Deborah Cohen , associate editor, The BMJ dcohen{at}bmj.com

An investigation by The BMJ has uncovered the use of a faulty device in a regulatory drug trial, potentially putting patients at unnecessary risk, Deborah Cohen reports

Doctors and scientists are calling for an independent investigation into the key trial underpinning use of rivaroxaban to prevent ischaemic stroke in non-valvular atrial fibrillation after The BMJ found that a defective point of care device was used in the warfarin arm of the trial.

Doctors and scientists have also told The BMJ that the validity of the trial—called ROCKET-AF and published in the New England Journal of Medicine in 20111—is in question until such independent analysis is done.

The drug was manufactured by Bayer and marketed in the United States by Janssen, part of Johnson and Johnson, and the companies relied on a single trial–ROCKET-AF—to gain approval from the US and European regulators. The trial included over 14 000 patients and found that rivaroxaban was non-inferior to warfarin for preventing ischaemic stroke or systemic embolism. There was no significant difference between groups in the risk of major bleeding—although intracranial and fatal bleeding occurred less often in the rivaroxaban group.

But there are now concerns about these outcomes. In a letter submitted to the NEJM (as yet unpublished) and shown to The BMJ, former FDA cardiovascular and renal drug reviewer, Thomas Marcinicak, says: “The care for the warfarin control arm patients [in ROCKET-AF] appears to have been compromised.”

Earlier last year, The BMJ found that the point of care device used to measure international normalised ratio (INR) in patients taking warfarin in ROCKET-AF had been recalled in December 2014. An FDA class I recall notice (the most serious kind) said that certain INR devices could deliver results that were “clinically significantly lower” than a laboratory method. It added that Alere—the device …