Xarelto was approved following the results of a trial in which a recalled blood clotting test device was used.
A new investigation suggests that the FDA approval of popular anti-clotting drug may have been based on faulty data.
In a report published in The BMJ, researchers questioned the findings of the ROCKET-AF trial, which compared rivaroxaban (Xarelto) with warfarin, another anti-clotting drug administered to prevent strokes in patients with an irregular heartbeat. The validity of the findings are in question after the blood clotting test device used in the trial was recalled in December 2014.
"In terms of the trial results, it could make rivaroxaban seem safer than it was with respect to the risk of bleeding and throws doubt onto outcomes used to support the use of the world's best-selling new oral anticoagulant," said The BMJ's Associate Editor, Deborah Cohen, PhD.
The blood clotting device INRatio was recalled after giving falsely low test results. The manufacturer of the device revealed these issues with test results date back to 2002. Physicians and scientists now want a new independent investigation launched, as well as access to the original trial data for clarification.
Patients administered Xarelto don’t have to get regular tests to check if the right amount of drugs are in their blood stream, specifically if levels are thin enough to protect against stroke and not too thin for risk of major bleeding. Xarelto, which is manufactured by Bayer and marketed by Johnson and Johnson, is marketed as a superior alternative to warfarin.
The FDA told BMJ that they were aware of the recalled device used in the trial and were reviewing relevant data.
"(There should be) an investigation by an independent group of experts to quickly determine if there are grounds for retraction," said Harlan Krumholz, who believed that an immediate Expression of Concern should be put on the paper in order to notify the medical community.
Although a new trial was performed by the Duke University Clinical Research Institute on behalf of the manufacturer, former FDA reviewer Thomas Marciniak told The BMJ data from a re-analysis conducted by Duke, Johnson and Johnson, or the FDA should not be relied on.
The best solution for an unbiased test would be to have access to the data. However, Bayer has put a stop to this, stating that they signed up for sharing information after January 1, 2014.
Unfortunately, the regulators lack a mandate to act without a safety signal once a drug has been released and is on the market.
"It is this lack of safety signal that appears to be hindering the FDA in their desire to pursue tailored dosing for [direct oral anticoagulants],” said clinical pharmacologist Bob Powell. “If it turns out that the issue with the INRatio device changes the safety profile of rivaroxaban, this very well may constitute the safety signal necessary for the FDA to act in this regard."
The investigation was able to show flaws in the United States device regulation system, which requires manufacturers to only show that their devices are “substantially equivalent” or similar to a device that is already on the market, the analysis noted.
This system has received backlash from the Institute of Medicine because it does not require much evidence to prove a device is safe and effective. However, Johnson and Johnson has lobbied against the idea of providing more evidence for devices in the past, according to the study.