PS08: Planning for Heterogeneous Treatment Effects: Enrichment for Treatment-Sensitive Patient Populations

In the era of precision medicine, understanding the wide-ranging responses of patient subgroups to interventions is critical for improving outcomes and enhancing clinical care. This session will address heterogeneous treatment effects (HTE) – variations in treatment efficacy across a patient population – and discuss adaptive clinical trials designed to respond in real time to emerging evidence of HTE. Enrichment designs have emerged as a key strategy for reacting to HTE, allowing for refined inclusion criteria and identifying patients most likely to benefit from specific therapies. By focusing on treatment-responsive subgroups, these designs enhance trial efficiency and increase the likelihood of successful results, paving the way for more targeted and effective interventions in clinical practice. In the first talk, Dr. Paulon will introduce and explore the application of enrichment strategies by examining two clinical trials of early minimally invasive surgical removal of intracerebral hemorrhage (ICH). The first trial discussed, ENRICH [Pradilla et al.], is a recently completed study that showed significant benefit in a pre-specified subgroup of the patient population based on the location of the hemorrhage. The second trial, REACH, seeks to further investigate if hemorrhage size is a meaningful variable in the subgroup where ENRICH did not demonstrate functional benefit. In the second talk, Dr. Elm will discuss the clinical motivation and trial design strategy for handling HTE in STEP, a platform trial designed with a domain to investigate the effect of endovascular therapy for patients with acute ischemic stroke. The trial can adaptively modify entry criteria and reach conclusions in pre-defined patient groups at interim analyses. Patient groups are defined by the vessel occlusion location and stroke severity at baseline. In the third talk, Dr. Walton will provide a regulatory perspective for anticipating heterogeneous treatment effects in clinical trials. He will discuss regulatory strategy, concerns, and generalizability of results. Pradilla, Gustavo, et al. "Trial of early minimally invasive removal of intracerebral hemorrhage." New England Journal of Medicine 390.14 (2024): 1277-1289.