(A-196) Clinical trials with real-world pragmatic elements: A scoping review of use cases

Background: Clinical trials with real-world pragmatic elements can capture broad patient populations, facilitate efficient long-term follow-up, and bridge the gap between experimental and routine clinical practice settings. There is a limited understanding of what makes a trial pragmatic, how real-world data (RWD) is used, and design features of such trials.

Objectives: We reviewed trials that incorporated real-world pragmatic elements in the conduct of the trial, as well as trials that utilized RWD for long-term follow-up, i.e., clinical trial extension studies with RWD.

Methods: Based on a systematic search of PubMed, EMBASE, and ClinicalTrials.gov (Jan-2016 to Jul-2024), a scoping review was conducted to characterize use cases of pragmatic clinical trials and extension studies with RWD. We assessed, specifically for each study, study purpose, therapeutic areas, design features, pragmatic elements, and RWD utilized.

Results: A total of 27 use cases were identified (22 pragmatic clinical trials; 5 extension studies with RWD). In pragmatic trials, nearly all employed randomization (n=21, 95.5%), open-label design (n=20, 90.9%), and studied medications in their approved indications (n=20, 90.9%), with usual/standard of care (n=13, 59.1%) as comparators in >50% of use cases. 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 are broad inclusion/exclusion criteria, flexible treatment management, minimal or no protocol-mandated follow-up, and streamlined endpoint collection. RWD (including electronic health records, claims, registries) was utilized in half of pragmatic clinical trials (n=4 to enrich patient-level data studies; n=7 to streamline recruitment, follow-up, and data collection). In the 5 extension studies, 4 utilized RWD for long-term follow-up purposes, while one utilized RWD to construct external controls to clinical trial infrastructure-based extension study. Specifically, two studies on the human papillomavirus vaccine used Nordic national registries linked by personal identification numbers, while one study on the respiratory syncytial virus vaccine employed tokenization for privacy for U.S. patients. One study leveraged multiple sclerosis patient registry, while another used claims data to construct external comparator arms.

Conclusions: Our review found that most pragmatic trials were randomized, open-label studies in approved indications, supporting broad eligibility, flexible treatment and data collection utilizing RWD, highlighting the importance of innovative design in bridging the gap between traditional trials and routine practice.