Good day from Bethesda, Maryland, where the Diabetes Technology Society’s (DTS) latest meeting on blood glucose monitoring wrapped up late Monday. The extremely packed (in terms of the agenda), solutions-oriented day gathered an impressive group of clinical, regulatory, and industry leaders to address the potential for surveillance of blood glucose meters following FDA clearance. After background presentations in the morning that reinforced the goings-on of the last DTS meeting in Washington, “Do Currently Available Blood Glucose Meters Meet Regulatory Standards?” (May 21 – see our report from this meeting at http://close.cx/DTS), the afternoon really got down to alternatives to address the accuracy issues, including Dr. David Klonoff’s presentation on the Diabetes Technology Society’s proposal for a Blood Glucose Monitor Surveillance Program (BGMSP). FDA, industry leaders, patients, and major associations weighed in on the program in three engaging and at times quite contentious panel discussions. Ultimately, the meeting wrapped up with a specific next action step: DTS will move forward with developing the surveillance program, starting with convening an expert steering committee to hammer out specifics.
The goal of DTS’ BGMSP is to address a critical issue – cases where meters are cleared by the FDA, but the analytical accuracy subsequently declines in the post-approval setting. (We also believe there are accuracy issues with low-cost meters that are cleared and the accuracy isn’t as the self-reported data says it is - but this was not the focus of the day.) The program involves the creation of a lab network, coordinated by DTS, which would independently test the accuracy of glucose meters. Meters and strips will be sourced from commercial outlets (very key in our view so that companies producing substandard strips can’t just give the “best” lots), and based on criteria from a yet-to-be-convened steering committee, will regularly be tested for performance. Results will likely be published online and made widely available to the diabetes community. The program is intended to 1) identify low performing meters and alert the FDA that action may need to be taken; and 2) provide patients, healthcare providers, and payers with important product quality information. Said Dr. Klonoff, “We hope and expect systems will pass, but there probably will be some that do not.” Whether or not the program is voluntary or required was open to question; Dr. Klonoff is only interested in a mandatory program. While FDA appeared unsure about whether the program would be required from the start, the agency seems clearly interested in addressing patient concerns, which was a positive. One option, if the program is not mandatory from the start, would be if CMS showed its commitment to accuracy by opting to reimburse only meters and strips that passed a certain accuracy threshold. We aren’t sure whether they would be willing to do this, however, since they are reimbursing strips and meters today that have accuracy concerns (based on warning letters); to boot, the CMS representative effectively said that accuracy was particularly important for some patients (implying type 1s) and much less important for type 2 patients on orals, etc. She did not address type 2s on insulin or those that should be on insulin but opted not to be due to hypoglycemia concerns.
Broadly speaking, we think the surveillance focus is a positive direction and could be a major improvement over the status quo (no independent third-party postmarket testing at all), though there are still plenty of very key unanswered questions, particularly funding. Who will fund this, given that FDA funding is low? It is unclear. BGM accuracy standards have not even been updated following a meeting back in 2010, and we are concerned that if there is not funding for this, funding for a program of this magnitude is a serious issue. CMS would be unlikely to fund this, and given that this comes at a time when CMS has slashed reimbursement to manufacturers, we believe it will be impossible for the low-cost meter companies (who now claim 40% market share) will be able to fund it either. Large companies are already doing significant quality control and so they will have lower costs compared to other companies not yet investing in accuracy; it will be interesting to see if the companies with the lowest “Competitive Bidding” prices will want to increase prices. Other questions also emerge. Who will be on the steering committee and will it be able to agree on program specifics? Will all companies have a representative? Who will the patient representatives be? If a program can be agreed upon (and Dr. Klonoff and his team, to their credit, want to move quickly), how long will it take to implement the program? How long will it take to get the first report on accuracy? Will it be a “pass/fail” as well as more specific information? How long will it take for reimbursement to be tied to results? FDA said that changing the official law will likely take five to six years (in the “best case scenario” outlined in FDA’s presentation) – is this the final word? Presumably CMS can change funding rules much faster – how will CMS respond? To end the meeting, Dr. Klonoff stated quite confidently that “diabetes surveillance for BGMs is going to happen with everybody’s help, and we’ll keep you posted.” We are very impressed with Dr. Klonoff’s ability to bring the entire diabetes ecosystem together around important issues (especially what appears to be a rock solid relationship with the FDA), though there is obviously still a lot to be hammered out.
On the cost front, potential program expenses were estimated afterwards in $6.0 - $8.0 million range; we are still trying to get our arms around the different cost components, but given the $247 billion spent on diabetes each year, we believe that Congress should be lobbied to give more funds to diabetes to reinforce the importance. It was raised that perhaps payers would fund this; given their absence at the meeting, we would not expect they would be eager to participate in funding, especially because for them, and for CMS, they are already used to saying about sub-standard strips “Well, they are FDA approved!” Clearly there is a lot of complexity here. As noted, while not a major focus of the meeting, CMS and competitive bidding came up multiple times throughout the day. The concluding panel discussion featured CMS representative Dr. Elizabeth Koller, who surprised attendees with statements about the low need to target hyperglycemia in the Medicare population; the acceptability of less accurate, lower quality meters in older patients with type 2 diabetes; and the actuarial considerations that “cannot be underestimated.”
Below, you will find our synthesis of the day’s key themes, followed by coverage of the afternoon presentations and panel discussions. If you have questions about the day, please write to us.
Who’s going to pay for this? – Funding was the clear elephant in the room all day. Dr. Klonoff’s 12-point presentation on DTS’ proposed surveillance program did not specifically address cost or funding, though he did answer the question during a subsequent panel – all avenues will be pursued, including the FDA, Congress, industry, philanthropists, private individuals, etc. The irony is profound from our view in targeting industry, since CMS action has resulted in a major hit to revenue and profitability, so the notion that industry would be prepared to fund work that they are already doing seems unlikely. Still, it was very obvious that patients were keen to get a program going that would knock out low-quality strip manufacturers; if CMS would refuse to reimburse such manufacturers who didn’t “pass” a minimum quality threshold, that would be very well received in our view. That said, industry, who was very well represented, appears game to participate. Assuming there will be business-aligned incentives for participating in the program, such as better reimbursement and the potential to make superiority marketing claims for meters that pass the testing, a program like this could serve industry well. There are of course a big range of interim steps that would have to be hammered out, but if funding can be arranged, this could work well in highlighting the “junk” glucose meters and in getting them off the market, which is a major patient priority. Dr. Klonoff did not give an estimate of headcount, startup cost, or ongoing cost of the surveillance program, though as a starting point, we imagine it would be at least a dozen full-time employees and cost several million dollars per year; $6 - $8 million was one estimate we received, though we imagine that will depend largely on structure.
Competitive bidding was not a focus of the meeting, though it was lurking in comments throughout the day. Several industry panelists and patients expressed clear frustration that CMS’ cost-saving program is making it very challenging to keep product quality and innovation high. We were glad to see CMS represented in the day’s concluding panel, though representative Dr. Koller was highly unpopular given multiple polarizing statements. Her comments disturbed many in the room and gave us little confidence that the payer is prioritizing anything above cost. That said, we think there is great potential for CMS to prove they are listening to patients and HCPs by putting in place reimbursement only for strips that pass the accuracy bar – this would reinforce, of course, that CMS cared about at least a minimum level of accuracy, which was in doubt following Dr. Koller’s commentary.
FDA conveyed through a range of comments that it is very interested in a credible surveillance program; we believe this reflects in part the agency’s recent direction to respond to patient priorities. The FDA made clear that it is willing to work with DTS to provide insight into what would make a surveillance program credible and said openly that it would like to hear input from patients, HCPs, and industry on such a program. Overall, the agency seemed quite positive (theoretically) and in favor of DTS’ proposed surveillance program. Dr. Courtney Lias (Director, Division of Chemistry and Toxicology Devices, FDA) did the vast majority of speaking on behalf of the agency, emphasizing the DTS program’s ability to help the FDA identify low-quality BGMs – a view that appeared to align everyone in the room! Dr. Lias highlighted that FDA is quite good at fixing problems when they are identified, and emphasized that surveillance would be very helpful in discovering problems the agency doesn’t know about. She raised a range of important questions about program specifics: 1) Will the program be mandatory or voluntary? 2) will it test strips with patients or in the lab setting? 3) What will the incentives be? Overall, Dr. Lias made it seem like FDA was clearly very open to moving forward with the program. We appreciated her obvious desire to get better products to patients, though we were also reminded of how slowly the agency moves, as the last FDA BGM-related regulatory meeting happened in 2010, and the FDA has still yet to release new accuracy standards.
Industry representatives (Abbott, Bayer, LifeScan, Nova Biomedical, Roche, Sanofi) expressed mixed feelings about the proposed surveillance program – most appeared to be fans in theory, but the potential ramifications were unclear. There was clear consensus that a program of this nature must be done optimally. Industry panelists worried that if the program is not mandatory, only the large companies will participate. That would simply perpetuate the current state of affairs, where big companies invest in quality systems at a significant expense, only to be at a disadvantage when it comes to offering competitively priced products. Many panelists liked the idea of incentives to encourage program participation, such as better reimbursement for their devices or the ability to make superior marketing claims based on the data. Others dove right into the weeds and expressed reservations about what reference method to use, how to standardize sample collection, etc. These details will clearly be major points of focus in the steering committee. An additional worry voiced by some panelists was what would happen to perfectly good meters that fail testing by chance.
Key diabetes associations in attendance – AADE, ADA, EASD, and JDRF – spoke favorably of DTS’ surveillance program. Drs. Jane Seley (AADE), Robert Ratner (ADA), and Aaron Kowalski (JDRF) did not have as much time to speak during the day’s concluding 12-member panel, since much of the discussion veered towards competitive bidding. However, many spoke positively about the program’s theoretical potential to bring more accurate strips to patients. Dr. Seley in particular highlighted the importance of funding, as did multiple patient advocates. We valued hearing from Dr. Andrew Boulton (EASD), who voiced his hope that this model could be brought to Europe, where the system is “woefully inadequate,” in his words. In line with his fellow panelists, he stated, “[The program] protects the safety of the patient, and that’s number one.”
