Accuracy and interrater agreement of death event adjudications by physician trainees: validation of the ISTH definition of pulmonary embolism-related death in an autopsy cohort.

BACKGROUND: We previously determined good agreement and high specificity of the International Society on Thrombosis and Haemostasis (ISTH) definition of pulmonary embolism (PE)-related death among an expert central adjudication committee (CAC). CACs are often composed of experts in the corresponding research field. Involving physician trainees in CACs would allow investigators to divide the workload and foster trainees' research experience. OBJECTIVE: To evaluate the accuracy of the ISTH definition of PE-related death for PE- versus non-PE-related deaths as confirmed by autopsy and its interrater agreement among physician trainees. METHODS: This retrospective autopsy cohort included all patients with PE-related deaths between January 2010 and July 2019 as well as patients who died in 2018 from a cause other than PE at the New York-Presbyterian Hospital. Based on premortem clinical summaries, two physician trainees independently determined the cause of death using the ISTH definition of PE-related death. We calculated the sensitivity and specificity of the ISTH definition to identify autopsy-confirmed PE-related death and its interrater agreement. RESULTS: Overall, 126 death events were adjudicated (median age, 68 years; 60 [48%] women), of which 29 (23%) were due to PE, as confirmed by autopsy. Sensitivity and specificity of the ISTH definition for autopsy-confirmed PE-related death was 48% (95% CI, 29-67) and 100% (95% CI, 96-100), respectively. Interrater reliability for PE-related death was good (percentage agreement, 93%; 95% CI, 87-96, Cohen's Kappa, 0.67; 95% CI, 44-85). CONCLUSION: Our findings are consistent with our previous validation study. They further support the use of the ISTH definition of PE-related death and revealed high agreement between adjudicators with varied experience.

Definitions of fatal bleeding in clinical studies evaluating anticoagulant treatment for venous thromboembolism: A scoping review.

BACKGROUND: Fatal bleeding is a component of the primary safety outcome in most studies evaluating anticoagulation for venous thromboembolism (VTE), but a standardized definition for fatal bleeding is lacking. OBJECTIVES: To summarize definitions of fatal bleeding and describe the range of case-fatality rates of major bleeding in VTE studies. METHODS: MEDLINE, Embase, and CENTRAL databases were searched from January 2008 to July 2021 for prospective studies that enrolled patients with VTE and evaluated the efficacy/safety of anticoagulation for VTE treatment or included fatal or major bleeding as primary outcome. Two authors independently performed study selection and data extraction. The primary outcome was the definition of fatal bleeding. The secondary outcome was the case-fatality rate of major bleeding. Data were analyzed using descriptive statistics. RESULTS: Of 4911 records identified, we included 132 articles representing 89 distinct studies. Twenty-seven (20%) articles and 7 of 89 (8%) studies reported a definition of fatal bleeding. Overall, we identified 3 different types of definitions that were either on the basis of a specific time interval between bleeding and death, bleeding location (intracranial) or clinical presentation (hemodynamic deterioration), or mainly relied on the judgment of the adjudication committee to determine the cause of death. The case-fatality rate of major bleeding ranged from 0 to 60% (median, 9.1%; interquartile range, 2.8%-18%). CONCLUSION: Less than 10% of studies assessing anticoagulant treatment for VTE reported a definition for fatal bleeding. The lack of a (standardized) definition for fatal bleeding may lead to inaccurate estimates of the risk of fatal bleeding, particularly when compared across studies.