Annie Wright

Importance: In recent years, trials have leveraged digital tools and remote methods to improve patient access and diversity, streamline operations, enhance data collection, and reduce costs and timelines. Regulatory terminology has defined these as decentralized clinical trials . While many earlier trials incorporated one or more decentralized elements (e.g. e-consent, remote monitoring), little is known about recent trials that adopt multiple elements and explicitly identify as decentralized. Objective: To determine, in trials explicitly identifying as decentralized, which decentralized elements they use, where they are occurring, and which therapeutic areas and interventions they involve. Methods: A search of MEDLINE, Embase, and CENTRAL from inception to September 9, 2024, yielded 4357 articles. Two reviewers independently and in duplicate screened titles, abstracts, and full texts to identify trials explicitly described as decentralized. Key data were extracted in duplicate to ensure accuracy. Additionally, the International Clinical Trials Registry Platform and ClinicalTrials.gov were searched on July 18, 2024, to identify unpublished and ongoing decentralized clinical trials. Results: Thirty-three publications (28 unique trials) met inclusion, all published since 2021, with numbers increasing annually. Only four trials described themselves as decentralized in their trial registration records. Of the 28 included trials, 54% were completed and 46% were ongoing, with a median sample size of 900 (IQR 192-1470). All were single-country studies, 96% from high-income countries, mostly in North America. Pharmacological interventions were most common (43%). Among nine decentralized components evaluated, e-consent was used in 71% of trials, and devices for outcome data collection in 75%. It was unclear if electronic health records were used for screening in 75%, and centralized monitoring in 79% of trials. Patient-reported outcomes were frequent, collected in 86% of trials and serving as the primary outcome in 61%. Conclusion: Since regulators introduced the terminology in 2018, adoption among trials explicitly identifying as decentralized has increased since 2021, although the overall number remains low. These trials occur mainly in high-income countries, suggesting potential inequities in implementation or reporting. No single decentralized element combination dominated, indicating variability in how decentralized approaches are implemented across disease areas and interventions. Improved reporting is needed to distinguish between underuse and underreporting of decentralized elements. PROSPERO registration number: CRD42024571898.