Assessing the Impact of COVID-19 on the Clinical Trial Objective and Analysis of Oncology Clinical Trials—Application of the Estimand Framework

Degtyarev, Evgeny; Rufibach, Kaspar; Shentu, Yue; Yung, Godwin; Casey, Michelle; Englert, Stefan; Liu, Feng; Liu, Yi; Sailer, Oliver; Siegel, Jonathan; Sun, Steven; Tang, Rui; Zhou, Jiangxiu

Abstract–Coronavirus disease 2019 (COVID-19) outbreak has rapidly evolved into a global pandemic. The impact of COVID-19 on patient journeys in oncology represents a new risk to interpretation of trial results and its broad applicability for future clinical practice. We identify key intercurrent events (ICEs) that may occur due to COVID-19 in oncology clinical trials with a focus on time-to-event endpoints and discuss considerations pertaining to the other estimand attributes introduced in the ICH E9 addendum. We propose strategies to handle COVID-19 related ICEs, depending on their relationship with malignancy and treatment and the interpretability of data after them. We argue that the clinical trial objective from a world without COVID-19 pandemic remains valid. The estimand framework provides a common language to discuss the impact of COVID-19 in a structured and transparent manner. This demonstrates that the applicability of the framework may even go beyond what it was initially intended for.