What Can We Learn from Medical Whistleblowers?
by Jeanne Lenzer
June 2, 2005
Their
experiences paint a troubling picture of American medicine's
ties with the pharmaceutical industry.
~Jeanne
Lenzer
A year ago, I received an E-mail from a research scientist at
a major pharmaceutical company. The scientist had read my
articles on whistleblowers who had raised concerns about the
undue influence of the pharmaceutical industry on American
medicine. My industry source had information for me about drug
company practices, but - out of fear of career ruin - would
only talk on the condition that I would conceal the
scientist's identity.
For the next year or so, I had repeated contacts with the
scientist. As I listened to this researcher - and to the other
medical whistleblowers that I continued to interview - it
occurred to me that each whistleblower was like the proverbial
blind man with a hand on the elephant. Each could describe one
piece of the puzzle, but the full picture could only emerge by
bringing these whistleblowers together.
With an eye to focusing on the systemic problems that have
allowed American medicine to be unduly influenced by industry,
on May 15, 2005, I brought together five whistleblowers in
Washington, D. C. I asked them each to tell their story and to
suggest ways to restore objectivity to medicine and medical
research.
The Whistleblowers
Four whistleblowers attended in person, and the anonymous
industry scientist participated via speakerphone. The
whistleblowers came from an extraordinary variety of different
professional backgrounds.
David Graham. This Food and Drug Administration (FDA)
safety officer raised concerns about the cardiovascular side
effects of rofecoxib (Vioxx) and other Cox-2 inhibitors. He
testified at a United States Senate Finance Committee hearing
on rofexocib, the FDA, and Merck [1,2]. Graham attended the
roundtable in his own personal capacity and was not
representing the FDA.
Allen Jones. This investigator at the Pennsylvania
Office of the Inspector General led an investigation into an
off-the-books account, funded in part by drug companies, from
which payments were made to state employees to develop a
medication treatment algorithm. He filed a civil rights
lawsuit against the Pennsylvania Office of the Inspector
General to protect his right to publicly discuss his findings,
and was later fired from his job for talking to the press [3,6].
Stefan Kruszewski. This Harvard-trained psychiatrist
was hired by the Bureau of Program Integrity in the
Pennsylvania Department of Public Welfare to oversee the
state's mental health and substance misuse programs. He filed
a law suit in a federal court in the Middle District of
Pennsylvania, charging that he was fired after uncovering
widespread abuse and fraud in the bureau [7,8].
Kathleen Slattery-Moschkau. This former drug
representative left the pharmaceutical industry after
witnessing marketing practices that she found disturbing. She
wrote and directed the movie Side Effects, a fictionalized
account of her experiences [9,10].
The anonymous research scientist. This is an industry
insider who said to me, ahead of the roundtable, that the
culture of secrecy at drug companies too often results in
claims that are closer to "propaganda" than science.
Lessons Learned from the Roundtable
Ties between drug regulators and industry may influence new
drug approval. David Graham described the frustrations he had
felt in his almost 20 years of experience as an FDA drug
safety officer. Although he was instrumental, he said, in
getting ten drugs off the market because of safety concerns,
his experience was like a salmon swimming upstream - "a single
individual ... against the tide." The tide, he said, "is an
entire institution whose mission is to approve drugs and make
industry happy."
The FDA, said Graham, is in a "collaborative relationship"
with industry. The FDA gets money from drug companies through
the Prescription Drug User Fee Act of 1992 (see
www.fda.gov/cber/pdufa.htm) "to
approve new drugs and approve them more quickly." The mindset
at the FDA, he said, is that "we will find a reason to approve
a drug no matter how small the indication for the drug."
Graham explained that a senior official at the FDA had told
him: "industry is our client."
When the FDA knows there is a serious problem with a new drug,
he said, the FDA deals with this by saying, "well, we'll
handle it in labeling" even though, said Graham, "FDA knows
labeling doesn't work."
"There is no independent voice for drug safety in the
United States," he said. The upper-level managers in the
FDA's Office of Drug Safety are appointed from the FDA's
Office of New Drugs, which approves new medicines. This makes
the Office of Drug Safety "captive," he said, to the Office of
New Drugs.
The anonymous scientist said that in order to speed up drug
approval, companies "don't measure things like whether we are
really curing the disease, or prolonging life, or preventing
hospitalization, or whether a patient is truly more
functional. Oftentimes, we're measuring intermediate, lesser
things, markers, predictors - we hope - of these clinical
endpoints, but they may or may not be accurate."
And the FDA, said the scientist, requires just two positive
studies to grant approval to a new drug, but there is no
limitation on how many negative studies can be done before one
or two positive studies are produced. This can lead to
approval of a drug even when most studies are negative or show
no effect.
Both Graham and the anonymous scientist suggested putting an
end to the Prescription Drug User Fee Act, and Graham argued
that there needs to be independent authority for those in
charge of drug safety. They indicated that two bills in
Congress, introduced by Senator Grassley and by Congressman
Hinchey, at least partly address these concerns.
"The pharma - FDA complex has to be dismantled," said
Graham, "and the American people have to insist on that,
otherwise we're going to have disasters like Vioxx that happen
in the future."
