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Review
. 2013 Oct 8;81(15):1350-5.
doi: 10.1212/WNL.0b013e3182a823e0. Epub 2013 Sep 4.

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

Nazem Atassi  1 , Padmaja Yerramilli-Rao, Jackie Szymonifka, Hong Yu, Marianne Kearney, Daniela Grasso, Jing Deng, Mark Levine-Weinberg, Jordan Shapiro, Alexandra Lee, Lucia Joseph, Eric A Macklin, Merit E Cudkowicz
Affiliations
Review

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

Nazem Atassi et al. Neurology. .

Abstract

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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Figures

Figure
Figure. Median start-up timelines for 4 Northeast Amyotrophic Lateral Sclerosis multicenter studies
CI = confidence interval; IRB = institutional review board.
See this image and copyright information in PMC

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