With growing interest in using real-world data (RWD) and real-world evidence (RWE) to support regulatory decision-making, stakeholders are considering how to develop robust real-world study endpoints to evaluate medical product effectiveness when fit-for-use data and valid methods are available. Despite extensive literature and guidance for developing clinical trial endpoints, few resources support real-world endpoint development. Some principles can be carried over from the clinical trial setting, but differences in patient populations, care settings, and data collection in the real-world setting result in unique considerations for endpoint development. Additionally, studies conducted in the real-world setting have the potential to capture outcomes that are more relevant to patients than outcomes captured in clinical trials.
This paper explores how key differences in study settings influence a researcher’s considerations for developing study endpoints in the real world. First, because stakeholders involved in the real-world endpoint development process have multidisciplinary backgrounds, this paper details the current landscape of endpoint development, provides standardized definitions of key concepts, and introduces existing frameworks. Second, this paper presents a roadmap for endpoint development, beginning with selection of a concept of interest and study outcome that reflect the research question. Within this roadmap, the paper details how real-world settings impact selection of a concept of interest, outcome, and endpoint components, raising challenges for researchers to consider when developing real-world endpoints. Third, this paper addresses key considerations for the validation of real-world endpoints. Finally, this paper examines opportunities to enhance the use of real-world endpoints through stakeholder collaboration.
Digital Health Policy Fellow
Adjunct Assistant Professor
Senior Team Member
Margolis Core Faculty
Chief of Staff
Senior Team Member
Director of Margolis Center
Robert J. Margolis, MD, Professor of Business, Medicine and Policy
Margolis Executive Core Faculty