Finally, a plan on how to include pregnant women in clinical trials

Among the stark changes for a woman during pregnancy is what she sees when she opens the medicine cabinet. The medications she wouldn’t have given a second thought to months earlier may now prompt worry and doubt. With any drug on the shelf, she may wonder: Is this medicine safe? Do I need to adjust the dose? Avoid it altogether? An expectant mom with just a cold or a headache will find drug labels suggesting she ask a health professional before use.

Turns out, those health professionals are in the same boat as their pregnant patients: There is very little, if any, information about whether many drugs are safe to give to expectant mothers. And that can lead to situations that put fear of harm to the fetus over the health of the mother.

Case in point: As a medical resident, bioethicist and obstetrician/gynecologist Anne Lyerly got a call from a friend and fellow resident working at a different hospital. The chief resident there was trying to resuscitate a dying woman who was pregnant, and instructed Lyerly’s friend to find out what drugs were safe to use. “I said, ‘you need to tell your chief resident that he needs to go save his patient’s life,’” Lyerly recalls, and not worry about possible harms from the drugs required to do so.

The widespread reluctance to provide medication to pregnant women stems from a dearth of data on treating illnesses with drugs during pregnancy. But because pregnant women have been generally excluded from clinical trials that study drugs, there isn’t much data to be had.

Now there’s a knock on the door that has been largely closed to this research. In April, the U.S. Federal Drug Administration released a draft of guidance on when and how to include pregnant women in clinical trials for drugs and therapies. It addresses considerations such as the effect pregnancy has on the absorption of drugs, nonclinical studies that should be conducted, and appropriate data collection and safety monitoring.

The key concern with pregnant women participating in clinical trials is safety of the fetus. The terrible birth defects that resulted from the wide use of the sedative thalidomide in the 1950s and ’60s weighed heavily on the eventual decision to largely exclude pregnant women from trials that test drugs. But that tragedy didn’t happen because pregnant women were studied, Lyerly says — it was because they weren’t studied.

“If you don’t study a drug in a highly controlled research setting,” Lyerly says, “it’s not like the risk that would be imposed on those individuals goes away.” Instead, the risk gets shifted to women who need the drug or women who get pregnant while on the drug. “If you are not going to conduct these research studies, it’s not like you’re off the hook, morally speaking, at all. It means the risk is going to be put somewhere else.”

The lack of clinical data doesn’t mean pregnant women aren’t using medications.  A 2011 study found that 94 percent of more than 25,000 pregnant women had taken at least one over-the-counter or prescription medication during their pregnancy. The same study reported the average number of medications used at any time during pregnancy increased from 2.5 in 1976-1978 to 4.2 in 2006-2008. Looking only at prescription medications, 70 percent of pregnant women had used at least one.

But for 172 drugs approved by the FDA from 2000 to 2010, a different 2011 study found that there wasn’t enough data to determine the risk of harm to the fetus for 168 — or 98 percent — of the drugs.

“There is widespread exposure, and people want to know if the drug they were taking is safe,” Lyerly, of the University of North Carolina at Chapel Hill, says.

Although there are unknowns regarding drug treatment, there are diseases that, if untreated, can harm a pregnancy. Women who have asthma attacks during pregnancy are three times as likely to have babies with a low birth weight compared with asthmatic women who don’t have attacks, yet undertreatment of the condition is common, researchers report. Pregnant women with uncontrolled diabetes have more than four times the risk of late miscarriages or stillbirths as nondiabetic pregnant women. Treating the diabetes brings that risk down.

“Drugs can be extremely protective of fetal health by treating maternal health conditions,” Lyerly says.

Lyerly’s own research suggests that pregnant women are interested in participating in clinical research. She and colleagues published a small study in 2012 of 22 pregnant women enrolled in clinical trials to study dosing of an H1N1 influenza vaccine. The researchers interviewed the women about why they participated; the trials had filled quickly, Lyerly says.

The women’s reasons for enrolling ranged from worries about the risk of H1N1 and the benefit of receiving the vaccine early, to the preference for receiving the vaccine in a research setting with close medical monitoring, to the desire to be part of a study that would help other pregnant women. Lyerly just finished another study of 140 pregnant women in the U.S. and Malawi who have HIV or are at risk of the disease and their views about participating in research.

Lyerly argues that the issue of including pregnant women in clinical trials is not just about fetal safety, “it’s also about maternal benefit,” such as the benefit of a vaccine or a treatment for a risky illness. “Drug treatment is not the enemy,” she says, “it’s a tool in a tool chest that is important to ensuring healthy moms and healthy babies.”

The FDA guidance is a welcome signal of support for conducting research in pregnant women, Lyerly says. During the public comment period, which closes June 8, Lyerly and her colleagues plan to offer their views, especially regarding the criteria for including pregnant women in clinical studies. The goal is to encourage the progress of research in this area, she says, and the guidance “is an important beginning to the conversation.”