FDA Researcher Who Raised Concerns About Vioxx, Other Medications Feared Losing Job, Consulted Whistle-Blower Group
FDA managers last month made anonymous telephone calls to a not-for-profit group that protects whistleblowers "in an attempt to discredit" David Graham, an agency safety reviewer who on Thursday testified before the Senate Finance Committee that FDA is "virtually incapable of protecting America," the Washington Post reports (Kaufman, Washington Post, 11/24).
At a hearing on the recent voluntary withdrawal of Vioxx, a COX-2 inhibitor manufactured by Merck, Graham, associate director of drug safety in the FDA Office of Drug Safety, testified that the company should have withdrawn the medication from the market years earlier and criticized agency actions related to the medication. He also said that FDA "as currently configured, is incapable of protecting America against another Vioxx" because of ties between agency reviewers and the pharmaceutical industry.
Graham said that, based on data from studies conducted by Merck, between 88,000 and 139,000 U.S. residents have experienced heart attacks or strokes as a result of Vioxx. He added that as many as 40% of those patients, or about 55,000, died as a result of Vioxx. Graham said that when he raised questions about the safety of Vioxx with other FDA officials, he was asked not to express his concerns or revise his conclusions.
In addition, according to Graham, five prescription drugs currently on the market present significant safety risks to consumers. Graham cited in his testimony safety concerns about the COX-2 inhibitor Bextra, manufactured by Pfizer, which he said presents cardiovascular risks similar to those of Vioxx; the anti-cholesterol medication Crestor, manufactured by AstraZeneca, which he said is the only such medication to cause acute kidney failure and likely to lead to serious muscle problems; the obesity treatment Meridia, manufactured by Abbott Laboratories, which he said could cause substantial increases in blood pressure; the acne medication Accutane, manufactured by Roche, which FDA has said could cause birth defects; and the asthma treatment Serevent, manufactured by GlaxoSmithKline, which he said could lead to an increased risk in asthma-related deaths and life-threatening episodes (California Healthline, 11/22).
Graham said that last month he sought advice from the Government Accountability Project because opposition from his supervisors about the publication of a study that he conducted on Vioxx. Graham said he called GAP over concerns that he was a whistleblower and that FDA would fire him.
Tom Devine, legal director of GAP, said that he received multiple telephone calls from "FDA management" several weeks after he discussed the issue with Graham (Grady, New York Times, 11/24). Devine said that he is "100% positive" FDA managers made the telephone calls based on their telephone numbers and the details in their arguments against research conducted by Graham (Washington Post, 11/24). Devine, who declined to make public the names of the FDA managers who allegedly made the telephone calls, said, "They were anonymous, but to test my research I started addressing them by their names. They didn't deny it."
According to Devine, the individuals said that the research conducted by Graham might include "scientific misconduct" and "alleged that he was a bully who had been harassing scientists at FDA for years and was a demagogue who manipulated Congress, the media and good-government groups like ours, and he had to be stopped." Devine questioned the allegations after the individuals could not provide evidence to support them (Grady, New York Times, 11/24).
According to Devine, after "it became clear" that Graham "could reasonably explain any questions about the research," he requested more documents from the individuals and "called their bluff ... that was the end of it." He added, "It was all a red herring, and it made me believe Dr. Graham far more." According to the online version of BMJ, a British journal that first reported on the alleged telephone calls from FDA managers to GAP, Devine said that FDA "attempted to discredit Dr. Graham rather than provide any scientific evidence contradicting his conclusions" (Washington Post, 11/24).
Graham said on Tuesday, "My concern is retaliation from these people."
FDA officials on Tuesday acknowledged that an agency employee had contacted GAP but denied any previous knowledge of the alleged telephone calls (Grady, New York Times, 11/24).
In a statement, FDA officials said that the agency "acknowledges the right of its employees to raise their concerns to oversight groups," adding, "The agency promotes vigorous debate of the tough scientific questions it confronts every day" (Washington Post, 11/24).
