gms | German Medical Science

Background: Registry-based Randomized Controlled Trials (RRCTs) can provide internally valid results in a real-world context at relatively low effort and cost. However, potential use options, the degree of registry use (e.g. proportion of data from registry), and limitations are not well characterized.

Objective: This methodological review of RRCTs aims to analyse the trial design features, describe potential use options, and identify possible limitations of using registry data for RCTs.

Methods: A systematic search in PubMed for ongoing and published RRCTs was conducted up to March 2023. In addition, published reviews were checked. Study selection and data extraction was independently performed by two reviewers. All data were extracted into a standardized table, and descriptive statistics were generated.

Results: We included 162 RRCTs (50 protocols and 112 studies). Most RRCTs come from Denmark (25.9%), followed by Sweden (17.9%) and the USA (14.8%). The inclusion and exclusion criteria of participants are mostly broadly defined. Types of interventions range from surgical procedures to behaviour therapy and almost half of the interventions (43.8%) have a preventive purpose. The primary registry endpoint is mostly a clinical endpoint (40.7%) or a composite endpoint of major clinical events (30.2%) that is objectively measurable. There are several ways of embedding registry data in an RCT and the extent to which registries are used varies greatly between studies. A few studies fully utilize registries for patient recruitment, randomization, complete endpoint ascertainment, and long-term follow-up, while other solely utilize the registry for data validation or long-term monitoring of previously published data. Limitations related to the use of registry data comprise failed linkages or insufficient data (e.g. due to under-recording of mild cases). Furthermore, differences may exist in event detection, information entry, and data collection across different sites or countries.

Implication for research and/or (healthcare) practice: A broad spectrum of potential use options and usage extent of registry data exist. Our analysis suggests that in many cases, the potential of using registry data and thus their benefits were not fully utilized. In addition, the analysis illustrates that there is not the one RRCT but that registries can support RCTs in various ways. Therefore, RRCTs should clearly specify for what purposes and to what extend registries were utilized. Moreover, a clear definition and taxonomy of RRCTs appears necessary for facilitating future dialogue and research on RRCTs.