David Gilden

280 11^th^ St.

Brooklyn, NY 11215

dgilden@pipeline.com

718/788-3060

September 13, 2002

Dockets Management Branch

FDA

5630 Fishers Lane

Room 1061

Rockville, MD 20852

(submitted electronically to fdadockets@oc.fda.gov)

**[RE: Docket No. 02N-0209]{.underline}**

To Whom It May Concern:

*The following comments on FDA Docket 02N-0209 are submitted on behalf
of Survive AIDS, a San Francisco AIDS activist organization and two
individuals, David Gilden of Brooklyn, NY and Jeff Getty of Oakland,
CA.*

The FDA's Federal Register notice of May 16 concerning the First
Amendment's applicability to drug industry promotional campaigns fills
us with grave concern. Although we are not experts on the legal
precedent, we know that widespread health misinformation, resulting in
serious physical and economic harm, has arisen from pharmaceutical
marketing campaigns. Our personal experience as HIV/AIDS treatment
activists and writers weighs heavily on our minds when considering
whether such activities should be deregulated on the grounds that they
constitute "commercial free speech."

**Misrepresentation and Misuse of the new HIV Drugs**

The FDA's December 1995 approval of the protease inhibitor Invirase 1995
marked a turning point in the fight against HIV. Or did it? The FDA
approval allowed Hoffmann-La Roche to sell this product as such, but in
fact, Invirase was poorly absorbed by the body and had little efficacy
against HIV. Persons who were persuaded to take Invirase in late 1995
and the early months of 1996 largely failed to suppress their HIV,
leading to the rise of drug-resistant HIV. When more absorbable,
effective protease inhibitors were approved in March 1996, these people
were unable to take full advantage of them, frequently again failing
treatment. Despite considerable community protest, Roche continued to
heavily promote Invirase as a new, breakthrough treatment for HIV --
safe from reprimand by the FDA and to the detriment of unwary HIV
doctors and their patients.

Sales of Invirase did decline after the introduction of potent competing
drugs from companies like Merck and Agouron. But the entry of these
other companies further spread the misinformation. The new drugs were
heavily promoted and accepted by medical authorities as usable in early
HIV infection. Again, the FDA did not restrain the promotional activity.
That promotion fell within the broad indication for these drugs, which
is simply, "for the treatment of HIV infection."

The problem was that there was little clinical research into the drugs'
most appropriate use. It was only discovered in the course of practice
that these extremely costly agents not only do not eradicate HIV, but
also are at constant risk of failure due to the emergence of
drug-resistant HIV. Their multiple side effects also present hardships
and dangers for patients taking them over the long-term. That is
especially true in early HIV infection when the side effects are
decidedly worse than the symptoms of the disease.

Under the influence of medically conservative AIDS activists and British
doctors, there was a growing realization that treatment for HIV usually
should be put off until there is significant, but still reversible,
decline in immune function. This attitude was incorporated in US
treatment guidelines only last years. In the meantime, the rush to
therapy has cost many people with HIV valuable treatment options as
their HIV's drug resistance increased, damaged their nerves, livers,
hearts and other organs and led to a still growing crisis in HIV health
care financing.

The industry promotion campaign for the new anti-HIV drugs relied
heavily on direct-to-consumer advertising. The ads depicted happy,
healthy people with HIV pursuing newly active lives, mountain climbing,
jogging, etc., as a result of the new drugs. The overall effect was to
reduce the seriousness with which the public perceived HIV, which now
seemed to be a manageable disease. True, death rates are down by 75%,
but only about a third of patients on treatment lead relatively normal
lives. Most are struggling with side effects, HIV that never becomes
undetectable or keeps rebounding, and immune systems that never recover
their full functionality.

