The FDA Perspective on the Ethical Barriers of Conducting Research in Pregnant Women

Abstract

The need for data related to medication use in pregnancy, especially for psychiatric medications, is undeniable. Onethird of pregnant women are exposed to medication for psychiatric conditions (American College of Obstetricians and Gynecologists 2008). Untreated psychiatric illness during pregnancy may be associated with preterm birth, low birth weight, increased social withdrawal, and reliance on alcohol and drugs. Pregnant women are an understudied population due to the ethical and medical–legal considerations of harming the fetus. Ironically, it is this fear of harming the fetus that often results in lack of data collection in pregnant women and uninformed prescribing without true knowledge of safety or efficacy. Although randomized controlled trials (RCTs) are the gold standard for safety and efficacy prior to approving new drug applications, these types of studies are not appropriate for pregnant women in most situations due to the ethical consideration of exposing a fetus to the risks of an investigational drug where efficacy has not been clearly demonstrated. In the premarketing setting, reproductive and developmental toxicity data are usually the only data available to inform risk in pregnant women. If there are no other treatment options available for a serious or life-threatening condition, it may be appropriate to study an investigational drug that may benefit the woman or the fetus. In the postmarketing setting, it may be ethically appropriate to include pregnant women in RCTs if there is an established safety database and the drug is already being used by pregnant women. However, in addition to RCTs, other study methods to collect data in pregnant women can provide valuable information without any additional studyrelated risks. Similar to the pediatric population, some estimates of efficacy can often be extrapolated from adult, female populations through pharmacokinetic studies. Safety data can be collected through prospective observational co-