Balancing risk and benefit in venous thromboembolism trials: concept for a bivariate endpoint trial design and analytic approach.
Balancing risk and benefit in venous thromboembolism trials: concept for a bivariate endpoint trial design and analytic approach.
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DOI：
10.1111/jth.12324
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发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
Antithrombotic Trials Leadership and Steering (ATLAS) Group
中科院分区：
文献类型：
--
作者：
Kittelson JM;Spyropoulos AC;Halperin JL;Kessler CM;Schulman S;Steg G;Turpie AG;Cutler NR;Hiatt WR;Goldenberg NA;Antithrombotic Trials Leadership and Steering (ATLAS) Group
Antithrombotic trials in venous thromboembolism treatment and prevention, including those evaluating the new oral anticoagulants, have typically evaluated thromboembolism risk as an efficacy endpoint and bleeding risk as a separate safety endpoint. Findings often occur in opposition (i.e., decreased thromboembolism accompanied by increased bleeding, or vice-versa), leading to variable interpretation of the results, which may ultimately be judged as equivocal. In this paper, we offer an alternative to traditional designs based on the concept of a bivariate primary endpoint that accounts for simultaneous effects on antithrombotic efficacy and bleeding harm. We suggest a bivariate endpoint as a general approach to the assessment of “net clinical benefit” in recently published trials and to the design of future trials. Lastly, we illustrate the bivariate endpoint design using two examples: a recently published superiority trial of rivaroxaban (RECORD1), and an ongoing non-inferiority trial of the duration of anticoagulant therapy in children with venous thrombosis (Kids-DOTT).
