Testing for similarity of dose response in multi-regional clinical trials

TL;DR

This paper develops bootstrap tests within a parametric framework to assess whether dose response curves in subgroups of multi-regional clinical trials are similar to the overall population, aiding in regulatory decisions.

Contribution

It introduces two novel bootstrap testing procedures for evaluating dose response similarity in multi-regional trials, with proven validity and demonstrated effectiveness through simulations and a case study.

Findings

Tests are valid for finite samples.

Simulation studies show good power and size.

Method applied successfully in a real case study.

Abstract

This paper addresses the problem of deciding whether the dose response relationships between subgroups and the full population in a multi-regional trial are similar to each other. Similarity is measured in terms of the maximal deviation between the dose response curves. We consider a parametric framework and develop two powerful bootstrap tests for the similarity between the dose response curves of one subgroup and the full population, and for the similarity between the dose response curves of several subgroups and the full population. We prove the validity of the tests, investigate the finite sample properties by means of a simulation study and finally illustrate the methodology in a case study.