Concerns over data in key dabigatran trialBMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g4747 (Published 23 July 2014) Cite this as: BMJ 2014;349:g4747
- Deborah Cohen, investigations editor, The BMJ
One of the key selling points of the new oral anticoagulant dabigatran for use in stroke prevention in non-valvular atrial fibrillation is that the drug requires no time consuming anticoagulant activity or drug plasma level monitoring. But the evidence on which these claims were based has been called into question by the publication of new material as a result of an investigation in The BMJ.1
Documents released during US litigation and those obtained through freedom of information show how Boehringer Ingelheim, the makers of dabigatran, failed to share with regulators information on how monitoring plasma levels of the drug and subsequent dose adjustment could reduce risk of major bleeds.
Boehringer, maintains, however, that the anticoagulant activity or plasma concentrations of dabigatran do not need to be monitored.
“Our scientists determined, and the Food and Drug Administration concurred, that the research does not support making dosage decisions based on plasma concentrations—a conclusion based solely on science and patient welfare,” a spokesperson told The BMJ.
Nevertheless there is evidence that there is a potentially higher bleeding risk with dabigatran than has been stated in publications of the single clinical trial used for regulatory approval and indeed, was previously stated to the regulators.
Right from the start the design and oversight of the only key trial, the RE-LY trial, was poor. Writing in the Canadian independent drugs bulletin Therapeutics Letter in early 2011, academics issued concern over many aspects of the trial. “[An] independent audit of RE-LY is needed to check for irregularities in conduct, sources of bias and the cause of the unusually high incidence of intracranial hemorrhage in the warfarin arm,” they said.2 Earlier this year authors …