The overly optimistic advertisements contributed to the widely observed
increase in unsafe sex by gay men. HIV cases are edging upward in the
gay community, as they are for other sexually transmitted diseases. The
potential social, personal and economic costs are enormous. In response
to complaints from the public, the FDA issued a warning letter in May
2001 telling the drug companies to produce ads that more realistically
depict the experience of people on anti-HIV therapy. Manufacturers have
toned down their ads but have done nothing to reverse the widespread
misperceptions that their previous ads helped to create.

**Hormone Replacement Therapy and Medical Miseducation**

It is not at all true that public "access to useful and truthful
information about medical products have skyrocketed," as the federal
register notice says. Rather, there is a cacophony of tendentious public
messages. These are mostly industry funded, whether they appear to come
from independent groups or not.

It is ironic that just after the agency notice appeared, the controversy
over hormone replacement therapy in menopausal women reached its peak.
Estrogen and estrogen/progesterone therapy have been long touted, both
by companies such as Wyeth and industry-funded professional societies,
for a variety of uses beyond their approved indication for hot flashes
and osteoporosis. Among these were prevention of heart disease and
breast cancer. Yet large placebo-controlled studies published this
summer found that hormone replacement therapy does little for such
off-label applications. It might actually cause additional
cardiovascular disease and ovarian and breast cancers. And other
therapies are probably better for osteoporosis. Meanwhile, 6 millions of
women are on HRT, at a cost of \$600 per year, not counting therapy for
the medical conditions that HRT might cause.

In all these cases, the FDA was passive before the pharmaceutical
industry's marketing campaigns. Indeed, industry was frequently
protected by the official indication. In each example, the problem was
that drugs were put on the market without sufficient consideration for
what is known and unknown. In the end, it turned out that their
usefulness was less than originally appeared.

Rather than inquire about whether constitutional free speech protection
limits regulation of industry marketing, the FDA would better inquire
how it can force more complete research, including post-approval study.
We are not talking about subjective political viewpoints here. It is
possible to arrive at definitive answers on many medical questions
through rigorously conducted studies. Without accurate information,
speculation prevails, and that leads to misrepresentation and fraud,
neither of which is protected by the US constitution.

**Ensuring Full Access to Medical Information**

The immediate trigger for the federal register notice was the Supreme
Court decision in Western States Medical Center vs. Thompson. That case
revolved around a special provision of the law: Congress as part of the
1997 FDA Modernization Act (FDAMA) prohibited compounding pharmacies
from advertising their specific custom-made products in return for
largely escaping FDA regulation. The Supreme Court said that it would be
better to regulate than put limits on commercial speech. The FDA, in its
compounding pharmacy guidance document issued May 29, has begun to chart
that course.

Congress has given the responsibility for protecting the public against
medical fraud and misrepresentation. Part of the agency's authority
involves reviewing promotional activities. The FDA guarantees against
harmful miseducation of the public and medical professionals by
attempting to ensure that a company's claims fall within the data that
it has meticulously reviewed and vetted during the new drug application
process, when it approved the drug for specific uses.

The FDA Modernization Act increased the claims permissible when
promoting drugs to include unapproved uses for which companies promise
to submit a supplemental approval application to the FDA backed by
rigorous research. This provision and the complicated FDA rules to
implement it were the subject of a major legal challenge based on free
speech concerns. That challenge prevailed in federal district court, but
ended inconclusively on appeal. (The current FDA chief counsel was also
the chief plaintiff counsel in this case.)

We as much as anyone are reluctant to put limits on speech, for fear
that they will come back to haunt us in our own activities, especially
those concerning disseminating treatment information to the AIDS. But,
in the course of our activities, we see that medical communication is
breaking down overall. To ease up on regulating drug marketing, and
create a situation that parallels that created by the Dietary Supplement
Health and Education Act, would heighten the loss of objectivity and
honesty.

