Glucose Monitor Accuracy – Overkill or Overdue?

Glucose Monitor Accuracy – Overkill or Overdue?

Looking back on the FDA Meeting which was entitled “Clinical Accuracy Requirements for Point of Care Blood Glucose Meters”, Diabetic Investor came away with mixed emotions. At first glance after reviewing everything that was said a strong case can be made that the FDA does not need to step in and change the standards. On the flip side, an equally strong case could be made SOME changes are necessary.

To provide some perspective to this issue it’s helpful to review a study at last year’s EASD conference and published in DIABETES TECHNOLOGY & THERAPEUTICS, entitled “System Accuracy Evaluation of 27 Blood Glucose Monitoring Systems According to DIN EN ISO 15197”. The authors of this study concluded; “More than 40% of the evaluated BG monitoring systems did not fulfill the minimum accuracy requirements of DIN EN ISO 15197:2003. As inaccurate BG monitoring systems bear the risk of false treatment decisions by the diabetes patient and subsequent possible severe health injury, manufacturers should regularly and effectively check the quality of BG meters and BG test strips.”

The authors also noted; “Thirteen BG monitoring systems had 100% of their results in error zones A and B, which are considered as ‘‘clinically uncritical’’; 14 BG monitoring systems additionally had results in error zones C–E, which are considered as ‘‘clinically critical.’’ According to Clarke et al.15 and Clarke,20 ‘‘clinically critical’’ results bear the risk of wrong therapy decisions, e.g., inappropriate adjustments to the insulin dose or inappropriate intake of carbohydrates. Depending on the degree and the direction of these inappropriate adjustments the consequences for the diabetes patient can vary from harmless to serious health injuries.” (Highlighting added by Diabetic Investor)

It is this last statement that best summarizes the problem faced by the FDA and manufacturers. As Barry Ginsberg, M.D., Ph.D. correctly pointed out during his presentation for the vast majority of patients the current standard is just fine. A type 2 patient taking oral medications really doesn’t need a highly accurate meter, whereas a patient following multiple daily injection (MDI) therapy or insulin pump therapy would benefit from more accurate meters. There was also universal agreement that in a hospital setting, particularly in the ICU unit and those following the Portland Protocol or tight glycemic control, monitors need to be more accurate.

On day two of the meeting Irl Hirsch, M.D. gave one of the better presentations when he examined the real world experiences of practicing tight glycemic control in a hospital setting. A noted expert in the field Dr. Hirsch put the issue in perspective when he noted that what we’re really talking about here isn’t necessarily meter accuracy rather when and how to use insulin to achieve tight glycemic control. While everyone else seemed fixed on hypoglycemia, Dr. Hirsch noted that hyperglycemia is actually a bigger problem or more accurately the lack of action taken when patients experience hyperglycemia. As Dr. Hirsch correctly stated that fighting hyperglycemia is just as important as avoiding severe hypoglycemic events, which in reality are much rarer than people think.

Several ideas were floated during the meeting for the FDA to consider. Many called for a set of standards and not a one standard fits all approach. The basic idea being that meters used at home meet one standard and those used in hospital meet a stricter standard. An offshoot of this idea was to match meters to a patient’s therapy option. Going back to what Dr. Ginsberg said this would mean meters for type 2 patients not on insulin therapy and another set of meters for patients on insulin pump or MDI therapy. Diabetic Investor relates this to the old way Sears used to sell various products, the Good, Better and Best concept. While we would like to say this is new concept it’s actually something Diabetic Investor mentioned many years ago.

Another idea was to put additional information on package insert that comes with test strips or put another establish some sort of rating system for meters so patients would better understand the limitations of their particular system. Not necessarily a bad idea but not overly practical in the real world where patients rarely read package inserts and basically believe since the product is approved by the FDA the system is accurate. In the real world the majority of patients have no idea that under current standards a meter reading may be off as much as 20%. When they see a reading of 100 mg/dl they believe it.