The race to approve new drugs without proper safety testing
may be compromising the public's health. "Drug companies
assiduously avoid acquiring information about side effects,"
said the industry scientist. "Drug companies will not conduct
safety studies unless they have to - meaning basically that
they're required by a regulator - and that rarely happens."
High-risk patients who might have a bad reaction to a drug,
said the scientist, "are excluded from studies deliberately,
even though, when the drug is approved, these patients will be
targeted for sales." When a safety study is proposed within
the industry, said the scientist, "a typical response will be
that if we conducted a study to find out if there was a safety
problem, people would learn about it and think we had a
problem [which] would destroy the image of safety that has
been so carefully constructed."
Studies are too small and are conducted over too brief a
period to properly assess safety: "The largest studies - the
phase three studies, [which] might be several thousand people
- last for a few months. If drugs kill one in several thousand
per year, this would be a public health catastrophe. A
blockbuster drug with that kind of hazard associated with it
could be associated with tens of thousands of deaths a year,
and it would never be detected in studies of the kind that we
routinely submit and are the basis for approval." These drugs,
said the scientist, and these kinds of risks, are "essentially
out there now, unlabeled, unnoticed, all beneath the radar."
The scientist said that, "to ensure that safety problems will
go unnoticed, we compound the problem of conducting small
studies by setting a statistical threshold for acknowledging
the safety problem that is so high that you know in advance it
could never be reached for any serious side effect, like
myocardial infarction." This practice, said the scientist,
"virtually ensures that if a bad side effect happens to show
up, it's not going to reach the arbitrary level that we call
statistically significant, and the company can maintain that
it's just bad luck." And if a bad result does happen,
"typically a company is not going to publish the study at all.
If they do publish it, the bad result can be omitted as `not
statistically important.'"
The funding of state officials by industry may be affecting
prescribing patterns. Allen Jones described how he
believed that drug companies were acting at the state level to
influence the prescribing of psychiatric medications.
"I began to investigate an account into which
pharmaceutical companies were paying money that was being
accessed by state employees," he said. "Additionally, I found
that various pharmaceutical companies were paying state
employees directly - also giving them trips, perks, lavish
meals, transportation, honorariums up to $2,000 for speaking
in their official capacities at drug company events. They were
given unrestricted educational grants that were deposited into
an off-the-books account - unregistered, unmonitored,
literally operated out of a drawer."
These same state officials, he said, were responsible for
dictating clinical policy and writing guidelines for the
treatment of patients in the state system. These officials
were, he said, receiving money from companies with a stake in
the guidelines. "The protocol they [the officials] were
developing was called the Texas Medication Algorithm Project,
TMAP, which began in Texas in the mid-90s. It outlined
detailed medication guidelines for schizophrenia, depression,
and bipolar disorder. It recommends almost exclusive usage of
newer, patented, very expensive atypical antipsychotics, SSRIs
[selective serotonin uptake inhibitors], and mood
stabilizers." The Texas Medication Algorithm Project, said
Jones, was based on "expert consensus" from industry-supported
meetings.
Jones said that when he wanted to investigate these
findings, he was shut down. "I was told point black,
'Look, drug companies write checks to politicians, they write
checks to politicians on both sides of the aisle - back off.'
He was told, he said, to "quit being a salmon, quit swimming
against a stream." He wouldn't back down from his
investigation, he said, and was demoted. On November 22, 2002,
he filed a civil rights lawsuit "to preserve my job and my
right to speak out." His employer, he said, took him off
investigative duties altogether.
Stefan Kruszewski, who has filed a lawsuit in a federal court
in Pennsylvania, raised concerns to his seniors in the
Pennsylvania Department of Public Welfare about prescribing
practices in the state that he did not feel were evidence
based, and said he lost his job for raising his concerns. For
example, he alerted his seniors to the off-label prescribing
of the anticonvulsant gabapentin (Neurontin) for mood
disorders and addictive disorders.
"The pharmaceutical industry is the single most powerful
lobbying group on Capitol Hill - outspending even the oil and
banking industries," said Jones. "It should come as no
surprise that the ties go far beyond just the mental health
officials who wrote the guidelines, but extend to many of the
politicians who, in the end, allowed an investigation into
pharma corruption to be dropped, and the investigator - me -
to be fired."
Efforts to detect and deter fraud and abuse due to these
conflicts, he said, "will be likely to be undermined as long
as those charged with detecting fraud and abuse, like the
[Pennsylvania] Inspector General, are appointed by politicians
who are themselves beholden to the drug industry. Such
positions should instead be filled by career civil servants
and not political appointees."
Regulatory agencies are not being held accountable. In
comments that echoed his testimony to the U.S. Senate Finance
Committee, Graham said that, "FDA was the single greatest
obstacle to doing anything effective with Vioxx. As a
result, nearly 60,000 people probably died from that drug.
That's as many of our soldiers that were killed in the Vietnam
war [who] died as a result of Vioxx use. And FDA had the
opportunity, the responsibility, to stop that and didn't. In
fact, FDA allowed it to continue. In my book, FDA shares in
the responsibility for those deaths and yet it's not being
held accountable by Congress." Congress itself, added Graham,
is deeply beholden to the drug industry since many politicians
receive "often quite a bit of campaign contributions" from the
industry.
