Title

Step-up procedures for non-inferiority tests with multiple experimental treatments

Publication Type

Journal Article

Publication Date

8-2016

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.

Keywords

assay sensitivity, control treatment, Familywise error rate, non-inferiority trial, placebo, stepwise procedure

Discipline

Econometrics | Health Economics

Research Areas

Econometrics

Publication

Statistical Methods in Medical Research

Volume

25

Issue

4

First Page

1290

Last Page

1302

ISSN

0962-2802

Identifier

10.1177/0962280213477767

Publisher

SAGE

Additional URL

http://doi.org/10.1177/0962280213477767