During panel discussions, patients voiced clear desire for accurate strips and for sub-standard strips to be removed from the market and they pressed the FDA and CMS on these fronts. Ms. Christel Aprigliano (Diabetes Advocates) expressed frustration that while Prodigy Diabetes Care had received warning letters, the company’s products were still on the market. FDA’s Dr. Courtney Lias sympathized with the view, though also made it clear that the FDA has a public relations problem – what’s communicated with the public isn’t always the full story, she said. Unfortunately, she would not go into specifics in the case of Prodigy, despite subsequent attempts from several questioners, though Dr. Lias noted that the FDA is doing its job and correcting the problem. Meanwhile, patient advocate Mr. Bennet Dunlap highlighted the FDA’s comprehensive and impressive oversight of the food industry – in a particularly dramatic example, the agency tracked down 21 recalled candy bars from New Zealand! [Details at http://blogs.fda.gov/fdavoice/index.php/2013/09/fda-systems-recognition-ensuring-imported-foods-are-safe/] He made a very compelling case for why accurate strips truly matter (will his two type 1 children wake up the next morning?), which was greeted by nods and enthusiasm from across the panel.
“The devil in the details” was the most commonly uttered phrase we heard all day. Clearly, countless details will need to be hammered out by the steering committee. Dr. Klonoff highlighted just a few, added to by others: the source of blood specimens; how many specimens and lots to test per blood glucose meter; the number of glycemic bins and cutoff levels to use; which reference methods to use (“an important issue”); what type of format to use for reporting results (e.g., pass/fail? Percent of values within 5%/10%/15%/20% of reference?); and what time interval to retest products exists (if any) if there is poor performance.
The length of time to develop and implement this surveillance program was an open and unanswered question. Making the program mandatory will require changing the law, which Dr. Courtney Lias believes will take five or six years “in the best case scenario.” Dr. Klonoff made it clear he is unsupportive of a voluntary program. However, given the time horizon to make it mandatory, we wonder if a voluntary program could be adopted in the interim where all strips would be tested and CMS and other payers would elect not to reimburse sub-standard strips. If a voluntary program had a reimbursement threshold, that would clearly make it far more attractive to various groups. For comparison, A1c standardization took about three years from the initial committee to a rolled out program.
Outside the main scope of the meeting, many spoke to the need for patients to be involved in analytical performance assessments of BGMs. This was critical, since error is so much higher in patients’ hands vs. the laboratory setting. FDA’s Dr. Courtney Lias seemed very receptive to incorporating such a requirement in the premarket setting. Norway’s Dr. Grete Monsen showed how the country has built a robust evaluation system that includes testing the accuracy of meters in the hands of patients. Overall, speakers emphasized that there are user errors that are not captured in clinical trials, as companies tend to focus on aspects of accuracy that are in their control. We think this is an important point that deserves much further discussion, since the lab accuracy means very little if patients are not adequately trained to achieve such accuracy in a real-world setting.
- Executive Highlights
- Detailed Discussion and Commentary
- Session One: Assuring the Availability of Safe and Effective Blood Glucose Test Strips
- Session Two: Surveillance Programs
- Session Three: A Solution
- The Diabetes Technology Society Blood Glucose Monitor Surveillance Program
- FDA Perspective on the Diabetes Technology Society Blood Glucose Monitor Surveillance Program
- Panel Discussion
- Session Four: Industry Perspectives
- Panel Discussion
- Katherine Serrano (Food and Drug Administration, Silver Springs, MD); Steve Scott, (Abbott Diabetes Care, Alameda, CA); David Simmons, MD (Head, Medical and Clinical Affairs, Bayer Diabetes Care); Alan Cariski, MD (Vice President, Worldwide Medical Affairs, and Medical Safety Officer, LifeScan, Milpitas, CA); Jeff DuBois, PhD (Vice President Medical and Scientific Affairs, Nova Biomedical Corp., Waltham, MA); Eric Kolodziej, PhD (Vice President Global Regulatory Affairs, Roche Diagnostics, Indianapolis, IN); Frank Flacke, PhD (Medical Director, Devices, Sanofi, Bridgewater, NJ); Courtney Lias, PhD (Food and Drug Administration, Silver Spring, MD)
- Panel Discussion
- Session Five: Clinical And Laboratory Perspectives
- Panel Discussion
- David Sacks, MD (American Association for Clinical Chemistry, Washington, DC); Jane Seley, DNP, MPH, BC-ADM, CDE (American Association of Diabetes Educators, Chicago, IL); Robert Ratner, MD (American Diabetes Association, Alexandria, VA); Hubert Vesper, PhD (Centers for Disease Control and Prevention, Atlanta, GA); Elizabeth Koller, MD (Centers for Medicare & Medicaid Services, Baltimore, MD); Bennet Dunlap, (Diabetes Online Community, StripSafely); Andrew Boulton, MD (European Association for the Study of Diabetes, Düsseldorf, Germany); Courtney Lias, PhD (Food and Drug Administration, Silver Spring, MD); Aaron Kowalski, PhD (Juvenile Diabetes Research Foundation, New York, NY); Guillermo Arreaza-Rubin, MD, PhD (National Institutes of Health, Bethesda, MD); Gary Puckrein, PhD (National Minority Quality Forum, Washington, DC); Robert Vigersky, MD (The Endocrine Society, Chevy Chase, MD)
- Session Six: Conclusions
Detailed Discussion and Commentary
Session One: Assuring the Availability of Safe and Effective Blood Glucose Test Strips
Before diving into panel discussions, the first session of the day provided a review of the current state of blood glucose accuracy and the problems with meter testing. Dr. Mitchell Scott (Washington University, St Louis, MO) reviewed key sessions from the May 21 Diabetes Technology Society’s meeting on blood glucose meters (for more information on these talks, read our full report at http://www.closeconcerns.com/knowledgebase/r/2e03af3f); one very important point that emerged (and reminded us of this meeting’s urgency) is that there are many FDA approved meters that do not meet the new ISO requirements. Since these meters are “FDA approved,” we’d also note that they can be put forward by the suppliers chosen in competitive bidding, and patients and providers often have little knowledge or recourse. Dr. Boris Kovatchev (University of Virginia, Charlottesville, VA) used model simulations to quantify the impact of poorly performing blood glucose monitors, noting that the more inaccurate a meter is, the bigger the problem, especially with hypoglycemia. His most striking slide showed how the probability of post-meal hypoglycemia is 1.5 times higher when 20% of meter values fall outside ISO 2013 standards. We were pleased that Dr. Kovatchev emphasized this point, however, we are disappointed that anyone had to make what we believe is such an intuitive association. Finally, Dr. Jan Krouwer (Krouwer Consulting, Sherborn, MA) spoke on the factors affecting postmarket performance of blood glucose meters, highlighting that the way we currently approach performance analysis does not reflect real life circumstances. He pointed out that these trials only test the first few lots of strips, a big limitation since later lots are those that affect patients. This point came up again throughout the day and was clearly a source of concern for many audience members.
Session Two: Surveillance Programs
The second session of the day focused on A1c standardization, cholesterol testing, the steroid hormone surveillance program, and blood glucose meter testing in Norway. All the presentations had a common theme: standardization and surveillance improve device performance and reduce variability in a variety of fields. The structure of these programs was generally similar, revolving around a central body coordinating the process and (if applicable) sending out samples for manufacturers or labs to test. Manufacturers were engaged in the standardization and monitoring programs, offering a key lesson for the blood glucose meter program being proposed by DTS – industry must be involved from the get-go.
In the case of steroid hormones, standardization was highly cost-effective. A cost benefit analysis from the CDC’s program showed a $338 million benefit vs. a $1.7 million cost (at a conservative estimate of $50,000/life). Said speaker Dr. Eric Sampson, very convincingly, “There is a compelling public health reason to standardize.”
Session Three: A Solution
The Diabetes Technology Society Blood Glucose Monitor Surveillance Program
David Klonoff, MD (University of California at San Francisco, San Francisco, CA)
In one of the most anticipated presentation of the day, Dr. David Klonoff presented the Diabetes Technology Society’s (DTS) proposal for a postmarketing blood glucose monitor surveillance program (BGMSP). He outlined its design, which centers around a network of independent testing laboratories. These labs would test the accuracy and performance of blood glucose meters on an ongoing basis. The BGMs would be sourced from commercial outlets (e.g., CVS, Walgreens) and distributed by a central administrative office. The program would then publicize the meter data on a website in an effort to: 1) provide an independent assessment of whether cleared BGMs perform according to FDA accepted standards; 2) deliver performance verification information to FDA to assist with surveillance and help uncover problems; and 3) to generate information that can assist product selection by patients, HCPs, and payers. Dr. Klonoff’s broad overview gave a valuable overview of the program’s skeleton, though also made it clear that a number of very specific questions (e.g., What reference method to use? How to obtain samples?) will need to be answered by an expert steering committee (the next step in the process). He concluded his presentation emphatically, “The best time to create the BGMSP is now.” His talk did not address how the program would be funded, though in Q&A, he made it clear that all potential sources will be solicited (e.g., FDA, Congress, industry, foundations, private funders, etc.). In Q&A, Dr. Klonoff also emphasized that he wants a mandatory program – he “has no interest” in a voluntary surveillance effort.
Marketed BGMs might not perform to the FDA standards for which they were initially cleared. Dr. Klonoff emphasized that this was a key takeaway from the May 25 meeting – academicians, clinicians, scientists, industry, patients, and FDA all concluded that there is most definitely a problem. All also agreed that inaccurate readings can lead to risky, dangerous outcomes. For our complete coverage of that meeting, see http://close.cx/DTS.
