BARRON'S: "Do We Have Too Many Drugs for AIDS?"

The August 15 issue of BARRON'S (the Dow Jones business and
financial weekly) has a cover article, "Do We Have Too Many
Drugs for AIDS?" The cover includes the following summary:
"In a turnabout, some AIDS activists are now asking the
government to slow down its drug-approval process. What it
means for pharmaceutical companies."

Inside the paper, the article is titled "Rushing to
Judgment." Its main points are that the FDA's accelerated-
approval process for speeding the approval of drugs for AIDS,
cancer, and other serious and life-threatening diseases has
not worked, and that AIDS activists are calling for the FDA
to go back to requiring placebo trials -- even if they take
thousands of patients and require many years for drug
approval.

This article addresses a subject which has become bitterly
controversial among AIDS activists. But it only presents one
side. Some widespread concerns are:

* The article is likely to damage AIDS, cancer, and other
research by making it less attractive to investors, if they
think that accelerated approval is about to be abandoned, and
that activists are likely to oppose approval of their drugs
by the FDA.

* Much of the article concerns AIDS treatment activists --
which carries the piece journalistically, as otherwise there
would certainly not be a cover article, and probably not an
article at all. Yet there is not a shred of evidence that the
reporter talked to any AIDS activist outside of a single
organization -- the Treatment Action Group (TAG), located in
New York, which has taken positions strongly opposed by other
treatment activists and people with HIV. The article mentions
TAG, but does not identify the only two activists it
interviewed as TAG members. And it devotes less than half a
sentence to acknowledging that other views exist.

But we have found little support for and much opposition to
the "activist" view described in the BARRON'S article, that
the FDA should delay approving new AIDS drugs in the name of
better data. Instead, once safety and activity of a drug have
been shown, people want the freedom to make their own
choices. But most patients and physicians have not heard that
the controversy exists, and have no idea what is being
advocated in their behalf.

* In discussing placebos, the article states, "While commonly
used in many other drug trials, placebos have been an
anathema in tests of AIDS drugs, in large part because AIDS
activists have vehemently protested against them." In fact,
placebos are commonly used in AIDS trials, with little or no
protest; for example, a placebo was used in the human growth
hormone trial reported in this issue, and while we know two
volunteers in that trial, and activists who have protested
other aspects of the study, we have not heard any controversy
about the placebo.

The real controversy is not about placebos, but about trials
designed to find statistically significant differences
between two or more treatments in the number of deaths or
major illnesses, often euphemistically called "clinical
endpoints." These trials present special ethical issues
(whether or not they use a placebo), because those who design
and conduct them know very well that unless they get quite a
number of these "endpoints," enough for statistical proof,
the whole trial will have been a waste. In theory, the
accepted standard of ethics demands that such a trial not be
run unless it really is not known which treatment arm is
best. But in practice, investors are unlikely to pay for the
trial unless they have reason for confidence about the
outcome.

Placebos are not an issue if the trial is designed to catch
people and get them into appropriate care before serious
damage is done. But how can one reconcile this approach to
patient care with a trial which is designed to record serious
damage and count the bodies?

Clinical Trial Design

How, then, will we ever test drugs and know for sure what
works, what keeps people alive longer? Our full answer to
that question would not fit into this short article. But the
first step is to realize that comparing the time to death or
deterioration implies that one is testing marginal
treatments. And these tests take several years, meaning that
we must wait several years for the definitive answers about
drugs already known to be marginal several years ago. Do we
really want to structure much of AIDS drug development around
getting good data, years late, on bad drugs?

The alternative is to realize that nobody can predict in
advance what is going to work. Therefore, we need to design
drug development systems so that hundreds of potential
treatments and approaches have a chance to begin to prove
themselves and build credibility, bit by bit, if they are
able to; eventually the best of these could progress into
formal trials of various kinds. But until now, the barriers
to any movement by new treatments and new ideas have been so
high that few can move at all without major corporate
support. Very few of them will have such support in the
beginning; and if it is true that no one can know in advance
what will work, then it follows that the drugs which do get
corporate support are not really the best prospects, but are
essentially selected at random. And the rest remain stuck
forever.

The new blood tests for viral RNA will allow some treatment
ideas to begin to move. Drugs which are already in human use,
or which can easily be used in clinical practice, will now be
able to begin developing credibility, if they merit it. We
should work with technological change to design more
flexible, individualized drug development, instead of
imposing rigid doctrines to address the problems of the past.

Consensus Statement Circulated -- How to Sign On

Project Inform is circulating a two-page "Consensus Statement
on Accelerated Approval, August 5, 1994." It supports the
current system of accelerated approval for early access to
new AIDS treatments, against proposals to make the system
more restrictive. Project Inform is seeking sign-on by
organizations, and most importantly by HIV physicians.
Current signers include the Community Consortium (which
represents most of the HIV physicians in San Francisco), ACT
UP/New York's Treatment and Data Committee, Project Inform,
AIDS TREATMENT NEWS, BETA, SEARCH Alliance, and Mobilization
Against AIDS.

Project Inform can fax or mail you a copy; call them at
415/558-8669.

Project Inform is also encouraging individuals and
organizations who want to support early access and
accelerated approval to write to Commissioner David Kessler,
mail code HF-1, U.S. Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857.