" HIVNET 012 focused on finding a use for the troubled AIDS drug Nevirapine.
The drug had been around since the early 1990s, and had a bad reputation for
toxicity. By 1998 it had earned the FDA's black-box label, announcing its known
toxic potential, including the ability to cause organ failure and bloody skin loss -
both of which had resulted in death in patients taking the drug. "

http://www.gnn.tv/articles/2058/Exclusive_The_Good_Man_at_the_NIH

Exclusive: The Good Man at the NIH
Mon, 30 Jan 2006 08:41:11 -0800
_NEWS IMAGE_
Mr. Fishbein goes to Washington
By Liam Scheff

Dr. Jonathan Fishbein's fight for medical ethics in AIDS medicine

Editor's note: In December 2005, GNN's Liam Scheff spoke with NIH
whistleblower Dr. Jonathan Fishbein. In an exclusive interview, Fishbein
discusses the controversial African AIDS drug trials he exposed, his firing
and reinstatement and how medical ethics and the public trust are violated
when profit and politics rule the day. - A.L.

"Science has become so severely politicized that one has to be skeptical
of nearly every research result that is reported." Says Dr. Jonathan
Fishbein, once and future NIH employee.

He should know. Fishbein just fought a two-year battle with the nation's
medical authority, his former employer, the National Institutes of Health
(NIH), for what he feels was no less a goal than restoring integrity to
science.

Dr. Fishbein had a nearly 20 year work history in medicine, specializing
in pharmaceutical safety and oversight, when he was hired at the NIH in
July, 2003, as Director of the Office for Policy in Clinical Research
Operations. His job was "to create, implement, and enforce research
policy in the Division of AIDS," to ensure studies were being conducted
according to ethical research standards.

The agency had some recent failures in maintaining ethical research
guidelines, both in the United States and abroad. In 2004, I broke a
story of NIH clinical trial abuse in a New York orphanage. The
Associated Press took the investigation national, and in 2005,
Fishbein helped bring it to Congress.

But when Fishbein first arrived at the NIH, his attention was on an
African drug trial completed in 1999, called HIVNET 012 - a study
of the drug Nevirapine in pregnant women in Uganda.

Fishbein learned that the study was deeply flawed, the drug dangerous,
and the results had been covered-up. But all of this was an open secret.
"The flaws were common knowledge inside the division when I arrived,"
Fishbein said. So why hadn't they been corrected?

Fishbein says that within the Division of AIDS he encountered "a
management system guided more by politics than sound science,"
and "an atmosphere of intimidation" that made it impossible to
properly address and correct the institutional flaws that led to
damaged study.

HIVNET 012 focused on finding a use for the troubled AIDS drug
Nevirapine. The drug had been around since the early 1990s, and
had a bad reputation for toxicity. By 1998 it had earned the FDA's
black-box label, announcing its known toxic potential, including the
ability to cause organ failure and bloody skin loss - both of which
had resulted in death in patients taking the drug.

So why study a drug for use in poor, rural Africa that is known to
be dangerous here? The answers are fairly straightforward: profit,
the illusion of progress, and misplaced faith in the purity of big
pharma's humanitarian motives by those who care about poverty
and illness in the developing world.

In 1998 in Kampala, Uganda, the Nevirapine study to prevent
transmission of HIV from mother to child was underway. The
study put 645 expectant mothers on the drug. The problems
started immediately. First, the study was carried on without a
control group - everyone received one drug or another -
AZT or Nevirapine.

A 20 percent rate of "serious adverse events" was reported in
newborns in both the Nevirapine and AZT groups, including
blood and tissue infection, pneumonia and severe rash. Eighty
percent of mothers exhibited laboratory and clinical abnormalities.
Twenty-two babies had grade 3 anemia.

Thirty-eight babies died. Sixteen on Nevirapine, twenty-two on AZT.

Nevertheless, Nevirapine found approval, and is being sold
and distributed throughout the developing world for use in
pregnant women who test reactive on HIV antibody tests.

How did this study get through?

Despite the toxicities, the HIVNET researchers concluded that
fewer children registered as HIV positive in the Nevirapine group,
at 13.1%, than in the AZT group, at 25.1%. It was decided that
this potential benefit outweighted the toxic burden. But, according
to Fishbein, the research was so flawed as to make the results
meaningless.

"The [Uganda] research was poorly conducted - record keeping
was atrocious and good clinical practice was not followed or was
severely violated," he explained. "There were irregularities
throughout the study - in safety oversight, informed consent,
and other human research protection issues."

But the major flaw in the study had to do with the reporting of
"serious adverse events" in the trial population.

Kampala, Uganda, where the study took place, is an area with
a high level of serious endemic illness, including TB, cholera,
sepsis, malaria and the general effects of poverty and lack of
access to food, clean water and basic medical supplies.

