title: Hypothermia pediatric head injury trial: the value of a pretrial clinical evaluation phase.
abstract: BACKGROUND
  The utility of a pretrial clinical evaluation or run-in phase prior to conducting trials of complex interventions such as hypothermia therapy following severe traumatic brain injury in children and adolescents has not been established.
  
  
  METHODS
  The primary objective of this study was to prospectively evaluate the ability of investigators to adhere to the clinical protocols of care including the cooling and rewarming procedures as well as management guidelines in patients with severe traumatic brain injury (Glasgow Coma Scale<or=8) treated with 24 h of hypothermia therapy. A secondary objective was to evaluate the ability of study research assistants to complete the study case report form using a procedures manual. The study was conducted at 18 sites in Canada, the United Kingdom and France prior to proceeding to a randomized controlled trial (RCT). After 2 patients were enrolled at each center, an independent clinical evaluation committee examined the process of care and the completeness of data collection. Centers were permitted to enroll patients in the RCT once they met pre-established adherence criteria.
  
  
  RESULTS
  Seventeen of the 18 centers completed the pretrial clinical evaluation phase demonstrating compliance with study procedures and proceeded to an RCT of hypothermia therapy. One center enrolled only 1 patient in the pretrial clinical evaluation phase due to small numbers of patients with traumatic brain injury, and therefore, did not proceed to the RCT. Three centers were required to enroll more than 2 patients in the pretrial clinical evaluation phase prior to proceeding to the RCT because of problems with adherence to the clinical protocols at two centers and the training of new study personnel at another center. Of the 39 patients enrolled during the pretrial clinical evaluation phase, 8 (20.5%) died and 22 (62.9%) had a good outcome defined as normal, mild or moderate disability assessed using the Pediatric Cerebral Performance Category score at 6 months following injury.
  
  
  CONCLUSIONS
  The pretrial clinical evaluation phase was useful to ensure compliance with complex hypothermia therapy and consensus-based clinical management guidelines of care successfully implemented across 17 of 18 centers. This study maneuver allowed us to complete a subsequent RCT in 225 children following severe traumatic brain injury.
authors.affiliation: Department of Critical Care Medicine, Hospital for Sick Children, and Interdepartmental Division of Critical Care, Faculty of Medicine, University of Toronto, Canada. Jamie.Hutchison@sickkids.ca
authors.forename: J
authors.initials: J
authors.lastname: Hutchison
authors.forename: R
authors.initials: R
authors.lastname: Ward
authors.forename: J
authors.initials: J
authors.lastname: Lacroix
authors.forename: P
authors.initials: P
authors.lastname: Hébert
authors.forename: P
authors.initials: P
authors.lastname: Skippen
authors.forename: M
authors.initials: M
authors.lastname: Barnes
authors.forename: P
authors.initials: P
authors.lastname: Meyer
authors.forename: K
authors.initials: K
authors.lastname: Morris
authors.forename: H
authors.initials: H
authors.lastname: Kirpalani
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.forename: P
authors.initials: P
authors.lastname: Dirks
authors.forename: D
authors.initials: D
authors.lastname: Bohn
authors.forename: D
authors.initials: D
authors.lastname: Moher
mesh_terms: D000465:Algorithms; D001831:Body Temperature / Q000502:physiology; D001929:Brain Edema / Q000175:diagnosis / Q000517:prevention & control / Q000628:therapy; D001930:Brain Injuries / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*; D002648:Child; D002985:Clinical Protocols / Q000592:standards*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced / Q000592:standards / Q000706:statistics & numerical data* / Q000639:trends*; D019586:Intracranial Hypertension / Q000175:diagnosis / Q000517:prevention & control / Q000628:therapy; D008297:Male; D009460:Neurologic Examination / Q000379:methods / Q000592:standards; D017063:Outcome Assessment, Health Care / Q000592:standards / Q000639:trends; D018579:Patient Selection; D017410:Practice Guidelines as Topic / Q000592:standards; D011237:Predictive Value of Tests; D011446:Prospective Studies; D020127:Recovery of Function / Q000502:physiology; D012107:Research Design; D016896:Treatment Outcome