Subgroup Identification in Survival Outcome Data Based on Concordance Probability Measurement

Abstract

Identifying a subgroup of patients who may have an enhanced treatment effect in a randomized clinical trial has received increasing attention recently. For time-to-event outcomes, it is a challenge to define the effectiveness of a treatment and to choose a cutoff time point for identifying subgroup membership, especially in trials in which the two treatment arms do not differ in overall survival. In this paper, we propose a mixture cure model to identify a subgroup for a new treatment that was compared to a classical treatment (or placebo) in a randomized clinical trial with respect to survival time. Using the concordance probability measurement (K-index), we propose a statistic to test the existence of subgroups with effective treatments in the treatment arm. Subsequently, the subgroup is defined by a limited number of covariates based on the estimated area under the curve (AUC). The performance of this method in different scenarios is assessed through simulation studies. A real data example is also provided for illustration.

Keywords

• concordance probability
• K -index%22%2C%22default_operator%22%3A%22AND%22%7D%7D%7D"> <named-content content-type="inline-formula"><inline-formula> <mml:math id="mm12000"> <mml:semantics> <mml:mrow> <mml:mi>K</mml:mi> </mml:mrow> </mml:semantics> </mml:math> </inline-formula></named-content>-index
• mixture models
• randomized clinical trials
• subgroups
• survival analysis