Sunday, March 05, 2006

Data on Drug Adverse Effects Delayed: Is It Data Denied?

In an annual report by the US Food and Drug Administration (FDA), the agency admitted that about two-thirds of the post-marketing drug studies it had mandated have never been finished. (See articles in the New York Times, and from the Associated Press.) According to the Times, one such study was mandated in 1955.

In the Times, US Representative Maurice D. Hinchey (Democrat- New York), "said while the agency insisted that it demanded that drug makers prove their medication safe, those demands 'continue to be blatantly ignored by the pharmaceutical industry.'"

In reply, Dr John Jenkins, director of the FDA Office of New Drugs, "emphasized that only 5 percent of promised drug trials were officially considered 'delayed.' In many cases, trials have been pending for more than a decdade but are not considered delayed because the agency never insisted on a specific timeline for them."

The AP quoted Harvard Professor Jerry Avorn, "This new information is an embarassing continuation of similar reports issued by FDA each year on the appalling state of the medication safety studies it has 'mandated' drug manufacturers to perform. It is scandalous that of the supposedly active studies, about two-thirds haven't even been started yet"

Demanding post-marketing studies to assess drug safety appears to be a compromise that the agency offered in the face of demands from patient advocacy groups and political conservatives that the agency approve potentially beneficial drugs more quickly, based on relatively limited data from small randomized controlled trials.

I agree that potentially beneficial drugs should be put on the market as soon as possible with the least red-tape. Randomized controlled trials that have adequate statistical power to determine if a drug has benefits when compared to a placebo may not have enough power to determine all its important adverse effects. Thus it may make sense, when a drug offers important benefits beyond any treatment currently available, to allow it on the market without complete safety information, and then to require post-marketing studies, with more statistical power (but perhaps also with more methodologic biases) to assess its adverse effects. But patients and physicians need to know about the all important possible hazards of potentially beneficial medicines to make optimal decisions about whether to use them. So it is crucial that these post-marketing studies get done as quickly as possible.

I don't understand why the FDA has been mandating these studies, but not mandating any deadlines for their completion. Patients and physicians are ill-served by delays (whether officialy defined or not) in accomplishing these studies.

If pharmaceutical companies really want to increase their trustworthiness to patients and physicians, they ought to consider completing all pending post-marketing studies expeditiously. And in my humble opinion, the FDA needs to hold pharmaceutical companies accountable for their failure to complete such studies in reasonable amounts of time.

1 comment:

InformaticsMD said...

The existing systems of post-marketing drug surveillance are largely inadequate as well. In approving a new drug, FDA may demand that a company conduct additional safety trials after release to the public, but the agency can't enforce these post-approval studies, and more than half of those agreed to by manufacturers never occur, according to a Department of Health and Human Services report in the March 15, 2004 Federal Register [ “Dangerous Practices: Critics see flaws in drug-safety monitoring”, Science News, Week of Feb. 5, 2005; Vol. 167, No. 6 , p. 90, ].

It is likely the drug industry will not yield on this issue without a protracted battle due to the expense involved. However, competing technologies may make cooperation from the industry less necessary. Specifically, the electronic medical record.

See my position paper "A Grand Challenge in Medical Informatics:
Pharmaceutical Post-Marketing Surveillance as a Pilot Environment Towards Broad National Health Data Initiatives" at: