Abstract
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 harm due to bleeding. 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).
Original language | English (US) |
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Pages (from-to) | 1443-1448 |
Number of pages | 6 |
Journal | Journal of Thrombosis and Haemostasis |
Volume | 11 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2013 |
Keywords
- Anticoagulants
- Safety
- Treatment efficacy
- Venous thromboembolism
ASJC Scopus subject areas
- Hematology