Validating national registry data for randomized trials: comparison of registry-derived cardiovascular events with and without adjudication in the BETAMI-DANBLOCK trial

Registry-based randomized clinical trials are increasingly applied in clinical research, providing advantages in feasibility and data capture. However, registry-based data may introduce bias through misclassification or missing information.

In the BETAMI-DANBLOCK trial, 5574 patients with myocardial infarction (MI) and no heart failure were randomized to beta-blocker or no beta-blocker therapy. The primary endpoint events (all-cause mortality, MI, ischemic stroke, heart failure, unplanned coronary revascularization, and malignant ventricular arrhythmias) were identified from the Danish/Norwegian national patient registries, self-reported questionnaires, and medical records. All registry-identified events, except all-cause mortality, underwent blinded adjudication. We compared non-adjudicated and adjudicated events by calculating incidence rates and hazard ratios (HRs) for beta-blocker therapy vs. controls. National registries captured 99.7% of primary endpoint events registered by self-report and medical records. Of the primary endpoint events identified through the registries, 75% were confirmed by adjudication (incidence rate 6.23 vs. 4.43/100 person-years). The confirmation rate was lower during the first 6 months and varied by event type (from 92% for ischaemic stroke to 45% for unplanned coronary revascularizations and heart failure). Estimated treatment effects were consistent for the primary endpoint with non-adjudicated and adjudicated events (HR 0.88, 95% confidence interval (CI): 0.78-0.98 and HR 0.85, 95% CI: 0.75-0.98, respectively), with no apparent differences across event types except for heart failure and revascularization.

Registry data provided effect estimates of beta-blockers comparable to adjudicated data. However, adjudication substantially reduced the number of cardiovascular endpoint events and event-specific misclassification appeared, particularly during the first months after the index event.

BETAMI-DANBLOCK ClinicalTrials.gov numbers, NCT03646357 and NCT03778554.