Measuring Effectiveness of Treatments in Rare Disorders, Evidence from Clinical Trials in Fragile X Syndrome

Abstract Fragile X Syndrome (FXS) is the leading cause of inherited intellectual disability and autism spectrum disorder (ASD). It results from mutations of the FMR1 gene and the subsequent loss of Fragile X mental disorder 1 protein (FMRP). FXS has been the focus of intense preclinical research leading to several clinical trials. Effect sizes compare the effectiveness of treatments for neurodevelopmental disorders, such as FXS. This paper reviews effect sizes of different drug treatments in clinical trials for FXS to understand potential issues with the designs of current trials which could affect efficacy detectability. We searched for "Fragile X Syndrome" query in PubMed and filtered the clinical trials and downloaded the list of all publication IDs. PubMed's API was then utilized to collect the abstract's content into a spreadsheet. Studies were narrowed down to those with sufficient statistics data to calculate effect size relative to placebo. Phase 2 and 3 clinical trials for arbaclofen and one trial for L-acetylcarnitine reported large effect sizes. No significant findings were present between placebo and treatment groups. Studies without a placebo group reported larger treatment effect sizes. Small sample sizes, scarcity of studies, and outcome measures based on caregiver reports prevented us from drawing conclusions.