The U.S. Food and Drug Administration (FDA) is evaluating whether the approval of Xarelto, a blood thinner manufactured by Johnson & Johnson, was impacted by the use of a recalled blood-testing device. The New York Times reports that clinical trial Rocket AF, which fueled the approval of Xarelto, involved the use of the INRatio sold by Alere. The blood monitoring device was recalled in 2014 because it underestimated the risk of bleeding.
In the United States, Xarelto was approved in 2010 for the prevention of blood clots. When it first hit the market, it was touted as a superior version of warfarin, a blood thinner that has been on the market for decades. Patients taking warfarin face dietary restrictions and regular blood tests to make sure they are receiving appropriate doses. Xarelto does not have these limitations, but it has raised other concerns. Unlike warfarin, there is no antidote to reverse bleeding in Xarelto patients.
The Rocket AF trial involved more than 14,000 patients worldwide from 2006 to 2010. It was led by Dr. Robert M. Califf. President Obama has nominated Dr. Califf from head of the FDA. According to legal documents filed by plaintiffs in Xarelto litigation, the agency has probed J&J over whether it knew the INRatio was faulty during the trial. Attorneys also pointed to documents indicating doctors were dissatisfied with leadership during the trial.
The INRatio was used to determine whether patients were getting the appropriate dosage of warfarin during the trial, which compared strokes and bleeding events between Xarelto and warfarin users. Last fall, J&J told regulators that the device was recalled because understated the risk of bleeding, NYT reports. The FDA is now investigating whether the doctors administered the wrong dose of warfarin, leading to additional bleeding episodes, as a result of the faulty blood monitor; if so, it could mean that Xarelto had an unfair advantage in the clinical trial that led to its approval.
Two analyses published this month suggest the INRatio did not affect the outcome of the Xarelto trial. According to NYT however, these findings have drawn criticism themselves.
The New England Journal of Medicine published the findings of researchers with the Duke Clinical Research Institute, who oversaw the trial. However, this analysis failed to mention central laboratory tests that could have been used to determine whether the blood monitor readings were accurate. The analysis published by the European Medicines Agency did take these readings into account, but was conducted by the companies themselves.