title: Characteristics and Outcomes of Eligible Nonenrolled Patients in a Mechanical Ventilation Trial of Acute Respiratory Distress Syndrome.
abstract: BACKGROUND
  Patients eligible for randomized controlled trials may not be enrolled for various reasons. Nonenrollment may affect study generalizability and lengthen the time required for trial completion.
  
  
  OBJECTIVE
  To describe characteristics and outcomes of eligible nonenrolled (ENE) patients in a multicenter trial of mechanical ventilation strategies.
  
  
  METHODS
  Within the OSCILLATE trial of high-frequency oscillation (HFO) versus conventional ventilation (CV) in adults with adult respiratory distress syndrome, and with approval from research ethics boards, we collected a minimal dataset on patients who satisfied eligibility criteria but were not enrolled. We categorized ENE patients as ENE-HFO and ENE-CV based on receipt of HFO at any time. We used multivariable logistic regression to assess the association between ENE status and mortality.
  
  
  RESULTS
  A total of 548 patients were randomized, and 546 were ENE. The most common reasons for ENE were no consent (42%), physician refusal (24%), missed randomization window (15%), and current HFO use (14%). Compared with randomized patients in respective arms of the trial, ENE-HFO patients were younger and had worse lung injury, whereas ENE-CV patients had lower illness severity. ENE status was independently associated with mortality (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.84; P = 0.02), with no significant interaction with ventilation treatment group.
  
  
  CONCLUSIONS
  Nonenrollment was common, with approximately one ENE patient for every randomized patient. Our study suggests that enrollment in trials of mechanical ventilation may be associated with improved outcomes compared with standard care and highlights the need for prospective tracking and transparent reporting of ENE patients as part of trial management.
authors.affiliation: 1 Intensive Care Department, King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
authors.forename: Yaseen M
authors.initials: YM
authors.lastname: Arabi
authors.affiliation: 2 Department of Medicine and.|3 Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Cook
authors.affiliation: 3 Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: 4 Critical Care Department & Keenan Research Center, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada.
authors.forename: Orla
authors.initials: O
authors.lastname: Smith
authors.affiliation: 3 Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Lori
authors.initials: L
authors.lastname: Hand
authors.affiliation: 5 Division of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, and.|6 Population Health and Optimal Health Practices Research Unit, Research Center of the CHU de Québec, Université Laval, Québec City, Québec, Canada.
authors.forename: Alexis F
authors.initials: AF
authors.lastname: Turgeon
authors.affiliation: 7 University Health Network, Toronto, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Matte
authors.affiliation: 8 Interdepartmental Division of Critical Care Medicine.|13 Department of Medicine.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Mehta
authors.affiliation: 14 Department of Physiology, and.
authors.forename: Russell
authors.initials: R
authors.lastname: Graham
authors.affiliation: 15 Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.
authors.forename: Kristin
authors.initials: K
authors.lastname: Brierley
authors.affiliation: 8 Interdepartmental Division of Critical Care Medicine.|9 Department of Medicine, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Neill K J
authors.initials: NK
authors.lastname: Adhikari
authors.affiliation: 2 Department of Medicine and.|3 Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Maureen O
authors.initials: MO
authors.lastname: Meade
authors.affiliation: 7 University Health Network, Toronto, Canada.|10 Memorial Hermann, Texas Medical Center, Houston, Texas.|11 University of Michigan Health System, Ann Arbor, Michigan.|12 Department of Critical Care Medicine, Sunnybrook Health Science Centre, Toronto, Canada; and.|16 Division of Respirology, Department of Medicine, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Niall D
authors.initials: ND
authors.lastname: Ferguson
mesh_terms: D005260:Female; D006612:High-Frequency Ventilation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011446:Prospective Studies; D012121:Respiration, Artificial / Q000379:methods*; D012128:Respiratory Distress Syndrome / Q000628:therapy*; D016896:Treatment Outcome
keywords: high-frequency ventilation; mechanical ventilation; mortality; patient recruitment; randomized controlled trial