Also suggested was the establishment of an “independent” entity which would test all meters for accuracy.  Besides looking at existing systems this entity would be part of the approval process for new products. Many felt such an entity would give some credibility to the whole process. The main issue here is just who would fund this entity and how much true independence would they have.

Some thought that many of the improvements made to meters over the years – smaller meters, faster test times, smaller blood samples – were part of the problem. A few of these “experts” even asked why manufacturers could not sell systems that required larger blood samples and took as long as sixty seconds to deliver a test result. Besides being very bad ideas they are also extremely impractical. The fact is consumers now expect small blood samples and fast test results. These statements also show a basic lack of understanding of what a real patient goes through every day when they perform multiple tests.

Unfortunately there were a mere handful of people who actually understood that accurate or not, all this fuss doesn’t matter all that much when patients aren’t testing on a regular basis and many who do test have no idea what that number means or what to do with it. Even less understood that a glucose reading is just one piece of a very complex puzzle, as Diabetic Investor has pointed out on numerous occasions a glucose test is used in conjunction with other variables to determine an insulin dose. Even if the results were 100% accurate errors would not be eliminated if a patient miscalculates their carb intake or fails to take into account insulin on board, duration of insulin action, exercise, etc.

Although it was discussed Diabetic Investor felt user error should have been given more attention. Or perhaps we should rephrase this as it really isn’t user error but the complex nature of performing what should be a simple test. While we doubt the FDA would go this far many errors would be eliminated by the elimination of test strip codes. Why all companies are not required to offer no-coding test strips is beyond Diabetic Investor as this technology is widely available. At a previous meeting years ago someone pointed out there 21 steps necessary to perform a glucose test, to Diabetic Investor this 20 steps too many.

Still even if all meters used no-coding strips or if it took fewer steps to perform a test, there are just some things that can’t be controlled. As Dr. Ginsberg noted most patients fail to wash their hands before a test and that any substance on the fingertip will transfer to the blood sample drawn. Or as someone else noted even when you wash your hands you better dry them thoroughly because water can deactivate a test strip. Finally there are a host of substances that can interfere with an accurate test result, not just maltose which we’ll discuss in greater detail in a moment.

Diabetic Investor can’t help but think this whole issue over accuracy is directly tied into the never ending quest to develop an artificial pancreas or closed-loop insulin delivery system. A quest which was made even more difficult when one speaker noted that if the continuous glucose monitoring (CGM) system used as part of the closed loop system is calibrated with an inaccurate blood glucose monitor the whole system will be off. While the CGM companies will dispute this statement, it does point out just how difficult it will be to develop a true closed-loop insulin delivery system where the patient is not an active participant in insulin dosing decisions.

Speaking of CGM this technology should receive a major boost from this meeting. Several speakers noted that while a single point measurement is fine for non-insulin using patients, CGM is better option for insulin pump and MDI patients. CGM will also receive a boost from the focus on tight glycemic control in a hospital setting as more than one speaker noted the time required by a nurse to monitor glucose in an ICU. As Diabetic Investor has said all along CGM in a hospital setting is not about accuracy rather productivity. In the real world nurses just don’t have the time to monitor the patient every hour which is a basic component of the Portland Protocol. Anyone who’s been in or seen someone in an ICU unit, chaos is the norm not the exception.

Staying inside the hospital Diabetic Investor sees a real opportunity for BGM companies who have been struggling with declining consumer demand and increasing price pressure. As we noted earlier there was near universal agreement that hospital systems must be more accurate, even if that accuracy comes at an increased cost. With more hospitals adopting the Portland Protocol or their own versions of tight glycemic control accuracy is critical.  One speaker went as far to state that the currently available hospital systems should be banned outright and replaced with laboratory tests only. Another impractical idea but it does illustrate the extent of the problem in a hospital setting.

