Increasing the Participation of Pregnant Women in Appropriate Clinical Research

by Eva May

Pregnant Women are Typically Excluded from Clinical Research

There is a longstanding belief that women who are pregnant or breastfeeding should be excluded from research studies due to potential harm to them and/or the fetus. Women of childbearing age who participate in research are routinely given pregnancy tests, and they may be removed from a study if they become pregnant. Although well-intentioned, these practices are not necessarily backed by evidence. In fact, the exclusion of pregnant women from clinical research has resulted in important medical treatment recommendations being made without scientific evidence of a treatment’s safety or efficacy.

Over 90 percent of pregnant women use at least one medication; about 70 percent use at least one prescription medication. Most drugs that were approved in the United States between 2000 and 2010 lacked substantial data to accurately assess the risk for birth defects. This insufficient research and data frequently result in a lack of reliable guidance regarding safe and proper care for pregnant women who need medical attention. This leads to inappropriate dosing or treatment recommendations, physician reluctance to prescribe a drug or patient avoidance of needed therapy.

Pregnant Women Should be Included in Appropriate Clinical Research

The FDA is committed to advancing research of pregnant and lactating women to promote their health and the health of their babies and helping to inform treatment decisions during pregnancy. This includes research of drugs that are already approved for use in the U.S., as well as drugs in development. An effort has been made to collect information about the use of these drugs and treatments in the post-marketing setting (after FDA approval). National research registries and other data sources can help researchers track outcomes and side effects in pregnant women who take different medications. These methods can also assess the safety and efficacy of medical treatments once they are approved for patient use.

In 2018 the FDA released a draft of a guidance document stating that pregnant women with a disease or medical condition that requires treatment can participate in clinical trials “if adequate nonclinical studies (including studies on pregnant animals) have been completed and there is a prospect of direct benefit to the pregnant woman and/or fetus that is not available outside the research setting.” The NIH also “strongly encourages including pregnant women in clinical research in all circumstances in which their inclusion is scientifically valid and ethically permissible.”

In February 2021, the Duke-Margolis Center for Health Policy, under a cooperative agreement with the FDA, held a public meeting to discuss the need for clinical research in pregnant women, as well as the scientific and ethical considerations for the inclusion of pregnant people in clinical trials. The information presented was evidence-based, thorough, thoughtful and compelling, and it is available online. Many presentations were given by members of the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC). This effort was established by the 21^st Century Cures Act to advise the Secretary of HHS about gaps in knowledge and research on safe and effective therapies for pregnant women and lactating women. In August 2020, the PRGLAC issued an 83-page report implementation plan that offers “feasible and actionable steps that could make progress toward ensuring that pregnant women and lactating women are more comprehensively and appropriately included in research.”

Research Advocates can Encourage Inclusion of Pregnant Women in Clinical Research

While the FDA and the HHS Task Force can provide excellent guidance and rationale for improved research design and broader inclusion, they cannot force drug developers or researchers to adhere to their guidelines. As research advocates, we sometimes have the opportunity to influence research design in ways that can truly improve a key cohort of patients’ lives and well-being. The presentations and discussions in the February workshop, along with the actionable recommendations made in the PRGLAC plan and their rationale, can provide research advocates (and others) with excellent advice and guidance regarding the appropriate inclusion of pregnant women in research.

When research advocates are evaluating research design for drug and biological product studies that may directly benefit pregnant women who are affected by a disease or medical condition, we can ask about and recommend proactive plans that ensure that reliable safety and efficacy data exist for this group.

Examples of questions advocates can ask (with links to detailed research guidance) include:

1. Are pregnant women being excluded from this study? If so, why? https://www.nichd.nih.gov/sites/default/files/inline-files/PRGLAC_Implement_Plan_083120.pdf 44, Recommendation 10: Implement a proactive approach to protocol development and study design to include pregnant women and lactating women in clinical research.
2. Has any safety testing been done on pregnant and lactating mammals and their babies? https://www.fda.gov/media/112195/download 7, l. 148
3. Can we include a proactive plan to recruit pregnant women for the Phase 3 study following safety testing and a successful Phase 2 study? https://www.fda.gov/media/112195/download  P 12, l. 342
4. Can women remain in the study if they become pregnant while participating? If not, why not? https://www.fda.gov/media/112195/download  11, l. 293
5. For pharmaceutical-sponsored trials, can we proactively include a plan to do a post-approval pregnancy safety study or a clinical trial if FDA approval is given?

I believe that becoming a voice for appropriate and timely inclusion of pregnant women in relevant clinical research can make patient research advocates change agents for significant improvements in the collection of the data and evidence needed to improve health outcomes and safety for mothers and babies everywhere.

Eva May is a multicultural marketing professional and patient research advocate involved in the development and implementation of patient-powered cancer research. She is a FORCE research advocate and Peer Navigator.