Unleashing the Full Potential of Digital Endpoints: Eight Questions that Need Attention

Abstract The use of Digital Health Technologies to measure endpoints in clinical trials opens new opportunities as well as methodological challenges. Digital endpoints may provide more sensitive and higher-frequency measurements of participants' health outcomes, but pose vital statistical challenges around how such endpoints should be defined and validated and how trials incorporating digital endpoints should be designed and analysed. This article presents eight methodological questions, exploring issues around decision making on key issues such as the length of measurement period, choice of summary statistic and definition and handling of missing data, as well as the potential for new estimands and new analyses to leverage the time series data from digital devices. A selection of the challenges are illustrated through a simulation study based on the 2019 Bellerophon INOPulse trial which used time spent in MVPA as a digital endpoint. These eight questions present broad areas where methodological guidance is needed to enable wider uptake of digital endpoints in trials.