External and Internal Validity of Open Label or Double-blind Trials in Oral Anticoagulation: Better, Worse or Just Different?

Currently, few topics in the field of anticoagulant therapy are as intensely discussed as the question: which is the best new oral anticoagulant? The most advanced substances in this field are the oral direct factor Xa-inhibitors rivaroxaban, apixaban and edoxaban and the oral direct thrombin inhibitor dabigatran. All of these substances are currently being tested in very similar phase III trials or are in the process of approval. In these trials, open-label or double-blind double-dummy designs are being used to evaluate the efficacy and safety in prevention and treatment of venous thromboembolism or stroke prevention in atrial fibrillation in several thousands of patients. As a consequence, an intense discussion of the advantages and disadvantages of open-label or double-blind trials is currently under way and interpretation of trial results is often focused on this matter. In general, a blinded trial is regarded as being less subject to bias than an open trial because it minimizes the impact of knowledge of treatment allocation on post-randomized treatment decisions and on reporting of outcomes. However, a blinded trial is not always feasible. Thus, in some respects, the two trial designs offer complementary strengths and weaknesses. This review addresses the risks of bias for internal and external validity of open-label and double-blind anticoagulation trials to help to objectify this debate.