Incidental genetic findings in randomized clinical trials: recommendations from the Genomics and Randomized Trials Network (GARNET)

During clinical research, investigators may discover information with important health implications for a participant but that is not relevant to the initial aims of the study. Investigators and ethicists have been grappling with the question of how to address such incidental research findings for years. The ethical and practical considerations underlying this question are complex and often involve issues such as the researcher-participant relationship, the ethical practice of research, the cost and burden of follow-up, and participant expectations, among many other factors. The question of how to address incidental research findings becomes even more complicated in the context of clinical trials, in which participants may expect investigators to keep their medical best interests in mind, or researchers may feel obligated to report potentially important health findings to their participants. Clinical trials that involve genomic analyses add another level of complexity to the reporting of incidental findings because genomic studies can generate data on hundreds of thousands of genetic findings, most with unknown or evolving clinical significance. As the field of genomics continues to develop, there will be an increased need for shared experience and guidance on how to handle the discovery of incidental genetic research findings.This paper discusses the process of developing the GARNET recommendations on incidental genetic findings in the context of clinical trials, and explores the ethical and practical issues considered in formulating our recommendations.GARNET comprises a series of genome-wide association studies (GWAS) of treatment responses in randomized clinical trials that aim to identify the genetic variants associated with response to treatments for conditions of clinical or public health significance [1]. The clinical trials that make up GARNET are the Women's Health Initiative (WHI) Hormone Therapy Trial, designed to identify genetic variations that alter t