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"FDA Has Been Asleep at the Switch"
A prescription-drug expert charges that the government is failing to uphold its public-health responsibilities, while pharmaceutical companies perform minimal due diligence
Jennifer Barrett Ozols–Over the past few months, Americans have been bombarded with bad news about popular medicines. In September, Merck voluntarily recalled Vioxx on concerns that the painkiller could increase the risk of heart attack or stroke. In October, the Food and Drug Administration announced it would require "black box" warning labels–the government"s strongest measure short of banning the drugs–on all antidepressants because of increased suicidal risks in some children and teenagers. The same month, the government said this season"s flu-vaccine supply would be basically halved because of production problems at the leading U.S. supplier. Shortly after, Pfizer revealed it may have to add a "black box" warning to the label of its drug, Bextra, a painkiller in the same class as Vioxx, because it sometimes leads to a rare but serious skin reaction. And last week, two researchers said their analysis showed Bextra can also pose a higher risk of heart attack or stroke (Pfizer has disputed those findings).
While the pharmaceutical companies have borne the brunt of the blame, the FDA has also come under fire for its oversight of the drug industry. On Thursday, the Senate will conduct hearings into what the FDA and Merck knew about the risks of Vioxx and when. The FDA has said it will re-examine its drug-safety standards, and has reportedly hired an outside consultant to evaluate its monitoring procedures. Will that be enough to reassure the public? NEWSWEEK"s Jennifer Barrett Ozols posed that question and others to Dr. Jerry Avorn, chief of the pharmacoepidemiology and pharmacoeconomics division at Brigham and Women's Hospital, an associate professor at Harvard Medical School and author of "Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs"(Knopf). Excerpts:
NEWSWEEK: Is the government falling short when it comes to protecting the public"s health?
Dr. Jerry Avorn: The FDA has been asleep at the switch on several fronts. As luck would have it, several of these issues have come to public view in the same two- to three-month period. But really these issues have been building up for a long time. There is pretty compelling evidence that the FDA is not meeting its responsibility to protect the American public when it comes to the safety and availability of drugs.
Was the FDA too hasty in letting some drugs, such as Vioxx, come to market?
Vioxx will give us an opportunity to take a hard look at FDA standards for approving drugs. All too often the standard is that a drug be better than a placebo in a brief study involving a modest number of patients–say, two or three thousand . . . It"s really the lowest-common-denominator set of standards that the [drug] industry has persuaded the FDA is acceptable. That clearly needs to change. We have also had, for many years, a shriveling of the postmarketing safety-surveillance program. All the emphasis at the FDA has been oriented around getting drugs approved quicker. While it is good to approve drugs in an efficient way, there has not been corresponding attention paid to looking at the safety of these drugs once they are in widespread use.
What happened with Vioxx?
It is nearly inevitable that safety problems will turn up after a drug has been marketed. That may be sometimes hard to prevent but one can make sure that there is a posture of vigilance on the part of the FDA, if not the company, that will look for such problems and jump on them as soon as there is any evidence that there may be a signal of a problem. With Vioxx, that would have meant two things: a clinical trial to target the issue of heart disease and stroke in Vioxx, and vigorous utilization studies of people taking Vioxx to determine whether they were having heart attacks and strokes at a rate higher than those taking other pain medicines. And neither of these was done in a timely way. A fraction of what Merck spent on its lavish direct-to-consumer advertising for Vioxx would have paid for all this research, which could have been done in 2000 and 2001.
How much influence do those ads have?
A lot. We in this country use far more drugs in the Vioxx and Celebrex [Cox-2 inhibitor] class proportionally, or per capita, than any other country on earth. That"s in part because of the consumer pressure these ads engender. As a result, ironically, far more people were exposed to the risks of Vioxx because it was so heavily marketed to consumers.
Do you think the public views drug ads differently now in light of the Vioxx recall?
What we will be left with on a permanent basis is much more consumer skepticism about the drug industry in general and its ads, in particular. And that"s probably a healthy thing.
The FDA this week asked Pfizer to pull some Viagra ads for failing to disclose the drug"s side effects and risks, and making unsubstantiated claims about sexual libido. Could that mean it"s taking a tougher stance?
We"re likely to see more of a change on the part of consumers than on the part of the government. There may be a couple more symbolic gestures like the Viagra ad [being pulled], but come spring it will be business as usual. The current FDA leadership, and the Washington leadership in general, does not believe in regulating the pharmaceutical industry more than we have done so far. Many of us in medicine feel that . . . the clear implications of many of these ads have gone well beyond the data. The Viagra ad clearly was implying some degree of libido improvement. There"s never been evidence of that . . . but somehow we have allowed our pharmaceutical industry to spend enormous amounts on advertising while the FDA is not compelling them to spend the much more modest amounts needed to get accurate information about the safety of these drugs.
How could the FDA compel them to do so?
One way is for the FDA to require a company to go back and do additional studies. There is a dramatic drop-off in the FDA"s regulatory vigilance between before a drug is approved versus after it is approved. There"s a spotty track record of the FDA requiring companies to do additional research after a drug has been approved for marketing. It"s almost as if both the companies and FDA feel that the FDA"s leverage drops off to negligible levels once they have given the OK for a drug to be marketed.
But doesn"t the FDA have leverage? It could pull a drug off the market.
Before the drug is marketed, the FDA can require any number of studies. The companies will comply eagerly because if they don"t, the drug won"t be approved. But once the drug is approved, the FDA has very few tools in its toolkit for what it can do about safety problems. It can take a drug off the market but that is a pretty draconian step to take. It"s as if there were a court whose only punishment was capital punishment. A judge might be reluctant to use that punishment for a burglary. If that is the only punishment he has, then he might let some criminals go unpunished . . . We need to have more attention and resources spent on other groups looking at drug safety, like university groups. If we want to study a drug"s side effect, the FDA has hardly any money to support this type of research.
There"s been some concern that Bextra–another Cox-2 inhibitor like Vioxx–might share the same risks. In that case, two researchers looked at the same data that Pfizer did but drew different conclusions about the risks.
What happens a lot is that companies use the statistical approach that we reserve for effectiveness studies and apply it incorrectly, in the view of many of us, to safety studies. So they can hide behind statements saying there was no statistically significant evidence that this drug causes heart disease. It"s a misuse of the concept of statistical significance. Also, one reason companies can say there is not enough data to show a relationship is that [specific] studies were not done. That"s one way of saying there"s no statistical evidence. It"s not a very forthcoming approach to protecting patient safety.
What should the government do differently?
Take these three back-to-back crises [the flu vaccine shortage, antidepressants and Vioxx] and bring some good out of it. . . . We can learn what went wrong and how we as a nation can do better going forward, and use this as a learning experience that might help make up for the clear personal medical tragedies we know are resulting. Specifically, it means having an FDA that is far more vigilant about balancing the needs of public health versus the needs of the drug industry.
How optimistic are you that this will happen?
Only modestly. In the end, an awful lot of this comes down to business and politics. If science were calling the shots, I"d be very optimistic. But if business and politics are calling the shots, I"m worried about the future.
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