DTS’ Blood Glucose Monitoring Surveillance Program (BGMSP) will provide an independent assessment of whether cleared BGMs perform according to FDA accepted standards. The program will also deliver valuable performance verification information to the FDA, which will assist the agency with uncovering quality problems and monitoring quality over time. Last, the BGMSP will generate information that can assist product selection by patients, HCPs, and payers.
The surveillance program will establish and oversee a network of laboratories that will test the analytical performance of currently marketed BGMs. DTS will furnish labor, facilities, and equipment for creating and maintaining the quality control program. The program’s central administrative center (see below) will buy blood glucose meters from retail sources and distribute them to the network of labs. The labs will then test the meters to yet-to-be-defined specifications (these need to be worked out by the steering committee; specifications may or may not be the same criteria use for approving the devices).
The network labs will be based inside and outside the US and will use a reference method calibrated by materials traceable to a higher metrological order of reference. Labs will maintain certification for any of their glucose reference methods. For analysis, bins will be created via glycolysis spiking for testing across the physiological range (Dr. Barry Ginsburg took issue with this approach during Q&A, as it creates problems with oxygen). Multiple lots of strips will be tested if possible. A data management processes will also be established.
Dr. Klonoff outlined several staffing needs for the program: a steering committee of experts, a central coordinator, administrative staff, data management staff, and network lab staff. Dr. Klonoff did not give an estimate of headcount, startup cost, or ongoing cost, though we imagine it would be upwards of 10-20 people and several million dollars per year.
The program’s steering committee will play a key role in providing expert direction for initiating and implementing the BGMSP. The committee will include a broad array of experts in blood glucose monitoring – individuals with backgrounds in clinical chemistry, clinical medicine, industry representatives, FDA, and others. Dr. Klonoff envisions it as “mostly US experts,” though the committee will have some international representatives. On an ongoing basis, the steering committee will review the policies, protocols, and reports submitted by the network labs.
The steering committee and the FDA will need to decide on several specific questions: the source of blood specimens (e.g., capillary, whole blood); how many specimens and lots to test per blood glucose meter; the number of glycemic bins and cutoff levels to use (ISO recommendations?); which reference methods to use (“an important issue”); what type of format to use for reporting results (pass/fail? Percent of values within 5%/10%/15%/20% of reference?); and what time interval to retest products if there is poor performance. Said Dr. Klonoff on the latter, “We hope and expect systems will pass, but there probably will be some that do not.”
An administrative center will implement the BGMSP per the steering committee’s recommendations – this will be a huge job and include: obtaining BGMs from commercial sources and distributing them to network labs; monitoring BGM results from network labs; analyzing data for blood glucose meter performance; coordinating policies with the FDA; issuing statements of performance; maintaining a website with information about the performance of FDA cleared BGMs; oversee a proficiency testing program for BGMSP lab reference instruments (i.e., ensure lab instruments are appropriately accurate and calibrated); and working with international organizations to standardize testing and reporting of blood glucose meter systems and accuracy.
Historically, we have heard that buying meters “off the shelf” in mail order is challenging. As we understand it, many of the mail suppliers did not sell their meters for cash. We look forward to better understanding how DTS will accomplish this aspect of the program.
A statement indicating performance results for each blood glucose meter tested will be issued on the BGMSP’s website. The format will be defined by the steering committee. We think this transparency is critical to ensuring the program’s success. It also has the potential to shift consumers to buying the highest performing meters, thereby cutting demand for lower quality products .
“Diabetes Technology Society has demonstrated leadership in standard development.” Dr. Klonoff gave several examples of DTS’ work in this area: CGM performance guidelines with CLSI and the FDA; CGM clinical guidelines (with The Endocrine Society); development of the concept of assisted monitoring of blood glucose (AMBG) with the CDC (later amplified by the FDA); insulin pump safety (co-presented and co-authored two reports with the FDA); personalized medicine for diabetes (with the Unites States Air Force); and development of a new error grid for blood glucose meter surveillance with the FDA, ADA, Endocrine Society, AAMI, and industry.
FDA Perspective on the Diabetes Technology Society Blood Glucose Monitor Surveillance Program
Courtney Lias, PhD (Food and Drug Administration, Silver Spring, MD)
After hearing Dr. David Klonoff’s proposal for DTS’ postmarket blood glucose surveillance program, Dr. Courtney Lias discussed pros and cons of the proposal, focusing on how it would address the key issue: maintaining blood glucose meter accuracy after FDA clearance (“What matters are the lots you make two or three or four years down the line”). Dr. Lias was broadly positive on the program and remarked that surveillance could be another valuable tool in the FDA’s toolbox. She stated, “FDA is very interested in a credible surveillance program. We are willing to work with DTS to provide insight into what would make it credible.” This was very encouraging to hear, as we would have guessed there would be less FDA enthusiasm for the program given the agency’s limited resources. After reviewing the pros and cons of DTS’ surveillance proposal, Dr. Lias also compared enforcement options, remarking that it would take at least five to six years (“best case scenario”) to make a surveillance program mandatory by law – a disappointingly long time for how fast the diabetes technology world is moving and how quickly sweeping moves like competitive bidding can change the landscape. In conclusion, Dr. Lias remarked that she was eager to hear input from and work with health care providers, patients, and industry, since these groups are surrounded by meters everyday.
Dr. Lias highlighted the pros of DTS’ surveillance program proposal: including independent data to monitor performance of meters/strips on the market; potentially identifying sources of error for further investigation; potentially deterring/discouraging detrimental manufacturing design issues; and possibly improving standardization alignment of system performance across manufacturers.
However, there are some possible downsides to the proposed program as well: limited participation may reduce the utility of the program; the inability to identify the source of errors (additional investigations would be necessary); difficulty in overseeing a quality program; high cost; and a small feasible sample size that may not detect outliers.
Dr. Lias also emphasized the need to minimize site bias – she believes this can be done using quality assurance and consistent standards.
Dr. Lias also raised many key question as to how the surveillance program would work:
Would the program be lab or user tested? She noted that it would be interesting to see if it was feasible to do user testing (as is done in Norway), though the program could probably go either way.
Would there be a retest option for meters that fail? The question is how to balance the bias of only retesting meters that fail vs. not retesting those who pass. Would such an approach allow a “second chance win” and not catch meters that initially passed but would fail a second time? We thought this was a fairly academic point, though certainly one worth considering. It’s of course necessary to draw the line somewhere, and we agree that perhaps one test is too few. That said, more testing makes the program more expensive. Given lot-to-lot variability, we would guess industry would favor multiple tests.
How will results be published and formatted? Pass/fail standards may not be as valuable as specifically publishing the results (e.g., X% of values fell within 10%).
What should the sample size be? In FDA’s experience, after about 350-360 samples, there are diminishing returns to more sampling. There is a balance between a tighter confidence interval and testing feasibility.
Would legacy meters be forced to comply with new ISO standards? While the 2013 ISO standards were recently announced, the FDA has not announced new standards of its own (though this was expected after the 2010 meeting) or whether or not it will adopt these ISO standards. It’s an open question as to whether older meters should be subject to new standards. While some would say they strongly believe they should, we can also see scenarios where some patients may not want a new meter and may see it as a “hassle factor”, particularly if they have to pay for it. What would be best would be if all meters were replaced within a given period; payers may not want to pay for this, however. While we don’t think patients who don’t want to change should be forced to change, especially if it causes out of pocket payments for them that they do not want to make, it would be better if patients could get new meters who wanted them. This, of course, is a cost that no one will want to bear – especially for patients whose strip funding has been cut 70%. We would assume with a long lead-in period like 36 months, the insurance companies or CMS could just send them a new meter though we also acknowledge that is probably naïve. Some payers expect patients to use meters longer than this. We also know that some meters are already meeting tighter guidelines; these meters, of course, would not have to be replaced, but the hassle factor of figuring out who has what meter and who deserves what won’t be low.
How should strips be sourced? In line with DTS’ proposal, Dr. Lias was in favor of “typical use” sourcing instead of manufacturer-selected lots. You need to “get at what the patient would experience at Walmart or CVS or mail order.”
Should the program be voluntary or mandatory? Mandatory programs, Dr. Lias noted, would require new regulations (rulemaking) or statutory change (through Congress). She highlighted that this process is lengthy – it takes about five or six years for the regulatory process through the FDA. The agency, she noted, has to 1) modify current blood glucose monitor regulations; 2) open the proposed rule for comments; 3) consider these comments; and 4) put the regulation through to the final rule. The other option is voluntary participation. Until the program is established, it is unlikely the FDA would rely solely on this program to take action; however, the agency would use the information as a signal to initiate further action. Many audience members clambered for mandatory involvement in the surveillance program. Dr. Klonoff was particularly vocal on this issue, noting that he “is not interested” in pursuing a voluntary program. We agree that mandatory is the way to go, though we’d assume the length of time means an interim voluntary solution might be needed.
Dr. Lias highlighted her role in diabetes monitoring by noting that 40-45% of her work at the FDA is related in some way to diabetes (e.g., monitoring of blood glucose meters, A1c measurement, continuous glucose monitoring, insulin pumps, artificial pancreas). Within blood glucose meters specifically, Dr. Lias noted the vast amount of data coming in: 25,000-30,000 device reports each year for blood glucose meters! This of course reflects the vast number of people with diabetes and multiple tests per day. Despite the bias that “more is better,” the vast amount of data makes monitoring challenging due to inter-manufacturer differences in reporting and decision-making, as well as loose/inadequate data. For example, what one manufacturer might choose to report as an injury, another might report as a malfunction.
Dr. Lias also noted some of the ways that the FDA is already trying to improve accuracy and reliability of glucose meter systems, including working on premarket guidance for glucose meter accuracy and reliability (due out soon, as we understand it), clarifications for manufacturers on medical device reporting (MDR), participating in the Diabetes Technology Society’s (DTS) error grid project to increase communication and risk assessment, and a potential new tool to increase consistency in risk assessment (to learn more about DTS’ error grid project, please see page 14 of our AADE 2013 report at http://close.cx/AADE2013FullReport).
