title: Primary Outcome Measures in Pediatric Septic Shock Trials: A Systematic Review.
abstract: OBJECTIVE
  To evaluate all published pediatric randomized controlled trials of patients with septic shock from any cause to examine the outcome measures used, the strengths and limitations of these measurements and whether the trial outcomes met feasibility criteria.
  
  
  METHODS
  We used a previously published database of pediatric critical care randomized controlled trials (PICUtrials.net) derived from searches of MEDLINE, EMBASE, LILACS, and CENTRAL.
  
  
  METHODS
  We included randomized controlled trials of interventions to children admitted to a PICU with septic or dengue hemorrhagic shock which were published in English.
  
  
  METHODS
  Study characteristics and outcomes were retrieved by two independent reviewers with disagreement being resolved by a third reviewer. We defined feasibility as 1) recruitment of at least 90% of the targeted sample size and agreement of the observed outcome rate in the control group with the rate used for the sample size calculation to within 10% or 2) finding of a statistically significant difference in an interim or final analysis.
  
  
  RESULTS
  Nineteen of 321 identified articles were selected for review. Fourteen of 19 studies (74%) provided an a priori definition of their primary outcome measure in their "Methods section." Mortality rate was the most commonly reported primary outcome (8/14; 57%), followed by duration of shock (4/14; 29%) followed by organ failure (1/14; 7%). Only three of 19 included trials met feasibility criteria.
  
  
  CONCLUSIONS
  Our review found that use of mortality alone as a primary outcome in pediatric septic shock trials was associated with significant limitations and that long-term patient-centered outcomes were not used in this setting. Composite outcomes incorporating mortality and long-term outcomes should be explored for use in future pediatric septic shock trials.
authors.affiliation: 1Division of Pediatric Critical Care, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON. 2Division of Critical Care, Seattle Children's Hospital, University of Washington, Seattle, WA. 3Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA. 4Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH. 5Department of Pediatrics, McMaster Children's Hospital, McMaster University, Hamilton, ON.
authors.forename: Kusum
authors.initials: K
authors.lastname: Menon
authors.forename: James Dayre
authors.initials: JD
authors.lastname: McNally
authors.forename: Jerry J
authors.initials: JJ
authors.lastname: Zimmerman
authors.forename: Michael S D
authors.initials: MS
authors.lastname: Agus
authors.forename: Katie
authors.initials: K
authors.lastname: O'Hearn
authors.forename: R Scott
authors.initials: RS
authors.lastname: Watson
authors.forename: Hector R
authors.initials: HR
authors.lastname: Wong
authors.forename: Mark
authors.initials: M
authors.lastname: Duffett
authors.forename: David
authors.initials: D
authors.lastname: Wypij
authors.forename: Karen
authors.initials: K
authors.lastname: Choong
mesh_terms: D002648:Child; D003422:Critical Care; D006801:Humans; D015278:Intensive Care Units, Pediatric; D017063:Outcome Assessment, Health Care / Q000379:methods*; D010372:Pediatrics; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012772:Shock, Septic / Q000401:mortality / Q000628:therapy*