title: Reproducibility of clinical events adjudications in a trial of venous thromboembolism prevention.
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.
  
  
  
  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.
authors.affiliation: Département Thoracique, L'Institut Mutualiste Montsouris, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Girard
authors.affiliation: Service des Urgences, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Penaloza
authors.affiliation: Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, Hôpital de Bicêtre, AP-HP; Université Paris-Sud, INSERM UMRS 999, Le Kremlin Bicêtre, France.
authors.forename: F
authors.initials: F
authors.lastname: Parent
authors.affiliation: Département de Médecine d'Urgence, CHU d'Angers, Angers, France.
authors.forename: B
authors.initials: B
authors.lastname: Gable
authors.affiliation: Service de Pneumologie, Hôpital Européen Georges Pompidou, AP-HP; Université Paris Descartes, Sorbonne Paris Cité, INSERM UMRS 970 and CIC 1418, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Sanchez
authors.affiliation: Département de Santé Publique et Informatique Médicale, Hôpital Européen Georges Pompidou, AP-HP; Université Paris Descartes, Sorbonne Paris Cité, INSERM UMRS 872, Centre de recherche des Cordeliers, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Durieux
authors.affiliation: Département des Urgences, Hôpital Pitié-Salpêtrière, AP-HP; Sorbonne Universités UPMC-Univ Paris 6, INSERM UMRS 1166, IHUC ICAN, GRC-UPMC BIOSFAST, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Hausfater
authors.affiliation: Département de Médecine d'Urgence, CHU d'Angers, Angers, France.
authors.forename: S
authors.initials: S
authors.lastname: Dambrine
authors.affiliation: Service de Pneumologie, Hôpital Européen Georges Pompidou, AP-HP; Université Paris Descartes, Sorbonne Paris Cité, INSERM UMRS 970 and CIC 1418, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Meyer
authors.affiliation: Département de Médecine d'Urgence, Centre Vasculaire et de la Coagulation, CHU d'Angers; Institut MITOVASC, EA3860, Université d'Angers, Angers, France.
authors.forename: P-M
authors.initials: PM
authors.lastname: Roy
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use; D026661:Clinical Trials Data Monitoring Committees; D003645:Death, Sudden; D023381:Endpoint Determination; D006470:Hemorrhage; D006801:Humans; D011655:Pulmonary Embolism / Q000097:blood / Q000517:prevention & control / Q000628:therapy; D015203:Reproducibility of Results; D012107:Research Design; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000097:blood / Q000517:prevention & control* / Q000628:therapy
chemical_list: D000925:Anticoagulants
keywords: anticoagulants; cause of death; clinical trial; reproducibility of results; venous thromboembolism