Glucose Test Accuracy Concerns Prompting FDA Action

Miriam E. Tucker

August 22, 2013

The US Food and Drug Administration (FDA) is poised to address both old and new concerns about the accuracy of home blood glucose testing.

On September 9, the FDA will participate in a meeting in Bethesda, Maryland, organized by the Diabetes Technology Society (DTS), aimed at establishing tighter performance standards for approval of blood glucose monitors and test strips and ramping up postlicensure surveillance of the devices. A variety of stakeholders are expected to attend, including both large and small glucose-testing equipment manufacturers.

Several converging factors have led to the move. The FDA has been working since 2010 on developing stricter standards for approval of glucose testing systems (meters and their compatible strips are regulated together). The need to revise the current standards, which date back to 2003, had been discussed extensively at a public meeting the FDA held in March 2010.

But at a DTS meeting held May 21 in Arlington, Virginia, investigators discussed a recently identified problem: About a third of the devices that had met FDA standards and were licensed for sale in the United States were no longer meeting those standards once they were in real-life use. Most of these less accurate meters are manufactured outside the United States and sold at lower cost than the name brands.

We all tend to think that if a product has been cleared by the FDA it is accurate and safe.

"We all tend to think that if a product has been cleared by the FDA it is accurate and safe. If products on the market don't meet standards for which they were approved, then patients are receiving incorrect information, making incorrect decisions, and are at increased risk for low blood sugar or high blood sugar," DTS president David C. Klonoff, MD, clinical professor in the division of endocrinology and metabolism at the University of California, San Francisco, told Medscape Medical News in an interview.

The May meeting preceded by just 6 weeks the July 1 launch of the Center for Medicare and Medicaid Services' (CMS) new competitive-bidding program, which limits to 18 the number of mail-order vendors of glucose test strips from which Medicare beneficiaries can order their supplies.

Those 18 suppliers, selected by a competitive-bidding process based primarily on their ability to keep down costs — resulting in an overall 72% reduction in Medicare reimbursement for testing supplies — are able to do so by limiting the number of glucose test strip brands available and stocking some of those same low-cost brands that demonstrated subpar performance in studies despite having met FDA standards for licensure.

Dr. Klonoff doesn't fault the CMS. "I think the CMS is doing their job, to provide what they believe are quality products. I'm guessing the CMS assumes that every product approved by the FDA meets standards indefinitely following clearance."

To be sure, the large brand-name manufacturers — which face considerable loss of revenue with the CMS program — have been pushing the accuracy issue. Roche Diagnostics funded 3 of the studies that were featured at the May DTS meeting, in which the company's Accu-Chek line of meters came out on top while some smaller brands failed to meet FDA standards.

However, Katharine Serrano, diabetes branch chief, division of chemistry and toxicology devices, Office of In Vitro Diagnostics and Radiological Health, Center for Devices and Radiological Health (CDRH) at the FDA, told Medscape Medical News that industry-funded study data account for only part of the information with which the FDA is working.

"Some of the studies presented at the May DTS meeting were funded by manufacturers of specific blood glucose meter systems, and the study design used in such studies can have a big impact on the results. Information presented in studies, such as those discussed at the May DTS meeting, is interesting and can be informative. However, any decision by the FDA to pursue regulatory action or change policy in this area would typically be based on a review of multiple sources of information on the postmarket performance of these systems," Ms. Serrano told Medscape Medical News.

Indeed, in the past few months there were 2 large voluntary recalls, one in March by the LifeScan unit of Johnson & Johnson of nearly 2 million of its OneTouch Verio blood glucose meters because they malfunction at extremely high blood glucose levels, the other in July of about 62 million Nova Max test strips by Nova Diabetes Care, after it was determined that some of them may report a false, abnormally high blood glucose result.

On July 31, the American Diabetes Association (ADA) issued a statement endorsing the FDA's efforts in enforcing preapproval standards and calling upon the agency to "extend beyond the initial premarketing approval to continual monitoring of the postmarketing product to ensure that accuracy remains within established standards."

The ADA's chief scientific and medical officer, Robert Ratner, MD, told Medscape Medical News, "ADA hasn't taken any stance on competitive bidding, but rather we focus on the quality of the systems that are available. We clearly want people with diabetes to have a level of accuracy and performance that allows them to manage their diabetes."

FDA's Challenges

Accuracy of glucose testing has been a priority for the FDA dating back to when they were first licensed in 1976, Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics in the Center for Devices and Radiological Health at the FDA, told Medscape Medical News.

"Glucose meters have always been a priority for the FDA. This is an area that's complex, where lots of things happen… It's always been high on our list."

In 2003, the FDA collaborated with the International Organization for Standardization (ISO) to come up with the standards it still uses today: In order to be approved, 95% of all measurements of a glucose testing system must be within 20% of reference values at or above 75 mg/dL and within 15 mg/dL below 75 mg/dL.

Glucose meters have always been a priority for the FDA.

