By Kate Greenwood
[Cross-posted at Health Reform Watch]
A week ago, the Food and Drug Administration announced the results of a review of the medical literature it conducted in response to “recent reports questioning the safety of prescription and over-the-counter (OTC) pain medicines when used during pregnancy.” The literature, FDA determined, is inconclusive. FDA found that all of the studies had “potential limitations in their designs” and that “sometimes the accumulated studies on a topic contained conflicting results that prevented us from drawing reliable conclusions.” As a result, the FDA chose not to update its current recommendations. The agency emphasized, though, that the use of pain medication should be “carefully considered” by pregnant women and their physicians.
One of the reports that triggered the FDA’s review was no doubt this study, published in JAMA in April 2014, which found an association between prenatal exposure to acetaminophen and a higher risk of developing attention deficit hyperactivity disorder. The study led to headlines like Acetaminophen Use While Pregnant Leads to ADHD, Study Says and Mom’s Tylenol Use, Dad’s Age Are Latest Suspects on ADHD Front. At the New York Times’ Motherlode, KJ Dell’Antonia wrote: “If there is a pregnant woman out there willing to take Tylenol after reading this research — or just the associated headlines — I’d be surprised.” But there are serious risks associated with other pain medications, too. Tylenol has long been considered a relatively safe option. Even white-knuckling it is not risk free. As the FDA pointed out in its announcement, untreated severe and persistent pain increases the change that a pregnant woman will develop anxiety, depression, and high blood pressure.
The bottom line is that careful consideration of the risks and benefits of taking a medication is very difficult to do without data on those risks and benefits. And, as the FDA’s announcement reveals, the data has not been forthcoming. In an article I wrote in 2010, I listed a number of steps that could be taken to build the evidence base. Among other things, I recommended that federal and state governments increase their support for maternal-fetal medication research, but the government is spending less on medical research these days, not more.
I also recommended that the pharmaceutical industry be required to take on some of the burden. Specifically, I suggested that Congress extend the Pediatric Research Equity Act to cover pregnant women, which would ensure that as new prescription drugs are approved appropriate studies are done, and that FDA use its authority to require post-marketing studies and clinical trials that are necessary to (1) assess a known serious risk of a prescription drug; (2) assess signals of serious risk; and (3) identify unexpected serious risks where the data indicates the potential for such risks. In a draft Guidance for Industry issued in July 2009, the FDA said that an example of how it might use this authority would be requiring a company to conduct a clinical trial to evaluate the safety of a drug in pregnant women.
These are not perfect solutions. The FDA’s authority to require post-marketing studies does not apply to over-the-counter drugs, like acetaminophen. Extending the Pediatric Research Equity Act would do nothing about the legion of already-approved prescription drugs that need to be studied. Both approaches involve industry-funded and industry-conducted research, which brings with it justifiable concern about conflict of interest. A pharmaceutical manufacturer undertaking research into the use of one of its drugs during pregnancy knows that if the drug is associated with an increased risk of fetal harm, the manufacturer could suffer a laundry list of negative sequelae, ranging from being asked to conduct additional testing or implement marketing restrictions, to a reduction in sales, to the withdrawal of their product from the market altogether.
Something bolder might be better. Borrowing from Christopher Robertson’s article The Money Blind: How to Stop Industry Bias in Biomedical Science, Without Violating the First Amendment, instead of extending the Pediatric Research Equity Act, perhaps Congress should require pharmaceutical manufacturers to fund, but not conduct, high-priority research into maternal-fetal medication risk.