Quality Requirements and Standards

On March 16 and 17, 2010, the FDA held a public meeting to discuss concerns about the quality of Blood Glucose Meters. As slides and transcripts have become available of this meeting, Dr. Westgard reviews some of the key points.

May 2010

James O. Westgard, PhD

On March 16-17, 2010, the Food and Drug Administration held a public meeting to discuss the quality of Blood Glucose Meters (BMG).  Transcripts of that meeting have become available, as well as the slide presentations.  There are many issues concerning quality, including the analytical quality required for patient monitoring, detection of hypoglycemia, and tight glycemic control, clinical needs and target concentrations for hypoglycemia and tight glycemic control, interferences in the common methodologies employed by Blood Glucose Meters, and even Quality Control. 

Given that BGM devices are “waived,” the main legal requirements for users are to be knowledgeable about the product labeling and to follow the manufacturer’s directions for use.  Understanding the product claims and directions for use is not trivial, and it is unlikely that all users comply with even these minimal requirements.  And because these devices are “waived”, that means the CLIA requirements for 2 levels of controls per day and periodic participation in proficiency testing do not apply unless the laboratory is also performing non-waived tests.  Thus there is concern not only with how good BGM devices need to be, but also how well they actually perform in the hands of the users.

Off-label applications. No one argues against the need for BGM devices, but it seems like they are sometimes being used for applications that require better quality, such as tight glycemic control.  A presentation that I found particularly interesting was titled “Malpractice issues in the use of blood glucose meters,” presented Jack Bierig, who is an attorney at Sidley Austin LLP.  The use of BGM devices for tight glycemic control is essentially “off label” because BGM devices have not been cleared by FDA for that clinical application.  Nonetheless, their use for tight glycemic control is acceptable because that practice represents the current standard of care as documented in the medical literature.  This is analogous to a drug being approved for one medical condition, then later being used for other medical conditions based on other studies and reports in the medical literature. 

One of the interesting aspects in the use of BGM devices for tight glycemic control is that the original study utilized higher quality analytical instrumentation (not BMG devices), as well as arterial and/or venious samples (not capillary fingerstick samples), plus the analytical testing was performed under better conditions of control.  Nonetheless, the quality of the measurements is not a criterion when it comes to transferring the practice to other clinical settings.  Any glucose test is assumed to be equivalent to any other glucose test! 

Quality requirements. ISO 15197 is widely recognized as the current standard for BGM performance, which is an allowable total error of 20% or ± 15 mg/dL at 75 mg/dL or lower.  Remember that the CLIA requirement for serum or plasma glucose is 10% or ± 6 mg/dL at 60 mg/dL or lower.   It seemed like most of the participants in the FDA meeting would support a new quality standard of 15% for BMG devices.  Some clinicians and scientists think better performance is needed for tight glycemic control, and they suggest an allowable total error of 10%.  The most demanding application is probably the detection of hypoglycemia, and unfortunately, that requirement should apply to all BGM testing, both home use and professional applications.   From the discussion at the meeting, it seems likely in the future that there will be a different standard of performance for BGM devices that are used for tight glycemic control. 

Of course, there will be practical difficulties in trying to implement a different standard for routine use and tight glycemic control because it will require upgrading current BGM devices and will likely result in having two or more types of BGM devices in use in many clinical settings.  Cost is expected to continue to be the driving force in the selection of BGM devices, regardless of the intended clinical applications.

Quality Control. There is little if any QC being done by patients themselves because the extra cost of control solutions limits their use.  Yet there are real problems due to the stability of test strips and their exposure to high temperatures (e.g., being left in the car on a hot day).  Advocates want manufacturers to include controls as part of their consumables in order to help patients identify problems with reagent stability.  In the clinical setting, QC is more likely to be run, but it is still considered to be a major hassle for non-laboratory personnel.  Here’s where the attorney offered some interesting advice:

“The best way to limit malpractice exposure in this area is to conduct QC in accordance with the manufacturer’s instructions – or, in the absence of such instructions, on a daily basis.  In making this recommendation, I recognize that glucose testing is a waived test under CLIA.  Thus, federal law does not mandate QC on glucose meters.  However, both the Joint Commission and the College of American Pathologists, as part of their respective accreditation programs, require QC in this area.

“If a hospital or practitioner were sued in this context, the Joint Commission and CAP standards are likely to be put into evidence.  Likewise, the package insert will almost certainly be introduced.  And there will be testimony on the importance of QC.  Thus, despite the waived status of this test under CLIA, malpractice considerations counsel strongly in favor of performing appropriate QC.”

Thus, professional standards of practice - and quality control - still matter.  Compliance with regulations may not be enough to assure the quality of test results.  We in the laboratory know that is true, but it is interesting to see that people outside the laboratory also recognize there is a difference between quality and compliance.