title: The choice of the noninferiority margin in clinical trials was driven by baseline risk, type of primary outcome, and benefits of new treatment.
abstract: OBJECTIVE
  To explore characteristics of clinical trials that influence the choice of the noninferiority margin (NIM) when planning the trial.
  
  
  METHODS
  We conducted an experimental survey among corresponding authors of randomized controlled trials indexed in MEDLINE. We described two hypothetical studies and asked the respondents' opinion on the largest loss of effectiveness that is clinically negligible (or the smallest lost of effectiveness that is clinically important in the superiority scenario). We randomly manipulated four study attributes in each vignette, using a factorial design.
  
  
  RESULTS
  A total of 364 researchers participated. The values for NIMs were significantly lower than the differences to be detected in a superiority trial. The NIM was smaller when the primary outcome was mortality compared with treatment failure, when baseline risk in the control arm was lower, and when the advantage of the new treatment was a lower cost compared with having fewer side effects. In contrast, the population age group under study and the difficulty to recruit patients showed no effect on the choice of the NIM.
  
  
  CONCLUSIONS
  In our experimental study, the factors associated with lower NIMs were mortality as a primary outcome, low baseline risk, and a less costly new treatment.
authors.affiliation: Division of Clinical Epidemiology, University Hospitals of Geneva and Faculty of Medicine, 6 Rue Gabrielle Perret-Gentil, 1211 Geneva 14, Switzerland. Electronic address: angele.gayet-ageron@hcuge.ch.
authors.forename: Angèle
authors.initials: A
authors.lastname: Gayet-Ageron
authors.affiliation: Division of Clinical Epidemiology, University Hospitals of Geneva and Faculty of Medicine, 6 Rue Gabrielle Perret-Gentil, 1211 Geneva 14, Switzerland; Department of Clinical Epidemiology & Biostatistics, Faculty of Health Science, McMaster University, 1280 Main St. W. Hamilton, Ontario, Canada L8S 4K1.
authors.forename: Thomas
authors.initials: T
authors.lastname: Agoritsas
authors.affiliation: Division of Clinical Epidemiology, University Hospitals of Geneva and Faculty of Medicine, 6 Rue Gabrielle Perret-Gentil, 1211 Geneva 14, Switzerland.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Rudaz
authors.affiliation: Division of Clinical Epidemiology, University Hospitals of Geneva and Faculty of Medicine, 6 Rue Gabrielle Perret-Gentil, 1211 Geneva 14, Switzerland.
authors.forename: Delphine
authors.initials: D
authors.lastname: Courvoisier
authors.affiliation: Division of Clinical Epidemiology, University Hospitals of Geneva and Faculty of Medicine, 6 Rue Gabrielle Perret-Gentil, 1211 Geneva 14, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Perneger
mesh_terms: D000328:Adult; D016001:Confidence Intervals; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic; D012108:Research Personnel / Q000523:psychology*; D018401:Sample Size; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
keywords: Clinical trial; Minimal clinically important difference; Noninferiority margin; Noninferiority study design; Primary outcome; Randomized controlled trials; Sample size