title: Credibility of claims of subgroup effects in randomised controlled trials: systematic review.
abstract: OBJECTIVE
  To investigate the credibility of authors' claims of subgroup effects using a representative sample of recently published randomised controlled trials.
  
  
  METHODS
  Systematic review.
  
  
  METHODS
  Core clinical journals, as defined by the National Library of Medicine, in Medline.
  
  
  METHODS
  Randomised controlled trials published in 2007. Using prespecified criteria, teams of trained reviewers independently judged whether authors claimed subgroup effects and the strength of their claims. Reviewers assessed each of these claims against 10 predefined criteria, developed through a search of existing criteria and a consensus process.
  
  
  RESULTS
  Of 207 randomised controlled trials reporting subgroup analyses, 64 (31%) made claims for the primary outcome. Of those, 20 were strong claims and 28 claims of a likely effect. Authors included subgroup variables measured at baseline in 60 (94%) trials, used subgroup variable as a stratification factor at randomisation in 13 (20%), clearly prespecified their hypotheses in 26 (41%), correctly prespecified direction in 4 (6%), tested a small number of hypotheses in 28 (44%), carried out a test of interaction that proved statistically significant in 6 (9%), documented replication of a subgroup effect with previous related studies in 21 (33%), identified consistency of a subgroup effect across related outcomes in 19 (30%), and provided a compelling indirect evidence for the effect in 14 (22%). In the 19 trials making more than one claim, only one (5%) checked the independence of the interaction. Of the 64 claims, 54 (84%) met four or fewer of the 10 criteria. For strong claims, more than 50% failed each of the individual criteria, and only three (15%) met more than five criteria.
  
  
  CONCLUSIONS
  Authors often claim subgroup effects in their trial report. However, the credibility of subgroup effects, even when claims are strong, is usually low. Users of the information should treat claims that fail to meet most criteria with scepticism. Trial researchers should report the conduct of subgroup analyses and provide sufficient evidence when claiming a subgroup effect or suggesting a possible effect.
authors.affiliation: Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA.
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: John J
authors.initials: JJ
authors.lastname: You
authors.forename: Elie A
authors.initials: EA
authors.lastname: Akl
authors.forename: Filip
authors.initials: F
authors.lastname: Mejza
authors.forename: Malgorzata M
authors.initials: MM
authors.lastname: Bala
authors.forename: Dirk
authors.initials: D
authors.lastname: Bassler
authors.forename: Dominik
authors.initials: D
authors.lastname: Mertz
authors.forename: Natalia
authors.initials: N
authors.lastname: Diaz-Granados
authors.forename: Per Olav
authors.initials: PO
authors.lastname: Vandvik
authors.forename: German
authors.initials: G
authors.lastname: Malaga
authors.forename: Sadeesh K
authors.initials: SK
authors.lastname: Srinathan
authors.forename: Philipp
authors.initials: P
authors.lastname: Dahm
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Johnston
authors.forename: Pablo
authors.initials: P
authors.lastname: Alonso-Coello
authors.forename: Basil
authors.initials: B
authors.lastname: Hassouneh
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Walter
authors.forename: Diane
authors.initials: D
authors.lastname: Heels-Ansdell
authors.forename: Neera
authors.initials: N
authors.lastname: Bhatnagar
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Altman
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Guyatt
mesh_terms: D003627:Data Interpretation, Statistical; D006801:Humans; D016239:MEDLINE; D015588:Observer Variation; D010506:Periodicals as Topic; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data*; D012107:Research Design / Q000592:standards* / Q000706:statistics & numerical data; D016896:Treatment Outcome