A comparison of five recursive partitioning methods to find person subgroups involved in meaningful treatment-subgroup interactions

In case multiple treatment alternatives are available for some medical problem, the detection of treatment-subgroup interactions (i.e., relative treatment effectiveness varying over subgroups of persons) is of key importance for personalized medicine and the development of optimal treatment assignment strategies. Randomized Clinical Trials (RCT) often go without clear a priori hypotheses on the subgroups involved in treatment-subgroup interactions, and with a large number of pre-treatment characteristics in the data. In such situations, relevant subgroups (defined in terms of pre-treatment characteristics) are to be induced during the actual data analysis. This comes down to a problem of cluster analysis, with the goal of this analysis being to find clusters of persons that are involved in meaningful treatment-person cluster interactions. For such a cluster analysis, five recently proposed methods can be used, all being of a recursive partitioning type. However, these five methods have been developed almost independently, and the relations between them are not yet understood. The present paper closes this gap. It starts by outlining the basic principles behind each method, and by illustrating it with an application on an RCT data set on two treatment strategies for substance abuse problems. Next, it presents a comparison of the methods, hereby focusing on major similarities and differences. The discussion concludes with practical advice for end users with regard to the selection of a suitable method, and with an important challenge for future research in this area.