"In a properly conducted clinical trial, all adverse events,
regardless of assumed relationship, are recorded," Fishbein
said,

But in the Ugandan study, "an assumption was made that
the adverse events were due to local endemic conditions.
The people recording data were poorly trained to assess
these local conditions. They looked at the patients and said,
'whatever's going on is probably malaria, so I'm not going
to write it down.'"

"You can't make determinations about drug safety this way,"
said Fishbein. "But that's what happened."

According to Fishbein, this lack of careful reporting invalidated
any data drawn from the study.

But he wasn't the first at the Division of AIDS to notice the flaws.
Dr. Betsy Smith, a researcher in the division, reviewed the data in
2003, and had reached the same conclusion. But Dr. Smith's
concerns about the study had been buried.

In collecting the HIVNET data, Fishbein discovered that Smith's
safety report had been rewritten without her knowledge by AIDS
Division director, Edmund Tramont. According to Fishbein,
Tramont's revisions shielded the investigators, the study and
the institute itself from urgent criticism and reform.

"In doing my job - creating clinical research policy - it was
essential for me to know the problems that occurred in HIVNET 012
and what had to be addressed to improve oversight, research
quality and integrity," said Fishbein. "But during the seven active
months in the division, I met considerable resistance from both
division and scientific leadership to make reforms."

Fishbein also found himself witness to grave professional misconduct
by high-ranking members of the Division of AIDS, including the sexual
harrassment of female employees and the bullying of researchers who
disagreed with department policy.

He voiced his concerns openly - and was quickly faced with a
choice - back down, or face an increasingly hostile work
environment himself.

Fishbein pursued the issue and filed an official complaint with the
division chief, Edmund Tramont. Although he was lauded for his
work in the division, even having his name submitted for a cash
performance award, On February 20, 2004, two weeks after
delivering his written complaint, Fishbein was demoted. Five
days later he was told his employment would be terminated.

He immediately filed appeals with Office of Management Assessment,
NIAID director Anthony Fauci, AIDS division head Edmund Tramont,
NIH chief Elias A Zerhouni, and Department of Health and Humand
Services (HHS) Secretary Tommy Thompson - but the appeals
were ignored.

At that point, he filed an Equal Employment Opportunity
Commission (EEOC) complaint and a Whistleblower Complaint
with the Office of Special Counsel. Fishbein then brought the
HIVNET data to Congressman James Greenwood (R-PA),
Chair of the House Energy and Commerce Committee, hoping
for an new, independent review.

Meanwhile, the NIH kept him on salary and on probation but with
no ability to return work or secure a job reference for over a year.
It was understood that at the end of the probation period, Fishbein
would be able to file an appeal with the Division. But they fired him
a day before the probation was up, dashing his hopes for a fair hearing.

During the same period, another AIDS drug scandal had been
brewing involving the use and abuse of orphans in NIH clinical
trials in one of the poorest boroughs of New York City.

In 2003, I began my investigation of the NIH trials conducted at
the Incarnation Children's Center (ICC) orphanage in Washington
Heights, just north of Harlem. Since the early 1990s, abandoned
children, mostly of drug-addicted parents, were being used to test
dangerous and toxic drugs like Nevirapine and AZT for the AIDS
market.

ICC, a Catholic orphanage, is operated by Columbia University's
Presbyterian Medical center, which also runs extensive drug trials
in conjunction with the NIH.

I published my first report, "The House That AIDS Built" at altheal.org
in January 2004. The story was picked up by other investigators, and
has appeared in multiple outlets - The New York Post, NY Press, UK
Observer, and as a BBC documentary for which I provided research -
but there has been no corrective action from the city or state.

In May 2005, an Associated Press investigation revealed that the
problem was widespread - orphans and wards of the state were
being used in clinical trials with dangerous drugs nationwide - with
little to no oversight.

Following the AP story, Dr. Fishbein wrote Daniel Levinson, the
Inspector General for the Department of Health and Human Services
(HHS), asking that a medical review and audit of study records
be performed by the Inspector General's office and that awarding
of further research funds be withheld from the site until completion
of an investigation.

In June 2005, the HHS held a subcommittee meeting on the scandal.
The committee concluded that the protected rights of foster children
had been violated in some of the AIDS drug trials. The HHS cited
Columbia Presbyterian, noting that the hospital's "records demonstrate
a failure . to obtain sufficient information regarding such safeguards
with respect to the enrollment of wards of the state or foster children."

The verdict looked good on paper, but nothing has changed at the
ICC orphanage. The drug regimen remains the same and is strictly
enforced, despite negative consequences in the children. Children
in ICC who refuse to take the drugs by mouth have them pumped
through nasal or surgically-inserted gastric tubes. Several children
have died in recent years - one on Thalidomide, and one after a
stroke that left her blind, which occurred within three months of
starting the drugs1.

