ACT UP Confronts U.S. Researcher about Trial of High-Dose Drug which
killed PWAs
ACT UP protested the presentation by Dr. David Cohn, an AIDS researcher
at the Univeristy of Colorado, at an afternoon breakout session on Mycobacterium
avium Complex (MAC).
Cohn presided over a clinical trial in which People living with HIV/AIDS
were knowingly admnistered deadly doses of clarithromycin. After dramatically
increased deaths on the high-dose arm of the study, that arm was discontinued
- but only over Dr. Cohn's objections.
He then rewrote the statistician's summary of the data in a way which downplayed
the severity of his results. The National Institue of Health (NIH) to this
day has refused to issue a clinical alert warning clinicians and patients
about the risks of the high dose.
Last year, Cohn pushed for and got approval for a MAC treatment trial by
the Community Programs for Clinical Research on AIDS (CPCRA), part of the
NIH. This trial compared two doses of Abbott Pharmaceutical's clarithromycin
as part of a 3-drug regimen. A Food and Drug Administration (FDA) analysis
of the two previous trials involving the drug found both to "demonstrate
an excess of deaths early in the course of therapy" in patients on
the higher dose of 1000mg twice daily.
Nevertheless, Cohn insisted on proceeding with the trial
because he claimed the scientific reason for the deaths was unclear.
Furthermore, the informed consent form the patients in the trial failed
to warn patients clearly about the safety issues surrounding the higher
dose. NIH officials, particularly, Dr. Richard Hafner, a medical officer
at the Division of AIDS, strongly encouraged and ratified proceeding with
this dangerous trial.
In Cohn's trial, 85 patients spent an average of 4 months on the two doses.
10 died on the lower dose and 17 on the higher dose. As a result, on February
5, 1996, the NIH Data Safety Monitoring Board intervened and discontinued
the high-dose arm of the study - but only over the objections of Cohn, who
still though there was no reason to be sure that the higher dose was responsible
for killing PWAs. Cohn then unsuccessfully appealed the decision to another
NIH committee.
Cohn then proposed rewriting the statistician's summary fo the data to
downplay the severity of the results, by substituting words like "survival
difference" for "excess of deaths". Other rewordings made
the study appear reasonable.
Yet even this report - revisd in March of this year - was never released
by NIH. No clinical alert was ever issued to warn the hundreds of physicians
using this drug, despite an admission that "the MAC experts who have
reviewed the data would strongly recommend that clari[thromycin] not be
used at a dose higher than 500 (mg) BID.
In March, Hafner said he would release a summary within a week, but it was
not released until this Conference - four moths later, and a public clinical
alert has still not been issued.
When questioned about why the summary was drafted, but not distributed,
Hafner said, "We don't want people to think we're Mengeles," -
refering to the genocidal Nazi doctor.
This entire set of events represents a total failure at every level of the
NIH/FDA review process. This type of unethical trial and after-the-fact
cover-up must never be allowed to happen again.
ACT UP demands that:
- NIH issue an immediate clinical alert, broadly disseminated to medical
media and mailed directly to doctors, hospitals, and clinics warning of
the dangers of a 1000 mg, twice-daily doe of clarithromycin.
- NIH invite community input to:
a) develop standards to avoid initiating clinical trials after
prior trials have resulted in deaths or serious adverse effects.
b) investigate and revise current criteria for issuing clinical alerts,
to guarantee that information on dangerous drug regimens is rapidly disseminated.
c) revise informed consent procedures to insure that patients are warned
in clear language about adverse results of previous trials of the same drugs.
- AIDS community advocates be added to NIH Data Safety Monitoring Boards.