But Dr. Gutierrez told Medscape Medical News that the FDA was never satisfied with those standards. Indeed, earlier this year, the ISO adopted stricter standards, as has the Clinical and Laboratory Standards Institute.

The FDA had been working on its own new standards following the 2010 meeting, but the 2012 Food and Drug Administration Safety and Innovation Act changed some of the legal aspects of device regulation, forcing it to basically start again from scratch.

And now, the recent information about postmarket accuracy problems will also influence the FDA's actions going forward.

One of the Roche-funded studies presented at the May meeting investigated 7 systems — Accu-Chek Aviva Plus, Redi-Code (Advocate Meters), Element (Infopia USA), Embrace (Omnis Health), Prodigy Voice (Prodigy), TRUEbalance (Nipro Diagnostics), and Presto (WaveSense) — and found that only 3 (Accu-Chek Aviva Plus, Element, and Presto) met the current FDA approval criteria. The other 6 systems failed to meet the criteria in at least 2 of 3 lots, showing lot-to-lot variability, high/low bias, and variations due to hematocrit (J Diabetes Sci Technol. 2013;7:144-152).

And in another Roche study conducted in Europe, 7 of 34 systems (TD-4225 [Biocheck Medical], Futura Monometer, Glucohexal II [Hexal], GlucoRx, Fidelity [IME-DC], SeniorLine GM210, and Wellion CALLA Light [Med Trust]) failed to meet minimal accuracy requirements of the ISO standard (J Diabetes Sci Technol. 2012;6:1060-1075).

Ms. Serrano told Medscape Medical News that the FDA routinely performs postmarketing surveillance when problems are reported and also inspects manufacturing facilities on a regular basis. But inspections of foreign facilities are more challenging, she said, because they're announced. "It's a lot easier for them to anticipate us coming and put their best face forward. The question is how to handle that."

We want to set standards to make sure devices continue to be accurate throughout their lives.

Dr. Gutierrez told Medscape Medical News that the FDA is now considering using the rulemaking process to change the law governing its authority over glucose test device regulation.

"We want to set standards to make sure devices continue to be accurate throughout their lives. The problem with just changing the [approval] standards is that all the meters on the market would still be legally marketed. By making a rule, we can enforce some of the same standards to the meters already on the market, so that everybody would be playing by the same accuracy rules," he told Medscape Medical News.

All of this will be discussed at the September 9 meeting, he said.

Advice for the Interim

Until all these changes are made, there are several measures physicians can take to help ensure that their patients are using accurate meters.

Within the CMS competitive-bidding program, there is a "50% rule" that says that each of the 18 contract suppliers must carry at least half of all the available testing supply brands on the market. So, although the formularies will largely comprise low-cost brands, there are still brand names available.

Another rule, known as the "antiswitching rule," prohibits the contract suppliers from influencing or incentivizing beneficiaries to switch their current glucose monitor and testing supplies to a lower-cost brand.

If the physician prescribes a particular brand of testing supplies — and documents why it is necessary to avoid an "adverse medical outcome" — the contract supplier has 3 options: furnish the specific brand as prescribed; consult with the physician to find another appropriate brand and obtain a new prescription; or assist the beneficiary in locating another contract supplier that can provide that specific brand.

Indeed, Dr. Ratner told Medscape Medical News that the ADA does have a position regarding brand switching: "In particular for the Medicare population, we don't want to see major disruption in their self-management. So, an individual who has been utilizing a particular meter/strip system successfully should probably continue on that system."

The simple fact is, there is no money saving in going to a cheaper system if the patient doesn't know how to use it.

He added, "We strongly encourage individuals who are not adaptable to continue on the glucose monitoring system they had been using previously, and if there is a change, appropriate education should be provided on the use of that system, ensuring that the individual can actually do it. The simple fact is, there is no money saving in going to a cheaper system if the patient doesn't know how to use it."

To ensure accuracy in meters and strips already in use, Dr. Klonoff suggested that patients perform a blood glucose test with their own equipment at the same time that they are having blood drawn at a clinical laboratory or in the physician's office and compare the results.

Patients should also be educated about the importance of using the control solution provided by the manufacturer to ensure that the system is working. And, if there's a discrepancy between how the patient feels and the value on their meter, they should perform another test using a different vial of strips, particularly if the strips have been exposed to heat or moisture.

However, Dr. Klonoff said it's ultimately the FDA's job to ensure that cleared glucose monitors are accurate. "There's a limit to what people can do, and there has to be a system of regulatory policy. You can't have a do-it-yourself system to ensure accuracy of blood glucose monitors."

He praised the FDA's efforts and the speed with which it has responded to the issues raised in May. "It's clear to me that the FDA is doing an outstanding job of recognizing and responding to this problem. The problem was pointed out May 25 and by September 9 the FDA will be mobilized to do something about it… When you think of how long it usually takes the federal government to respond to a problem, this is unusual. I think they deserve credit."

Dr. Klonoff is a consultant for Sanofi. Dr. Ratner, Ms. Serrano, and Dr. Guitierrez have reported no relevant financial relationships.


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