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. 2012 Mar 1;46(2):175-179.
doi: 10.1177/0092861512436579.

Testing in a Prespecified Subgroup and the Intent-to-Treat Population

Mark D Rothmann  1 , Jenny J Zhang, Laura Lu, Thomas R Fleming
Affiliations

Testing in a Prespecified Subgroup and the Intent-to-Treat Population

Mark D Rothmann et al. Drug Inf J. .

Abstract

In many settings, testing has been proposed to assess the effect of an experimental regimen within a biomarker-positive subgroup where it is biologically plausible that benefit is stronger in such patients, and in the overall population that also includes biomarker-negative subjects less likely to benefit from that regimen. A statistically favorable result in the biomarker-positive subgroup would lead to a claim for that subgroup, whereas a statistically favorable result for the overall population would lead to a claim that includes both biomarker subgroups. The latter setting is problematic when biomarker-negative patients truly do not benefit from the experimental regimen. When it is prespecified that biomarker-negative patients should not be included in the primary analysis of treatment effect in biomarker-positive patients because of the likelihood that treatment effects would differ between the 2 subgroups, it is logically inconsistent to include biomarker-positive patients in the primary analysis of treatment effect in biomarker-negative patients.

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Conflict of interest statement

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. This article reflects the views of the authors and should not be construed to represent FDA’s views or policies.

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