FDA Underhanded Tactics Against Medical Officer Who Blew the Whistle

Mon, 29 Nov 2004

The Food and Drug Administration is the epicenter of a collision between medical officers in the drug safety office and senior officials in managerial positions whose focus is on facilitating new drug approvals. Officials at the Center for Drug Evaluation and Research (CDER) are obstructing the release of safety information about lethal drug side-effects. This contentious debate has spilled into the public arena due largely to the courageous stand taken by two senior medical officers in the drug safety division, Dr. Andrew Mosholder and Dr. David Graham, who would not keep silent about widely marketed drugs that kill.

FDA’s credibility has been badly undermined by senior FDA officials who turned a blind eye to evidence of fatal risks linked to drugs the agency approved as safe and exacerbated by their attempts to muzzle, intimidate and discredit senior medical officers. The boiling point came following Dr. Graham’s compelling testimony before the Senate Finance Committee on November 21. He testified how the FDA, as currently constituted, is “virtually incapable” of protecting the public from hazardous drugs: “The catastrophe of Vioxx, a pain-reliever estimated to have caused fatal heart attacks in 55,000 people, is only a “symptom of a broken regulatory system that is currently incapable of preventing further such tragedies.” [1]

He further testified that five currently marketed drugs needed closer review because of safety issues. He named: Crestor, AstraZeneca’s cholesterol drug); Bextra, Pfizer’s pain drug similar to Vioxx; Meridia, Abbott’s obesity treatment; Serevent, GlaxoSmithKline’s asthma drug; and Accutane, Roche’s severe acne treatment. Of note, FDA Œs MedWatch received the greatest number of suicide reports involving children under 18, were attributed to accutaine.

In the course of Dr. Graham’s 20 year career at the FDA he had recommended that 12 drugs be taken off the market because they harmed people. He valiantly fought with FDA officials and did get 10 of these drugs removed: among them, the diabetes drug Rezulin, the diet pills Fen-Phen and Redux, the cholesterol-lowering drug Baycol, the heartburn remedy Propulsid, and the antihistamine Seldane. [2, 3, 4]

The latest maneuvers include legally questionable actions, such as: anonymous phone calls by high ranking FDA officials who pretended to be whistleblowers, made false accusations in a malicious effort to discredit Dr. Graham. These maneuvers were reported by Jeanne Lenzer in the British Medical Journal, followed by The Washington Post, The New York Times, USA Today. Senator Charles Grassley has called upon the Inspector General to investigate the charges that high ranking FDA officials have attempted to discredit Dr. Graham: “it appears that these activities may have been coordinated by FDA management and may have involved the misuse of government resources, including government property and time.” [5]

AHRP has also learned that Dr. Graham is being threatened with exile from his field of expertise in the division of drug safety – FDA managerial officials would transfer him to a bureaucratic job in the commissioner’s office with no access to safety data.

The harassment began when the findings of Dr. Andrew Mosholder’s embargoed report linking antidepressants to an increased suicide risk for adolescents, reached the public (February 1, 2004). At that time, senior FDA officials initiated an illegal criminal investigation naming Dr. Mosholder and Dr. Graham.

On October 9, Dr. Paul Seligman, FDA’s deputy director of CDER admitted under oath at a Congressional hearing before the subcommittee on oversight and investigations of the House Energy & Commerce Committee, that he and Dr. Steven Galson, CDER director, had discussed the criminal investigation, apparently supporting it. This illegal investigation was stopped when Senator Grassley intervened.

Following the November Senate hearing, Dr. Sandra Kweder, deputy director of FDA’s office of new drugs, defended the benefits of Vioxx on National Public Television. Dr. Kweder claimed that the deaths linked to Vioxx are “not real deaths.” [6] Furthermore, she stated: “You can’t just look at the cardiovascular risks of this drug. One has to look at the full spectrum of risks and potential benefits.” [6] Merck’s decision to withdraw its drug from the market is an indication that company executives disagreed with Dr. Kweder’s judgment.

FDA officials whose decisions are contradicted by the scientific evidence have made false allegations and tried to block Dr. Graham from publishing his scientific findings about the lethal cardiac risks posed by Vioxx. His articles were accepted by two major medical journals – The Lancet and the Journal of the American Medical Association. Dr. Galson publicly accused Dr. Graham of engaging in “junk science” while FDA officials continued to claim that Vioxx was safe up until Merck’s withdrawal of the drug, conceding the cardiac risk. One wonders what science these senior FDA officials relied on when they claimed Vioxx was safe.

