Drugs, Pregnancy & Lactation

Safe, effective therapies: Establishing a path forward


I have had friends and colleagues visibly shrink away when I say that my work involves the study of medication safety in pregnancy. “Yikes! I would never let my daughter participate in a clinical study if she was pregnant!” I hear. It’s an interesting response. Understandably protective of a loved one, except that the loved one is an adult woman who presumably can make her own choices. And the response reveals an assumption that medications are tested in all populations before approval for market. Sadly, the response is ill-informed given that pregnant women are still excluded from most if not all clinical research. My work, by the way, is focused on postapproval studies.

A pregnant woman takes pills Antonio_Diaz/Thinkstock

Translating the above response to a larger picture, health care providers and pharmaceutical manufacturers also have their concerns about pregnant women and lactating women participating in clinical research. Along with the patient and her loved ones, all parties’ concerns are valid. However, there is a harsh reality: According to a study in the American Journal of Obstetrics & Gynecology, an estimated 50% of U.S. women take one or more prescription medications during pregnancy. Once marketed, therapies are prescribed to pregnant women, knowingly and unknowingly, and without evidence-based knowledge of their safety. If postapproval safety studies are undertaken, decades may pass as data accrue and before results become available. In general, even less is known about the safety of medications in breastmilk.

Without a path forward that includes pregnant women and lactating women in clinical research, we will remain without timely knowledge of medication safety. Further, our understanding of efficacy will be based on clinical studies of nonpregnant women. Recognizing the need for this information, the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC) was convened in 2017 and tasked with determining this path forward.

The PRGLAC was established by the 21st Century Cures Act, a law designed to help speed up medical product development. Managed by the National Institutes of Health, the PRGLAC is made up of representatives of all federal agencies with responsibilities for women’s health and research, as well as clinicians, industry experts, and other experts. The PRGLAC’s work has been conducted in two phases.

Dr. Janet R. Hardy, a consultant on global maternal-child health and pharmacoepidemiology

Dr. Janet R. Hardy

In Phase I, PRGLAC was charged with identifying gaps in knowledge and research regarding safe and effective therapies for pregnant women and lactating women. The Task Force conducted four public meetings in 2017 and 2018, and submitted their conclusions to Congress and the Secretary of Health & Human Services in a publicly available report. The report provides 15 specific recommendations, several of which are directly relevant to obstetricians: No. 3 recommends expanding the workforce of clinicians and research investigators with expertise in obstetric and lactation pharmacology, No. 6 recommends the development and implementation of evidence-based communication strategies with health care providers, and No. 13 recommends optimization of registries for pregnancy and lactation. Obstetricians can make a positive contribution to accruing medication safety data by being aware of pregnancy registries and indicating their availability to eligible patients.

In the spring of 2019, the PRGLAC reconvened with a 2-year mandate and a new charge for Phase II: to develop plans for implementing the recommendations laid out in the Phase I report. Four working groups (WGs) were identified to address the recommendations of the report: WG1 Research and Training, WG2 Regulatory, WG3 Communication and Registries, and WG4 Discovery. The four groups have deliberated, and a new report is being finalized. The PRGLAC’s efforts provide a fresh conversation to address long-standing issues to provide evidence-based information for the treatment of pregnant and lactating women. Once available, the final report will be posted on the PRGLAC website.

The recommendations in this report, when implemented, are directly relevant to patient care and clinician training and will provide a path forward for the inclusion of pregnant and lactating women in clinical research or a firm justification for their exclusion.

Dr. Hardy is a consultant on global maternal-child health and pharmacoepidemiology. She also represents the Society for Birth Defects Research and Prevention and the Organization of Teratology Information Specialists at PRGLAC meetings. Dr. Hardy disclosed she has worked with multiple pharmaceutical manufacturers regarding medication safety studies in pregnancy, most recently Biohaven. Email her at [email protected].

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