Last September Merck took the painkiller Vioxx off the market after a clinical trial showed it increased the risk of heart attack. Soon after, Pfizer pulled its ads for Celebrex, a prescription drug similar to Vioxx, when a government-funded cancer study showed that in high doses it, too, multiplied heart problems.

The U.S. Senate Finance Committee held a hearing in November on why the pharmaceutical companies downplayed early warning signals of heart risk and what role the U.S. Food and Drug Administration played. A key witness was physician David Graham, associate director for science in the FDA’s Office of Drug Safety and a 20-year veteran of the agency, who gave his assessment of FDA safety procedures. He also testified that the FDA managers last summer suppressed his studies showing the link between Vioxx and heart attacks.

In January the FDA granted Graham permission to publish his findings in the journal Lancet. In a statement, the agency said it would not comment on specific personnel issues, but "as with any institution, sometimes an individual within FDA may ultimately disagree with a consensus scientific judgment for a variety of reasons. Nevertheless, FDA is required to base its decisions on the best available, verifiable science. In the end, we must weigh all the evidence and decide on behalf of our citizens whether the products should be available." The FDA is sponsoring a review of its drug safety system by the quasi-governmental Institute of Medicine.

Graham talked about the pain pill dilemma in an AARP Bulletin interview with writer Merrill Goozner.

Q. How serious are the heart risk problems with newer pain relievers like Vioxx, which is now off the market, Celebrex and Bextra?
Any individual patient’s absolute risk for developing a heart attack might be small, but if you have millions of people taking the drug, many thousands of people will get heart attacks. A recent clinical trial showed an almost fourfold increase in heart attack risk with high doses of Vioxx. We estimate 100,000 people had heart attacks due to Vioxx, with 30,000 to 40,000 dying. And the ones who didn’t die had their life expectancy shortened because they’ve had a first heart attack. This is a major safety problem.

Q. Why weren’t physicians and consumers more cautious about prescribing and taking these new drugs?
The direct-to-consumer advertising magnified the risk [by encouraging consumers to ask doctors for the drugs]. It is difficult for people to comprehend what these [risk-factor] statistics mean. If a person has diabetes, is a smoker or has high cholesterol or blood pressure, the risk is even higher. It is also difficult for the physicians, who rely on the drug companies for most of the information they get about the drugs. You would expect that people should be able to rely on the FDA for information about drugs. But in the case of Vioxx, the FDA let the American people down.

Q. Why wasn’t the scope of the problem identified before the FDA approved the drugs?
Before those drugs were marketed, there were theoretical concerns that they may cause heart problems in some cases. But these concerns were not properly evaluated. This is typical. Before a drug is brought on the market, the tests are usually small and focused on whether the drug works: does it cure arthritis pain? But they weren’t large enough to quantify how often serious problems occur— in Vioxx’s case, heart attack.

Part of this has to do with how the FDA makes its decisions. They are responsible for determining if drugs are safe and effective. The effective part is fairly well done. They ask for 95 percent certainty that it will have the effect they think it will. But they don’t require the same 95 percent certainty on safety. They assume the drug is safe and require studies to show it is not safe. Yet they don’t require big enough studies to show that.

Q. Do these problems extend beyond these pain relievers? You mentioned five other drugs at the hearing.
This is a systemic problem at the FDA [because] the FDA has an inherent conflict of interest. They approved the drug, so why on earth would they turn around and say, "We made a mistake" and pull it off the market? Obtaining [safety] evidence is almost impossible once a drug is on the market because it is not in the company’s interest to do the studies that might show safety problems. And they’re the only ones with the wherewithal to do it. The FDA doesn’t have the money for these large studies. The agency has focused on reviewing and approving drugs as quickly as possible to the detriment of safety. The approval process is driving the bus while safety is at the back of the bus.

Q. People are confused when conflicting studies come out. Despite the revelations about some pain relievers, can consumers generally be confident about the drugs they take?
There’s no deliberate attempt to confuse people. What we’re seeing is that there are insufficient studies to determine safety. For most drugs, consumers can be reasonably confident that they work and that they’re safe. Most drugs have been on the market for many years and have been very well studied. But with newer drugs, we don’t generally have good safety information. They usually haven’t been studied in the many thousands of patients you need to adequately show the safety profile.

If there is a drug on the market that has been taking care of a problem for 10 years, stick with it. If that isn’t working for you, and your doctor thinks there is a new drug on the market that might be worthwhile, then follow your doctor’s advice, realizing that we probably have a lot less information about the safety of the newer drug.

Q. What could the FDA do to help patients and doctors sort this out?
The FDA does not compare one drug with another to determine which is better, although this might be the most valuable information to have. If there are five or seven cholesterol-lowering drugs out there, it would be very valuable to know that they all work the same or that two or three work better than the others. If you can get the generic version, and you knew it worked every bit as well as the name brand, why spend $3 a tablet for the name brand that is on your television screen when you can get a generic that might cost 50 cents a tablet to do the same thing?

Q. Did you have problems bringing these issues to the forefront at the FDA?
When I presented the Vioxx data to my managers at the FDA, they wanted to change my conclusions. When [Republican Sen. Chuck] Grassley’s office began to investigate what the FDA knew before Vioxx came off the market, these same FDA managers accused me of scientific misconduct; they tried to block the publication of my paper in the Lancet, a prestigious medical journal; and they called the Government Accountability Project to convince them not to represent me as a whistleblower. There is a Whistleblower Protection Act, but that doesn’t necessarily protect government employees. The only people who know when the government isn’t doing its job well are the people within government. But if they can’t protect themselves when they go public, then it is going to be impossible for them to protect the consumer.

Q. What led you to speak out?
It was conscience more than courage. I would have to live with the knowledge that many people had been hurt or killed because I didn’t act. Where does my conscience come from? For me, it has to do with my Christian beliefs and trying to live those Gospel principles. My faith is a part of my life. It is interwoven into everything that I do. I’m acting based on the science, but I feel I have a moral responsibility.

Merrill Goozner is the author of The $800 Million Pill: The Truth Behind the Cost of New Drugs.