For those who thought John LeCarre’s ‘fictional’ Book / Movie, The Constant
Gardner, was over the top in its depiction of a ruthless pharmaceutical
company and corrupt practices in AIDS drug research, read this non-fictional
account.
This riveting, informative article begins by describing the toxic effect of
the AIDS drug, Nevriapine, and the rapid physical deterioration and ultimate
death of, Joyce Ann Hafford, a 33-year old pregnant mother of a 13 year old
boy. As the facts of the case unfold, it seems that her life was sacrificed
on the altar of AIDS research . Hafford was told she was HIV positive on the
basis of a single screen which, unbeknown to her, is a test known to have a
high rate of false-positives. [1] Though she was perfectly healthy and
showed no signs of any of the HIV markers, she agreed to participate in a
Phase III clinical trial (PACTG 1022) of nevirapine because she was told it
would protect the baby she was carrying.
"The objective of the trial, PACTG 1022, was to compare the “treatment
limiting toxicities” of two anti-HIV drug regimens." However, women in AIDS
drug experiments such as this are not informed that "Of the four drugs in
this study, three belong to the FDA’s category “C,” which means that safety
to either mother or fetus has not been adequately established."
Hafford was enrolled in the trial and in early June, 2003, and "on June 18
took her first doses of the drugs.” Her older sister, Rubbie King, recalled:
“She felt very sick right away, within seventy-two hours, she had a very bad
rash, welts all over her face, hands, and arms. That was the first sign that
there was a problem. I told her to call her doctor and she did, but they
just told her to put hydrocortisone cream on it. I later learned that a rash
is a very bad sign, but they didn’t seem alarmed at all.”
Hafford was on the drug regimen for thirty-eight days. “Her health started
to deteriorate from the moment she went on the drugs,” says King. “She was
always in pain, constantly throwing up, and finally she got to the point
where all she could do was lie down.”
"On July 16, at her scheduled exam, Hafford’s doctor took note of the rash,
which was “pruritic and macular- papular,” and also noted that she was
suffering hyperpigmentation, as well as ongoing nausea, pain, and vomiting.
By this time all she could keep down were cans of Ensure. Her blood was
drawn for lab tests, but she was not taken off the study drugs, according to
legal documents and internal NIH memos. Eight days later, Hafford went to
the Regional Medical Center “fully symptomatic,” with what legal documents
characterize as including: “yellow eyes, thirst, darkening of her arms,
tiredness, and nausea without vomiting.”
She also had a rapid heartbeat and difficulty breathing. Labs were drawn,
and she was sent home, still on the drugs. The next day Hafford was summoned
back to the hospital after her lab reports from nine days earlier were
finally reviewed. She was admitted to the hospital’s ICU with “acute and
sub-acute necrosis of the liver, secondary to drug toxicity, acute renal
failure, anemia, septicemia, premature separation of the placenta,” and
threatened “premature labor.” She was finally taken off the drugs but was
already losing consciousness." The family could not afford the $3,000 for an
autopsy, so none was performed.
"There was a liver biopsy, however,which revealed, according to internal
communiqués of [NIH Division of AIDS] DAIDS staff, that Hafford had died of
liver failure brought on by nevirapine toxicity.
What the family was told about the cause of Hafford’s death:
“They told us how safe the drug was, they never attributed her death to the
drug itself, at all. They said that her disease, AIDS, must have progressed
rapidly.”
But her sister realized something was very wrong: "‘On the one hand they’re
telling us this drug is so safe, on the other hand they’re telling us
they’re going to monitor the other patients more closely. If her disease was
progressing, they could have changed the medication.’ I knew something was
wrong with their story, but I just could not put my finger on what it was.”
In fact, Farber reports, “Joyce Ann Hafford never had AIDS, or anything even
on the diagnostic scale of AIDS." Of note: Nevirapine was one of the
experimental drugs tested in children and babies in foster care in violation
of federal regulatory protections. [2] And many of the foster babies in the
AIDS drug / vaccine trials did not have AIDS either.
