title: The ABC of non-inferiority margin setting from indirect comparisons.
abstract: In a non-inferiority trial to assess a new investigative treatment, there may need to be consideration of an indirect comparison with placebo using the active control in the current trial. We can, therefore, use the fact that there is a common active control in the comparisons of the investigative treatment and placebo. In analysing a non-inferiority trial, the ABC of: Assay sensitivity, Bias minimisation and Constancy assumption needs to be considered. It is highlighted how the ABC assumptions can potentially fail when there is placebo creep or a patient population shift. In this situation, the belief about the placebo response expressed in terms of a prior probability in Bayesian formulation could be used with the observed treatment effects to set the non-inferiority limit.
authors.affiliation: Medical Statistics Group, Health Services Research, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, England. S.A.Julious@Sheffield.ac.uk
authors.forename: Steven A
authors.initials: SA
authors.lastname: Julious
mesh_terms: D001499:Bayes Theorem; D015982:Bias; D016001:Confidence Intervals; D035061:Control Groups; D006801:Humans; D015233:Models, Statistical; D010919:Placebos; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards* / Q000706:statistics & numerical data; D012107:Research Design / Q000706:statistics & numerical data*; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D010919:Placebos