title: Co-enrollment of critically ill patients into multiple studies: patterns, predictors and consequences.
abstract: BACKGROUND
  Research on co-enrollment practices and their impact are limited in the ICU setting. The objectives of this study were: 1) to describe patterns and predictors of co-enrollment of patients in a thromboprophylaxis trial, and 2) to examine the consequences of co-enrollment on clinical and trial outcomes.
  
  
  METHODS
  In an observational analysis of an international thromboprophylaxis trial in 67 ICUs, we examined the co-enrollment of critically ill medical-surgical patients into more than one study, and examined the clinical and trial outcomes among co-enrolled and non-co-enrolled patients.
  
  
  RESULTS
  Among 3,746 patients enrolled in PROTECT (Prophylaxis for ThromboEmbolism in Critical Care Trial), 713 (19.0%) were co-enrolled in at least one other study (53.6% in a randomized trial, 37.0% in an observational study and 9.4% in both). Six factors independently associated with co-enrollment (all P < 0.001) were illness severity (odds ratio (OR) 1.35, 95% confidence interval (CI) 1.19 to 1.53 for each 10-point Acute Physiology and Chronic Health Evaluation (APACHE) II score increase), substitute decision-makers providing consent, rather than patients (OR 3.31, 2.03 to 5.41), experience of persons inviting consent (OR 2.67, 1.74 to 4.11 for persons with > 10 years' experience compared to persons with none), center size (all ORs > 10 for ICUs with > 15 beds), affiliation with trials groups (OR 5.59, 3.49 to 8.95), and main trial rather than pilot phase (all ORs > 8 for recruitment year beyond the pilot). Co-enrollment did not influence clinical or trial outcomes or risk of adverse events.
  
  
  CONCLUSIONS
  Co-enrollment was strongly associated with features of the patients, research personnel, setting and study. Co-enrollment had no impact on trial results, and appeared safe, acceptable and feasible. Transparent reporting, scholarly discourse, ethical analysis and further research are needed on the complex topic of co-enrollment during critical illness.
authors.forename: Deborah
authors.initials: D
authors.lastname: Cook
authors.forename: Ellen
authors.initials: E
authors.lastname: McDonald
authors.forename: Orla
authors.initials: O
authors.lastname: Smith
authors.forename: Nicole
authors.initials: N
authors.lastname: Zytaruk
authors.forename: Diane
authors.initials: D
authors.lastname: Heels-Ansdell
authors.forename: Irene
authors.initials: I
authors.lastname: Watpool
authors.forename: Tracy
authors.initials: T
authors.lastname: McArdle
authors.forename: Andrea
authors.initials: A
authors.lastname: Matte
authors.forename: France
authors.initials: F
authors.lastname: Clarke
authors.forename: Shirley
authors.initials: S
authors.lastname: Vallance
authors.forename: Simon
authors.initials: S
authors.lastname: Finfer
authors.forename: Pauline
authors.initials: P
authors.lastname: Galt
authors.forename: Tim
authors.initials: T
authors.lastname: Crozier
authors.forename: Rob
authors.initials: R
authors.lastname: Fowler
authors.forename: Yaseen
authors.initials: Y
authors.lastname: Arabi
authors.forename: Clive
authors.initials: C
authors.lastname: Woolfe
authors.forename: Neil
authors.initials: N
authors.lastname: Orford
authors.forename: Richard
authors.initials: R
authors.lastname: Hall
authors.forename: Neill K J
authors.initials: NK
authors.lastname: Adhikari
authors.forename: Marie-Clauide
authors.initials: MC
authors.lastname: Ferland
authors.forename: John
authors.initials: J
authors.lastname: Marshall
authors.forename: Maureen
authors.initials: M
authors.lastname: Meade
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016638:Critical Illness / Q000453:epidemiology / Q000628:therapy; D005544:Forecasting; D018579:Patient Selection; D013923:Thromboembolism / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy; D015912:Thrombolytic Therapy / Q000379:methods