title: Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials.
abstract: BACKGROUND
  Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome.
  
  
  METHODS
  We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes.
  
  
  CONCLUSIONS
  A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials.
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada. sunx26@mcmaster.ca
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Matthias
authors.initials: M
authors.lastname: Briel
authors.forename: Jason W
authors.initials: JW
authors.lastname: Busse
authors.forename: Elie A
authors.initials: EA
authors.lastname: Akl
authors.forename: John J
authors.initials: JJ
authors.lastname: You
authors.forename: Filip
authors.initials: F
authors.lastname: Mejza
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Bala
authors.forename: Natalia
authors.initials: N
authors.lastname: Diaz-Granados
authors.forename: Dirk
authors.initials: D
authors.lastname: Bassler
authors.forename: Dominik
authors.initials: D
authors.lastname: Mertz
authors.forename: Sadeesh K
authors.initials: SK
authors.lastname: Srinathan
authors.forename: Per Olav
authors.initials: PO
authors.lastname: Vandvik
authors.forename: German
authors.initials: G
authors.lastname: Malaga
authors.forename: Mohamed
authors.initials: M
authors.lastname: Alshurafa
authors.forename: Philipp
authors.initials: P
authors.lastname: Dahm
authors.forename: Pablo
authors.initials: P
authors.lastname: Alonso-Coello
authors.forename: Diane M
authors.initials: DM
authors.lastname: Heels-Ansdell
authors.forename: Neera
authors.initials: N
authors.lastname: Bhatnagar
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Johnston
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Walter
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Altman
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Guyatt
mesh_terms: D002985:Clinical Protocols; D003627:Data Interpretation, Statistical; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012107:Research Design; D018401:Sample Size; D000078202:Systematic Reviews as Topic