The Side Effects of Truth

[Guest guest]

http://www.motherjones.com/news/feature/2005/05/david_graham.html

 

The Side Effects of Truth

 

News: In exposing the deadly threat posed by Vioxx, FDA researcher

David Graham was serving the public interest. His bosses had other

interests in mind.

 

By Michael Scherer

Photo: Henry Leutwyler

 

May/June 2005 Issue

 

 

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.