title: Inconsistent trial assessments by the National Institute for Health and Clinical Excellence and IQWiG: standards for the performance and interpretation of subgroup analyses are needed.
abstract: OBJECTIVE
  The methodology for the critical assessment of medical interventions is well established. Regulatory agencies and institutions adhere, in principle, to the same standards. This consistency, however, is not always the case in practice.
  
  
  METHODS
  Using the evaluation of the CAPRIE (Clopidogrel versus Aspirin in Patients at risk of Ischemic Events) trial by the British National Institute for Health and Clinical Excellence (NICE) and the German Institute for Quality and Efficiency in Health Care (IQWiG), we illustrate that there was no consensus for the interpretation of possible heterogeneity in treatment comparisons across subgroups.
  
  
  RESULTS
  The NICE concluded that CAPRIE demonstrated clinical benefit for the overall intention-to-treat (ITT) population with sufficient robustness to possible sources of heterogeneity. The IQWiG interpreted the alleged heterogeneity as implying that the clinical benefit only applied to the subgroup of patients with a statistically significant result irrespective of the results of the ITT analysis.
  
  
  CONCLUSIONS
  International standards for the performance and interpretation of subgroup analyses as well as for the assessment of heterogeneity between strata are needed.
authors.affiliation: Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, LMU München, Marchioninistrasse 15, Munich, Germany. has@ibe.med.uni-muenchen.de
authors.forename: J
authors.initials: J
authors.lastname: Hasford
authors.forename: P
authors.initials: P
authors.lastname: Bramlage
authors.forename: G
authors.initials: G
authors.lastname: Koch
authors.forename: W
authors.initials: W
authors.lastname: Lehmacher
authors.forename: K
authors.initials: K
authors.lastname: Einhäupl
authors.forename: P M
authors.initials: PM
authors.lastname: Rothwell
mesh_terms: D001241:Aspirin / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000517:prevention & control*; D000077144:Clopidogrel; D004739:England; D019317:Evidence-Based Medicine / Q000592:standards*; D005858:Germany; D006801:Humans; D057194:Intention to Treat Analysis; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin