Supplementary Material for: Understanding late-stage clinical trial failure in multiple sclerosis: insights from ClinicalTrials.gov

Introduction. Clinical trial failure —when a study is withdrawn or terminated for reasons unrelated to safety or efficacy— wastes resources and exposes patients to unnecessary risks. We examined such failures in the field of multiple sclerosis (MS).

Methods. We searched ClinicalTrials.gov for phase III and IV MS drug trials conducted in 2008-2024. Trials were classified as normally ended or failed based on recruitment status and reported reasons. When information was missing, we reviewed publications and contacted principal investigators (PIs). Kaplan-Meier method was used to assess time to trial end and multivariate logistic regression was used to identify factors associated with failure.

Results. The 282 clinical trials included in our analysis involved 62 experimental drugs, primarily disease-modifying therapies (n=213 trials). Most studies aimed to evaluate drug efficacy (n=197 trials). Overall, 74.8% of trials ended normally while 25.2% failed. On average, failed trials ended ten months earlier than the rest of studies (trial actual duration: 17.8 vs. 28.2 months, p<0.001). Main reasons for failure were low recruitment (28.2%), unspecified business decisions (26.8%), and logistical problems (12.7%). In 28.2% of occasions it remained undisclosed. Trials evaluating drug safety (OR 0.35, 95%CI 0.13–0.94) and those with ≥50 participating centres (OR 0.10, 95%CI 0.02–0.38) seemed to have a lower risk of failure. Failure was not significantly associated with other factors such as study start date, PI location, or industry involvement.

Conclusion. One out of four late-stage MS clinical trials fails. Increasing the number of study sites and improving recruitment strategies could enhance their success rates.