Another major blow to FDA’s credibility was time delivered by the Journal of the American Medical Association (JAMA). A highly critical editorial–Postmarketing Surveillance – Lack of Vigilance, Lack of Trust – by JAMA’s editor in chief and two deputy editors, echoes Dr. Graham’s testimony before the Senate assessing the FDA’s broken regulatory system. Their review underscores the credibility of Dr. Graham. Other independent analysts who conducted a cumulative metaanalysis of randomized trials of rofecoxib (Vioxx) against control groups found that “by the end of the year 2000, the relative risk for cardiovascular events among those taking rofecoxib was 2.30 (95% confidence interval, 1.22-4.33; P=.01). Yet, more than 3 years later, when the cardiovascular risks of rofecoxib were documented by FDA researchers several months before the data that ultimately led to removal of the drug from the market became publicly available, FDA officials allegedly attempted to ‘suppress’ the conclusions of the report.” [7]

Industry’s corrosive effect on the integrity of the scientific process and the culture at the FDA high level FDA officials resort to unseemly cut throat maneuvers, clearly demonstrate the need to erect an impenetrable fire wall between scientists and industry. Indeed, JAMA editors call for a separation of the pre-and post-marketing surveillance systems for prescription drugs and independent drug approval and monitoring free of pharmaceutical industry influence. The editorial notes that the pharmaceutical industry provided $825 million in user fees to the FDA and spent $4.9 million to lobby the FDA.

In press reports Catherine DeAngelis asked: “Why are they allowed to lobby the FDA?” She noted that the current self-regulating system is “like putting the fox in charge of the hen house. It has to be a separate unit responsible for the post-marketing, free of any influence of the people who approved it in first place.”

Among Dr. Graham’s attackers are senior FDA officials who are officers in the Public Health Service (PHS) Commissioned Corps (one of 7 uniformed services of the US). If PHS officers have engaged in covert, underhanded, possibly criminal maneuvers aimed at discrediting a highly respected scientist whose track record of weeding out lethal drugs has earned him the respect and admiration of both scientists and the public, their actions will add fuel to discredit the agency and its leadership.

FDA officials must not be allowed to abuse their authority by retaliating against a scientist who takes FDA’s mission seriously – i.e., protecting the public from unsafe drugs and informing the public about evidence of hazards linked to marketed drugs. Dr. Graham must be allowed to analyze drug safety data within the office of drug safety.

References:

1. ANNA WILDE MATHEWS and HEATHER WON TESORIERO Medical Journal Seeks FDA Overhaul THE WALL STREET JOURNAL November 23, 2004; Page A6

2. Jeanne Lenzer Public interest group accuses FDA of trying to discredit whistleblower. British Medical Journal, Nov. 24, 2004 http://bmj.bmjjournals.com/cgi/content/full/329/7476/DC2?ehom .

3. Marc Kaufman Attempt to Discredit Whistle-Blower Alleged. Washington Post, November 24, 2004, http://www.washingtonpost.com/wp-dyn/articles/A8715-2004Nov23.html

4. DENISE GRADY F.D.A. Employee Seeks Legal Help From Whistle-Blowers’ Group The New York Times November 24, 2004 A-21

5. Shankar Vedantan, Probe Urged of Allegations Against FDA, Washington Post, November 25, 2004. A-15.

6. Phil B. Fontanarosa, MD Drummond Rennie, MD Catherine D. DeAngelis, MD, MPH Postmarketing Surveillance – Lack of Vigilance, Lack of Trust. JAMA, December 1, 2004 – Vol 292, No. 21

7. NewsHour DRUG FAILURE, Public Broadcasting Station. November 18, 2004. http://www.pbs.org/newshour/bb/health/july-dec04/vioxx_11-18.html

Contact: Vera Hassner Sharav
212-595-8974
veracare@ahrp.org

http://bmj.bmjjournals.com/cgi/content/full/329/7476/DC2?ehom

British Medical Journal
Public interest group accuses FDA of trying to discredit whistleblower
November 24, 2004
New York
Jeanne Lenzer

A public interest group that aims to protect whistleblowers claimed last week that an attempt had been made by a member of staff at the Food and Drug Administration to discredit Dr David Graham, the FDA executive who testified to the US Senate committee on 18 November.

Dr Graham, associate director in the FDA’s Office of Drug Safety, had carried out a study with Kaiser Permanente of northern California that looked at the cardiovascular risks in patients taking rofecoxib (Vioxx). He had submitted the results of the study to the Lancet. Dr Graham withdrew the study, however, after getting a warning from his supervisor about publication.

The FDA issued a statement after the Senate hearing last week, claiming that Dr Graham had failed to adhere to agency protocol when he submitted his data to the Lancet. When the BMJ inquired about the FDA’s statement and the possible publication of the rofecoxib study in the Lancet, Dr Graham referred the BMJ to his attorney, Tom Devine, for comment.

Mr Devine, legal director of the Government Accountability Project – a public interest group based in Washington, DC, that helps whistleblowers in order to promote governmental and corporate accountability – said Dr Graham, fearing for his job, had sought the group’s help in connection with the rofecoxib study about a month ago. The group’s decision on whether to provide legal counsel for Dr Graham was delayed after it received another request for aid from someone claiming to be an anonymous whistleblower at the FDA who was being “bullied” by Dr Graham. The anonymous caller also said that Dr Graham’s study could reflect scientific misconduct.

After some investigation the project found out that the “anonymous” charges actually came from FDA management, which, according to Mr Devine, had “full control” over Dr Graham. “We made demands to call whichever side was bluffing,” said Mr Devine. “The FDA flunked every test of credibility, while Dr Graham passed all of them. The FDA was employing a classic law of whistleblower reprisal – the smokescreen syndrome – which shifts the spotlight from the message to the messenger.

“The agency attempted to discredit Dr Graham rather than provide any scientific evidence contradicting his conclusions.” Mr Devine said the FDA’s attacks on Dr Graham’s credibility were implausible. His scientific findings about the dangers of 12 drugs, including troglitazone (Rezulin), concomitant fenfluramine and phentermine (Phen-fen), and temafloxicin (Omniflox), were upheld when the agency withdrew 10 of the12 drugs from the market. Many whistleblowers, said Mr Devine, find themselves isolated and shunned at work. It was some measure of the esteem with which Dr Graham is regarded by his colleagues that when he returned to work on Friday after his Senate testimony his colleagues greeted him with applause.

The FDA’s statement after the hearing alleging that Dr Graham did not adhere to agency protocol on the Kaiser Permanente study can be found at www.fda.gov/bbs/topics/news/2004/NEW01136.html

Attempt to Discredit Whistle-Blower Alleged
Group Says His FDA Colleagues Made Calls
By Marc Kaufman
Washington Post Staff Writer
Wednesday, November 24, 2004; Page A19

Managers at the Food and Drug Administration last month anonymously called a group that protects whistle-blowers in an attempt to discredit an outspoken agency safety officer who was challenging the FDA’s drug safety policies, the legal director of the whistle-blower group said yesterday. Tom Devine of the nonprofit Government Accountability Project (GAP) said the anonymous callers did not identify themselves but he is “100 percent positive” they were managers at the FDA because of their phone numbers and other identifying information. He said he initially took the callers’ concerns seriously but later came to see the calls as an effort to smear the whistle-blower, Associate Director David J. Graham of the Office of Drug Safety.

Last week, Graham, a 20-year FDA veteran, said at a Senate hearing that FDA policies have left the American public “virtually defenseless” against the kind of safety problems that led to the abrupt withdrawal in September of the popular arthritis drug Vioxx. He named five other prescription medications that he said pose serious safety risks that are not being adequately addressed by the FDA. Although the FDA initially sharply criticized Graham’s testimony — one top official called him “irresponsible” and a practitioner of “junk science” — the agency yesterday tightened the restrictions on one of the five drugs Graham had criticized, the acne medication Accutane.

In a statement regarding the GAP allegations, the FDA said yesterday that it “acknowledges the right of its employees to raise their concerns to oversight groups.” The agency said that it had no prior knowledge of any employee’s contact with the whistle-blower group and that it is working to improve a process for ensuring that internal differences of scientific opinion are fully incorporated into its decision-making. “The agency promotes vigorous debate of the tough scientific questions it confronts every day,” the statement said.

The allegation that the FDA used deceptive practices against Graham came two days after the Government Accountability Project agreed to take him on as a client. Devine said Graham had asked five weeks ago for advice about overcoming his supervisors’ opposition to the publication of his critical findings about Vioxx. The anonymous calls followed several weeks later, Devine said.

