Sample Size Considerations to Assess Sex-Related Treatment Effects

This state-of-the-art review examines how trial design and sample size affect the assessment of sex-related treatment effects. Traditional unstructured recruitment often underrepresents women and limits the evaluation of sex-by-treatment interactions. Structured strategies, including recruitment proportional to disease burden, fixed 50:50 enrolment, or sex-specific power calculations, improve precision but may slow recruitment or increase sample size requirements. The authors recommend clinical trial innovations to ensure representative participation relative to disease burden, routine reporting of sex-specific findings complemented by other evidence, and greater diversity within research teams to strengthen sex-specific inference.