Robert Vigersky, MD (Walter Reed National Military Medical Center, Bethesda, MD); David Klonoff, MD (University of California at San Francisco, San Francisco, CA); Courtney Lias, PhD (Food and Drug Administration, Silver Spring, MD)
Q: David did a nice job of outlining the 12 parts of the surveillance program. Courtney, your responsibilities are for premarketing approval, marketing approval, and postmarketing surveillance. What is the difference between what you currently do and what he is proposing? I thought the FDA is unlimited in its ability? I’m curious where you have enforced something that’s inaccurate that needs to be removed.
Dr. Lias: We do have the authority to regulate BGMs. We give them marketing clearance. We have authority to enforce the law. If we were to go inspect a manufacturer and find out they are making strips that they knew did not perform as well as they are supposed to, we can issue civil money penalties or criminal penalties. If there is evidence of wrongdoing, there are lots of tools. We have the ability to work with companies on recalls. What we don’t have as a program is an active surveillance program for strips. The actual program would go out and test strips from different manufacturers and see how they’re doing. What I said is we can use that information to figure out if there is enforcement action that needs to be taken.
Q: Have you taken enforcement actions?
Dr. Lias: Yes, we have enforced against blood glucose meter manufacturers. Our enforcement activities are broad.
Catherine Price: I am a journalist, but I am also a patient with type 1 diabetes. Today I am here with a patient perspective. I already think of living with diabetes as trying to steer with a cliff on both sides. Having a test strip that isn’t accurate is like having someone cover your eyes while you’re still driving. It’s really scary steering with a cliff on both sides. Having a test strip that’s not accurate is like having someone covering your eyes. It’s really scary. You have a strip which is CMS approved and you think is safe, but then experts everywhere are telling you that this lot is not interchangeable with another. It is terrifying for patients who don’t know that this is an issue, for patients that don’t know that there is an inaccuracy. My question is: how far out is a voluntary program if everyone is involved and supportive? If test strips are not reimbursed, how would the program work? How would you get quality without reimbursement?
Dr. Klonoff: I did not use the word voluntary at any point during my presentation. The program could be voluntary, or it could be mandatory. I want this program to be mandatory. I might be convinced to do some work on a voluntary program, but that’s not my interest. If there is no way to make this mandatory, then this is probably not something that I want to get involved with. You also asked another question about strips and quality and reimbursement, and I’m not getting into that. My talk is based on quality and safety for patients.
Ms. Christel Aprigliano (Diabetes Advocates): I have blood in the game – I have had type 1 for 30 years. I applaud DTS for having this program. Like Larry, I’m very concerned about enforcement. When we talk about enforcement, Prodigy meters have received warning letters, but they are still actively on the market. People are still using their strips. You can throw money at it with civil penalties. But what will it take to completely remove a meter from the market?
Dr. Lias: I sympathize with the point of view. If problems are being found, and nothing is being done, how will that help? It would take me two hours to explain all of FDA’s enforcement options. I cannot go into the Prodigy example. We make companies correct problems immediately. By the time the warning letter is out there, the problem is usually corrected. We take actions to make sure product is not out there. It’s a public relations problem. It’s not always public facing. If a company is being inspected and making dangerous strips, those are not going to patients. If a company has quality problems that prevent strips from being made, they are not making strips. We don’t have an enforcement problem. Surveillance would be helpful, because it would help discover problems we don’t know about. When we know a problem right now, we’re good at tackling it. The goal is to make our enforcement better. If there is something that we can do to make you feel more at ease, or change the way we’re doing things, we’re happy to work hard and try to make that happen. We want to hear that point of view. But the appearance of not having done anything when a warning letter comes out is an incorrect one.
Dr. Barry Ginsberg (Diabetes Technology Consultants, Wyckoff, NJ): I want to apologize for asking a technical question, however, there are some technical problems with your proposal. One, I don’t like the idea of using glycolysis and spiking because with glycolysis you do two things: you increase the oxygen level, and you decrease the pH. There are a number of meters that are perfectly good but will show badly because of those measures. The other technical point I have is that we are getting to a point where some meters are getting more and more accurate. A sub-5% MARD is not uncommon. A device with 2-3% inaccuracy has trouble serving as the reference if the meter has a 4% inaccuracy. I’m worried we will have to start to use gas chromatography spectrometry.
Dr. Klonoff: I consider those technical questions that should definitely be considered. There will be people on the steering committee whose whole lives will be dedicated to that. Without going through specifics, every times you make a decision, there is a trade off. If you say you are opposed to something and change to something else, you run into another problems,
Comment: You could just use fasting type 1s for your low blood glucose levels.
Dr. Klonoff: You are making good point, but there is a tradeoff. You are absolutely correct that there are issues with this surveillance program proposal that the steering committee will have to address.
Mr. Chris Parkin (President, CG Parkin Communications, Las Vegas, NV): This morning, 1.7 million Americans over age 65 tested their blood glucose and dialed in an insulin dose based on that number. According to Prodigy – and since we’ve already mentioned them, they’re fair game – the company has 40% of the Medicare market. That means 680,000 people got up this morning, tested their blood glucose with a Prodigy meter, and made a determination based on the insulin dose. There is good news and bad news associated with that. These were 680,000 really cheap tests; CMS saved quite a bit of money this morning. The bad news is that the 680,000 were really cheap tests. We really don’t know what the repercussions were. There may have been 10-20% inaccurate results. How many headaches were there due to resulting hypoglycemia? How many were hospitalized? How many people died today as a result of dosing insulin based on inaccurate meter readings? Why is this company continuing to market its products? We know you can question accuracy. I’ve already heard from the general counsel of Prodigy on our data. What we cannot dispute is these people don’t have any process in place for investigating adverse events and for reporting events. And, they haven’t even defined an adverse event. I’m pulling that from FDA letter in February of this year. That’s coming back from when the FDA inspected them in March-April of last year. These people are in direct violation, but they are continuing to market their products. They are marketing to 680,000 people – these are the most vulnerable patients. If Roche or Abbott or LifeScan were to notify the FDA that they were no longer reporting adverse events, what would the FDA do with that? Would they allow them to continue marketing products?
Comment: Can you state your affiliation?
Mr. Park: CG Parkin Communications.
Comment: And a consultant for Roche.
Mr. Parkin: I consult for many companies.
Mr. Manny Hernandez (Diabetes Hands Foundation, Berkeley, CA): There are many of us that don’t have that affiliation that would like to hear that as well.
Dr. Lias: I’m hearing the concern: FDA is not policing companies that are out there. We won’t resolve that today. I hear that loud and clear. I don’t agree that nothing been done, but I’m not at liberty to say. It’s an overstatement to say nothing has been done. When it goes public, most of those things are already corrected or on the way to be doing done. We need surveillance to give us a better tool to find and look for evidence of wrongdoing. Surveillance can give us an extra tool in our arsenal. It’s not the only answer. I hear the point of view that patients want to hear test strips on the market are reliable and safe. I hear that loud and clear. That’s why we’re taking those steps.
Mr. Parkin: There are a number of violations in that letter. Half of them are critical.
Dr. Lias: Reporting is critical. We are taking steps. In our division, we do more direct inspections in the area of blood glucose meters than any of the other type of device that we regulate. Part of that is because we’re concerned. We’re trying to find evidence. We share your concern and we’re working very hard.
Mr. Parkin: There is variability in reporting. It’s not a black and white issue of reporting and not reporting. Are you telling me they are now reporting at a level that is adequate to protect the American public?
Dr. Lias: I don’t want us to get off topic and discuss a single manufacturer. I don’t want to hijack this meeting.
Mr. Parkin: I think postmarketing surveillance is important, but we need to know that the FDA is going to enforce a problem. We have a large percentage of meters that are coming in from countries that don’t have to play by those rules.
Ms. Kelly Close (diaTribe/Close Concerns, San Francisco, CA): Thank you both to Dr. Klonoff and the FDA for having such an open, honest, and direct conversation with patients, for which we were all grateful. I know that the FDA is working to hard in so many facet of diabetes but is also so under-resourced. I am concerned about this and also about how CMS has less money to spend in the diabetes arena. So my question is, how would this surveillance be funded? I understand that this is not the focus of this meeting, but I think it is a fair question from the patient perspective; we are concerned about funding for many reasons, particularly since the FDA has not come back with revised accuracy guidelines from 2010 – presumably the lack of funding is part of the problem.
Dr. Klonoff: Kelly, you asked about funding. Clearly the program has to be funded. We have heard from a number of people today, and we are going to go to all of them. We are going to go to the FDA, and we are going to go industry; we know they are interested. Congress may end up being involved. We will talk to other sources of funding, including individuals and other organizations. If there is an interest in moving from the FDA, industry, different organizations, hospitals… we will be sure to move forward.
Mr. Andy O’Hara (General Counsel, Prodigy Diabetes Care, Charlotte, NC): What the FDA published was the warning letter, as every large manufacturer has seen in its divisions. As stated, Prodigy has been working with the FDA since last May, right after the inspection. We continue to work with the FDA. We expect a meeting in the beginning of October. We talk about devices needing accuracy and precision. Those of you who are experts in the field should remember that we should be accurate and precise in our wording. In the executive highlights from the May 21 meeting, representatives from academia and industry consistently identified low cost meters as the source of devices inaccuracies on the market. That’s an unfair and inaccurate statement. That puts every low-cost meter into the same category. Three Roche funded studies from the lab in Germany found Prodigy meters to be within the current and new ISO standards. Regarding FDA’s comment, we take them seriously and we follow up. A single warning letter does not mean a meter and system should be removed from the market. Regarding postmarket surveillance, there is an issue of selective publication. We must look at the IDT study in 2011. The FDA inspection in 2011 made no 483 observation of Prodigy, while the 2012 inspection did. The Duke study found that the Prodigy Auto-code as well within the FDA range. The point is to remember that there are selective publications that large marketing firms put out. As you say, the publicly facing information is only one piece of the story.
