A Roadmap for Developing Study Endpoints in Real-World Settings

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.