The following policy recommendations are intended to address disparities in representation and expand the inclusion of women in clinical trials, including pregnant and lactating women (Figure 3): –Improve enrolment of women in clinical trials to drive new and effective treatments. Building on the FDA Diversity Action Plan, regulatory bodies should have the authority to mandate the inclusion of women in clinical trials. Enrolment goals should be based on sex, race, ethnicity and age – from 18 to post-menopausal women – aligned with the prevalence in the intended use population. Additionally, women of childbearing age must be presumed eligible for participation rather than routinely excluded, with clear justification required for any exceptions. Further, contraception guidelines should be harmonized based on actual reproductive risks rather than broad, inconsistent requirements, while ensuring the availability of highly effective contraceptives and appropriate education, to avoid unnecessarily excluding women from research. –Introduce a maternal investigation plan to support research for pregnant and lactating women. Modelled on the FDA’s Pediatric Study Plan and the EMA’s Paediatric Investigation Plan, this structured approach integrates reproductive health considerations early in clinical trials, potentially even using non-animal models (such as organ-on-a-chip). By the time Phase 3 clinical trials are being undertaken, at the latest, thorough benefit-risk evaluations should guide the inclusion or exclusion of pregnant and lactating women. Additionally, collecting global pregnancy outcome data using national and international registries, including from LMICs, can help promote inclusion and inform evidence-based clinical guidelines. –Require research on pregnant and lactating women to close critical data gaps. In an intervention modelled on the PREA, mandating studies on the safety, efficacy and dosing of medications in pregnant and lactating women will help address the long-standing absence of data – first in preclinical research and, depending on safety outcomes, also in clinical research. Post-authorization safety studies should be considered the absolute minimum. The routine inclusion of available data on pregnant and lactating women in periodic benefit-risk evaluation reports and risk management plans should also be required, with systematic investigations triggered when a concern is identified. Additionally, when benefit- risk assessments are incomplete, establishing post-market registries, such as Medication Safety in Pregnancy (EUROmediSAFE), can generate real-world evidence to refine clinical guidelines and improve maternal and infant health outcomes.42 –Incentivize research on pregnant and lactating women to advance maternal and infant health. In an intervention modelled on the BPCA, offering incentives for studies on both on- and off-patent drugs as well as other bioactive substances (e.g. nutraceuticals) will help fill critical knowledge gaps and ensure safer treatment options. Additionally, making clinical trial insurance more affordable for research involving pregnant and lactating women will help remove financial barriers for investigators and sponsors, supporting and encouraging greater inclusion in clinical studies and ultimately improving healthcare outcomes for these populations.2.4 Policy recommendations to expand the inclusion of women in clinical trials Prescription for Change: Policy Recommendations for Women’s Health Research 14

Prescription for Change 2025