Dietary supplements -- vitamins and herbs -- are now sold with
unreviewed and poorly substantiated general health claims. The
supplements may be relatively nontoxic and cheap compared to drugs, but
their promotional claims are frequently specious. Their unrestricted
marketing threatens to supplant treatments with documented efficacy.
This is alarming in itself. If conventional drugs were handled in the
same laissez-faire manner as dietary supplements, the results would be
much scarier. HIV drugs would be advertised as virtual cures -- and
hormone replacement therapy as a fountain of youth. Only the tort system
would have any policing authority, and massive lawsuits over injuries,
such as occurred with breast implants, would become much more common.
Indeed, there already are lawsuits arising over hormone replacement
therapy.

The Western States Medical Center case may not really apply to FDA's
general activities to regulate marketing, but the court's thinking does
suggest a valuable approach: The government should seek alternatives
that both reduce the threat to free speech and achieve the FDA's
mandated goals. These are in any case now poorly fulfilled in this area.

The marketing of drugs and dietary supplement has impaired our medical
system both economically and clinically. FDA's activities to rein in
these claims have created little order, as the HIV and HRT examples
indicate. The real issue is not so much what a company says in public,
but what data are publicly available. Rather than concentrate on
regulating industry marketing in an environment in which truth is hard
to find, we propose the following major policy changes that would
improve the flow of information.

As a condition for approval, the agency could require a drug's sponsor
to conduct more comprehensive trials on a drug's potential benefits and
risks. Such studies should include monitoring of the post-marketing uses
and outcomes via carefully constructed observational cohorts.

Alternatively or in addition, the FDA could work with the NIH and the
CDC to conduct this research. (Note that an enormous observational
cohort -- the CDC's Adult Spectrum of Disease study -- was instrumental
in showing that HIV disease could be delayed until later in the disease
without harm. The new data on hormone replacement comes from two very
large randomized trials, one organized by the NIH and a more specialized
study sponsored by Wyeth.)

The FDA or some other agency of the government could regulate drug
prices. At least, government medical care programs such as Medicaid, the
Veterans Affairs medical system, the AIDS Drug Assistance Program and
Medicare (assuming that Congress finally adds a prescription drug
benefit) should not have to pay for marketing. These programs already
receive special discounts that could be increased to deny public funding
for private corporations' advertising. At the very least, the government
could deny companies the ability to take tax deductions for marketing
and related expenses. Right now, even with the present FDA restrictions,
about half of drug revenue goes to the pharmaceutical industry's vast
marketing campaigns. Cutting pharmaceuticals' excessive costs would make
it difficult for drug companies to continue their extravagant promotions
that even now border on deception.

The FDA could support full disclosure of both currently available
information and the new data arising from the research that it
instigates. Full, objective disclosure of information goes far beyond
tinkering with typeface and images in advertisements. Who can expect a
Roche or a Wyeth to present information that would drastically cut
sales? Rather than allowing drug companies tax breaks for marketing
expenses, the federal government, with the FDA as the central authority,
should fund independent community and professional health education
organizations. A myriad such organizations exist, but at present they
are forced to go to industry for funding. The result of this close
relationship is that those with industry-pleasing viewpoints have lavish
budgets. Their communications overwhelm those of the truly independent
critical thinkers, who are poorly funded. To protect society's interest
in the free flow of information, the FDA should see that these
independent voices can make themselves heard over the marketing
cacophony. The goal would be to create an open public forum, not support
one side over another.

**Conclusion**

The FDA already has the authority to begin to implement some of these
measures, but most would require congressional action and a change in
the agency's focus. Surely, those who are most interested in freeing
commercial speech would find such a focus even more onerous than the
present marketing restrictions. But we are facing a growing crisis in
medical information, in which the confidence in the truthfulness of that
information is undermined to a greater and greater extent. Unleashing
companies' marketing activities without simultaneously taking
substantial countermeasures would deepen the crisis. Once unleashed,
competitive pressure would force each company to expand its marketing
presence while making increasingly dubious claims for its products.
Doctors and the public alike will be ill served by all the obfuscation.
Poorer medicine for all would be the final price of a poorly conceived
focus on freedom for industry.

Sincerely yours,

Survive AIDS

David Gilden

Jeff Getty