Journal of Thrombosis & Haemostasis vol:6 issue:2 pages:232-234
Regulatory authorities prefer double-blind studies, but do not state that these are the only trial designs with regulatory value. The additional problems encountered when VKAs are the comparator are acknowledged, and this will remain an issue for several years to come, as VKAs will not be easily overtaken. A package comprising both open-label and double-blind pivotal randomised trials, preferably with internal consistency, offers the highest level of information as a basis for marketing authorisation. In case of discrepancy between the open-label and double-blind studies results, the latter would prevail. PROBE trials might be cheaper and simpler than double-blind ones, but are less precise . An MAA based on a single pivotal open-label study of, e.g., an oral thrombin or factor Xa inhibitor versus a VKA would probably be regarded very suspiciously by regulatory authorities. On the other hand, an open-label study would nicely complement at least one double-blind confirmatory trial.