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A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition
Published on: September 20, 2019
Analysis of start-up, retention, and adherence in ALS clinical trials
Nazem Atassi1, Padmaja Yerramilli-Rao, Jackie Szymonifka
1From the Neurological Clinical Research Institute, Department of Neurology (N.A., P.Y.-R., H.Y., M.K., D.G., J.D., M.L.-W., J.S., A.L., L.J., M.E.C.), and Biostatistics Center (J.S., E.A.M.), Massachusetts General Hospital, Boston; and Harvard Medical School (N.A., P.Y.-R., E.A.M., M.E.C.), Boston, MA.
Objective:
To investigate 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 < 0.001) coordinators. IRB approval was faster at sites with more ongoing trials (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 < 0.001) coordinators. Twenty-two percent of surviving participants withdrew before completing the trial. Better participant functional score at baseline was an independent predictor of trial completion (odds ratio 1.29, 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 participants' retention may include enrolling people at early disease stages.
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