Dr. Lias: What do you think of the surveillance program?
Mr. O’Hara: I think it’s a great idea.
Dr. Klonoff: I would encourage people to get up and cover the idea of a surveillance program. Talk about what you like or don’t like. I don’t think it makes sense to focus on other topics. The focus from this point on should be on the surveillance program. We’ve got to try to get something done by end of day.
Mr. O’Hara: I’m wondering about the issue of funding. You mentioned sources and perhaps independent sources or associations that have a concern. When you consider industry funding, it must be done in a way that doesn’t influence the steering committees and bodies. No one industry player can provide additional funding and create an appearance of a conflict. They pay for testing, but they don’t pay to be able to participate.
Dr. Jonathan Javitt (CEO, Telcare, Bethesda, MD): I am excited to participate in a program as soon as it is available. There are two aspects to postmarket surveillance that are not on the table. Why not have the manufacturers do their own postmarket surveillance in a common way? You could control for the solution test and just have the manufacturers do the ongoing monitoring of their own product. Industry will come together around simple things like that. The other side of that is not only doing surveillance when it comes out of the box. This is the first medical device that deteriorates like a pharmaceutical, but we don’t let patients stick fingers into a pharmaceutical that’s contaminated. Why don’t we examine the open shelf stability of product? It may be the tests were good the day the vial was open but not 10 days later.
A: That is an interesting issue about open shelf stability. I haven’t seen much in the medical literature about this, but it is a concern. I don’t have much to go on. It is an important issue that will be brought up to the steering committee and could be addressed. To address your other point, I had envisioned that the manufactures would not be involved. The manufacturers can do what they want, and notify who they want, but manufacturers are not a part of the program.
Session Four: Industry Perspectives
Questions and Answers
Q: I would like to start out by getting the panelists’ opinions of such a surveillance program that was just described.
Mr. Scott: I have been in the business for 25 years. I work in research and design at Abbott. At Abbott, the quality of our product is at the core of what we do. Our emphasis is on the importance of patients’ getting the right answer when they test their blood glucose. I think the companies in the panel share my passion to produce quality products, I believe these organizations have a process to ensure we get quality products. The problem here today is that we have seen literature that suggests that systems are not meeting quality standards. We consistently see certain systems that fail that, systems that now have up to a 20% portion of the market. Sometimes we see a test that represents premarket notification, and when we test later, it no longer meets that accuracy. Abbott’s position is that we are proud of what we produce, and we have a process to ensure the accuracy o strips. We welcome a process that would ensure this accuracy in the market at all times. The surveillance program is a good option, and we would be willing to participate in that. In fact, we urge timeliness on the matter. However, this surveillance has to be done consistently across the board.
Dr. Simmons: I would echo the comments that we just heard. In the 2010 meeting on accuracy, we heard that accuracy needed to be improved. Bayer responded with a significant R&D investment. We rolled out a new line that improved the accuracy of our products. We brought a level of accuracy that meets the newly defined ISO standards and addresses precision bias and interferents. We have made an immense commitment to R&D. We have published all of our data and the results of our hypothesis-testing studies. Those are peer reviewed. We have made an immense commitment to quality. We test every lot, we retain samples, and we maintain a very vigorous program of customer service and customer response. We can only promise performance when it leaves our hands. Not when it’s in patients’ hands. We have gone a long way to ensuring our product is safe in their hands as well. AdvaMed has come out with a statement about what industry might support. We would strongly endorse a post-marketing surveillance program. If we can overcome the technical and funding issues, and if there is even and fair application, we would endorse it.
Dr. Cariski: I would also like to say that LifeScan has a good quality system, and we do lot testing prior to releasing every lot. We test product; on real patients – 5,000 patients a year in different clinics, and we publish our data. We have a robust postmarket surveillance system. It is ironic that the companies that are least concerned about their performance are the ones at the table here talking about what should be done. LifeScan’s position is that the FDA already has broad regulatory activity. There may be a place for what David [Klonoff] has suggested, but it has to be integrated into a larger program. We need other programs in addition to the postmarket surveillance. As David said himself, the devil is in the details. The last thing I want to say is that I don’t think today is the day to come to a conclusion. I know everyone wants a conclusion as quickly as possible, but I don’t think this is the correct forum. This is the first time we are hearing the proposal, and I would like more times to think about it. I think we should have a committee meet that is made up of experts, FDA members, and patient advocates; this committee would try to work toward a solution that ensures that patients are receiving the safe and effective products to which they are entitled.
Dr. DuBois: I think postmarket surveillance is very important, but how to do it is equally important. There is a challenge to what you’re proposing, Dr. Klonoff. The data that was presented is very good, but we also need to understand the inherent variability and error in the reference methods. You listed a definitive method – isotope dilution of mass spectrometry. There is also the structure of the program and how to accomplish proper assessment of performance – that needs a lot of attention from the manufacturers, clinical chemists, and endocrinologists. We all are concerned about biases in published studies. We now have to disclose whether or not a study is funded. But a product can also be given to PIs to have the freedom to conduct studies. I think that kind of freedom is important when relationships are established with certain KOLs or investigators. In May, lots of people presented from centers in Europe and the US that are paid consultants that conduct these studies. I do understand the concern about industry and biases when studies are paid for by manufacturers. But not all postmarket studies in peer-reviewed journals have that bias. What also needs to be clearly discriminated is between SMBG and hospital BGM. In Gaithersburg in 2010, we had a nice open forum, but so far today I have not heard any of that addressed. How we deal with that through a postmarket surveillance program?
Dr. Kolodziej: Obviously, the surveillance is a key element of larger strategy. I completely agree with how Courtney put it. There is clearly a larger strategy. The surveillance David outlined is a good start. I am of the opinion that this surveillance program has to be mandatory. It is clear that you could get to the point where it is mandatory. I would love to see what the incentives you discussed would be… maybe not being able to be on CMS’ money. I would also like to hear more about what are the other tools in our toolbox that could provide patient safety? We are here to talk about solutions. This surveillance is one solution set we should be embracing. We should also talk about the 5- and 10K processes. The FDA should have standards that we follow. They need to articulate what it is and how industry can get there. The review process should be earlier, and there should be no discrimination on how to do the test. Maybe it should be prescriptive. Whatever the FDA decides, they need to articulate what it is so everyone else will provide them with the correct data. We talk about inspections, and it is an emotional issue. International and US inspections are not the same. The key is not whether or not you do them, but if the quality of the investigation is the same. Is the quality of a US investigator the same as the quality of an international investigator? The answer is clearly no. It is not meaningful to send an FDA investigator who has food expertise into a blood glucose plant. It doesn’t make any sense. I see the solution to this strip quality as a continuum. There needs to be a better process around 5- and 10ks; surveillance is part of the solution. Once you have the continuum, we will deliver. I agree completely with the analysis. The devil is in the details. I would personally like to see us get to the point where postmarket surveillance is mandatory, either by rulemaking or by incentive.
Dr. Flacke: Some of you might be saying, “What is Sanofi doing up here?” We made a decision to go beyond the molecule and to get to integrated and personalized care. We are also linked to BGMs. We partnered with a company that also shares the quality concerns that we have. At Sanofi, we’re a drug manufacturer delivering high quality products – we’re used to being scrutinized. There are some things in the toolbox that go beyond the testing institute. It’s fruitful to do this. I think rather than just discussing it now, it’s maybe a broader step forward that has to be taken to ensure the quality that patients deserve.
Dr. Lias: I have said quite a bit already, so I won’t repeat myself. I appreciate all of you coming up here and being prepared to talk about this issue. I know that’s not easy. I suppose I will start off the discussion. Someone brought up the question of whether the surveillance program would target hospital use or self-monitoring blood glucose (SMBG). I don’t know what David thinks, but what I was thinking about was mainly SMBG. That does not mean you cannot do surveillance in hospitals, but they already have surveillance in hospitals. It is our aim to give the what and how.
Dr. Kolodziej: We are looking forward to it.
Dr. Klonoff: I’ve heard some industry people say, “I think it’s a good idea.” Some are not so sure. Some say that it’s not critical and must be part of a larger package. The final bullet of my final slide, said, “The time to create the BGMSP is now.” Movements have a time. Ideas have a time. I believe that the time for this movement is now. It may be that the community doesn’t want this program. It may be that the disadvantages outweigh the advantages. But to delay is to deny. What I plan to do is get a sense of what the diabetes community thinks. I want to hear from any company that thinks there is something wrong with this program. This is going to be a lot of work. I’m not going to do this work if there is not a reason to do it. I look forward to hearing from people. If the consensus from the community is that this is something we don’t want, then no problem – it’s not going to happen. I don’t see any benefit in delaying. We can work together in making it happen. If everybody says let’s make it happen, remember that’s the beginning of a long road to raise money, go to Congress, etc.
Dr. Simmons: I have a couple of things to clear up. If we believed we had, at this moment, the perfect postmarket surveillance with funding, I don’t think anyone would disagree that now is the time to pursue this program. There are a lot of technical issues that have already been raised, and there are some that still haven’t yet been raised. There are products that have been cleared for market, but then they do not perform as they once did. There are other issues. Will this program assure industry or reward industry with reimbursement? Will it be comparative? Will there be multiple levels of reimbursement? Will it compare meters globally or will it only compare meters in the US? Will it use ISO guidelines? A lot of things will start to kick into play. You need to define these things beyond asking if the products perform as they did when it was cleared.
Dr. Kolodziej: The key is something Dr. Klonoff said earlier. The devil is in the details. What are the ramifications? What will trigger a recall event? That has got to be crystal clear. If participation is voluntary, what are the guidelines? Defining the framework and the ramifications is absolutely critical.
