Analysis of start-up, retention, and adherence in ALS clinical trials

Objective: To investigated predictors of trial start-up times, high attrition, and poor protocol adherence in amyotrophic lateral sclerosis (ALS) trials. Methods: Retrospective analysis of start-up times, retention, and protocol adherence was performed on 5 clinical studies conducted by the Northeast ALS Consortium and 50 ALS clinical trials identified by PubMed search. Predictors of start-up times were estimated by accelerated failure time models with random effects. Predictors of retention and protocol deviations were estimated by mixed-model logistic regression. Results: Median times for contract execution and institutional review board (IRB) approval were 105 days and 125 days, respectively. Contract execution was faster at sites with more ongoing trials ( p = 0.005), and more full-time ( p = 0.006) and experienced ( p p = 0.010) and larger ALS clinics ( p = 0.038). Site activation after IRB approval was faster at sites with more full-time ( p = 0.038) and experienced ( p p = 0.002) and fewer protocol deviations (odds ratio 0.86, p = 0.030). Conclusion: Delays in IRB review contribute the most to prolonged trial start-up times, and these timelines are faster in sites with more experienced staff. Strategies to improve protocol adherence and participants9 retention may include enrolling people at early disease stages.