“6 Choose 4”: A Framework to Understand and Facilitate Discussion of Strategies for Overall Survival Safety Monitoring

Advances in anticancer therapies have contributed significantly to decreasing death rates in certain disease and clinical settings. However, they have also made it difficult to power a clinical trial in these settings with overall survival (OS) as the primary efficacy endpoint. Therefore, two approaches have recently been proposed for the pre-specified analysis of OS as a safety endpoint. We provide in this paper a simple unifying framework that includes the aforementioned approaches—and a few others—as special cases. By highlighting each approach’s focus, priority, tolerance for risk, and strengths or challenges for practical implementation, this framework can help facilitate discussions between stakeholders on “fit-for-purpose OS data collection and assessment of harm”. We apply this framework to a real clinical trial in large B-cell lymphoma to illustrate its application and value. Several recommendations and open questions are also raised.