"The conclusion of the PACTG 1022 study team was published in the journal
JAIDS in July of 2004. “The study was suspended because of greater than
expected toxicity and changes in nevirapine prescribing information.” The
authors reported that within the nevirapine group, “one subject developed
fulminant hepatic liver failure and died, and another developed S t e v e n
s -Johnson syndrome” (i.e. skin necrolysis—a severe toxic reaction that is
similar to internal third-degree burns, in which the skin detaches from the
body).
Patients recruited for clinical trials in experiments that involve high risk
and high financial stakes—particularly those from disadvantaged
populations—all too often encounter an arrogance bordering on unconscionable
disregard for the rights and dignity of the subjects whose lives are
devalued by an elitist corps of powerful intersecting self-interest groups
who are not held accountable by anyone. Disadvantaged, members of a minority
cannot possibly challenge powerful doctors who are shielded by powerful
institutions. They and subsequently their families have no leverage.
John Solomon, of the Associated Press, who first reported about the
controversy surrounding Nevirapine, and Joyce Ann Safford’s death, noted
that Nevirapine had been hailed by the vested AIDS community as a "life
saving" drug and a “very important tool” to combat HIV in the Third World.
In fact, President Bush allocated $500 million for the drug to be given to
African nations as a "cheap solution" for protecting African babies from
AIDS. AP reported the President had not been informed by NIH officials that
the drug had in fact been found to cause "thousands of severe reactions
including deaths." [3]
Farber sheds light on the apparent disconnect between what the evidence from
clinical trials (PACTG 1022) and the highly publicized Nevirapine trials
conducted in Uganda (HIVNET 012) show, and the false claims made for public
consumption.
When the drug’s manufacturer, Boehringer Ingelheim inspected the Uganda
trial (HIVNET 012): "They were the first to discover what a shambles the
study was.” According to Boehringer’s pre-FDA inspection report, “serious
non-compliance with FDA regulations was found” in the specific requirements
of reporting serious adverse events. Problems also were found in the
management of the trial drug and in informed-consent procedures.”
Farber writes that the DAIDS then hired a private contractor, a company
named Westat, to go to Uganda and do another pre-FDA inspection. This time
the findings were even more alarming: the major problems that clearly
disqualified the trial included:
• “loss of critical records” including “one of two master logs” that
included follow-up data on adverse events, including deaths.”
• “The records failed to make clear which mothers had gotten which
drug, when they’d gotten it, or even whether they were still alive at
various follow up points after the study.”
• “Drugs were given to the wrong babies, documents were altered, and
there was infrequent follow-up.”
• “The infants that did receive follow-up care were in many cases
small and underweight for their age. It was thought to be likely that some,
perhaps many, of these infants had serious health problems.”
• “The Westat auditors looked at a sample of forty-three such infants,
and all forty-three had “adverse events” at twelve months. Of these, only
eleven were said to be HIV positive."
Clearly, the Uganda trial failed to meet minimal safety and scientific
standards.
Yet, Farber reports, though the two inspections had now declared HIVNET to
be “a complete mess,” and DAIDS officials were well aware of the facts, “the
ways in which the various players were tethered together made it impossible
for DAIDS to condemn the study without condemning itself.” Thus, according
to DAIDS’ public version of events, which was dutifully echoed in the AIDS
press, “the trouble with HIVNET was that it was unfairly assailed by
pedantic saboteurs who could not grasp the necessary difference between U.S.
safety standards and the more lenient standards that a country like Uganda
deserved.”
Framed another way, DAIDS trivializes Ugandans’ human right to protections
ensured by minimal standards of safety and scientific validity in medical
experiments that they are asked to participate in. Within two weeks of the
devastating report by Westat, DAIDS officials knowingly deceived the public
by issuing the following patently false statement:
“There is no question about the validity [of the HIVNET results] . . . the
problems are in the rather arcane requirements in record keeping.”
Farber then comments on the politics and undisclosed pervasive conflicts of
interest that undermine the credulity of most claims made by vocal AIDS
activists about treatment success, noting the uncritical media that
broadcasts propaganda:
"So-called community AIDS activists were sprung like cuckoo birds from
grandfather clocks at the appointed hour to affirm the unwavering AIDS
cathechism: AI D S drugs save lives. To suggest otherwise is to endanger
millions of African babies. Front and center were organizations like the
Elizabeth Glaser Pediatric AIDS Foundation, which extolled the importance of
nevirapine. Elizabeth Glaser’s nevirapine defenders apparently didn’t
encounter a single media professional who knew, or cared, that the
organization had received $1 million from nevirapine’s maker, Boehringer
Ingelheim, in 2000."
