FDA Tackles Regulatory, Scientific Issues With Point-of-Care Coagulation Monitoring Devices
As issues related to potential
problems with the device used to monitor warfarin therapy in the ROCKET AF
trial continue to be discussed, the US Food and Drug Administration (FDA) is
taking a deeper look at ways to avoid problems with all similar point-of-care
devices.
The agency held an all-day public workshop aimed at hashing out both regulatory and scientific matters associated with the devices on March 18, 2016.
“We are aware that this is an area where we have seen lots of issues,” Alberto Gutierrez, PhD (FDA’s Center for Devices and Radiological Health), said in opening remarks.
In a discussion document released before the meeting, the agency says it has become aware of problems associated with the devices that raise patient safety concerns, noting that numerous reports of serious adverse events have been submitted.
“The accuracy, reliability, result reporting, and device usability of the PT/INR [prothrombin time/international normalized ratio] devices appear to have led to erroneous patient INR results,” the document states. It highlights, in particular, challenges in evaluating substantial equivalence of point-of-care PT/INR devices.
The overall issue of accuracy in the point-of-care tests has come to the forefront recently because of problems surrounding the device used to monitor warfarin therapy in the ROCKET AF trial, which supported the approval of rivaroxaban (Xarelto; Bayer/Janssen) for stroke prevention in A-fib. The INRatio and INRatio2 PT INR Monitor Systems (Alere) were both used.
The devices first came under fire from the FDA more than a decade ago—before ROCKET AF started. In a warning letter sent in October 2005, the agency told then-manufacturer HemoSense that its review determined that the company knew about problems with the INRatio device providing “clinically significant erroneous values.” That was followed in November 2006 by another warning letter listing violations uncovered during an FDA inspection.
Then, in December 2014, Alere issued a Class I recall notice for its systems, saying that patients with certain conditions—including anemia with a hematocrit less than 30%, unusual bleeding or bruising, and conditions associated with elevated fibrinogen levels—should not be tested with the system because of the possibility of obtaining INR results lower than would be expected with laboratory testing.
ROCKET AF investigators said they became aware of the issue in October 2015 and then performed post hoc analyses to see whether problems with the device might have skewed the results of the trial. They concluded that the results were unaffected by the issue.
The same week, the European Medicines Agency came to a similar conclusion, stating “that there is sufficient evidence to conclude that the benefit/risk balance remains unchanged and favorable for treatment with rivaroxaban in the prevention of thromboembolism in nonvalvular atrial fibrillation.”
The FDA continues its review of
the specific issue regarding the Alere devices and appeared to expand the scope
of its investigation to include more general issues with point-of-care devices
by holding the workshop last week. The workshop included perspectives from
Alere and fellow device makers Accriva, CoaguSense, and Roche.
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Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …
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