Emulating Clinical Trials with the Mayo Clinic Platform: Cardiovascular Research Perspective.

BACKGROUND

Randomized controlled trials (RCTs) provide the highest level of clinical evidence but are often limited by cost, time, and ethical constraints. Emulating RCTs using real-world data (RWD) offers a complementary approach to evaluate the treatment effect in a real clinical setting. This study aims to replicate clinical trials based on Mayo Clinic Platform (MCP) electronic health records (EHRs) and emulation frameworks. In this study, we address two key questions: (1) whether clinical trials can be feasibly replicated using the MCP, and (2) whether trial emulation produces consistent conclusions based on real clinical data compared to the original randomized controlled trials RCTs.

METHODS

We conducted a retrospective observational study with an adaption of trial emulation. To assess feasibility, we applied a refined filtering method to identify trials suitable for emulation. The emulation protocol was carefully designed on top of the original RCT protocol to balance scientific rigor and practical feasibility. To minimize potential selection bias and enhance comparability between groups, we employed propensity score matching (PSM) as a statistical adjustment method.

RESULTS

Based on our predefined search criteria targeting phase 3 trials focused on drug repurposing for heart failure patients, we initially identified 27 eligible trials. After a two-step manual review of the original eligibility criteria and extraction of the patient cohorts based on MCP visualizer, we further narrowed our selection to the WARCEF trial, as it provided an adequate sample size for the emulation within the MCP. The experiment compares the WARCEF trial and a simulation study on Aspirin vs. Warfarin. The original study (smaller sample) found no significant difference (HR = 1.016, p < 0.91). The simulation (larger sample) showed a slightly higher HR (1.161) with borderline significance (p < 0.052, CI: 0.999-1.350), suggesting a possible increased risk with Warfarin, though not conclusive.

CONCLUSION

RCT emulation enhances real-world evidence (RWE) for clinical decision-making but faces limitations from confounding, missing data, and cohort biases. Future research should explore machine learning-driven patient matching and scalable RCT emulation. This study supports the integration of RWE into evidence-based medicine.