Cases bolster calls for drug safety overhaul

CHICAGO – Pfizer Inc.’s revelation Friday that its popular Celebrex arthritis pain reliever might increase heart disease risks is bolstering calls to overhaul federal drug safety regulation.

Drug giant Pfizer’s announcement came less than three months after another drug giant, Merck, pulled its big-selling Vioxx arthritis drug off the market after tests showed increased risks of heart attack and stroke.

Both drugs have been heavily marketed directly to consumers, a practice that’s been criticized as leading to unnecessary prescriptions.

And now both drugs have critics of the federal Food and Drug Administration basically saying, “I told you so.”

“The FDA is broken and needs to be fixed,” said Catherine DeAngelis, editor of the Chicago-based Journal of the American Medical Association. “We’re certainly not alone in believing it.”

The FDA isn’t adequately monitoring safety after a drug has been approved for commercial sale, DeAngelis said, so after-the-fact announcements like the ones involving Celebrex and Vioxx will increasingly occur.

Pfizer made its announcement after the National Cancer Institute suspended use of Celebrex in a study.

On Friday, the FDA said patients in a cancer prevention trial who took two 400 milligram doses of Celebrex a day had 3.4 times the risk of cardiovascular events than those who took a placebo.

For patients in the trial taking 200 mg of Celebrex twice a day, the risk was 2.5 times greater, the agency said.

The average duration of treatment in the trial was 33 months, the FDA said.

“A similar ongoing study comparing Celebrex 400 mg once a day versus placebo, in patients followed for a similar period of time, has not shown increased risk,” the FDA said.

Pfizer called the results unexpected, but said it has no plans to take Celebrex off the market. Vioxx, a drug based on a similar chemical structure, was pulled off the market after it doubled patients’ risks of heart attacks and strokes.

In the aftermath of the Vioxx fiasco, a high-ranking FDA official told a U.S. Senate committee that his agency had immense problems in ensuring drug safety.

The country was “virtually defenseless” against unsafe drugs finding their way into people’s homes, David Graham, an associate director in the FDA’s Office of Drug Safety, told senators.

“I would argue that the FDA, as currently configured, is incapable of protecting America against another Vioxx,” Graham said.

Graham was disparaged by his supervisors and “vilified” for taking his stand, DeAngelis said. And it has taken a toll on him, said DeAngelis, who said she recently talked with Graham.

He looks “gaunt,” and said he had lost about 15 pounds, DeAngelis said.

His criticism is right on, she said, and the Journal of the American Medical Association officially endorsed major drug safety reforms earlier this month.

A drug must pass a battery of tests to get FDA approval for commercial use. But once in the market, the oversight process is rife with problems, the respected medical journal said in an editorial.

Drug companies themselves are largely responsible for collecting and evaluating data from the post-marketing studies of their own products.

Plus, reporting of adverse drug effects by physicians and other health-care professionals is voluntary and spotty at best.

To complicate matters, the FDA is responsible for approving drugs, and then pulling them off the market if troubles arise. There is an inherent conflict in such an arrangement, DeAngelis said.

“If I approve something, it’s going to be very hard to say, ‘Oh, I was wrong,’ ” DeAngelis said. Her magazine called for a de-coupling of the FDA’s approval and monitoring functions, possibly by creating a new drug safety board.

DeAngelis’ view has a fan in Charles Grassley.

The Republican from Iowa, as Senate Finance Committee chairman, will introduce two pieces of legislation next year that would distance the FDA’s Office of Drug Safety from the Office of New Drugs. His bills would also create a public registry for all clinical trials on prescription drugs.

“At this point, no one can say with confidence whether the worst drug safety problems are behind us or ahead of us,” said Grassley, whose committee handles drug industry issues.

“Given these problems, it seems the time has come for a comprehensive review of drug safety and of how federal government agencies oversee drug research and approve, license and regulate drugs.”

Should the FDA or Congress not act to transform the agency, drug-makers could face reform through the state and federal court system as plaintiffs’ attorneys circle the wagons.

“This could increase pressure on the government to do something different with the FDA,” said St. Louis University law professor Jesse Goldner. “It also could lead to the same flurry of legal activity that we saw with Vioxx.”

Since Merck & Co pulled Vioxx, the company has been bombarded with class-action lawsuits and attorneys regularly appear in print and TV ads searching for patients.

The drug industry doesn’t see the need for a big fix.

Jeff Trewhitt, a spokesman for the Pharmaceutical Research and Manufacturers of America, said Friday that “by and large, the current system is working. … It is not at all clear to us that there is a need for change.”

Fewer than 3 percent of all pharmaceutical products introduced in the past 20 years have been recalled for safety reasons, he said. “There are more than 10,000 medications on the market and in the vast majority of cases, they are safely treating patients.”

Trewhitt said the FDA has responded quickly to regulatory worries this fall by asking for a drug-safety review by the Institute of Medicine, a nonprofit organization that is part of the National Academy of Sciences.