"This was no scandal but simply part of a landscape. Pharmaceutical
companies fund AIDS organizations, which in turn are quoted uncritically in
the media about how many lives their drugs save. This time the AIDS
organizations were joined by none other than the White House, which was in
the midst of promoting a major program to make nevirapine available across
Africa."
[note] "Africa, as the news media never tires of telling us, has become
ground zero of the AIDS epidemic. The clinical definition of AIDS in
Africa, however, is stunningly broad and generic, and was seemingly designed
to be little other than a signal for funding. It is in no way comparable to
Western definitions. The “Bangui definition” of AIDS was established in the
city of Bangui in the Central African Republic, at a conference in 1985. The
definition requires neither a positive HIV test nor a low T-cell count, as
in the West, but only the presence of chronic diarrhea, fever, significant
weight loss, and asthenia, as well as other minor symptoms. These happen to
be the symptoms of chronic malnutrition, malaria, parasitic infections, and
other common African illnesses. "
AIDS advocates may be largely responsible legislation (1997 FDA
Modernization Act , FDAMA) that speeded up the drug approval process by
short circuiting safety tests. The unintended consequences are that the bar
for drug safety has been lowered. Furthermore, their lobbying efforts have
undermined the sin quo non of medicine—which requires proof of safety and
effectiveness for treatments. This has set us back to the time when snake
oil purveyors roamed the countryside selling their, at best, worthless
potions, at worst, lethal ones.
The buzzword in AIDS (as well in psychiatry) is neither effectiveness nor
safety—it is “access,” which has the advantage of short-circuiting the
question of whether the treatments actually work.
Prior to FDAMA, the burden of proof that a drug was safe and effective
rested on manufacturers. Since then, under pressure from manufacturers who
were emboldened by the AIDS activists’ demand for speedy approval, the FDA
(in essence) presumes safety and efficacy unless someone proves otherwise.
Hence, we are again confronted with unsafe, lethal drugs such as Vioxx being
approved without evidence of their safety.
While reading Farber’s riveting account of the documented scientific facts
that emerged in clinical trials of the AIDS drug, Nevirapine—evidence that
belies the claims made by stakeholders in the AIDS drug enterprise–one is
struck by the similarity of the disconnect in psychiatry between the
scientific data and claims made. One is also struck by the similarity
between the politics of AIDS and psychiatry. In both there is a disconnect
between the scientific data and the ideology upon which practice guidelines
rest. In both of these contentious fields the prevailing opinions rest on
theories, but no firm scientific knowledge. And most troubling of all, in
both fields there is an aversion for debate and intolerance of critics who
dare to challenge the prevailing ideology in AIDS and psychiatry–critics
are shunned as pariahs.
This sorry state of affairs–so antithetical to the essence of academia and
the Socratic tradition–leads one to suspect that those in the seats of
power–in AIDS and psychiatry –are unable to refute any opposing arguments.
Thus, they adopt a position akin to academic Stalinism or, if one prefers,
religious dogma that tolerates no dissent.
By abusing their power to stifle ideas that contradict their own for fear
their authority and the status quo would be toppled, they impose
intellectual stagnation that hinders discovery of new improved paradigms of
care.
References:
1. Is a Positive Western Blot Proof of HIV Infection? Eleni
Papadopulos-Eleopulos, Valendar F. Turner and John M. Papadimitriou
BIO/TECHNOLOGY VOL.11 JUNE 1993
http://www.virusmyth.net/aids/data/epwbtest.htm ; see also,
http://www.virusmyth.net/aids/index/hivtests.htm
2. See, letters of determination by the Office of Human Research
Protections,
May, 2005: http://www.hhs.gov/ohrp/detrm_letrs/YR05/may05c.pdf
February, 2006: https://ahrp.org/cms/content/view/82/31 /
3. See: Woman Died During Aids Study
https://ahrp.org/infomail/04/12/16.php
Contact: Vera Hassner Sharav
veracare@ahrp.org
OUT OF CONTROL: AIDS and the corruption of medical science, By Celia Farber
in the current issue of Harper’s magazine.