Kruszewski reflected upon the problems he said he had
encountered in Pennsylvania, saying that "there is no
accountability in the system for oversight [agencies]." He
has become "a stronger advocate than ever for a federal
patient bill of rights."!!
Marketing departments can influence doctors' prescribing
habits. The research scientist said that the job was
attractive because of the "many excellent drugs" developed,
such as drugs to treat HIV, but the scientist "also saw drugs
marketed in a way that will exaggerate the benefits and
conceal the risks."
Kathleen Slattery-Moschkau gave an insider's view of drug
marketing practices, from her former experiences as a drug
rep. She clutched her head in disbelief as she told the
roundtable that doctors would come up to her with patients'
charts asking her for advice on treating patients. Slattery-Moschkau,
like most of the drug representatives she came to know over
the years, had no science background at all.
"Drug companies assiduously avoid acquiring information
about side effects."
The various techniques drug representatives were trained in to
"educate doctors" eventually proved to be not just "comical"
but "also scary," she said. "Whether it was hiring, training,
what we were told to say about drugs and what we were told not
to say," it was marketing, not science, that dominated. One of
the techniques used by drug companies was to buy doctors'
prescribing records so drug representatives knew "to the dime"
what drugs doctors were prescribing and could tailor their
marketing to them. Drug representatives developed
"personality profiles" on doctors and were taught to pitch
their sales to specific personality types. Representatives
were compensated, she said, by "how many prescriptions we
could encourage."
Both Slattery-Moschkau and the industry scientist described
tensions within drug companies between marketing departments
and industry scientists. "The marketing spin on things," said
the scientist, "carries the day."
The published medical literature contains many biases. "When
studies are published," said the scientist, "they are
frequently written not by the trained research scientist, who
might have designed and analyzed the study, but by a
designated medical writer with little if any background in
research, but who is trained instead to craft the findings of
the study in the best possible way for the company."
The body of literature available to the public, said the
scientist, "is a biased sample of what companies want people
to see." The research scientist described "a culture of
secrecy," which makes it hard even for industry scientists
tasked with ensuring drug safety to obtain the full datasets
needed to genuinely understand a drug's risk - benefit
profile.
Conclusion
Whistleblowers have been compared to bees - they have just one
sting to use and using it may lead to career suicide [11].
Many of the whistleblowers at the roundtable said they had
experienced retaliation from their employers for raising
concerns, but all had felt obligated to speak out about
practices in medicine and medical research that they believe
are risking the public's health or safety. Graham said he felt
"trapped by the truth" and had to act. "There are bigger
issues here," said Kruszewski. "I felt right from the start
[that] if I wallowed in self-pity about being fired and having
my belongings piled in the gutter that I would never
understand why all these things were happening. The bigger
issue is that we've got people in the pharmaceutical industry
and the health-care industry all acting in synchrony."
Each of these whistleblowers, in very different ways - from
making a satiric film to speaking out in Congress - has shone
light on how this "synchrony" may be compromising the
integrity of American medicine. We should not have to rely on
medical whistleblowers to alert us to these fault lines. If we
are to restore objectivity to drug development, prescribing,
and safety monitoring, we must be willing to examine and
change all of the institutions that allow this synchrony to
occur.
Acknowledgments
The roundtable was co-sponsored by the Public Library of
Science and the Government Accountability Project (www.whistleblower.org),
a public interest group that helps whistleblowers in order to
promote governmental and corporate accountability.
References
1. Kaufman M (2004 October 8) FDA official alleges pressure to
suppress Vioxx findings. Washington Post. Accessed 18 May
2005.
2. Lenzer J (2004) FDA is incapable of protecting US "against
another Vioxx". BMJ 329: 1253. Find this article online
3. Lenzer J (2004) Whistleblower removed from job for talking
to the press. BMJ 328: 1153. Find this article online
4. Lenzer J (2004) Bush plans to screen whole US population
for mental illness. BMJ 328: 1458. Find this article online
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officials. BMJ 328: 306. Find this article online
6. Petersen M (2004 February 1) Making drugs, shaping the
rules. New York Times. Available here: Accessed 18 May 2005.
7. Lenzer J (2004) Whistleblower charges medical oversight
bureau with corruption. BMJ 329: 69. Find this article online
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for exposing abuse. Philadelphia Daily News. Available here.
Accessed 18 May 2005.
9. Lenzer J (2005) Confessions of a drug rep. BMJ 330: 911.
Find this article online
10. Associated Press (2005 March 10) Film exposes
pharmaceutical secrets. Associated Press - Available here.
Accessed 18 May 2005.
11. Vinten G (1994) Whistle while you work in the
health-related professions? J R Soc Health 114: 256 - 262.
Find this article online
Jeanne Lenzer is a freelance medical investigative journalist
based in
Kingston, New York, United States of America. E-mail:
jeanne.lenzer [at] gmail.com
Competing Interests: The author declares that she has no
competing interests.
(Published on Public Library of Science website)