The House Energy and Commerce Committee, which has opened an investigation into FDA and Merck on their actions related to Vioxx, has issued "extensive record requests" over how the agency and the company monitored the safety risks of the medication before its withdrawal, the Los Angeles Times reports (Alonso-Zaldivar, Los Angeles Times, 11/24). The committee has requested Merck records on Vioxx safety studies, as well as internal documents related to the potential safety risks of the medication.
In addition, the committee asked FDA to identify employees who reviewed the final Merck study on Vioxx and provide internal documents on safety reviews of the medication.
The committee also requested from FDA internal documents related to the potential safety risks of the COX-2 inhibitors Bextra and Celebrex, also manufactured by Pfizer (Hallam, Bloomberg/Philadelphia Inquirer, 11/24). According to the Newark Star-Ledger, a congressional source familiar with the investigation said that the committee also might ask Pfizer to submit related internal documents (Silverman, Newark Star-Ledger, 11/24).
In a letter to Merck CEO Raymond Gilmartin, committee Chair Joe Barton (R-Texas) and ranking member John Dingell (D-Mich.) wrote, "The high usage rate of Vioxx, considering its relatively narrow set of approved indications, raises questions about how Vioxx was being marketed and advertised."
Merck spokesperson Tony Plohoros said that the company would cooperate with the investigation. "The House and other government bodies have a legitimate interest in confirming that Merck's actions, as well as those by the FDA, were responsible, appropriate and timely," Plohoros said (Bloomberg/Philadelphia Inquirer, 11/24). Merck and FDA must submit the requested documents to the committee by Dec. 7.
A committee spokesperson said that hearings on issues related to Vioxx could begin early next year and that the committee has not decided whether to introduce legislation to revise FDA prescription drug safety review procedures. According to the Los Angeles Times, the "influential" committee, which previously has investigated antidepressant regulation, has a "reputation for carrying out high-profile investigations of corporate and regulatory failures" (Los Angeles Times, 11/24).
A majority of U.S. residents remain confident in the ability of FDA to ensure drug safety, "although trust differs along party lines," according to a CNN/USA Today/Gallup Poll, USA Today reports. The telephone poll of 1,015 adults found that 70% of respondents have "a great deal or moderate amount" of confidence in FDA, compared with 29% who said they had "not much" or no confidence, USA Today reports.
The poll also found that 37% of respondents said their confidence in FDA has decreased in the past year, compared with 54% who said their confidence remained the same and 8% who said their confidence has increased. According to the poll, about 25% of Republican respondents said they had a great deal of confidence in FDA, compared with 15% of Democratic respondents.
Senate Finance Committee Chair Chuck Grassley (R-Iowa) said that FDA for "decades" has performed "good work," but he added that "congressional scrutiny of the mistakes we know about" could help FDA maintain the confidence of U.S. residents. "The FDA can do a lot to enhance its credibility by being more open and transparent," Grassley said.
However, Rep. Henry Waxman (D-Calif.) said, "The debacles at the FDA in their handling of the flu vaccine and Vioxx will eventually undermine confidence in the agency" (Appleby, USA Today, 11/24).
- The AP/New York Times on Wednesday examined states that have used their interstate prescription drug purchasing pools to take "a closer look at a half-dozen existing studies" on the safety of a number of medications, such as Vioxx (Henderson, AP/New York Times, 11/24).
- The New York Times reports that although Merck "has always pointed to one virtue" of Vioxx -- the medication was less likely to cause stomach bleeding or ulcers than over-the-counter pain treatment -- company officials as early as 2001 were aware that "this might not be true for potentially hundreds of thousands of Vioxx users." According to the New York Times, early safety studies on Vioxx indicated that middle-aged and older patients who took Vioxx on a regular basis in combination with low doses of aspirin to reduce their risk of heart attack or stroke could have a higher risk for gastrointestinal problems (Meier, New York Times, 11/24).
- Stark, "Nightline," ABC, 11/23.
- Senay, "The Early Show," CBS, 11/23. The segment is available online in RealPlayer.
- Dentzer, "The NewsHour with Jim Lehrer," PBS, 11/23. A transcript and audio of the segment are available online.