See excerpt below:
“…..Joyce Ann Hafford was thirty-three years old and had always been
healthy.
She showed no signs of any of the clinical markers associated with AIDS—her
CD4 counts, which measure the lymphocytes that are used to indicate how
strong a person’s immune system is, and which HIV is believed to slowly
corrode, were in the normal range, and she felt fine. In early June 2003,
she was enrolled in the trial and on June 18 took her first doses of the
drugs. “She felt very sick right away,” recalls her older sister, Rubbie
King. “Within seventy-two hours, she had a very bad rash, welts all over her
face, hands, and arms. That was the first sign that there was a problem. I
told her to call her doctor and she did, but they just told her to put
hydrocortisone cream on it. I later learned that a rash is a very bad sign,
but they didn’t seem alarmed at all.”
Hafford was on the drug regimen for thirty-eight days. “Her health started
to deteriorate from the moment she went on the drugs,” says King. “She was
always in pain, constantly throwing up, and finally she got to the point
where all she could do was lie down.” The sisters kept the news of Hafford’s
HIV test and of the trial itself from their mother, and Hafford herself
attributed her sickness and nausea to being pregnant. She was a cheerful
person, a non-complainer, and was convinced that she was lucky to have
gotten into this trial. “She said to me, ‘Nell’ —that’s what she called
me—‘I have got to get through this. I can’t let my baby get this virus.’…….
"This situation has had particularly tragic ramifications on the border
between the class of Americans with good health insurance, who are
essentially consumers of pharmaceutical goods, and those without insurance,
some of whom get drugs “free” but with a significant caveat attached: They
agree to be experimented on. These people, known in the industry as
“recruits,” are pulled in via doctors straight from clinics and even
recruited on the Internet into the pharmaceutical industry and the
government’s web of clinical trials, thousands of which have popped up in
recent years across the nation and around the world. Such studies help
maintain the industry’s carefully cultivated image of benign concern, of
charity and progress, while at the same time feeding the experimental
factories from which new blockbuster drugs emerge. “I call them what they
are: human experiments,” says Vera Hassner Sharav, of the Alliance for Human
Research Protection in New York City. “What’s happened over the last ten to
fifteen years is that profits in medicine shifted from patient care to
clinical trials, which is a h u g e industry now. Everybody involved, except
the subject, makes money on it, like a food chain. At the center of it is
the NIH, which quietly, while people weren’t looking, wound up becoming the
partner of industry.”
By June 2004, the National Institutes of Health had registered 10,906
clinical trials in ninety countries. The size of these trials, which range
from the hundreds to more than 10,000 people for a single study, creates a
huge market for trial participants, who are motivated by different factors
in different societies but generally by some combination of the promise of
better health care, prenatal
care, free “access” to drugs, and often—especially in the United States—cash
payments. Participating doctors, whose patient-care profits have been
dwindling in recent years because of insurance-company restrictions, beef up
their incomes by recruiting patients. Dr. Jonathan Fishbein is hardly a
rabble-rouser. But he is a passionate advocate of “good clinical practice,”
or GCP, a set of international standards that were adopted in 1996, as
clinical-trial research boomed. The GCP handbook states: “Compliance with
this standard provides public assurance that the rights, safety,
and well-being of trial subjects are protected, consistent with the
principles that have their origin in the Declaration of Helsinki, and that
the clinical trial data are credible.”
