The consequences of this research gap are significant, but when studies are designed to account for sex differences, the benefits are clear. For example, Novartis discovered that its heart failure drug Entresto, launched in 2015, was particularly effective for women, who are twice as likely as men to develop heart failure with preserved ejection fraction – also known as diastolic heart failure, in which the left ventricle, the organ’s main pumping chamber, becomes stiff and is unable fill properly.33 After conducting clinical trials on target subgroups, a 2019 Phase 3 trial revealed that the drug reduced hospitalizations for women by 33%. This finding led to expanded FDA approval, allowing more than 2 million additional patients to benefit and underscoring the urgent need for research that prioritizes sex-specific data. Two decades ago, the United States implemented policies to drive paediatric drug development. In 2002, the Best Pharmaceuticals for Children Act (BPCA) provided marketing exclusivity incentives for sponsors that voluntarily conducted paediatric studies; the following year, the Paediatric Research Equity Act (PREA) introduced a requirement for paediatric studies using appropriate formulations to obtain paediatric labelling with the option to request a waiver if, for example, evidence strongly suggests that the drug is unsafe in paediatrics. This regulatory requirement proved significantly more effective than just incentivization, leading to 475 drug approvals, compared to 199 approvals under the BPCA’s voluntary approach.34 Additionally, an initial paediatric study plan was established to ensure that paediatric considerations were incorporated early in drug development. The European Medicines Agency (EMA) has put similar requirements in place with the EU Paediatric Regulation and the Paediatric Investigation Plan.35,36 The success of these policies highlights that requirements have a far greater impact on approvals than incentives alone. Applying this approach to pregnant and lactating women – by requiring research on medication safety, efficacy and dosing, paired with targeted incentives to overcome increasing costs – can ensure that this demographic of women is no longer excluded from essential clinical trials.2.2 Success in paediatrics: Requirements and incentives drive inclusion Although the United States has recently made changes to broaden clinical research to include more women, a global push to improve policies that promote better representation is still needed. In 2024, the FDA Diversity Action Plan was put in place to improve enrolment of participants from under-represented populations in clinical trials.37 In the same year, the National Academies of Science, Engineering, and Medicine released the report Advancing Clinical Research with Pregnant and Lactating Populations: Overcoming Real and Perceived Liability Risks to improve representation of pregnant and lactating women in clinical trials.38 Other regulatory bodies such as the EMA, Health Canada and the United Kingdom’s Medicine and Healthcare products Regulatory Agency (MHRA) initiated similar guidelines and projects. Most recently, the FDA introduced draft guidance on studying sex differences in the clinical evaluation of medical products highlighting the need to include women in clinical trials, particularly pregnant and lactating women, and to conduct sex-specific data analysis.39 Further, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) currently develops a guideline on the inclusion of pregnant and breastfeeding individuals in clinical trials.40 Finally, the 2024 Access to Medicine Index is a testament to this shifting landscape. It highlights early progress within the pharmaceutical industry in addressing this issue, with some companies taking steps to include pregnant and lactating women in HIV clinical trials.41 This lack of sex-specific research is contributing to a major absence of data and thus knowledge regarding the treatment safety and efficacy in women throughout their lives. Policy changes requiring and incentivizing the inclusion of diverse women in clinical trials are necessary to address these gaps and better understand sex-specific differences in treatments.2.3 Recent guidelines and initiatives start to focus on inclusion Prescription for Change: Policy Recommendations for Women’s Health Research 13

Prescription for Change 2025