The Good, The Bad and The Particularly Ugly. Days after scientist warned of Vioxx danger, FDA approved it for CHILDREN.

Motherjones Article on David Graham, FDA and Vioxx


"In exposing the deadly threat posed by Vioxx, FDA researcher David Graham was serving the public interest. His bosses had other interests in mind.

Michael Scherer
May 01 , 2005

DR. DAVID GRAHAM IS LOSING WEIGHT AGAIN. His wife noticed first, then his colleagues at the Food and Drug Administration. Graham is a skinny man, and when he drops weight, his cheekbones seem to sit higher on his face. His striped cotton shirts, the frumpy uniform of a government scientist, hang more loosely on his narrow frame. But he isn’t eating, and no wonder: Graham, the scientist who brought the Vioxx scandal to the nation’s attention, feels like a marked man.

“I’m no longer welcome,” he says, sitting in a Rockville, Maryland, coffee shop in early February. He has just left another frustrating day at work, where his boss warned him not to disclose new safety findings about a popular class of painkillers called Cox-2 inhibitors. In a few minutes, he is due at his son’s Boy Scout meeting, but all he can talk about now is the exhaustion of working in a drug-safety system in turmoil. “I’m hoping things will calm down, but I don’t think the FDA will let that happen,” he says. “How do you get off the merry-go-round?”

In August 2004, Graham told his supervisors that, in light of his research, high-dose prescriptions of the painkiller Vioxx, which appeared to triple heart attack rates, should be banned. They told him to be quiet. Their reasoning was circular: That’s not the FDA’s position; you work here; it can’t be yours. Dr. John Jenkins, the FDA director of new drugs, argued that because Graham’s findings didn’t replicate the drug’s warning label, Graham shouldn’t be raising the warning. Another supervisor, Anne Trontrell, called Graham’s position “particularly problematic since FDA funded this study.” Days after Graham’s pronouncement, the agency approved Vioxx for use in children.

But Graham was right. The following month, Merck pulled Vioxx from the market after its own research found that the drug, even when taken at low dosages, doubled the risk of heart attack. The announcement provided Graham no vindication. With a scandal on the horizon, the FDA brass now saw him as a danger. They couldn’t silence the message, so they tried to take out the messenger.

Dr. Steven K. Galson, the acting director of the drug-evaluation division at the FDA, told reporters that Graham’s work “constitutes junk science.” Then he sent an email to an editor at the prestigious British medical journal The Lancet, questioning the “integrity” of Graham’s data—a suspicion that proved baseless. The FDA’s acting commissioner, Dr. Lester Crawford, criticized Graham for evading the agency’s “long-established peer review and clearance process.” Another official made calls to at least one Senate staffer, disparaging Graham personally and professionally.

Eventually, he was heard. In November he went before the Senate Finance Committee hearing on Vioxx. Gaunt (he’d lost 12 pounds over three months) but very lucid, Graham took his place before a bank of cameras, wearing his only sport coat, a 20-year-old blue blazer with brass buttons. He explained his conclusion that patients taking high doses of Vioxx were suffering heart attacks. “The estimates range from 88,000 to 139,000 Americans,” he said. “Of these, 30 to 40 percent probably died. For the survivors, their lives were changed forever.” According to the top end of those projections, the toll Vioxx had already taken was comparable to the number of Americans killed in Vietnam. “The FDA, as currently configured,” Graham told the committee, “is incapable of protecting America against another Vioxx. We are virtually defenseless.”

But three months later, as Graham sips iced tea in a Rockville café, the FDA is again trying to suppress his research, this time on the effects of pain medications similar to Vioxx. “I think we’ve already articulated our preference,” his supervisor, Dr. Paul Seligman, wrote him in a terse email. The agency doesn’t want Graham presenting his latest research to scientists who will be meeting in a few days to discuss the drugs.

David Graham is headstrong, but not insubordinate. He cannot afford to lose his job. His family has just moved to a new house. His wife, Nancy, stopped working as a lawyer so she could homeschool their six children. Really, though, he has no more time to sit here worrying. The Boy Scouts are competing for their merit badges this evening. He finishes his iced tea.

“I’ve made a commitment,” he says, before walking out the door. “I’ll weigh myself this evening.”



WE LIVE IN THE pharmaceutical era of medicine, a time of tablet-sized miracles and blockbuster serums. More than 70 new drugs are approved every year, adding to the thousands for which American doctors already write some 3 billion annual prescriptions. The medications prolong countless lives and cause millions of harmful side effects. For most patients, the benefits far outweigh the dangers. An aging man will risk diarrhea to restore his virility. A cancer patient will lose her hair in the hope that chemotherapy will save her life. FDA safety officers like Graham spend their lives searching out the other type of pills, the unexpected killers that harm patients after the FDA has approved them.

Since 1988, Graham has called for the removal of 12 drugs from pharmacy shelves, leading to 10 recalls that have likely saved hundreds, if not thousands, of lives. Each recall is an embarrassment for Graham’s employer, the FDA’s Center for Drug Evaluation and Research, which approved the drugs in the first place. The trouble is that the roughly 2,300 staffers who support the approval process, and the 109, like Graham, who study the safety of drugs after their release, all fall under the same leadership, and that leadership is highly responsive to industry. In recent years, nearly half of the center’s $400 million budget has been paid for by drug companies. This arrangement stems from a 1992 agreement, made partly at the urging of AIDS activists, that the FDA would speed up approvals in exchange for “user fees” from industry. “The focus at FDA is efficacy,” says Dr. Curt Furberg, a scientist at Wake Forest University who advises the agency. “Safety is a stepchild.”

For the pharmaceutical companies the system works just fine. “The drug-approval process [in the United States] is second to none,” says Jeff Trewhitt, a spokesman for PHRMA, the drug industry’s trade group. “This is an exhaustive process.”

Companies eventually recall about 3 percent of their drugs for safety reasons. Behind many of these recalls are scientists like Graham, who often find themselves pitted against their own supervisors. “If you say something negative about a drug, they try to shut you up,” says Dr. Sidney Wolfe, an FDA watchdog for the group Public Citizen, which has been exposing dangerous drugs for three decades. “David is not the only one, by any means, who has raised issues that later proved to be correct.”

In 1998, for instance, an FDA drug reviewer named Dr. Robert Misbin wrote a paper showing that the diabetes drug Rezulin had caused liver failure in a patient during a controlled study. When his bosses tried to prevent him from publishing, Misbin saw firsthand how the system encouraged the sacrifice of public health to the interests of the industry. “One of my supervisors said something to me that I have never forgotten,” Misbin says, “that we have to maintain good relations with the drug companies because they are our customers.” Misbin eventually went public with his concerns, and the drug was pulled a year later. But he has paid for sticking to his principles. “I am no longer given any good projects,” he says.

Dr. Andrew Mosholder, another FDA reviewer, faced similar pressures last year when he completed a study showing that antidepressants increased suicidal behavior in children. Further studies proved that Mosholder’s science was spot on. But his bosses told him not to report the findings. When someone with access to the study passed his results to the press, the FDA launched an investigation into the leak. According to Tom Devine at the Government Accountability Project, who later became Graham’s lawyer, several scientists were interrogated and threatened with possible jail time.

Such intimidation has worked. In 2002, about one in five FDA scientists told federal investigators that they felt pressure to approve drugs despite reservations about safety and efficacy. Two-thirds said they lacked confidence that the agency adequately monitors drug safety after approval.



Michael Scherer is the Washington correspondent for Mother Jones. "