The Justice Department is investigating the performance of error-prone INRatio blood testing devices that were scrutinized in POGO reports over the past year.
Alere Inc., the maker of the devices, disclosed in a recent regulatory filing that it has received a Justice Department subpoena seeking “various documents related to the accuracy, reliability and performance of the INRatio system."
The probe apparently focuses on communications with the Food and Drug Administration.
The subpoena includes “documents relating to prior interactions with the FDA and others regarding the system,” Alere said in the Aug. 8 filing with the Securities and Exchange Commission.
Alere's brief disclosure left unclear whether the probe is civil or criminal, who the Justice Department suspects of wrongdoing, and what kind of wrongdoing is suspected.
Alere recently announced that, at the FDA’s request, it was withdrawing the devices from the market.
The INRatio devices have been used in patients’ homes and doctors’ offices to test clotting rates in patients taking the blood thinner warfarin. They played a key role years ago in a clinical trial that compared the new blood thinner Xarelto to warfarin. The Food and Drug Administration was relying on that manufacturer-sponsored trial in 2011 when it approved Xarelto for patients with a heart condition called atrial fibrillation.
POGO reported last year that INRatio devices had been the subject of FDA warnings before the clinical trial began and that, according to a notice later posted on the FDA website, INRatio devices were prone to potentially deadly malfunctions.
The FDA has been trying to determine how the faulty devices might have affected the Xarelto trial. “Our analyses so far indicate that effects on strokes or bleeding, including bleeding in the head, were minimal,” an FDA spokeswoman told POGO in July.
In product liability litigation claiming patients were harmed by Xarelto, plaintiffs have alleged that drug maker Janssen, which markets Xarelto in the United States, gave the FDA “a misleading, inaccurate and/or incomplete portrayal of the facts.”
“Documents produced in recent discovery in this litigation disclose that Defendants possess substantial evidence indicating that they knew prior to the start of the ROCKET AF trial that the INR monitoring device chosen for the trial was prone to malfunction and that risk of error in the INR readings was great,” the plaintiffs said in a February court filing. “Indeed, substantial evidence exists that the device did malfunction during the course of the ROCKET AF trial and that Defendants were aware of the malfunctions during the trial but did not provide that information to the FDA and other regulators around the world.” [Emphasis in original.]
A report this year by the FDA’s European counterpart, the European Medicines Agency (EMA), described extensive discrepancies in blood test results from the Xarelto trial. Nonetheless, the European regulator said it was not revising its assessment of Xarelto’s risks and benefits.
The drug companies have been defending themselves against the product liability lawsuits.
In response to questions for this article, spokeswomen for Janssen, a subsidiary of Johnson & Johnson, and Bayer, manufacturer of Xarelto, said they were not aware of any Department of Justice investigations involving Xarelto.
“Bayer and Janssen have been fully transparent with health authorities, including the FDA and EMA, regarding but not limited to the ROCKET AF trial,” Bayer spokeswoman Stephanie Prate added by email.
Prate also commented on developments years after the Xarelto trial ended.
“In December 2014, Alere Inc. issued a device correction notice for their INR device that is used to monitor INR values in patients using warfarin. Bayer and Janssen were not notified at that time,” Prate said.
“When the companies became aware of the device correction notice, in September 2015, they promptly reached out to the manufacturer for more information. Upon confirmation from the manufacturer that the devices used in ROCKET AF should have been included in the device correction notice, Bayer and Janssen proactively and quickly notified health authorities around the world, including EMA and the FDA,” Prate said.
The Xarelto trial was co-chaired by Robert Califf, who was based at Duke University at the time and has since become the head of the FDA.
The Justice Department subpoena was issued by the U.S. attorney for the District of New Jersey, Alere said in the Aug. 8 regulatory filing.
It is unclear why the Justice investigation is being conducted by the U.S. attorney in New Jersey.
Alere is based in Massachusetts.
Janssen and its parent company, Johnson & Johnson, are based in New Jersey.
Alere spokeswoman Jackie Lustig said by email that Alere “is fully cooperating” with the government “in responding to subpoenas or requests for information,” but she declined to provide additional information. A spokesman for the U.S. attorney’s office in New Jersey, William Skaggs, declined to comment.