FDA still too chummy with pharmaceutical industry, critics say

11/22/2007- Ten years ago, two wildly popular obesity drugs were withdrawn from the market by their maker after being linked to thousands of cases of severe heart and lung damage and several deaths.

The recall ended the fen-phen diet-drug craze.

But it opened the door to problems within the pharmaceutical industry and the Food and Drug Administration (FDA) that is supposed to regulate it.

Since then, the FDA has been criticized for its handling of nearly a dozen other drugs and medical devices that have been pulled from the market amid safety concerns, including the cholesterol drug Baycol, pain relievers Vioxx and Bextra, and the Guidant heart defibrillator.

Last month, an FDA panel recommended that popular over-the-counter cough and cold medications should not be used by children younger than 6. The panel said there's insufficient evidence the drugs work and they may not be safe for young children.

Investigations into the drug controversies have found that the FDA and drug companies were slow to react to evidence of drug dangers, and the FDA tried to squelch agency doctors who raised alarms internally.

In addition, FDA and drug-industry critics complain that the relationship between medical researchers and drug companies was too close, and that the industry tried to turn medical-education seminars for doctors into drug-promotion campaigns.

The FDA says it has improved its reaction to danger signals in drugs already on the market and has created a channel for its scientists to raise concerns about drugs internally without fear of reprisal.

The Pharmaceutical Research and Manufacturers of America, one of the most powerful lobbies, has called the drug-safety system "the best in the world."

It notes that the industry invested more than $55 billion in researching new medicines last year and agreed to some expansion of safety testing.

Congress last month passed a drug-safety bill that, among other things, promotes tracking of adverse reactions after a drug is approved and in wide use, a move the drug industry fought for years.

But questions remain about whether that is a substantive fix or a public-relations move by the FDA and industry designed to fend off stronger government demands.

Two doctors — one a veteran FDA epidemiologist, the other a noted cardiologist at the University of Washington — said they have doubts.

"I'm thinking there are not huge advances between 10 years ago and today," said Dr. Bruce Psaty, of UW. "[But] I am hopeful some new changes are possible."

Dr. David Graham, of the FDA, is less sanguine. "The FDA remains stuck in a view that gives the companies and drugs a free pass," he said.

An estimated 8 million prescriptions were written for fen-phen during the height of its popularity, from 1994 to 1997. The "fen" stood for fenfluramine, which the company Wyeth first sold as Pondimin, and, starting in 1996, as a slow-release version called Redux. The "phen," for phentermine, is still available, though not widely used because it disrupts sleep.

Pondimin and Redux were withdrawn amid lawsuits over links to a fatal lung disease and, in 1997, the discovery of their connection to heart-valve damage.

Patients were mostly women. Attorney Michael Woerner of Seattle represented a woman in her 20s who died months after her claim against the company was settled.

"We had another client, a woman in her 40s, die while we were litigating the case," Woerner said.

Roughly 100,000 people took the drugs in the Puget Sound area, according to data previously compiled by lawyers dealing in a federal lawsuit.

In the end, about 300,000 claims nationwide were collected into the federal case and settled according to a complex grid based on patients' ages and severity of illness.

Thousands of others sued in state courts, which led to public disclosure of thousands of pages of documents showing what the company knew, when it knew it and how the FDA resisted taking action until an outcry from the medical community and a barrage of news stories.

In 1999, Wyeth officials insisted the problem was small and could not be proved. But as of last year, the company had set aside nearly $21 billion for legal fees and claims.

Some 150 to 200 cases were handled in Seattle, either through formal suits or participation in the federal settlement.

"Pro-industry culture"

Once documents were opened, they revealed that the company had been receiving increasing reports of serious side effects, including deaths possibly linked to their diet drugs.

Inside the FDA, three doctors had expressed serious concerns about the drugs. Graham questioned the way the company tracked heart-valve damage.

"The FDA has allowed companies to set the standards and handle the reviews," he said recently.

Graham sought whistle-blower protection from a senior senator in early 2004, after the FDA began an investigation to find out who had leaked information about potential links between antidepressants and teenage suicides. Today, Graham's protector, Sen. Chuck Grassley, R-Iowa, is a determined critic of the FDA and the drug industry.

But Graham, speaking for himself, said that within the FDA, "The pro-industry culture and its decision-making hasn't changed."

The office that promotes drug approvals is still twice the size, and, Grassley said, twice as important as the office for drug safety.

The same people who approve drugs also help decide whether those drugs should be withdrawn.

"It creates a conflict of interest," Graham said.

Graham noted a controversy over the diabetes drug Avandia as an example of the FDA's lack of change.

Avandia was approved in 1999. In recent years, some studies, including one last month, linked it to increased risk of heart attacks. The FDA voted this summer to beef up warnings on its label but keep it on the market.

"A watershed event"

Psaty, a UW professor of cardiology and epidemiology, has become an outspoken advocate of drug safety.

In 2004, he published a study that questioned whether the makers of Baycol had known about its links to a fatal muscle disease well before its withdrawal in 2001.

Psaty since has testified several times to Congress, once with Graham in 2004, just after Vioxx was withdrawn. The popular painkiller was linked to a higher risk of heart attacks.

"That was a watershed event," he said, adding that some problems with the Vioxx crisis — the company and FDA's slowness to act — had been "the same issues for fen-phen."

In 2005, Psaty was asked to join the Institute of Medicine's review of the FDA on drug safety. The institute, part of the National Institutes of Health, issued a scathing report in September 2006, calling the FDA dysfunctional.

Psaty said the imbalance of power between the Office of New Drugs and Office of Drug Safety is a major weakness in the system.

"Whatever the FDA develops, industry has immense resources and talent, many people, and will continue to market their drugs in ways advantageous to their companies," he said. "That hasn't changed."