Fishbein says that he is unaware of any investigation into these matters.

"I went to the House Ways and Means human resources subcommittee
hearing and it appears that there is some interest in legislating better
protections for children in research," he said. Fishbein cited a pointed
comment from the hearing, issued by Congressman Pete Stark
(D-CA), "in drug trials, children should at least be elevated to the
level of protections we provide prisoners."

In July 2005, The New York Times put out a front-page piece
on the ICC orphanage drug trial scandal, but painted my investigation
as so much internet hyperbole, excluding mention of the AP investigation
or the forced-drugging. The Times even colored AZT, one of the drugs
tested on the children, as a benign wonder-drug, but omitted any
reference to it's well-documented and often fatal toxicity.

Fishbein rebuffed the story; "The New York Times piece was not
investigative journalism at all," he said. "The _Times_' big problem
with the story was that they didn't break it first! So they tried to
make believe there was no story. No surprise there."

Back in the summer of 2004, Fishbein was still in the fight over
HIVNET. He had been looking for help in Congress and had
already given the HIVNET data to Congressmen Greenwood,
"But when Greenwood suddenly announced his retirement that
summer to go work as the chief of the biotech lobby, I knew he
had no intent to hold NIH accountable," Fishbein explained.

He again rebounded, and brought the evidence to Senator Charles
Grassley [R-Iowa], who as Chairman of the Senate Finance
Committee was just launching his investigation into the arthritis
drug Vioxx, which was pulled from the market after being linked
to thousands of deaths.

"Grassley looked at it, and commenced his own investigation into
HIVNET 012 - and requested that the Inspector General of HHS
do the same." Fishbein said. "That investigation is in progress."

In January, 2005, Fishbein testified before the Institute of Medicine
Committee (a division of the National Academy of Sciences) that
"gross violations of Good Clinical Practice in the conduct of the
HIVNET 012 study rendered the data invalid."

He spent the rest of the year fighting for his case before the EEOC.
"I had irrefutable evidence in my hands that substantiated the
allegations I made," Fishbein said.

On December 12, 2005, after two years of battle over
HIVNET 012, Dr. Jonathan Fishbein was reinstated to the NIH.

Senator Grassely said: "Dr. Fishbein brought to light serious
allegations of systemic problems at the National Institutes of
Health.As is typical, Dr. Fishbein suffered mightily for being a
whistleblower and for exposing the truth, until now."

But it's not a total victory; Fishbein's reinstatement is not to the
Department of AIDS. He is being given time to find another job
within the NIH - begging the question - how committed is the
Department of AIDS to cleaning up its act?

But, Fishbein says, this is the very reason he looks forward to
returning to work.

"I hope to help the Agency achieve its mission and become a
better environment in which to work. I will, of course, continue
to promote scientific integrity, research safety, and protection
of human research subjects," he explained.

"I have never strayed from my desire to contribute to finding an
end to the epidemic and I still care a great deal about the NIH.
I believe in its mission and I believe in scientific integrity." said
the doctor. "That's really what this fight was all about: scientific
integrity."

At the end of our conversation, Dr. Fishbein referred me to an
apparently unrelated story - the December 29, 2005 Wall Street
Journal story on Perchlorate - a chemical used in solid-rocket
fuel that is at the center of an ongoing battle between the Department
of Defense (DOD) and the Environmental Protection Agency (EPA).

The EPA says perchlorate causes neurological damage in fetuses
in anything over one part per billion; the DOD says that it's safe
at much higher levels than the EPA is allowing for - as much as
200 parts per billion.

Following the EPA guidelines could necessitate clean up of water
sources in 35 states, including the massive Colorado River.

"The cleanup would bankrupt the DOD," said Fishbein.

To settle the fight, the DOD took its case to the White House, who
told the EPA to halt any further action in the case. The White House
then appointed its own committee to come up with a ruling.

The result? Based on their committee's review, the allowable level
of perchlorate in drinking water is 24 parts per billion - 24 times
that of the EPA safety recommendation.

"That's how political considerations get in the way of science," said
Dr. Fishbein, the good man at the NIH.

Resources:

Dr. Jonathan Fishbein's official website and documents

Nevirapine (Viramune) Warning Label - 2005

The Trouble with Nevirapine by Anthony Brink, Treatment Information Group 2001

AIDS drugs in Mothers and Children and AZT studies Alberta Reappraising AIDS Society

The Fight to Limit Regulation of a Military Pollutant (Perchlorate) Peter Waldman, Wall Street
Journal, Dec 29, 2005

1 Inside Incarnation by Liam Scheff, NY Press, July/Aug 2005