Dr. Lias: Do you have suggestions?
Dr. Kolodziej: If you have a program like this that is voluntary, and if you fail some process, you’re not reimbursable. That eliminates that part of the equation. Or the concern from the compliance standpoint, if I put out a product that doesn’t meet label, I know you’re coming to see me. There’s going to be some heat. Is that the case?
Mr. Scott: Is there a need? It’s not a level playing in the current world. Organizations are putting processes and systems in place to ensure that they have continued quality. That’s why I say I welcome anything that moves towards holding things accountable. I’m very confident that such a program will prove that our systems are operating. We need to do something now, or this problem will continue.
Q: Are we going to pull industry together?
Dr. Klonoff: Industry and the academic community need to come together and start a fundraising initiative. But the way to bring industry together would be to have a steering committee with industry and academia and non-industry and the FDA – and see if we can find solutions. I did use the term “the devil is in the details,” but even though the details are difficult, I believe we can find a certain point that would work for everybody. I’m actually a little surprised about the negativity from the industry today because I’ve heard from other people in industry that this is something they would like to see happen. I’ve heard from patients, academia, and organizations that this is a good idea. But industry is a big part of this. If we have industry, we would be able to bring people together and figure out what would be the use of surveillance, or how many samples we would need. We have brought people together in the past, but maybe we cannot right now. I think it could happen, but if we can’t then there is no reason for this program to exist. There are many different reasons industry might be opposed – from the technical to political side – but I think that the patient community deserves a program like this. My next step is a steering committee.
Dr. Lias: I think that the feedback I’ve heard from industry has been relatively positive.
Dr. Klonoff: I think that we should be moving forward. We should take industry’s views into account. No one at the table will get everything that they want – patients, FDA, or industry. We’ll find some middle ground that will be better than what we have today.
Dr. Simmons: If you think that what I said was negative, I just want to say that we heartily endorse a program. However, it could harm those companies that already invest a lot in postmarket surveillance. A steering committee will address more than postmarket surveillance; whenever you put together a third party, it will do more than you intend it to.
Dr. Klonoff: I want to say to the FDA people, I hope that if this moves forward, you guys at FDA will talk to payers and try to incentivize them to work with this program. For instance, companies could get a favored position for reimbursement if they receive a good report. I’m medical, not a businessperson. Payers are not who I work with. I don’t have a way or talent with talking to payers. People with the FDA might have better contacts. We can look at what they did in Norway – it’s a mandatory program, but if you pass, you get to sell your product.
Dr. Kolodziej: We all want the same thing in the end. We all want the same thing, and there are a number of avenues to use. There have to be clear definitions. If we have that in place, this could be brilliant as part of the larger strategy. We don’t know what the FDA’s larger strategy is, but we’re assuming this is one of those aspects.
Dr. Klonoff: Industry knows payors better than the FDA does. Industry, you must have contacts with the payor community, and I am hoping you will go to payors and say, “if we go through with this postmarket surveillance and show you that our meters work, and those other meters don’t work, you should use our meters.”
Dr. Lias: It is important to bring payors into the discussion. We are happy to talk to people. I think you are overestimating the FDA’s pull. But there are certain people who have certain responsibilities to uphold. I don’t think that we should presume what they can and cannot do. I think it would be more productive to bring them into the discussion. I think finding out if this is possible to tie to reimbursement is important. We need to work with people rather than making assumptions.
Ms. Serrano: Are there incentives for this type of program? Even with the FDA, there are challenges with a mandatory program. There is that possibility, but it’s a long road. I imagine that CMS would have a similar situation. Are there incentives in the mean time that would be intriguing to companies to begin to participate in a voluntary program?
Dr. Lias: Particularly incentives for companies not at this table.
Dr. Cariski: Some individuals have already mentioned that the ramifications of failing have to be clearly spelled out. We also need to spell out the ramifications of non-participation. And is passing vs. non-participation going to be persuasive to a payer? I don’t know. In some instances, CMS is taking the stance that if a product is approved, “that’s good enough for us”. If you don’t participate in the surveillance program, you’ve still got an approved product.
Dr. Kolodziej: Ideally, from my perspective, this program would start as a voluntary program with incentives. We know it takes a long time for a program to become mandatory. The program may start as a sort of requirement for meters in order for them to move forward. The golden star now is “do you have FDA clearance?” but we know based on data that this is not acceptable. I think you could start talking about special control, which could include reporting summary of MDRs. The FDA would have visibility, and you could say to companies, “you only reported x MDRS but put out y strips.” It would be a reality check. There are a number of things that could cascade. If you need to have a surveillance program, and you need to consider a mandatory program, but there have to be definitions because the ramifications could be awful.
Dr. Klonoff: My interest is only in a mandatory program. If it’s voluntary, I’m not going to lead that.
Dr. Lias: What about pass/fail criteria? The NGSP approach vs. simply publishing accuracy results?
Mr. Kolodziej: If the results of this testing get published, how can we use it from a promotional standpoint? Are we allowed to make superiority claims? If they publish the data that says that X meter is superior?
Dr. Lias: It’s an interesting idea. And depending on how the program was run, that might be possible.
Dr. Kolodziej: If certain meters are outperforming others, would the FDA allows us to make a superiority claim based on the data?
Dr. Lias: Depending on how it is run, that is a possibility.
A: The data presented on the A1c program [NGSP] affected all manufacturers. If you look at the timeline David presented, peer pressure would have that happen. People and research centers will know where the quality is.
Dr. Lias: The NGSP and steroid hormone surveillance program peer pressure existed because laboratories were looking to partner with manufacturers. It may be different in our case because there are patients who do not know about the program. How do you have peer pressure if the patients don’t know? There is a portion of patients that are not engaged. There are a large number of patients that are passionate, but some just are not as involved.
Dr. Simmons: I think honesty and transparency are critically important. To pass/fail a large volume of data is reductionist. More information is better. One of the ramifications of the program is that simple clearance for marketing doesn’t address the quality issues. You could have other things as well. For instance, published information about a company’s quality system. You could have an evaluation of not just strips, but what does the customer service look like? What does the company do? We have an interest in transparency – there are high manufacturing, quality, and R&D expenses involved. That’s against decreasing profitability. We would welcome that. That’s why I heartily endorsed the program.
Dr. Klonoff: Here is a question for the FDA: it is easy to understand how this could affect a new product on the market. However, if there is an existing product on the market that may have been approved based on different rules, how would we regulate that? Is this part of the five to six year plan you described?
Dr. Lias: Any rule making would take a long time. If we want special control, we have to create special requirements. If the meter does not meet some of the requirements, then the meter is not allowed to be on the market. This is how special control could actually get at what is legally marketed.
Ms. Serrano: This would affect all meters on the market.
Dr. Lias: Even if they did meet the special control from 2003, or what-have-you, they are no longer allowable.
Mr. Bennet Dunlap (Your Diabetes May Vary; ydmv.net): How could that work?
Dr. Lias: These are class II devices. Class II not completely low risk. They require special controls to mitigate risk. That could mean a whole gamut of things. One is performance standards – you must meet this level of performance. Or you could say that there are labeling statements that you must include. All BGMs would have to do those things to be cleared for marketing. The FDA could choose the postmarketing aspect as a special control. We created a new regulation for A1c tests for the diagnosis of diabetes. One of the special controls is that you must maintain annual certification for NGSP. If they don’t do that, they are no longer legally marketed. Dr. Cariski: If you have a product that was cleared under 2003 ISO guidelines and now there are new ISO guidelines that endorse tighter standards, what will happen to the product that is approved under the old ISO standards but doesn’t meet the newer standards?
Dr. Lias: if we straight up write new regulation, all glucose meters must meet special controls. This is unless we choose to write in a grandfathering of devices currently on market, or unless we allow for a phase in period to give the devices time to meet the new requirements. We have options. If we didn’t do anything like this, all regulations would affect all meters.
Dr. Robert Vigersky (Walter Reed National Military Medical Center, Bethesda, MD): In talking about reporting, what do you do with it and how can that be used for incentivization? Who is the audience? There are at least three. It’s not just payers. It’s also providers who are prescribing these instruments. And it’s the patients themselves. They don’t know that these products may be hurting them. Publicizing the information is not just putting things up on a website. It’s about getting providers, patients, and payers to get the information. At least in the spirit of transformation, we can have that information add deal with it. Very vigorous reporting and publication of this program will be really key. It would fit all of the stakeholder desires.
Dr. Klonoff: I agree.
Dr. Simmons: We’ve just gone from postmarketing surveillance to a broadly available survey of the market. I heartily endorse the program. But I think that echoes my point that there are wider ramifications of the program. Mr. Andy O’Hara (General Counsel, Prodigy Diabetes Care, Charlotte, NC): I have a question about the samples that would be tested by this program. We have heard “typical use samples.” There is potential for a significant impact on the quality of test strips. The question is, to industry, is there an appropriate test of typical sample use? Would we use retail vs. what is released by manufacturers?
Dr. Klonoff: My vision is not that this is a patient-use program. Patient-use has already been taken into account by the FDA. Overtime, products can change, biologically; ingredients might work now but might not work later. That is why we need to do analytical testing. As for patient testing, I don’t understand why patients would operate differently one year vs. two years down the road. I think it would be expensive, but the patient part is not as important as the analytical part.
Mr. O’Hara: Would the test strips be released by manufacturers?
Dr. Lias: I think we need to look at what is most reflective of how a patient would get information.
Ms. Serrano: I would agree, and I would say that stability is part of what you build into your product. You should expect certain changes to affect the product. You should define what those are and distribute the product within a certain amount of time.
Mr. Kolodziej: In the development of these products, we design and release them throughout the life of the label. That’s our commitment when we secure clearance.
