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May 30, 2005

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Public Library of Science - Medicine

What Can We Learn from Medical Whistleblowers?

Their experiences paint a troubling picture of American medicine's

ties with the pharmaceutical industry

Jeanne Lenzer

Jeanne Lenzer is a freelance medical investigative journalist based in

Kingston, New York, United States of America. E-mail:

jeanne.lenzer

Competing Interests: The author declares that she has no competing

interests.

Published: May 27, 2005

DOI: 10.1371/journal.pmed.0020209

distributed under the terms of the Creative Commons Attribution

License, which permits unrestricted use, distribution, and

reproduction in any medium, provided the original work is properly cited.

Abbreviation: FDA, Food and Drug Administration

Citation: Lenzer J (2005) What Can We Learn from Medical

Whistleblowers? PLoS Med 2(7): e209

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.

Each whistleblower was like the proverbial blind man with a hand on

the elephant.

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

http://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. "

" There is no independent voice for drug safety in the United States. "

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 law suit 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 US 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. Available:

http://www.washingtonpost.com/wp-dyn/articles/A16546-2004Oct7.html.

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

5. Moynihan R (2004) Drug company targets US state

health officials. BMJ 328: 306. Find this article online

6. Petersen M (2004 February 1) Making drugs,

shaping the rules. New York Times. Available:

http://psychrights.org/Articles/NYTMakingDrugsShapingtheRules.htm.

Accessed 18 May 2005.

7. Lenzer J (2004) Whistleblower charges medical

oversight bureau with corruption. BMJ 329: 69. Find this article online

8. Weisenseegan N (2004 July 7) Lawsuit: State

fired shrink for exposing abuse. Philadelphia Daily News. Available:

http://www.philly.com/mld/dailynews/news/special_packages/phillycom_front_dn/103\

52527.htm?template=contentModules/printstory.jsp.

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:

http://www.forbes.com/associatedpress/feeds/ap/2005/03/11/ap1878239.html.

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

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