Clinical Trial Designs for Rare Disorders

Collectively, existing pharmacologic trials in FXS have demonstrated limited and inconsistent treatment effects, with interpretation constrained by small sample sizes, heterogeneity in designs and outcome measures, and differences in participant characteristics. Greater standardization of trial design and outcome assessment, improved alignment between outcome measures and treatment mechanisms, and careful consideration of participant stratification are critical to improving signal detection in future trials. These insights have broader relevance for RD research, where methodological rigor is essential to translating promising mechanisms into effective therapies.