title: Addressing continuous data for participants excluded from trial analysis: a guide for systematic reviewers.
abstract: BACKGROUND
  No methods directly address the impact of missing participant data for continuous outcomes in systematic reviews on risk of bias.
  
  
  METHODS
  We conducted a consultative, iterative process to develop a framework for handling missing participant data for continuous outcomes. We considered sources reflecting real observed outcomes in participants followed-up in individual trials included in the systematic review, and developed a range of plausible strategies. We applied our approach to two systematic reviews.
  
  
  RESULTS
  We used five sources of data for imputing the means for participants with missing data. To impute standard deviation (SD), we used the median SD from the control arms of all included trials. Using these sources, we developed four progressively more stringent imputation strategies. In the first example review, effect estimates diminished and lost significance as strategies became more stringent, suggesting rating down confidence in estimates of effect for risk of bias. In the second, effect estimates maintained statistical significance using even the most stringent strategy, suggesting missing data does not undermine confidence in results.
  
  
  CONCLUSIONS
  Our approach provides a useful, reasonable, and relatively simple, quantitative guidance for judging the impact of risk of bias as a result of missing participant data in systematic reviews of continuous outcomes.
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, 1200 Main St. West, Hamilton, Canada, L8S 4K1.
authors.forename: Shanil
authors.initials: S
authors.lastname: Ebrahim
authors.forename: Elie A
authors.initials: EA
authors.lastname: Akl
authors.forename: Reem A
authors.initials: RA
authors.lastname: Mustafa
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Walter
authors.forename: Diane
authors.initials: D
authors.lastname: Heels-Ansdell
authors.forename: Pablo
authors.initials: P
authors.lastname: Alonso-Coello
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Johnston
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Guyatt
mesh_terms: D015982:Bias; D003627:Data Interpretation, Statistical; D006801:Humans; D059012:Lost to Follow-Up; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic; D012196:Review Literature as Topic; D012306:Risk
keywords: Continuous outcomes; Lost to follow-up; Meta-analysis; Missing participant data; Risk of bias; Systematic reviews