Methods for the Clinical Validation of Digital Endpoints: Protocol for a Scoping Review Abstract

BACKGROUND: Clinical trials often use digital technologies to collect data continuously outside the clinic and use the derived digital endpoints as trial endpoints. Digital endpoints are also being developed to support diagnosis, monitoring, or therapeutic interventions in clinical care. However, clinical validation stands as a significant challenge, as there are no specific guidelines orienting the validation of digital endpoints. OBJECTIVE: This paper presents the protocol for a scoping review that aims to map the existing methods for the clinical validation of digital endpoints. METHODS: The scoping review will comprise searches from the electronic literature databases MEDLINE (PubMed), Scopus (including conference proceedings), Embase, IEEE (Institute of Electrical and Electronics Engineers) Xplore, ACM (Association for Computing Machinery) Digital Library, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science Core Collection (including conference proceedings), and Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports. We will also include various sources of gray literature with search terms related to digital endpoints. The methodology will adhere to the Joanna Briggs Institute Scoping Review and the Guidance for Conducting Systematic Scoping Reviews. RESULTS: A search for reviews on the existing evidence related to this topic was conducted and has shown that no such review was previously undertaken. This review will provide a systematic assessment of the literature on methods for the clinical validation of digital endpoints and highlight any potential need for harmonization or reporting of methods. The results will include the methods for the clinical validation of digital endpoints according to device, digital endpoint, and clinical application goal of digital endpoints. The study started in January 2023 and is expected to end by December 2023, with results to be published in a peer-reviewed journal. CONCLUSIONS: A scoping review of methodologies that validate digital endpoints is necessary. This review will be unique in its breadth since it will comprise digital endpoints collected from several devices and not focus on a specific disease area. The results of our work should help guide researchers in choosing validation methods, identify potential gaps in the literature, or inform the development of novel methods to optimize the clinical validation of digital endpoints. Resolving these gaps is the key to presenting evidence in a consistent way to regulators and other parties and obtaining regulatory acceptance of digital endpoints for patient benefit. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/47119