Dr. Little: I want to touch on voluntary and mandatory. With NGSP, we have to get participation from the manufacturers because they do the certification and testing. I assumed that you would look at all the products on the market and do the testing yourself. In other words, that has nothing to do with the manufacturer saying, “I want my product tested. I’m going along with that.” My second question is that there will be lots of testing to do. How do you select what to test first? Do you divide up and report all at once? I’m not sure about that. And just a quick comment about manufacturers saying they have better or worse products based on the results. Just looking at our A1c certification data, one has 10% of results passed, meaning 40/40. Another has 37/40. Both are passing grades. I’m not sure you could say that one is necessarily better than another. You have to see if there is a statistically significant difference. There is a risk for misuse in advertising.
Dr. Klonoff: Thank you, Randie. On the sequence of testing, that could be defined arbitrarily by a serial number or month of the year. Regarding reporting and FDA allowing use for superiority, I think the FDA and industry will find some solution there. I’ve heard from industry that this is something they want. I’m hearing concerns it has to be done in the right way. I look forward to hearing those concerns to figure out how to make this work. I would echo what we heard from Dr. Kovatchev showed us this morning. If you have monitors that are so bad that 20% of the data is outside standards, that means there is a 5% risk of hypoglycemia. That’s one in twenty tests. If you are testing three times a day, that’s once per week. That’s shocking. That’s just unacceptable. That’s why we want to do this program – to get those poorly performing products off the market. If there’s a way to make it work, we will. Otherwise, we won’t.
Session Five: Clinical And Laboratory Perspectives
Dr. Sacks: Briefly, I want to give one caveat: I cannot speak on behalf of AACC, because only the president and executive committee can speak on behalf of the group. However, the AACC strongly supports quality lab testing and would support anything that supports patient outcomes in terms of lab testing. I would suspect that that AACC would support, conceptually, the monitoring of glucose meters. I know that the AACC supports NGSP.
Dr. Seley: I represent that AADE. We focus on education, so I’m not really management. We spend a lot of time educating patients on how to use blood glucose meters. However, we also spend a lot of time teaching patients to check their glucose at all. I have concerns about meters that may not be up to par and what that means when a patient gets a result that is not accurate and may take insulin. Also, I am grateful to Dr. Klonoff for organizing this meeting.
Dr. Ratner: The ADA is clearly interested in patients with diabetes and their success in managing their own disease. In order to do that they need accurate and precise devices to make decisions. The question is from where do we draw that accuracy and precision. We need to identify values that will make a difference. We are pleased to be part of Dr. Klonoff’s program that looks at the error grid and looks at what is a meaningful reading. You need to see if the difference will alter what the patient does. The idea is that none of us really cares if the value on the meter reads 31 mg/dl if the true value is 30 mg/dl. What we care about when the value on the meter reads 85 mg/dl and the true value is 55 mg/dl. That may not be a statistical definition, but a clinical definition. We are interested in access. We need to get the meters that patients can use, and not tell them that they have to change to meters that they cannot use. Patients also need to be able to have access to strips. This needs to happen in a longitudinal fashion. It does not end with FDA approval.
Dr. Vesper: The goal of our activities in the clinical field is diagnoses, treatment, and prevention of disease. I think our standardization programs clearly show that there is a benefit to having consistent performance criteria monitored over time.
Dr. Elizabeth Koller: Before I make any comments, what I say may or may not represent what my agency believes. I am an endocrinologist. I think that Medicare serves a specific patient population. As a result, Medicare is concerned about outcomes of diagnostic and therapeutic interventions for its patient populations. When we talk about diabetes in the Medicare population, it’s mostly type 2 diabetes. Medicare has already looked at some of these issues in the past. We did have an advisory committee meeting on glucose meters and glucose control. All of that information is on our website, including slides and transcripts. One question that was asked was whether meters impact glucose control if you are not using insulin. And the answer to that was, “Not really.” [Editors’ Note: We were surprised by this as studies using structured testing (e.g., STeP) and educational programs have shown benefits of SMBG in type 2 diabetes.]
Another question was, “How much does glucose control matter?” That was also addressed at the advisory committee. There is emerging information that type 1 diabetes and type 2 diabetes are very different disorders. [Editor’s Note: The use of the word “emerging” was quite odd to us, given that this documented fact. It was clear over time that hypoglycemia in type 2 patients was a safety concern for Dr. Koller, but not hyperglycemia, given her believe that complications are not caused by hyperglycemia.] Glucose in type 2 diabetes is more of a marker than a mediator. In our patient population, cardiovascular disease is a major killer. Aggressive glucose control does not mitigate cardiovascular disease. Similarly, a major cause of visual disturbance is not retinopathy – it’s macular edema, and that’s not mitigated by glucose control. We had a meeting in 2012 on this particular topic – the slide sets and transcripts are all available online. In the same way, peripheral sensory neuropathy, unlike type 1 diabetes, is not mitigated by glucose. For renal disease in type 2 diabetes, there are multiple causes. It can be microvascular, but it can also be underlying metabolic syndrome: hypertension and macrovascular. Neither of those are mitigated by glucose. What I’m driving at is that the goals and what is needed by our patient population might not represent what other patient populations need. Even for type patients on insulin, they may have endogenous insulin. In addition, there are actuarial considerations for our patient population. This cannot be underestimated. There are different issues with excepted life span and the burden of co-morbid disease. [Editor’s Note: Many in the room later voiced how disturbing they found Dr. Koller’s mention of “actuarial considerations”.]
One of the things that HHS is very concerned about is avoidance of adverse events. One of the things in this initiative is hypoglycemia. It’s been supported by a number of other geriatric groups. The performance of the meter really may be very important in the lower glucose range. It’s less important in the higher range. This is more germane to some patient populations than others. We do want to avoid hypoglycemia. That is a primary goal in terms of management. We do know that hypoglycemia is different in type 1 diabetes and type 2 diabetes – that’s because there is still endogenous insulin and not the same problems with counterregulatory disorders. In type 2 diabetes, hypoglycemia is about one-tenth as common as it is in type 1 diabetes. The issues are somewhat different. And the frequency is different. One also has to really consider what the severity is and what are the clinical implications. If you are looking at values and seeing that hypoglycemia occurs at 80 mg/dl, 50 mg/dl, or 30 mg/dl, this becomes very complicated. When you start talking about values, maybe that hypoglycemia occurs at 80. But then there are a whole lot of events that are really non-events. You create a lot of noise in the system. For events that are a meter value of less than 30 mg/dl and/or requiring third party assistance, those are likely to be true events. It’s a much smaller percentage of events. For that reason, when I reviewed drugs and some of the new insulin analogs, we used that definition: 30 mg/dl on a glucose meter and/or intervention by a third party. That needs to be looked at in terms of how you look into various errors and the precision and accuracy of glucose meters.[Editor’s Note: We feel that this definition of hypoglycemia is too tight and excludes lots of clinical meaningful hypoglycemia.]
Q: Can you comment on the surveillance program?
Dr. Koller: CMS is interested in the safety of patients. The question is does every meter have to meet every the performance standard? In other words, it may be that in our patient population, a big safety concern is hypoglycemia. You want to know what those values mean in the lower range. Glucose control is less important at the upper end of the range. It will be very different if you have type 1 diabetes at age 20 vs. type 2 diabetes. We’re assuming all meters should have the same level of functioning. [Editor’s Note: The comment that glucose control “is less important at the upper end of the range” is flat out wrong in our view. It’s the long-term complications from high glucose levels that drive much of CMS’ spending on diabetes. Moreover, we felt the division between young type 1s and all type 2s was simply absurd – plenty of type 2s are on insulin and have an equally high risk of hypoglycemia as those with type 1 diabetes.]
Mr. Dunlap: I am not a PhD, and I am not a manufacturing representative. I bet they are happy I am not a regulator. I have type 2 diabetes, and I have two kids with type 1 diabetes. We are not seeking perfection, but we are seeking something better. We need FDA to help with this. I know the FDA can use their powers for good. Since August, FDA has issued ~30 recalls, mostly for food. For example, cilantro was recently recalled. I am happy it wasn’t on my nachos. I want that same level of enforcement and safety for my kids and for the millions who use glucose meters. Substandard accuracy can cause serious and sometimes deadly injections of insulin. People with diabetes don’t care if there are inaccurate systems, but they care that the FDA defines inaccuracy. I know that the FDA can do incredible things. The FDA can send out an email notifying the public that there are 21 candy bars that have been somehow tainted. They tracked down each and every one of them. If they need resources to protect my kids, I’m happy to go down and holler and make noise to get that. It is clear from the meeting in May that there is a problem. It is clear that there are meters as unsafe as cilantro and they need to get off the market. Here’s why glucose accuracy matters. How many of you have teenagers? Do you know how hard it is to get them up in the morning? I need to make sure that my kids will get up in the morning. I need to make sure that they won’t die because of the insulin they took the night before. I need to ensure that my kids will get up in the morning. It is clear this is just the first step. This surveillance needs to be mandatory. I want to protect my kids, and I want to protect the hundreds of thousands of other kids with diabetes. And adults need protection, too. However, this is a good first step. We need to make sure that the FDA knows that blood glucose meters are as dangerous cilantro and candy bars. My only additional comment is that there was one group missing from the proposed steering committee: loudmouth patients like me.
Dr. Boulton: With your permission, I will show you a few slides. EASD has membership of over 7,500 people in over 130 countries, and we have annual meetings. Many of you will be in Barcelona later this month. Last time EASD was in Barcelona 15 years ago, UKPDS presented their data. This year in Barcelona, one symposium will be on UKPDS after 15 years, and another one will look at DCCT after 30 years. The time I took over at EASD was when there was a scandal for every medical event. EASD should be involved in safety of devices, and we will also have major symposium on topic at this year’s meeting. In 2012 in Belgium, the European commission brought everyone together to discuss device safety. If you think FDA is bad, you should have seen us at Brussels. We will have another meeting this year, and we will have a third meeting next year. Next year’s meeting, in Dusseldorf, will look at serious questions about the safety of diabetes devices. It will be opportunity to present data on the safety of devices.
