Step-up procedures for non-inferiority tests with multiple experimental treatments. (August 2016)

• Record Type: Journal Article
• Authors: Kwong, Koon Shing; Cheung, Siu Hung; Hayter, Anthony J
• Other Names: Lawson Andrew B guest-editor.; Lee Duncan guest-editor.; MacNab Ying guest-editor.
• Is Part Of: Statistical methods in medical research. Volume 25:Number 4(2016:Aug.)
• Page Start: 1290
• Page End: 1302
• Publication Date: 2016-08
• Subjects: Familywise error rate -- stepwise procedure -- non-inferiority trial -- control treatment -- placebo -- assay sensitivity; Medicine -- Research -- Statistical methods -- Periodicals; Research -- Periodicals; Review Literature -- Periodicals; Statistics -- methods -- Periodicals; Médecine -- Recherche -- Méthodes statistiques -- Périodiques; 610.727
• DOI: 10.1177/0962280213477767
• Languages: English
• ISSNs: 0962-2802

Abstract

Non-inferiority (NI) trials are becoming more popular. The NI of a new treatment compared with a standard treatment is established when the new treatment maintains a substantial fraction of the treatment effect of the standard treatment. A valid NI trial is also required to show assay sensitivity, the demonstration of the standard treatment having the expected effect with a size comparable to those reported in previous placebo-controlled studies. A three-arm NI trial is a clinical study that includes a new treatment, a standard treatment and a placebo. Most of the statistical methods developed for three-arm NI trials are designed for the existence of only one new treatment. Recently, a single-step procedure was developed to deal with NI trials with multiple new treatments with the overall familywise error rate controlled at a specified level. In this article, we extend the single-step procedure to two new step-up procedures for NI trials with multiple new treatments. A comparative study of test power shows that both proposed step-up procedures provide a significant improvement of power when compared to the single-step procedure. One of the two proposed step-up procedures also allows the flexibility of allocating different error rates between the sensitivity hypothesis and the NI hypotheses so that the assignment of fewer patients to the placebo becomes possible when designing NI trials. We illustrate the new procedures using data from a clinical trial.