BARDS Merck

References 1 EMA, “Guideline on the Investigation of Subgroups in Confirmatory Clinical Trials,” accessed December 19, 2021, https://www.ema.europa.eu/en/investigation-subgroups-confirmatory-clinical-trials. 2 and , “Comparing Approaches to Treatment Effect Estimation for Subgroups in Clinical Trials,” Statistics in Biopahrmaceutical Research 9, no. 2 (2016): 160–171, https://doi.org/10.1080/19466315.2016.1251490.

1 INTRODUCTION Recent advances in immuno-oncology (IO) therapies for the treatment of cancer have led to the development of a variety of treatments which show great potential for improving long-term patient outcomes. While very promising, patient response to such immunotherapies is often quite different when compared to more traditional cytotoxic agents such as chemotherapy.