BLEEDING CLASSIFICATION IN CLINICAL-TRIALS - OBSERVER VARIABILITY ANDCLINICAL RELEVANCE

To evaluate the bleeding classification in a recent trial on venous th rombosis treatment, a selection of reported bleeding episodes was adju dicated twice by an independent committee and graded by the treating p hysician and independent clinical experts on the clinical severity and impact on the patient's life. The kappa values for the dichotomy majo r bleeding versus minor or no bleeding were 0.79 (95% CI, 0.57-1.0) fo r the agreement between the two members of the adjudication committee and 0.77 (95% CI, 0.52-1.0) for the agreement between both adjudicatio n sessions. The kappa values for the dichotomy major or minor bleeding versus no bleeding were 0.42 and 0.44. The weighted kappa values for the agreement between the treating physician and the independent exper ts were 0.76 for the clinical severity and 0.79 for the impact on the patient's life (95% CI, 0.63-0.88 and 0.70-0.89). The association betw een the adjudication result expressed as major bleeding or minor or no bleeding and the clinical grading by the treating physician resulted in an ROC curve with an area under the curve of 0.98 for the clinical severity and 0.99 for the impact on the patient's life. The dichotomy major or minor bleeding versus no bleeding resulted in areas under the curve of 0.70 and 0.66. In conclusion, the applied criteria for major bleeding are reproducible and clinically relevant. The criteria for m inor bleeding are not reproducible and are less associated with the ob served clinical relevance.