For some time, there have been serious questions about the ROCKET-AF trial, the clinical study of the anti-coagulant medication Xarelto (rivaroxaban), prescribed for patients at risk for stroke. The study compared the performance of  Xarelto to that of warfarin, the standard treatment for nearly seven decades. Specifically, the medical community has been raising serious concerns about the objectivity and accuracy of the results. At the center of the controversy is a defective blood analysis device, which had been generating tens of thousands of reports over malfunctions – some of which have resulted in serious patient injuries. Questions about ROCKET-AF results came up earlier last year, when the British Medical Journal (BMJ) began its own investigation into the results of the study.

That investigation came about as the result of a letter, originally addressed to the New England Journal of Medicine (NEJM), in which the author wrote, “The care for the warfarin control arm [in the ROCKET-AF study] appears to have been compromised.”

The device in question is a blood meter manufactured by Alere. Known as the INRatio, its function and purpose is similar to that of blood meters used by diabetics to measure glucose levels to determine the amount of insulin needed. The difference is that the INRatio measures the amount of clotting agent present in the bloodstream. Like the diabetic blood meter, the INRatio employs an expensive (and for Alere, very profitable) paper strip, on which a blood sample is placed. The strip is then inserted into the INRatio, which measures the amount of Factor Xa (the clotting agent) in the blood. This measurement determines the amount of anticoagulant necessary to prevent blood clots as well as the effectiveness of the drug.

During the ROCKET-AF trial, the INRatio was used specifically to measure the performance of Xarelto against that of warfarin. The official results of the study stated that for patients with atrial fibrillation (AF, the medical term for irregular heartbeat), Xarelto was “non-inferior (i.e., no worse than) warfarin for stroke.” The trial summary also claimed that patients treated with Xarelto “had less hemmorhagic strokes, systemic embolism [blocking of an artery] and bleeding (critical, fatal and intracranial) versus warfarin.” The results of the study were first published in the NEJM in 2011.

Last year, the BMJ discovered that the INRatio had been subject to a Class I recall by the U.S. Food and Drug Administration in December 2014. However, the manufacturer had received nearly 19,000 reports of device malfunctions dating back to 2002 – almost a decade prior to the ROCKET-AF trial. The INRatio had been giving off readings significantly lower than would have been obtained under laboratory conditions. Because of this, ROCKET-AF subjects may have received unnecessarily high doses of warfarin, raising the risk of hemorrhaging – and making Xarelto look safer by comparison.

Last September, the BMJ contacted the authors of the NEJM article. Among them were researchers from Xarelto manufacturer Bayer AG, and Johnson & Johnson subsidiary Janssen Pharmaceutica, Bayer’s marketing partner, as well as scientists from the Duke Clinical Research Institute, where the study was carried out. One of them was Dr. Robert Califf, President Obama’s current nominee for head of the FDA. Dr. Califf has significant financial ties to Big Pharma, and has been a paid consultant for Janssen Pharmaceutica as well as its parent company, in addition to several others.

Naturally, authors of the NEJM paper denied any knowledge of the INRatio’s recall by the FDA. It required several months of hounding by BMJ investigators before any of the parties involved in ROCKET-AF were inclined to look into the matter themselves.

Given the history of Big Pharma’s psychopathic greed and reckless behavior, combined with the lucrative and growing market for Xarelto, it is difficult to believe that the researchers didn’t know about the INRatio’s defect – or that officials at the FDA didn’t know that the clinical trials had been carried out with such a defective device. The FDA had been aware of the INRatio’s defect even before the original manufacturer, HemoSense, had been taken over
by Alere. In a letter to that company, dated October 4th 2005, the FDA said, “Both high and low test results have the potential to cause or contribute to a death or serious injury, because they may result in erroneous dosing and thus improper control of coagulation.

Yet the FDA went ahead and granted approval for later versions of the INRatio by way of the infamous 510(k) Pre-clearance process which has arguably been responsible for the approval of numerous defective and dangerous medical products.

Cardiologist Dr. Harlan Krumholz, who teaches at the Yale University Medical School, wants the NEJM to publish a warning to the medical community, and says the ROCKET-AF study “…should be considered of uncertain validity until a more thorough review can be done…[by] an independent group of experts.”

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K.J. McElrath is a former history and social studies teacher who has long maintained a keen interest in legal and social issues.