(SLB-065) New FDA Guidance On Sex Differences In Post-Marketing Studies: How Much Further Do We Need To Go?

Background: In January 2025 the FDA released new draft guidance around the study of sex differences in the evaluation of medical products. They recommend: 1) Increasing enrolment of female patients in clinical trials and non-interventional studies, 2) Analysing and interpreting sex-specific data, and 3) Including sex-specific information in regulatory submissions of medical products. The FDA guidance will impact the design and reporting of non-interventional studies evaluating the safety and effectiveness of medicines.

Objectives: This study looked to the past to understand how well these requirements were fulfilled previously in the US and EU and to identify any areas of improvement.

Methods: The HMA-EMA catalogue of RWD sources and studies was searched for studies that met the following criteria: 1) classed as safety or effectiveness studies, 2) non-interventional, 3) did not evaluate a vaccine, 4) required by a regulator, 5) had to be finalised. Available protocols and study reports were evaluated for study type, gynaecological outcomes, and whether safety or effectiveness outcomes were reported by sex.

Results: A total of 84 studies were identified, with a study start date between 2008-2022. Most (61.9%) studies were EU RMP category 3 (required). Six studies (7.1%) were single-sex studies, of which two were pregnancy-specific studies. Of eligible studies, 22.4% listed pregnant women as a ‘special population’, and 10.8% included gynaecological-related safety or effectiveness outcomes. Where reporting was available, 79.5% (58/73) of studies described the sex ratio of their study population. Where results were reported, 22.8% (13/57) of studies reported safety events by sex, and 21.1% (4/19) reported effectiveness by sex. In paediatric-only studies, no studies (0/6) were found to report safety or effectiveness by sex.

Conclusions: These results showed a low level of reporting of safety and effectiveness outcomes by sex. Additionally, pregnancy was reported as a population of special interest in a limited number of studies. This information further highlights the need to consider sex differences in the evaluation of medicinal products in non-interventional studies.