FDA holds meeting to weigh increased regulation of diagnostics for monitoring warfarin therapy

Alere INRatio2 PT/INR monitoring system--Courtesy of Alere

The FDA convened a workshop on point-of-care diagnostics for monitoring warfarin medication therapy, as it weighs increasing scrutiny of the devices.

The agency said the device's inaccuracy is suspected of contributing to 18 deaths in 2014 and 2015, according to The Wall Street Journal.

Devices (and drugs) in the spotlight

One device that received particular scrutiny during the meeting is Alere's ($ALR) INRatio. The device was recalled in 2014 following patient complaints that the measurements of the test strips, used to measure blood clotting time in patients on warfarin, were lower than the results from lab tests. The recall was initiated as a result of 9 serious adverse event reports, including three patient deaths involving bleeding (the main undesirable side effect of warfarin), Alere (soon to be acquired by Abbott) said at the time.

Disconcertingly, the device was used in the clinical trial that led to the 2011 approval of anticlotting drug Xarelto, sold by Bayer and Johnson & Johnson ($JNJ). "After more than four years on the U.S. market and more than 15 million patients prescribed worldwide, real-world research continues to confirm that the benefit-risk profile of Xarelto remains favorable and consistent with clinical trials," the Big Pharma companies said, according to The Wall Street Journal.

Alere also defended its product, posting a statement on its website that pointed to a study in the New England Journal of Medicine which "found no significant difference in serious adverse events between patients who used the Alere INRatio device and those who did not."

Evaluation challenges and possible regulatory enhancements

In a discussion paper distributed prior to the meeting, the FDA said evaluating point-of-care devices for monitoring warfarin pose many challenges. They include the use of various clot detection technologies and the device's broad spectrum of patients and end users--which can range from healthcare professionals to the patients themselves, who use the devices at home.

The FDA mentioned some specific actions it is considering to strengthen evaluation of the diagnostic devices, saying in a meeting document that "technology-specific interference studies should be a part of the 510(k) submission for these devices." Interferents can include antibiotics and patient specific sample differences.

Currently, the FDA requires a comparison between whole-blood based point-of-care devices and a lab-based assays that use plasma as a condition for clearance. But it said in the document that "validation studies designed exclusively for demonstrating equivalence between plasma-based devices and POC (point-of-care) PT/INR devices may not be sufficient for complete validation of devices measuring whole blood."

During the meeting, the panelists were asked to provide input on a variety of topics related to FDA's concerns and plans for increased regulatory scrutiny, including improvements to operator training materials, the types of quality control enhancements needed and possible improvements to premarket comparison studies of candidate point-of-care devices to more reliable but less convenient laboratory-based testing methods.

- read the meeting literature
- here's more from The Wall Street Journal

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