Opening the black box ...

As reported in a news blurb that nearly escaped my attention because the major newspapers and websites either failed to report it or buried it deep, the US Food and Drug Administration (FDA) is proposing to replace its current pregnancy labels for a new system that clearly lists what is known and not known about use of particular drugs by pregnant or lactating women.

Under the old system, drugs were categorized into one of five categories - A, B, C, D and X – based on the amount of animal and human safety data available. Only a handful of currently marketed drugs fall into category A: safe for use based on extensive animal and human safety data. More drugs fall in category X: conclusive animal and human data demonstrating fetal risk.

The problem is that the vast majority of drugs fall into categories B and C. For most these compounds, there may or may not be data from animal models to suggest that the drug is safe and no good human studies to confirm these pre-clinical results. Use of these drugs by pregnant or lactating women is thus a crap shoot, with women and their physicians given little guidance to help them weigh the risks and benefits of these treatments. The new labeling rules would provide more information about the potential risks and benefits to pregnant or lactating women and their children or fetuses.

Still, I wonder whether the FDA realizes the Catch-22 that many researchers face regarding pregnant and lactating women. In the HIV prevention field, for example, microbicide and PrEP (pre-exposure prophylaxis) studies generally exclude pregnant and lactating women from enrolling, and study participants who become pregnant must discontinue product use. However, in the resource-poor countries when many of these trials take place, women spend approximately one-third to one-half of their reproductive years pregnant or breastfeeding. Not only do unexpected pregnancies adversely impact the power of these studies to detect a protective effect, but these restrictions also mean that a large number of women in the developing world who want to participate in these HIV prevention trials cannot. Alternatively, they be required to use a limited number of contraceptive methods that might otherwise be unacceptable to them.

Finally, it is unclear how HIV prevention researchers can collect the necessary data to demonstrate that these products are safe and effective for pregnant and lactating women to use. Most of these data come from pregnancy exposure registries, in which women who use category B, C and D drugs are monitored for the effect of these compounds on fetal development. But does it make sense to rely on such “natural experiments” rather than collect the necessary safety data in a controlled clinical trial using fully informed and willing participants? … particularly for compounds like topical microbicides and PrEP which, if effective, will be used primarily in countries in which collecting data for pregnancy exposure registries is likely to be difficult at best?

Closing the Loopholes for Big Pharma

Today's New York Times reports that about a third of the studies done on Paxil and Prozac went unpublished and (not surprisingly) if those studies were included these drugs were much less effective than when only the positive studies were published. http://www.nytimes.com/2008/01/17/health/17depress.html?
This is only the latest in a series of revelations about the way that pharmaceutical companies (“Big Pharma”) control the data about new drugs which they make available to the FDA in seeking approval and then to the public. No one disputes that these failures to disclose are harmful to the public’s health. Doctors prescribing drugs and using medical devices must have complete information in order to make the best treatment decisions. However, what is lost amidst the hand-wringing is that there is a very simple way to end this pattern and to make this information available to those who need it: require that all information, positive and negative, about drugs submitted for approval to the FDA be made available to a public data base. Current regulatory changes to require greater disclosure are inadequate because if there are any places left to hide negative data, Big Pharma will find a way to get there. Moreover, the arguments that it is somehow unfair to require companies to benefit from information about what doesn't work makes no sense because companies would only have to disclose AFTER they decide it is worth submitting the drug for approval.

Pharmaceutical companies are businesses like any other and are entitled to make a profit and to keep business information private—but only to the extent that it does not harm the public’s health. Having a drug approved for sale in the United States by the FDA is a privilege and it should come with the responsibility of making available all the available information—not just the information which the company chooses to disclose.

While it has always been the case that pharmaceutical companies were able to hide negative results in studies they conducted themselves, the need is much greater following a recent Supreme Court decision, Garcetti v. Cebalos, which held that government employees do not have First Amendment protection for divulging information—even information vital to the public’s safety-which they learn at work. Most people do not know that a growing number of research companies conducted by pharmaceutical companies are channeled through academic medical centers. While Garcetti v. Cebalos, did not involve research scientists it clearly suggests that a medical researcher at a state university which conducts drug trials for pharmaceutical companies could put his or her job at risk by divulging negative results. This silencing of whistleblowers means that without specific legislation that requires the disclosure of all data, wherever acquired, companies can continue to shield negative results from public view.

Of course is o.k. for pharmaceutical companies to make a profit, just as it is for auto companies, but when the product is one that can endanger the public’s health there must be a requirement of full disclosure.


Jennifer S. Bard, J.D., M.P.H.
Alvin R. Allison Professor of Law and Director, Health Law Program Texas Tech University School of Law Associate Professor (Adjunct) Texas Tech University School of Medicine
1802 Hartford Avenue
Lubbock, Texas 79409-0004
Jennifer.Bard@ttu.edu
806.742.3990, ext. 349


http://www.nytimes.com/2008/01/17/health/17depress.html?ex=1201237200&en=bff3cb16e49ff5f0&ei=5070&emc=eta1