Reproducibility of clinical events adjudications in a trial of venous thromboembolism prevention. (1st March 2017)

• Record Type: Journal Article
• Authors: Girard, P.; Penaloza, A.; Parent, F.; Gable, B.; Sanchez, O.; Durieux, P.; Hausfater, P.; Dambrine, S.; Meyer, G.; Roy, P.‐M.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 15:Number 4(2017)
• Page Start: 662
• Page End: 669
• Publication Date: 2017-03-01
• Subjects: anticoagulants -- cause of death -- clinical trial -- reproducibility of results -- venous thromboembolism; Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.13626
• Languages: English
• ISSNs: 1538-7933

Abstract

Abstract : Essentials The reproducibility of Clinical Events Committee (CEC) adjudications is almost unexplored. A random selection of events from a venous thromboembolism trial was blindly re‐adjudicated. 'Unexplained sudden deaths' (possible fatal embolism) explained most discordant adjudications. A precise definition for CEC adjudication of this type of events is needed and proposed. Summary: Background: When clinical trials use clinical endpoints, establishing independent Clinical Events Committees (CECs) is recommended to homogenize the interpretation of investigators' data. However, the reproducibility of CEC adjudications is almost unexplored. Objectives: To assess the reproducibility of CEC adjudications in a trial of venous thromboembolism (VTE) prevention. Methods: The PREVENU trial, a multicenter trial of VTE prevention, included 15 351 hospitalized medical patients. The primary endpoint was the composite of symptomatic VTE, major bleeding or unexplained sudden death (interpreted as possible fatal pulmonary embolism [PE]) at 3 months. The CEC comprised a chairman and four pairs of adjudicators. Of 2970 adjudicated clinical events, a random selection of 179 events (121 deaths, 40 bleeding events, and 18 VTE events) was blindly resubmitted to the CEC. Kappa values and their 95% confidence intervals (CIs) were calculated to measure adjudication agreement. Results: Overall, 18 of 179 (10.1%, 95% CI 6.5–15.3%) adjudications proved discordant. Agreement for the PREVENU composite primary endpoint was good (kappa = 0.73, 95% CI 0.61–0.85). When analyzed separately, agreements were very good for non‐fatal VTE events (1, 95% CI not applicable), moderate for all (fatal and non‐fatal) VTE events (0.58, 95% CI 0.34–0.82), good for fatal and non‐fatal major bleeding events (0.71, 95% CI 0.55–0.88), and moderate for all fatal events (0.60, 95% CI 0.40–0.81). Unexplained sudden death interpreted as possible fatal PE was responsible for nine of 18 (50%) discordant adjudications. Conclusion: The reproducibility of CEC adjudications was good or very good for non‐fatal VTE and bleeding events, but insufficient for VTE‐related deaths, for which more precise and widely accepted definitions are needed.