During the decade prior to his arrival at DAIDS, Fishbein had overseen and
consulted on hundreds of clinical trials for just about every pharmaceutical
company. Fishbein knew,
before he took his job as director of the Office for Policy in Clinical
Research Operations at DAIDS, that there was a troubled study haunting the
whole division. Nobody was supposed to talk about it, but it hung heavily in
the air. “Something about Uganda, that’s all I knew,” he says. There was a
trial staged there, a big one, that had been plagued with “problems,” and
there was also a lot of talk about one particular employee connected to this
trial who would need to be disciplined. Soon he discovered just how bad the
situation was. “The HIVNET thing,” he recalls, “it hit me like a fire hose
when I walked in there.” Fishbein’s position was new. “It sounded like a
very important position,” he says. “I was to oversee the policies governing
all the clinical research operations, both here and abroad.” He was told he
would have “go–no go” authority over individual trials. It wasn’t long
before Fishbein realized that he was, in effect, taking a job that was the
equivalent of piloting an already airborne plane. “They had all these trials
going on, and hundreds of millions of dollars flowing in every year, but
there was apparently no one in a senior position there who really had
clinical expertise—who knew all the nuances, rules, and regulations in the
day-today running of clinical trials.”
DAIDS, when Fishbein came to work there in 2003, was running about 400
experimental trials both in the United States and abroad. A DAIDS project
officer close to the HIVNET study closed the door when she had her first
meeting with Fishbein. She had also crossed over from the private sector,
and so she and Fishbein shared disillusionment over how much shoddier and
more chaotic the research culture was within the government, compared with
industry. “I’m really frightened about the stuff that goes on here,” she
told him. “We really need somebody.” This project officer, who for her own
protection cannot be named, told Fishbein that the division’s fla gship
study in Africa—HIVNET 012—had been wracked with problems and completely
lacking in regulatory standards. She told Fishbein that the trial
investigators were “out of control,” and that there was no oversight of
them, and nobody with either the inclination or the authority to make them
adhere to safety standards. What Fishbein subsequently learned entangled him
in a story with eerie echoes of John Le Carré’s Constant Gardener.
For our purposes, the story of nevirapine begins in 1996, when the German
pharmaceutical giant Boehringer Ingelheim applied for approval of the drug
in Canada. The drug had been in development since the early 1990s, which was
a boom time for new HIV drugs. Canada rejected nevirapine twice, once in
1996 and again in 1998, after the drug showed no effect on so-called
surrogate markers (HIV viral load and CD4 counts) and was alarmingly toxic.
In 1996, in the United States, the FDA nonetheless gave the drug conditional
approval…"
…….
Although HIVNET was designed to be a randomized, placebocontrolled,
double-blind, Phase III trial of 1,500 mother/infant pairs, it wound up
being a no-placebo, neither double- nor even single-blind Phase II trial of
626 mother/infant pairs. Virtually all of the parameters outlined for HIVNET
012 were eventually shifted, amended, or done away with altogether,
beginning with perhaps the most important— the placebo controls. By a
“Letter of Amendment” dated March 9, 1998, the placebo-control arms of
HIVNET were eliminated. The study as reconstituted thus amounted to a simple
comparison of AZT and nevirapine. On September 4, 1999, The Lancet published
HIVNET’s preliminary results, reporting that “Nevirapine lowered the risk of
HIV-I transmission during the first 14–16 weeks of life by nearly 50
percent.”
The report concluded that “the two regimens were well-tolerated and adverse
events were similar in the two groups.” The article also reported that
thirty-eight babies had died, sixteen in the nevirapine group and twenty-two
in the AZT group. The rate of HIV transmission in the AZT arm was 25
percent, while in the nevirapine group it was only 13 percent. As H o p k i
n s Medical News later reported, the study was received rapturously. “The
data proved stunning. It showed that nevirapine was 47 percent more
effective than AZT and had reduced the number of infected infants from 25 to
13 percent. Best of all, nevirapine was inexpensive—just $4 for both doses.
If implemented widely, the drug could prevent HIV transmission in more than
300,000 newborns a year.” With the results of the study now publ ished in
The Lancet, Boehringer, which previously had shown little interest in
HIVNET, now pressed for FDA approval to have nevirapine licensed for use in
preventing the transmission of HIV in pregnancy.
There were complications, however. On December 6, 2000, a research letter
in The Journal of the American Medical Association warned against using
nevirapine for post-exposure treatment after two cases of life-threatening
liver toxicity were reported among health-care workers who’d taken the drug
for only a few days. (One of them required a liver transplant.) The January
5, 2001, issue of the CDC’s M o rbidity and Mortality Weekly Report (MMWR)
contained an FDA review of MedWatch—an informal reporting system of drug
reactions—that highlighted an additional twenty cases of “serious adverse
events” resulting from fairly brief nevirapine post-exposure prophylaxis.
