Identifying homogenous subgroups for individual patient meta-analysis based on Rough Set Theory

Failure to detect and manage heterogeneity between clinical trials included in meta-analysis may lead to misinterpretation of summary effect estimates. This may ultimately compromise the validity of the results of the meta-analysis. Typically, when heterogeneity between trials is detected, researchers use sensitivity or subgroup analysis to manage it. However, both methods fail to explain why heterogeneity existed in the first place. Here we propose a novel methodology that relies on Rough Set Theory (RST) to detect, explain, and manage the sources of heterogeneity applicable to meta-analysis performed on individual patient data (IPD). The method exploits the RST relations of discernibility and indiscernibility to create homogeneous groups of patients. We applied our methodology on a dataset of 1,111 patients enrolled in 9 randomized controlled trials studying the effect of two transplantation procedures in the management of hematologic malignancies. Our method was able to create three subgroups of patients with remarkably low statistical heterogeneity values (16.8%, 0% and 0% respectively). The proposed methodology has the potential to automatize and standardize the process of detecting and managing heterogeneity in IPD meta-analysis. Future work involves investigating the applications of the proposed methodology in analyzing treatment effects in patients belonging to different risk groups, which will ultimately assist in personalized healthcare decision making.