Pregnant Women: An Underrepresented Group in Clinical Trials

Kristin Tolbert, Associate VP of Health Equity Strategy at Jumo Health

Pregnant women have long been excluded from clinical trials. Despite women of childbearing age accounting for over 20% of the US population, they represent less than 1% of study participants.¹ This lack of inclusion has resulted in a significant knowledge gap: only 10% of drugs approved by the FDA have sufficient data to determine their safety during pregnancy² and 98% of medicines approved between 2000 and 2010 lack reliable information about the risk to the fetus.³

This circumstance leaves millions of pregnant women and their doctors to make critical decisions about their healthcare with minimal evidence to guide them. 70% percent of pregnant women report taking at least one prescription medicine during pregnancy,⁴ often for serious conditions like depression, lupus, or cancer. In recent years, the scientific, ethical, and legal frameworks that have historically justified excluding pregnant women from trials are being reconsidered. Many researchers and organizations are coming to the conclusion that failing to include pregnant women in clinical research may actually present greater risks than including them.

Addressing the physiological and clinical realities of pregnancy

Pregnancy introduces profound physiological changes, including a doubling of blood volume, altered levels of circulating binding proteins, slower gastrointestinal transit time, and changes in drug metabolism and excretion.⁵ These shifts can vary significantly across trimesters, meaning the therapeutic effect and appropriate dosing of medicines may fluctuate throughout gestation. Without studying these changes in the context of clinical trials, we risk administering treatments that are suboptimal—or worse, harmful—during pregnancy.

For example, psychiatric disorders affect over 20% of pregnant women globally,⁶ yet treatment often relies on data derived from non-pregnant female populations. This can lead to ineffective dosing or unanticipated side effects for both the woman and the fetus. Similarly, pregnant women undergoing treatment for chronic or life-threatening conditions such as heart disease or cancer face limited options, as their needs are rarely addressed in clinical research. By designing trials that consider these physiological nuances, the clinical trials industry can better understand how to optimize care for this population.

Shifting the narrative around ethical and legal risk

Concerns about the potential risks to the fetus have often been cited as the primary reason for excluding pregnant women from trials. However, failing to conduct necessary research does not eliminate risk. It merely shifts it to the clinical context, where physicians and patients must make decisions with incomplete information. This hardly represents an ethical approach to healthcare.

The historical tragedy of thalidomide serves as a cautionary tale of what can happen when drugs are inadequately studied during pregnancy. The lack of rigorous, evidence-based research at the time when thalidomide was widely prescribed led to devastating consequences for fetuses, including severe birth defects in the limbs, organs, and sensory systems. Yet paradoxically, the lessons of thalidomide have contributed to a culture of excessive caution, stalling progress in understanding how to safely and effectively treat pregnant women.

Legal concerns also play a significant role in this hesitancy. However, a case law analysis commissioned by a National Academies committee found no liability claims arising from the participation of pregnant or lactating women in clinical trials since 1962.⁷ In contrast, numerous liability claims have been filed by pregnant women who experienced adverse outcomes from using drugs already approved and on the market. These events underscore the need for robust pre-market data to mitigate risks and provide clear guidance to healthcare providers and patients.

The case for inclusion

Excluding pregnant individuals from clinical trials perpetuates a cycle of harm. Post-marketing data, while valuable, is no substitute for the insights gained from trials specifically designed to address pregnancy-related considerations. By including pregnant women in studies, our industry can collect data on safety and efficacy in a controlled environment, rather than relying on retrospective analyses or anecdotal evidence.

One way in which sponsors can make it easier for pregnant women to participate in research is by partnering with obstetric services to facilitate trial participation. Embedding clinical trial activities within obstetric practices or at convenient locations for participants can improve both recruitment and retention.⁸ This approach not only enhances accessibility, but also fosters trust between researchers and patients.

Finding pregnant women to take part in research is just the beginning. The most critical task is educating them about the risks and benefits of clinical trial participation. One of the most effective ways to address potential hesitancy is through clear patient education and informed consent. Consent forms should include pregnancy-specific language and should be transparent in outlining potential risks and benefits based on evidence collected from non-clinical studies. This approach empowers potential participants with the information they need to make decisions about their involvement in clinical research.

The humane and scientific benefits of inclusion

The real risk to healthcare lies not in conducting trials that include pregnant women, but in continuing to exclude them. By disregarding this population, the clinical trials industry denies pregnant women—and their healthcare providers—the evidence necessary to make informed decisions. It also misses vital opportunities to improve outcomes for both parents and their babies.

It is a humane and scientific responsibility to prioritize inclusion of pregnant women in clinical trials. It is imperative for advancing maternal and fetal health. Through thoughtful trial design, rigorous safety protocols, and transparent education, we can ensure that new therapies are developed with safety and efficacy in pregnant women in mind.

Inclusive clinical research leads to better scientific results and more equitable healthcare for all. The question is no longer whether we can afford to include pregnant women in clinical trials; it is a question of whether we can afford not to do so.

Kristin Tolbert, Associate VP of Health Equity Strategy at Jumo Health

References

1. Blehar MC, Spong C, Grady C, et al. Enrolling Pregnant Women: Issues in Clinical Research. Women's Health Issues. 2013;23(1):e39-e45. doi:10.1016/j.whi.2012.10.003
2. Pregnancy and Lactation Labeling (Drugs) Final Rule. U.S. Food and Drug Administration. December 3, 2014. Accessed January 27, 2025. https://www.fda.gov/drugs/labeling-information-drug-products/pregnancy-and-lactation-labeling-drugs-final-rule
3. Andrade SE, Raebel MA, Morse AN, et al. Use of prescription medications with a potential for fetal harm among pregnant women. Pharmacoepidemiol Drug Saf. 2006;15(8):546-554. doi:10.1002/pds.1235
4. Mitchell AA, Gilboa SM, Werler MM, et al. Medication use during pregnancy, with particular focus on prescription drugs: 1976–2008. Am J Obstet Gynecol. 2011;205(1):51.e1–51.e8.
5. Pharmacokinetics of Drugs in pregnancy. March 28, 2016. Accessed January 27, 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC4809631/
6. Howard LM, Molyneaux E, Dennis CL, et al. Non-psychotic mental disorders in the perinatal period. Lancet. 2014;384(9956):1775–1788. doi:10.1016/S0140-6736(14)61276-9
7. National Academies of Sciences, Engineering, and Medicine. The Ethics and Regulatory Landscape of Including Pregnant Women in Clinical Research. Washington, DC: National Academies Press; 2018.
8. Shields KE, Lyerly AD. Exclusion of pregnant women from industry-sponsored clinical trials. Obstet Gynecol. 2013;122(5):1077-1081. doi:10.1097/AOG.0b013e3182a9ca67