Registry-Based Randomized Controlled Trials: Conduct, Advantages and Challenges – A Systematic Review.

Abstract Background: Registry-based Randomized Controlled Trials (rRCTs) have been described as pragmatic studies utilising patient data embedded in large scale registries, to facilitate key clinical trial procedures including recruitment, randomization and the collection of outcome data. While the practice of utilising registries to support the conduct of randomized trials is increasing, the use of the registries within rRCTs is inconsistent. The purpose of this systematic review is to explore the conduct of rRCTs using a patient registry to facilitate trial recruitment and the collection of outcome data and to discuss their advantages and challenges. Methods: A systematic search of the literature was conducted using five databases from inception to June 2020: PubMed, Embase (through Ovid), CINAHL, Scopus, and the Cochrane Controlled Register of Trials (CENTRAL). The search strategy comprised of MESH terms and key words related to rRCTs. Study selection was performed independently by two reviewers. A risk of bias for each study was completed. A narrative synthesis was conducted. Results: A total 47862 titles were screened and 24 rRCTs were included. Eleven rRCTs (45.8%) used more than one registry to facilitate trial conduct. Six rRCTs (25%) randomized participants via a specific randomization module embedded within a registry. Recruitment ranged between 209 to 106,000 participants. Advantages of rRCTs are recruitment efficiency, shorter trial times, cost effectiveness, outcome data completeness, smaller carbon footprint, less participant burden and ability to conduct multiple trials from the same registry. Challenges are: data collection/management, quality assurance issues and the timing of informed consent. Conclusion: Optimising the design of rRCTs is dependent on the capabilities of the registry. New registries should be designed, and existing registries reviewed to enable the conduct of rRCTs. At all times, data management and quality assurance of all registry data should be given key consideration. We suggest the inclusion of the term ‘registry-based’ in the title of all rRCT manuscripts and a clear simple breakdown of the registry-based conduct of the trial in the abstract, to facilitate indexing in the major databases. Systematic Review Registration: PROPSERO CRD42020192419