Clinical Trials With Pragmatic Elements: A Review of Use Cases and Real-World Data Utilization.

Abstract

Clinical trials with pragmatic elements can capture diverse patient populations, enable efficient follow-up, and reflect routine clinical practices; yet there is limited understanding of their design features, characteristics, and use of real-world data (RWD). Based on a targeted search of PubMed/EMBASE (Jan-2016 to Jul-2024), a review was conducted to characterize clinical trial use cases with pragmatic elements during the design and conduct of trials, as well as clinical trials that utilized RWD for long-term follow-up in the extension phase of the original ("parent") trial. A total of 27 use cases were characterized. There were 22 use cases with pragmatic elements, and nearly all employed randomization (n = 21, 95.5%), open-label design (n = 20, 90.9%), with usual/standard of care (n = 13, 59.1%) as comparators. Most generated evidence on both effectiveness and safety (n = 18, 81.8%), primarily in diabetes and cardiovascular disease areas (n = 14, 63.6%). The most common pragmatic elements were broad eligibility criteria, flexible treatment management, minimal or no follow-up, and streamlined endpoint collection. RWD (including electronic health records, claims, registries) was utilized in half of the use cases (n = 4 to enrich trial data with additional information abstracted from RWD; n = 7 to embed trials within routine healthcare databases/systems). In addition, 5 use cases were identified that utilized RWD in the extension phase of the original "parent" trials (4 utilizing RWD for long-term follow-up purposes, and one utilizing RWD to construct external controls for clinical trial infrastructure-based extension study). This review underscores the emerging role of pragmatic elements in enhancing trial efficiency, generalizability, and evidence generation on long-term outcomes.