The choice of the noninferiority margin in clinical trials was driven by baseline risk, type of primary outcome, and benefits of new treatment

OBJECTIVES: To explore characteristics of clinical trials that influence the choice of the noninferiority margin (NIM) when planning the trial. STUDY DESIGN AND SETTING: 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. CONCLUSION: 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.

The choice of the noninferiority margin in clinical trials was driven by baseline risk, type of primary outcome, and benefits of new treatment Journal Articles