“The calls came under the guise of being anonymous whistle-blowers,” Devine said. “They were clearly working together and shared allegations — mostly that Dr. Graham’s research was unreliable and that there were serious questions of possible scientific misconduct with his study. They said Graham wouldn’t address their concerns, and that he was a demagogue and a bully.” Devine said that after several conversations, he persuaded the callers to provide documents to support their accusations, and Devine then challenged Graham based on what was provided. “It became clear to me that Dr. Graham could reasonably explain any questions about the research, and that the callers were trying to smear him,” Devine said. “After that, I called their bluff for more information and that was the end of it. It was all a red herring, and it made me believe Dr. Graham far more.”

Devine said that, under his organization’s rules, he could not identify the callers because they initially contacted GAP as whistle-blowers themselves. But he said he is certain they were supervisors at the FDA because of the details of the arguments they made and the phone numbers from which they called. In addition, he said that, after identifying the callers to his satisfaction, he referred to them by name during subsequent phone conversations. He said the callers were surprised by his identifications but did not tell him he was wrong.

The allegations follow weeks of bruising criticism of the FDA, which has been accused of being lax on drug safety and was sharply assailed in Congress over its oversight of the British plant that was supposed to produce half of this winter’s U.S. supply of flu vaccine. The plant was closed by British health officials because of contamination problems. The criticism on drug safety issues has led to calls for the creation of a more independent Office of Drug Safety within the FDA, or perhaps outside of it.

Currently, the office is overseen by the Center for Drug Evaluation and Research, which also supervises the Office of New Drugs. To critics of the current setup, the much larger and better-financed Office of New Drugs dominates the safety office, in part because drug reviewers involved in approving a new drug for marketing also play a role in deciding whether the drugs should be withdrawn when safety issues crop up.

In his Senate testimony, Graham said a more independent drug safety office is essential. His position was supported this week by the editors of the Journal of the American Medical Association. “The drug approval process must be decoupled from the post-marketing safety and surveillance system,” the editorial said. “It is unreasonable to expect that the same agency that was responsible for approval of drug licensing and labeling would also be committed to actively seek evidence to prove itself wrong.”

The FDA and drug industry officials have generally opposed a more independent safety office, saying it is unnecessary and would serve to de-emphasize the benefits of medications. But the FDA recently asked the congressionally chartered Institute of Medicine to review its drug safety procedures, and top officials said the agency will consider whatever recommendations the institute makes.

Although the drug safety issue involves a number of medications, companies, patients and officials, it has increasingly revolved in recent days around Graham’s personality and positions. He has been at the center of the Vioxx controversy and has touched off more heated words and debate with his congressional criticisms of five other drugs, but his impact on drug safety issues goes well beyond those.

During his 20 years in the Office of Drug Safety, he fought passionately to bring about the recall of the diabetes drug Rezulin, the diet pills Fen-Phen and Redux, the cholesterol-lowering drug Baycol, the heartburn remedy Propulsid, and the antihistamine Seldane.

Graham, 50, was trained as a physician at Johns Hopkins and Yale universities and has spent his entire career at the FDA’s drug safety office. A deeply religious Roman Catholic, he has said that his faith serves as a spur to his work. Some see him as a crusading hero, while others believe he unfairly fixates on certain drugs and fails to take into account the patients who are helped by those medications.

His influence has been enormous. In his congressional testimony, Graham said that, in the course of his career, he had recommended that 12 drugs be taken off the market, and that 10 of them were subsequently removed. The news that Graham had sought whistle-blower assistance and protection — and that FDA managers had sought to undermine his credibility — was first reported yesterday in the online edition of BMJ, formerly known as the British Medical Journal.

In that account, Devine said the FDA was “employing a classic law of whistleblower reprisal — the smokescreen syndrome — which shifts the spotlight from the message to the messenger. The agency attempted to discredit Dr. Graham rather than provide any scientific evidence contradicting his conclusions.”

Graham could not be reached yesterday for comment. One of the two drugs whose recall Graham has unsuccessfully sought is Accutane, which was approved to treat severe acne but, critics say, is widely prescribed for milder cases. The drug’s distribution is restricted to prevent its use by pregnant women because Accutane can cause fetuses to die or develop birth defects. Nonetheless, some women have been getting pregnant while taking the drug.

Under an expanded monitoring program announced by the FDA yesterday, manufacturers will have to keep records of which doctors prescribe the drug, which pharmacies distribute it and which patients take it. Doctors and pharmacies will also have to inform women about the drug’s risks, and pharmacists will have to see a signed proof that the patient is not pregnant before they dispense the drug, the FDA said.

In its news release, the agency said the changes stemmed from the recommendations of an advisory panel in February.

© 2004 The Washington Post Company