The FDA will likely start making immediate changes to hospital based systems by banning the use of any systems that uses the now notorious GDH-PQQ enzyme. Courtney C. Harper, Ph.D., Director, Division of Chemistry and Toxicology Devices -Office of in Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health gave a detailed presentation entitled “FDA Perspective – Public Health Notification: Potentially Fatal Errors with GDH-PQQ Glucose Monitoring Technology  During her presentation Dr. Harper made the following observations of the 100 deaths related to glucose monitoring from 1992- 2009, 13 can be directly linked to Maltose/non-glucose interference. Of those 13 deaths nearly half, six have occurred since 2008 plus all of these death occurred at a healthcare facility.

Dr. Harper also outlined the numerous steps the FDA has taken since 2005 to increase awareness of this issue. The first recommendation advocated by Dr. Harper was “Avoid using GDH-PQQ glucose test strips in healthcare facilities.”

Also during this presentation Dr. Harper made some additional observations which although not directly related to meter accuracy do shed some additional light on the issue. Dr. Harper noted that the FDA receives more than 12,000 Medical Device Reports related to glucose meters each year and that from 2004 to 2008 there were 12,672 serious injuries related to glucose meters. And as we just noted there have been 100 deaths associated with meters from 1992 to 2009. Just by way of comparison according to the FDA MAUDE database in 2009 there were 136 deaths related to insulin pumps.

Putting some additional perspective to this issue are some statistics provided by Alan Cariski, M.D., J.D., FACP, FACE and Mike Flis, members of the AdvaMed BGM Working Group (AdvaMed is the world’s largest association representing manufacturers of medical devices, diagnostic products, and medical information systems.). Dr. Cariski is employed by LifeScan while Mr. Flis is employed by Roche.  During their presentation they noted that more than 6.2 BILLION glucose tests are performed each year in the United States.

Doing some simple math that basically means there is one Medical Device Report per 516,667 tests performed. Taking this simple math even further while it took less than one year for the number of insulin pump associated deaths to reach 100, it took 17 years for deaths related to glucose meters to reach 100 plus 13 of those deaths can be directly linked to the maltose/PQQ issue. It’s equally important to note while there are millions of glucose meters in circulation and even the most aggressive estimates puts the number of insulin pumps at around 400,000 in the United States.

Before we go any further Diabetic Investor in no way wishes to convey the impression that patients should not use insulin pumps or that insulin pump therapy is dangerous. Numerous studies have proven the effectiveness of insulin pump therapy. It is also well known that insulin pump therapy is highly complex and unfortunately sometimes prone to user error.

The point here should be obvious; even if you believe meters are inaccurate the facts tells us this inaccuracy has not had devastating consequences. Based on patient usage these devices can be considered safe. Even in a hospital setting it would be difficult to state unequivocally that meters are unsafe; as noted before this issue can easily be solved by eliminating any GDH-PQQ systems from hospital usage.

On the flip side consider the numerous advancements in glucose meters over the years. It wasn’t that long ago when meters cost more than $300 and tests required huge amounts of blood while taking minutes to deliver test results. Today a patient can walk into almost any pharmacy, receive a FREE meter which needs a small blood sample while delivering a test result in just five seconds. A meter that is likely to come with software so the patient can download readings to their PC and better manage their diabetes. While there is still much to do when it comes to patient education, meter companies do offer educational tools on their web sites.

Based on all available evidence it would be difficult to argue that meters in their present form have harmed patients with diabetes. Diabetic Investor believes there is enough evidence to argue that as imperfect as these meters may be their benefits far outweigh any perceived risks. This does not mean that meters cannot or should not be improved, as Diabetic Investor has noted before who could logically argue that more accurate meters are a bad thing.

The real question is should these accuracy improvements be imposed by the FDA or should we let market forces, which are already at work, move this process. While there are some who would argue market forces will not work, Diabetic Investor is skeptical the FDA can get the job done. All one needs to do is look at how the agency handled the PQQ issue; an issue which could have been simply handled by telling healthcare facilities not to use any PQQ system and by giving these facilities the exact systems which should not be used.  Instead the FDA created an unnecessary panic which has cost some companies millions of dollars.

