title: Temporal compliance trends in a cluster randomization with crossover trial of out-of-hospital cardiac arrest.
abstract: BACKGROUND
  Low compliance to randomized nondrug interventions can affect treatment estimates of clinical trials. Cluster-randomized crossover may be appropriate for increasing compliance in the out-of-hospital cardiac arrest setting.
  
  
  OBJECTIVE
  The purpose was to determine whether the elapsed time from start of a nonblinded treatment period to episode enrollment date in a cluster-randomized crossover trial is associated with compliance to either a period of brief cardiopulmonary resuscitation (CPR) with electrocardiogram (ECG) rhythm analysis or a period of longer CPR with a delayed ECG rhythm analysis in patients with out-of-hospital cardiac arrest.
  
  
  METHODS
  The Resuscitation Outcomes Consortium PRIMED Analyze Late (AL) versus Analyze Early (AE) trial was a cluster-randomized crossover trial at 10 North American regional sites. Clusters were created based on local service preference with treatment periods varying from 3 to 12 months depending on the expected enrollment rate of each randomizing unit. Episodes on the AL arm had a target of 180 s from CPR start to shock assessment and were deemed compliant if total time was between 150 and 210 s. Episodes on the AE arm had a target of <30 s from CPR start to shock assessment and were deemed compliant if total time was <60 s. We used logistic regression to examine the association between compliance (yes/no) and the elapsed number of days from the start of the treatment period to the episode in the framework of generalized estimating equations, controlling for randomized treatment (Late, reference = Early) and treatment period length (reference = 3, 4-5, 6, 7-11, and 12 months).
  
  
  RESULTS
  We had 8769 episodes in our analysis population. Overall compliance to the randomized arm was 63.5%. After adjusting for treatment arm and treatment period length, the odds of compliance for episodes occurring >300 days from treatment period start were 33% lower (odds ratio (OR): 0.67; 95% confidence interval (CI): 0.52, 0.86) than for those <60 days from treatment period start. There was no significant difference in compliance between episodes before and immediately after a cluster crossed over to the opposite arm (OR: 0.81; 95% CI: 0.57, 1.16).
  
  
  CONCLUSIONS
  A major challenge was the lack of synchronicity between training cycles and agency crossover dates.
  
  
  CONCLUSIONS
  We found a significant decrease in compliance to the AL versus AE cardiac arrest intervention as the elapsed time from start of treatment period increased. We did not find a difference in compliance immediately before and after a crossover. While these results suggest that future cluster with crossover trials in the out-of-hospital setting be designed with short treatment periods and frequent crossovers, provider logistical concerns must also be considered.
authors.affiliation: Clinical Trials Center, University of Washington, Seattle, 98036, USA. rschmick@uw.edu
authors.forename: Robert H
authors.initials: RH
authors.lastname: Schmicker
authors.forename: Brian G
authors.initials: BG
authors.lastname: Leroux
authors.forename: Gena K
authors.initials: GK
authors.lastname: Sears
authors.forename: Ian
authors.initials: I
authors.lastname: Stiell
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Morrison
authors.forename: Tom P
authors.initials: TP
authors.lastname: Aufderheide
authors.forename: Ray
authors.initials: R
authors.lastname: Fowler
authors.forename: Rusty
authors.initials: R
authors.lastname: Lowe
authors.forename: Stanley
authors.initials: S
authors.lastname: Morrow
authors.forename: Ed
authors.initials: E
authors.lastname: Plumlee
authors.forename: Sheldon
authors.initials: S
authors.lastname: Cheskes
mesh_terms: D016887:Cardiopulmonary Resuscitation / Q000379:methods; D018592:Cross-Over Studies; D004632:Emergency Medical Services / Q000379:methods*; D019983:Guideline Adherence / Q000706:statistics & numerical data*; D006801:Humans; D015337:Multicenter Studies as Topic; D058687:Out-of-Hospital Cardiac Arrest / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors