Change-Plane Analysis for Subgroup Detection and Sample Size Calculation

ABSTRACT

We propose a systematic method for testing and identifying a subgroup with an enhanced treatment effect. We adopts a change-plane technique to first test the existence of a subgroup, and then identify the subgroup if the null hypothesis on nonexistence of such a subgroup is rejected. A semiparametric model is considered for the response with an unspecified baseline function and an interaction between a subgroup indicator and treatment. A doubly robust test statistic is constructed based on this model, and asymptotic distributions of the test statistic under both null and local alternative hypotheses are derived. Moreover, a sample size calculation method for subgroup detection is developed based on the proposed statistic. The finite sample performance of the proposed test is evaluated via simulations. Finally, the proposed methods for subgroup identification and sample size calculation are applied to a data from an AIDS study.

KEYWORDS:

• Change-plane analysis
• Doubly robust test
• Sample size calculation
• Semiparametric model
• Subgroup analysis

Acknowledgment

The authors would like to thank an associate editor and two referees for their thoughtful and constructive comments, which help to improve an earlier version of the article.

Funding

This work was partly supported by a NIH grant P01 CA142538.