title: Analysis of start-up, retention, and adherence in ALS clinical trials.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: From 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.
authors.forename: Nazem
authors.initials: N
authors.lastname: Atassi
authors.forename: Padmaja
authors.initials: P
authors.lastname: Yerramilli-Rao
authors.forename: Jackie
authors.initials: J
authors.lastname: Szymonifka
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Marianne
authors.initials: M
authors.lastname: Kearney
authors.forename: Daniela
authors.initials: D
authors.lastname: Grasso
authors.forename: Jing
authors.initials: J
authors.lastname: Deng
authors.forename: Mark
authors.initials: M
authors.lastname: Levine-Weinberg
authors.forename: Jordan
authors.initials: J
authors.lastname: Shapiro
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lee
authors.forename: Lucia
authors.initials: L
authors.lastname: Joseph
authors.forename: Eric A
authors.initials: EA
authors.lastname: Macklin
authors.forename: Merit E
authors.initials: ME
authors.lastname: Cudkowicz
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000523:psychology* / Q000628:therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D016015:Logistic Models; D015337:Multicenter Studies as Topic; D010349:Patient Compliance / Q000523:psychology; D018579:Patient Selection; D011237:Predictive Value of Tests; D039781:PubMed / Q000706:statistics & numerical data; D012107:Research Design; D012189:Retrospective Studies