This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
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.
GLOSSARY
- ALS=
- amyotrophic lateral sclerosis;
- CI=
- confidence interval;
- CIRB=
- central institutional review board;
- IRB=
- institutional review board;
- NEALS=
- Northeast Amyotrophic Lateral Sclerosis;
- NeuroNEXT=
- Network for Excellence in Neuroscience Clinical Trials;
- OR=
- odds ratio
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
- Received March 13, 2013.
- Accepted in final form July 8, 2013.
- © 2013 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Disputes & Debates: Rapid online correspondence
NOTE: All authors' disclosures must be entered and current in our database before comments can be posted. Enter and update disclosures at http://submit.neurology.org. Exception: replies to comments concerning an article you originally authored do not require updated disclosures.
- Stay timely. Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- 200 words maximum.
- 5 references maximum. Reference 1 must be the article on which you are commenting.
- 5 authors maximum. Exception: replies can include all original authors of the article.
- Submitted comments are subject to editing and editor review prior to posting.