Abstract 89: Effects of the Endpoint Adjudication Process on the Results of the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial

Abstract

Introduction: Misclassification of outcome events can potentially lead to biased treatment effect estimates. Efforts to avoid endpoint misclassification in large-scale multicenter randomized clinical trials such as POINT have included an independent adjudication committee blinded to study treatments to standardize assessment of outcomes and reduce risk of ascertainment bias of main study endpoints. Debate continues about the scientific value of such committees and whether independent assessments improve reliability of study results, particularly when compared to the considerable time and resources consumed by the process. Methods: An independent adjudication committee adjudicated 467 primary and secondary efficacy outcomes and major and minor bleeding events, including the primary efficacy endpoint, a composite of new ischemic vascular events: ischemic stroke, myocardial infarction or ischemic vascular death at 90 days. The impact of the adjudicated endpoint process was studied by comparing the primary results using site-assessed endpoints versus adjudicator-assessed endpoints. Time from randomization to first endpoint of interest was calculated using the log-rank test and the hazard ratio and 95% CI were computed using a Cox proportional hazards model. Rate of agreement between site-assessed and adjudicator-assessed outcomes was also calculated. All analyses were completed according to the intention-to-treat principle. Results: The primary results of POINT have been published. The hazard ratios (HRs) (95% confidence interval [CI]) for clopidogrel versus aspirin therapy for the primary composite endpoint were 0.75 (0.59-0.95) for adjudicator-assessed events and 0.76 (0.60-0.95) for investigator-assessed events. Agreement between the composite endpoint for adjudicated-assessed and investigator-assessed events was 90.7%. Conclusion: Independent endpoint adjudication did not significantly impact estimates of the primary efficacy treatment effect in POINT compared to site-assessed endpoints. If misclassification of outcome events is infrequent, and careful site selection, study design and outcome definitions are in place, independent adjudication may have no meaningful impact on estimates of treatment effect.