A Systematic Approach for Post Hoc Subgroup Analyses With Applications in Clinical Case Studies

Ther Innov Regul Sci. 2019 Jun 16;2168479019853782. doi: 10.1177/2168479019853782. Online ahead of print.

Abstract

Background: The analysis of subgroups in clinical trials is essential to assess differences in treatment effects for distinct patient clusters, that is, to detect patients with greater treatment benefit or patients where the treatment seems to be ineffective.

Methods: The software application subscreen (R package) has been developed to analyze the population of clinical trials in minute detail. The aim was to efficiently calculate point estimates (eg, hazard ratios) for multiple subgroups to identify groups that potentially differ from the overall trial result. The approach intentionally avoids inferential statistics such as P values or confidence intervals but intends to encourage discussions enriched with external evidence (eg, from other studies) about the exploratory results, which can be accompanied by further statistical methods in subsequent analyses. The subscreen application was applied to 2 clinical study data sets and used in a simulation study to demonstrate its usefulness.

Results: The visualization of numerous combined subgroups illustrates the homogeneity or heterogeneity of potentially all subgroup estimates with the overall result. With this, the application leads to more targeted planning of future trials.

Conclusion: This described approach supports the current trend and requirements for the investigation of subgroup effects as discussed in the EMA draft guidance for subgroup analyses in confirmatory clinical trials (EMA 2014). The lack of a convenient tool to answer spontaneous questions from different perspectives can hinder an efficient discussion, especially in joint interdisciplinary study teams. With the new application, an easily executed but powerful tool is provided to fill this gap.

Keywords: R package; consistency; homogeneity/heterogeneity; sensitivity analysis; subgroups visualization.