Subject: Scandal over AIDS Drug Nevirapine Deepens

The scandal over the testing of the AIDS drug Nevirapine on pregnant
African women deepens (you may remember that the manufacturer withdrew
this drug from FDA approval in the US when major problems surfaced
about the Uganadan clinical trial -- yet, despite this, all major AIDS
organizations are claiming that it is still safe and effective for
women in the third world). Jonathan Fishbein MD, the fired
whistleblower at the US National Institutes of Health has a new article
that provides a good summary at:
http://www.foxnews.com/story/0,2933,146199,00.html

For more information, turn to Fishbein's website at:
http://www.honestdoctor.org

THE ARTICLE IS REPRODUCED BELOW.  The original has HOTLINKS to original
documents which you may wish to consult, at
http://www.foxnews.com/story/0,2933,146199,00.html

Flawed AIDS Drug Study Exposes NIH Misconduct

Friday, February 04, 2005

By Jonathan M. Fishbein

In a White House ceremony on June 19, 2002, President Bush announced an
important new AIDS initiative to combat the spread of HIV from mothers
to their newborns.

It was a bold and courageous effort to deal with one of the greatest
public health scourges of our time.Yet, it is a vision marred, perhaps
irrevocably, by a rash of allegations of scientific and professional
misconduct now swirling around the National Institutes of Health
Division of AIDS (search) (DAIDS).

DAIDS is the focal point for a considerable portion of government
funded clinical trials on new AIDS therapies and preventive strategies.
If these allegations are not promptly addressed, many of us in the AIDS
community feel they could undermine not only U.S. international AIDS
initiatives, but U.S. credibility in the field of AIDS research across
the board.

Until recently, I was the Director of the Office of Policy in Clinical
Research Operations at the National Institute of Allergy and Infectious
Disease Division of AIDS. In that capacity, I was responsible for
ensuring the integrity of government-funded AIDS drug trials by
insisting upon good clinical practice and the rigorous oversight of all
AIDS-related field work.

It was an impossible task. At every turn I found my efforts frustrated
by a management system guided more by politics than by sound science.
Nepotism and bureaucratic intrigue permeate DAIDS. Scientists are
pressured to produce results at the expense of regulations whose
purpose is to protect the safety, rights and welfare of study subjects,
not to mention the preservation of scientific integrity.

For seven months, I learned of numerous instances of scientific and
professional misconduct at DAIDS. I brought some of these to the
attention of my supervisor as I am required to do by law. My vigilance
was rewarded with a notice of termination and slander against my good
name and reputation. Frustrated, I decided to step forward as a
whistleblower in the hope that public exposure would bring about the
needed change. That has yet to happen. Instead, NIH has worked
fervently to suppress my allegations and delegitimize my credibility.
They will not succeed.

According to the U.N, at least 38 million people are infected with the
HIV/AIDS (search) virus worldwide and approximately 3 million die each
year. I refuse to sit idly by and let NIH perpetuate bad science while
the list of AIDS victims continues to grow. As a physician, as a
scientist, my duty is to them.

Among the most serious charges I have leveled against NIH is that the
agency knowingly and cunningly covered-up evidence of shoddy conduct in
a trial examining the safety and efficacy of nevirapine (search) to
prevent the maternal-to-child ("vertical") transmission of the deadly
AIDS virus.

In announcing the United States' New Mother and Child HIV Prevention
Initiative (search) on June 19, 2002, President Bush stated "we will
support programs that administer a single dose of nevirapine to the
mother at the time of delivery, and at least one dose to the infant
shortly after birth."

Unfortunately, the agency permitted the president to make that
statement knowing that it was unable to verify the integrity of the
data at that time. Nor did they advise the president that they were
aware that nevirapine can have serious side effects.

Far from being a wonder drug, nevirapine can be very dangerous. It has
been subjected to numerous changes in its labeling by the FDA, owing to
reports of liver toxicity (search) and a potential for fatal rashes
when administered in multiple doses. But with the administration of
just one dose, viral resistance can result in half the patients to whom
the drug is prescribed. In resource-poor countries, there are often no
other affordable options available to treat these infected women once a
nevirapine-resistant virus emerges.

This was not the conclusion reached by NIH-backed researchers from The
Johns Hopkins School of Medicine when they undertook a landmark study
of nevirapine in Uganda in the late 1990s. The study, known as HIVNET
012 (search), purported to show that the drug was safe and effective in
preventing HIV transmission to newborns.

What was not immediately apparent was that some of the most basic
procedures of Good Clinical Practice (search) were absent from their
work.

The original HIVNET results were published Sept. 4, 1999 in Lancet, one
of the world's foremost medical journals. They were hailed by many in
the AIDS community as an unqualified victory in the fight against AIDS.

As most of the international AIDS research community, as well as the
World Health Organization (search), embraced these findings, the NIH
and the investigators are unwilling to admit to any flaws.

However, when third party auditors from nevirapine's manufacturer,
Boehringer Ingleheim, looked into how the Uganda trial was run, they
found critical compliance issues that compromised the integrity of the
study. Boehringer had only recently used the HIVNET data to support its
application to the FDA to obtain licensure of nevirapine for preventing
vertical transmission of HIV (search). A second audit sponsored by
DAIDS essentially confirmed what the manufacturer discovered. With the
validity of the data very much in question, Boehringer Ingelheim
withdrew its license application to the U.S. FDA.

The NIAID swung went into action. Deputy Director LaMontagne assured
the public "there is no question about the validity of the data,"
citing only that "the problems are in the rather arcane requirements in
record keeping." This was quite an understatement and a willful
deception of the public. From there, DAIDS maintained the deceit by
concocting an expensive and elaborate "remonitoring" of HIVNET 012 in
which the conclusions were never in doubt.

And as if that weren't enough, DAIDS used threats and intimidation to
silence those employees who knew the truth and might potentially speak
out.

I, for one, will not succumb to such behavior and be silenced.

In 2002, President Bush stood shoulder to shoulder with Senate Majority
Leader Bill Frist, Secretary of Health and Human Services Tommy
Thompson and Dr. Anthony Fauci, the Director of the National Institute
of Allergy and Infectious Diseases (NIAID), and announced the African
AIDS initiative with much fanfare. It now appears that this endorsement
of nevirapine may have been premature. No policy, no matter how well
intentioned, should be based on poor science. Yet that is what HIVNET
012 was.

Of even greater importance is what the experience with HIVNET 012 has
taught us about one government agency. NIH is broken and needs to be
overhauled. Those responsible for suppressing the truth about poor
scientific conduct and deceiving the public should themselves be
reprimanded and removed from positions of authority. Acts of
retaliation by senior managers against employees simply doing their job
should be fully and fairly investigated.

What is clear is that in the battle against the world's most deadly
diseases, scientific misconduct of whatever stripe cannot, and should
not, be tolerated.

For the good of Americans suffering from HIV/AIDS and for the millions
overseas so afflicted, the Bush administration's leadership in this
matter is urgently needed.

Jonathan M. Fishbein, M.D.is a former Director, Office for Clinical
Research Policy at the Division of AIDS (DAIDS) at the National
Institute of Allergy and Infectious Disease (NIAID), the National
Institutes of Health (NIH). A full discussion of Dr. Fishbein's case,
including supporting documents, can be found at: HonestDoctor.org.