Enserro, Danielle M

Abstract Prevention trials in oncology are some of the most important cancer clinical trials that can be designed, implemented, analyzed, and interpreted. They are pivotal in the goal of stopping the development of cancer before it starts. Prevention trials are unique in that they not only have some of the same requirements and challenges as treatment trials but also have challenges that may make their design more complex. This paper aims to discuss some types of prevention trials and highlight their most common design challenges, including large sample size requirements, slow accrual rates with long accrual duration, extended follow-up periods with trial adherence issues and missing data, endpoints that require extended follow-up or have a high level of confounding, and problems with optimizing study design. This article provides real study examples and suggestions for designing prevention clinical trials while mitigating the known issues they face.

Abstract Examining treatment effects in subgroups of patients defined by demographic, genetic, or clinical characteristics is increasingly of interest given the pursuit of personalized medicine and the importance of representation and equity in treatment decisions. The magnitude or even the direction of the treatment effect may vary across subgroups, and these differential treatment effects could have clinical implications. Subgroup analyses require caution in their interpretation, however, because of the high probability of a false-positive or false-negative conclusion. We outline study design and analysis considerations for responsibly investigating and reporting differential treatment effects across subgroups in oncology trials, with examples from the National Cancer Institute’s National Clinical Trials Network and Community Oncology Research Program. Recommendations include ensuring appropriate representation of patients from subgroups of interest, recognizing power and multiplicity limitations, and treating exploratory subgroup analyses as hypothesis generating rather than practice changing.