Multiple assessments of non‐inferiority trials with ordinal endpoints

Non‐inferiority (NI) trials are implemented when there is a practical demand to search for alternatives to standard therapies, such as to reduce side effects. An experimental treatment is considered non‐inferior to the standard treatment when it exhibits clinically non‐significant loss of efficacy. Ordinal categorical responses are frequently observed in clinical trials. It has been reported that responses measured using an ordinal scale produce more informative analysis than when responses collapse into binary outcomes. We study the NI trials using ordinal endpoints. We propose a latent variable model for ordinal categorical responses. Based on the proposed latent variable model, the mean efficacy of the different treatments is denoted by the corresponding mean parameter of the underlying continuous distributions. A two‐step procedure is proposed for model identification and parameter estimation. A non‐inferiority analysis can then be conducted based on the latent variable model and the corresponding estimation procedure. We also develop a method and an algorithm to produce an optimal sample size configuration based on the proposed testing procedure. Two clinical examples are provided for demonstrative purposes.