So just what will come of all this discussion? Diabetic Investor believes the FDA will follow the path of least resistance. Already AdvaMed has issued a statement that says; “AdvaMed member companies share the goal of enhancing meter accuracy standards, and support updates to ISO 15197, the current industry accuracy standard for self-monitoring/home use blood glucose meters. Specifically, we support a tightened accuracy standard in Section 7 of ISO 15197 for self-monitoring/home use meters from the current standard of +20% to +15%, a 25% improvement over the current minimum accuracy.”  Given the support of the industry it’s almost a slam dunk the FDA will go for +/- 15% standard.

Second say goodbye to PQQ, while it may be overkill, there is enough evidence to support a ban of any PQQ system. Here market forces will make this an almost mute ruling as companies which still use PQQ are aggressively moving towards alternate enzymes. That is until the next interference issue comes up and we go through this whole process all over again. Try as they might to regulate a perfect system, the FDA should know by now that there are no absolutes.

Third, hospital systems will be held to a higher standard. The real question is can this higher standard be achieved. As we noted several times the issue here isn’t technology per se rather the complexities of the hospital environment. Besides the interference issues the very nature of the hospital environment make this quest for accuracy problematic.

With these expected changes, the next question that needs to be answered is – will anything really change? The real answer is yes and no. New standards won’t change market share or reverse negative pricing trends. In the consumer market things will stay pretty much as they are today. The simple fact is once everyone is held to the new standard it will no longer be considered a marketing advantage to tout the accuracy of your system. Like alternate site testing and fast test results once a feature is offered by everyone it is no longer unique.

It’s possible that some manufacturers could try and boost market share by advertising the fact their meters exceed the new standards however this is a dubious strategy. This is exactly what happened as blood sample sizes became smaller and test times got faster. Does it really matter all that much to the average consumer if one meter is accurate to a 12% +/- and another is 11% +/-?

The fact is the BGM market has fully transformed into a commodity market where price and controlling costs is about the only thing that really matters.

As we noted previously it is the hospital market which offers the most compelling opportunity as manufacturers will likely be able to command higher price points for more accurate systems. The hospital market also carries with it more favorable reimbursement terms. The biggest threat isn’t improved accuracy rather CGM systems which offer a more favorable productivity argument. There is no question CGM systems are becoming more accurate and given the time it takes a nurse to perform a single point test it’s difficult to make a compelling case against increased CGM usage in a hospital, especially in the highly critical ICU setting.

Hopefully some additional issues will be discussed even though they don’t directly relate to meter accuracy. Issues such as tight glucose control in a hospital setting, the value of CGM technology for insulin using patients and improved use of insulin to combat hyperglycemia. It would also be wonderful if everyone begins to understand that diabetes is an extremely complex disease state and there is no such thing as a silver bullet. Effective control involves more than just an accurate glucose monitor.

More accurate monitors will not make patients stay compliant on their therapy regimen. More accurate meters are meaningless if patients continue to test infrequently or not all. More accurate meters are worthless when the patient has no idea what accurate readings mean or how to use this accurate to more effectively manage their diabetes.  More accurate readings in hospital won’t matter when the hospital staff is not properly educated on how to combat hyperglycemia.

The reality here is the meter is just one tool, which provides one piece of information used by patients and healthcare professionals who are fighting a multifaceted disease state.  Improving the accuracy of the meter is just one step in a long journey. Diabetic Investor strongly supports improved meter accuracy as it is an important step towards the ultimate goal which is improved outcomes. As Lewis Mumford noted; “The final goal of human effort is man’s self-transformation.”

With a cure still years, more likely decades away, any effort that helps patients with diabetes more effectively manage their diabetes is a worthy goal.