a huge amount of work
into this, and I know the hotel staff have also put a lot of work into
creating a good environment for us here to have this meeting.

And, of course, I\'d especially like to thank the participants who
shared their information and views with us. We do appreciate the work
that was put into preparing these presentations we\'ve heard, and we
appreciate the cost in time and expense that people have assumed in
participating in this meeting.

We appreciate the substantial and thoughtful comments that we\'ve
received, and the questions we had posed in the meeting notice have had
some answers put to at least some of them. We have a lot of work to do
yet there.

Oops, there\'s the timer.

(Laughter.)

DR. DeLAP: We will be carefully examining the comments, and along with
the other written comments that we receive to our public docket on this
matter, and again, the public docket will remain open until, I believe,
August 25th, and we will be looking at all of the comments we receive
very carefully.

Some of these comments are obviously going to be helpful to us in the
near term. We do have an advisory committee meeting coming up in July
regarding possible OTC availability of some cholesterol lowering drugs,
and we had a lot of useful discussion on that subject at this meeting.

Other comments that we had in the last couple of days will be helpful in
our longer term consideration of how we can work on our processes and
our approaches to better server our public health mission.

And this meeting is a step in that longer term process, but certainly
not the last step, and this process is going to continue.

I would, again, encourage people to continue to submit information,
ideas, comments that they may have to our public record for this
particular effort, and we did provide information outside on how to
access that, and if you have any, please, you\'ll see on our Web site at
least ways of accessing things, and please call or otherwise let us know
if you\'re having difficulty and you cant to make comments.

I don\'t have any other comments now, and unless someone on the panel
has a need to make a last comment, I think it\'s been a very useful
time, and we\'re kind of talked out.

We\'re finished, and this concludes our open public hearing on
over-the-counter drug products. Thank you all very much for attending.

(Whereupon, at 3:48 p.m., the hearing in the above-entitled matter was
concluded.)