“Serious adverse events” were defined as anything “life-threatening,
permanently disabling,” or requiring “prolonged hospitalization, or [. . . ]
intervention to prevent permanent impairment or damage.” The MMWR stressed
that there probably were more unreported cases, since the reporting by doctors to MedWatch is “voluntary”
and “passive.” But NIAID was on another track altogether, either oblivious
of or undeterred by the toxicity controversy."
In 2001, Boehringer Ingelheim submitted its supplemental licensing request
to the FDA. The request was submitted based entirely on the results of
HIVNET, as published in The Lancet. Since Boehringer had not originally
intended to use this study for licensing purposes, it decided to perform its
own inspection before the FDA arrived. Boehringer’s team arrived in Kampala
and did a sample audit. They were the first to discover what a shambles the
study was.
According to Boehringer’s preinspection report, “serious non-compliance with
FDA Regulations was found” in the specific requirements of reporting serious
adverse events. Problems also were found in the management of the trial drug
and in informed-consent procedures. DAIDS then hired a private contractor, a
company named Westat, to go to Uganda and do another preinspection. This
time the findings were even more alarming. One of the main problems was a
“loss of critical records.” One of two master logs that included follow-up
data on adverse events, including deaths, was said to be missing as the
result of a flood. The records failed to make clear which mothers had gotten
which drug, when they’d gotten it, or even whether they were still alive at
various followup points after the study. Drugs were given to the wrong
babies, documents were altered, and there was infrequent follow-up, even
though one third of the mothers were marked “abnormal” in their charts at
discharge. The infants that did receive follow-up care were in many cases
small and underweight for their age. “It was thought to be likely that some,
perhaps many, of these infants had serious health problems.” The Westat
auditors looked at a sample of forty-three such infants, and all forty-three
had “adverse events” at twelve months. Of these, only eleven were said to be
HIV positive."
The HIVNET team had essentially downgraded all serious adverse events
several notches on a
scale it had created to adapt to “local” standards. That downgrade meant,
among other things, that even seemingly “life-threatening” events were
logged as not serious. Deaths, unless they occurred within a certain time
frame at the beginning of the study, were not reported or were listed as
“serious adverse events” rather than deaths. In one case, “a still birth was
reported as a Grade 3 adverse event for the mother.”
As a defense, the HIVNET team often cited ignorance. They told the Westat
monitors that they were unaware of safety-reporting regulations, that they’d
had no training in Good Clinical Practice, and that they had “never
attempted a Phase III trial.” The principal investigators
and sub-investigators “all acknowledged the fin dings [of the audit] as
generally correct,” the Westat report said. “Dr. Guay and Dr. Jackson noted
that many (‘thousands’) of unreported AE’s
and SAE’s occurred. . . .They acknowledged their use of their own
interpretation of ‘serious’ and of severity.”
“All agreed” that the principal and subinvestigators “had generally not seen
the trial patients,” and “all agreed” that in evaluating adverse and
serious adverse events “they had relied almost entirely on second or third
hand summaries . . . without attempting to verify accuracy.”
Westat also discovered that half the HIVpositive infants were also enrolled
in a vitamin A trial, which effectively invalidates any data associated with
them.
In light of the Westat report, DAIDS and Boehringer asked the FDA for a
postponement of its inspection visit. The FDA responded by demanding to see
the report immediately. On March 14, 2002, the FDA called a meeting with DAIDS, Boehringer, and the trial
investigators. “They reprimanded the whole gang,” says Fishbein. Then they
said to Boehringer: Withdraw your application for extended approval, if you want to avoid a public rejection.”
Boehringer complied with the FDA ’ s demand, though statements put out by
NIAID made it sound as if the company had withdrawn the application for FDA
approval in a spirit of profound concern for protocol. In South Africa, a few months later, the news focused
on the angry chorus of AIDS experts and activists, speaking as one.…….cut
…..
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