Dr. Kowalski: Bob said essentially what we at JDRF feel as well. At this meeting, there is violent agreement about the issue at hand. People with diabetes need accurate, reliable, and precise meters. I commend Courtney and the team at FDA for proactively looking at post-market issues. JDRF, like the ADA and the rest of the room, is anxious to look at all options on the table. We want to explore how we ensure that devices on the market continue to maintain accuracy standards.
Dr. Arreaza-Rubin: I’m a program director at NIDDK/NIH in charge of the diabetes technology program. I want to confirm what Aaron said. We believe this is an important program. I would like to congratulate the FDA and Dr. Klonoff. The concept is something I would personally agree 100% with. I agree with Dr. Klonoff that this is the time to do it. And as we think about development of the artificial pancreas, I think this is important. CGM is calibrated using BGMs. If we want an artificial pancreas that works properly and efficiently, we really need to make sure that these glucose meters really work well.
Dr. Gary Puckrein: I must say the most profound words I heard in Ms. Koller’s presentation about the thinking at CMS was her use of the word “actuarial table” to refer to patients – that’s scary. The fact that CMS would allow patients to be hypoglycemic – there is clearly a profound need to have a conversation about that. It is so shocking that the government thinks that it is ok to have meters that say hyperglycemia is ok because patients will have a heart attack and die anyway. By 2050 over 50% of be minorities will have diabetes. We need to get them under control. It is absolutely stunning. We get variation in monitors between minorities. There is no single population. We are getting variations when patients have the sickle cell trait. If you are putting together a committee, you have to understand the patient population. I didn’t hear anything about the patient population – who are using the strips and how may they vary based on cultural diversity? If you don’t consider the patient population, we will fight you like dogs, especially as we gain more and more biodiversity.
Dr. Vigersky: I’m going to wear my other hat as representative of the Endocrine Society. The Society has over 16,000 members. It’s really an international organization at this point. We are extremely interested in diabetes. Close to 50% of the articles in our journals are related to diabetes or lipid metabolism. The Endocrine Society has taken special care to address diabetes scientifically in publications and meetings. Even though we’re a professional organization, we have a patient arm called the Hormone Health Network that distributes patient information sheets. The organization has become very much part of the diabetes community over the last 10-15 years. I have really pushed the Society to work with the other organizations to work together. We certainly can accomplish much more together than anyone of us can accomplish individually. We are very much impressed by the proposal that Dr. Klonoff put forth. The devil is in the details, but the details do not seem to be insurmountable. We could come to some amicable conclusions fairly easily if we put our minds to it. As an endocrinologist, instead of practicing medicine that is treating people for what has already been happening and playing catch-up all the time, I think the most important thing is practicing preventative medicine. It’s a preventative program. Prevent the adverse events had an effective surveillance programs not been in effect. And ounce of prevention is worth a pound of cure. And this program fits that quite well.
Ms. Serrano: What are your opinions on pass/fail vs. actually publishing the data? What I am curious about is how valuable pass/fail will be compared to publishing the data. What would people use it for, and how would it move us forward?
Ms. Serrano: Special controls will still require rulemaking [Laughter]. So it’s an important part of that process.
Mr. Dunlap: The conversation about the devil in the details is a good conversation to have. We should speak of the devil. In addition to a loud mouth patient on the steering committee, we should also have someone from the payer community on there. The conversation needs to be focused on being penny wise and pound-foolish. We can save money on a strip here or there, but the cost of diabetes is really in ER admissions, particularly in the group over age 65. Insulin is either the number one or number two ADR. Let’s bring the payers in and make the case that this is in everybody’s interest. We are all interested in a better healthcare system. And we need to look at the totality of the process.
Dr. Seley: I want to reinforce that, to me, it doesn’t make a difference how this program is implemented. I am happy if it is pass/fail; all that matters is that we know that the meters and test strips are accurate enough to correctly dose insulin. If reimbursement for test strips is so low that manufacturers make meters that patients cannot afford, the whole thing will blow up. Right now, the price is $10.41 for 50 test strips. There are a lot of companies that make quality meters. I want to know how they can make meters at that low of a rate. I want to look at reimbursement so accurate meters can stay on the market.
Dr. Boulton: In Europe, the system is woefully inadequate. There is no postmarketing evaluation. My hope is that this model could be brought to Europe as well. It protects the safety of the patient, and that’s number one.
Dr. Koller: If you delineate performance qualities to each meter, payors would be able to select the kind of meters that would be appropriate for their patient. There have been questions and allusions to CMS during this meeting. Medicare pays for meters and durable medical equipment (DME). In the past, a lot of DME is considered rentable, but there are also purchase programs. If CMS had information that would be appropriate for their patient populations, they would be able to select device qualities that are required in various programs such as competitive bidding. Without that information, they are not able to make those kinds of decisions. I think until this point of information, there is the assumption that CMS makes decisions based on whether or not a device is cleared by the FDA. However, CMS would potentially be able to determine qualities that they wanted in their meters, and those would be the meters that would be part of the bidding requirements. It would be reversible if meters don’t perform well. This is a more complicated process, and simple pass/fail may not address all of this.
Dr. Vigersky: I would support pass/fail. Taking a lesson from the NGSP, it can evolve over time as the technology improves. The level of pass/fail might progressively ratchet down to something that is acceptable to this room. It might not start that way, but it could progress that way quite quickly. In trying to assess whether or not you should have different kinds of meters for different kinds of diabetes – and this will be coming out in a publication –we worked on a consensus error grid that gave scenarios of both type 1 diabetes and type 2 diabetes patients. Over 200 clinicians weighed in on the criteria for what was a risk. It was same for type 1 and type 2 diabetes. The notion that you would want to cherry pick a meter for a certain patient population is probably not realistic, at least in the clinician’s eyes.
Dr. Lias: In terms of pass/fail vs. publication of data, you could probably do both.
Ms. Serrano: Where I was going with that was from the last session – we talked about incentives. It sounds like there is support for a mandatory program. That is a slow-go; there are legal and regulatory hurdles that will take time. In the mean time, are there soft incentives that your groups can participate in that you can enforce and get this project off the ground?
Dr. Sacks: I think there will be strict criteria that will allow the FDA to pull meters off the market. I think that the companies that make meters and strips will know where the program is going, and they will see what they need to do to make quality strips.
Dr. Seley: Not all meters are created equal. Amongst the members of my organization, I will inform them of what has happened today, and I will tell them what meters we will use. It is important to keep your members informed and to talk to clinicians and patients! Patients need to drive this, as well. I have come to learn that many of my peers have no ideas there are differences in accuracy in meters, and they don’t know that meters that were approved years ago do not have to continue to produce accuracy data. I think that is also important.
Mr. Dunlap: The pass/fail question is a great idea for a program. But it will take time for it to be worked out, be implemented, and have an impact on the market. In the short term, we need to get those products off the market just like we did for cilantro. What was compelling to me was in the Q&A following Dr. Klonoff’s talk at AADE. A diabetes educator was looking for help. She highlighted that all the devices are not good and wanted to know how to choose between unacceptable and simply awful. She was specifically talking about the vulnerable population with limited eyesight – they were using talking meters. She was distraught that those particular meters were very poor performing. I am tremendously supportive of Dr. Klonoff’s proposal, but we need to do something soon.
Dr. Koller: I would like to make another comment with respect to meters as currently available. It has been pointed out that there have been meter problems and recalls. Although I don’t deal with this directly, I interact with people who do. Since meters are considered DME, if the meter is purchased, then the meter belongs to that person for five years and cannot be replaced if it is lost or stolen. However, there are significant protections in place for people with meters. Suppliers must furnish items approved by the FDA as safe and effective. One might argue that this bar not satisfactory. All suppliers must be in compliance with the Medicare safety standards. If a meter is purchased through Medicare, that supplier is responsible for replacing it. That includes recalls. I think there is a platform available there that existed prior to competitive bidding and still exists. Medicare is concerned with the quality of meters and has some system that if the systems Medicare beneficiaries receive do not work, they will be replaced.
Dr. Klonoff: Does the problem with the meter have to stem from a recall? Or could it just be that the individual meter has a problem?
Dr. Koller: I am not sure at what level of nonfunctioning the meter must be at in order for the supplier to replace it. I would have to talk to my people at CMS.
Mr. Puckrein: On the hypoglycemia side, the events that we are usually talking about acute events that require third party assistance. But repeated hypoglycemia events do damage as well. To say that in meters on the market, we don’t see elevations in acute events, we need to pay a lot more attention to those other hypoglycemia events. Hypoglycemia events are a really bad thing in any circumstance. If the meter is contributing to that, whether a patient is on insulin or an oral agent – I think all of that needs to be taken into consideration as we’re looking into these meters. When you look at African Americans in Medicare, 65% of them are dead before the age of 65. If you use an actuarial table on an African American with diabetes, they should have been dead before got into Medicare. An African American male on Medicare is an unusual circumstance. When the system locks in on actuarial tables and what tables to use, it gets very, very scary and inappropriate.
Manny Hernandez (Diabetes Hands Foundation, Berkley, CA): First of all, thank you so much, Gary. I commend you for speaking up about that. I should say that I’m still in shock about your remarks, Dr. Koller, for two reasons. One, for what Gary was pointing out. Two, maybe you didn’t mean to make it sound like there are two types of citizens with diabetes; type 1 and type 2. There are 85% of type 1 patients that are no longer children. These patients will very soon start entering the Medicare system. Are you telling me that what I’m going to find is a second-class product that will likely ensure that I will dose incorrectly?
Dr. Koller: Medicare is very concerned with patient outcomes for everyone. But sometimes you need to know where the patient is in order to deliver the best kind of care. The best kind of care might be different based on biological age or the comorbid disease. This is the key to personalized medicine. The kind of therapeutic interventions that are appropriate at age 15 or 40 or 65 or 90 are not the same. Medicare would like the best treatment at the place where the patient is. I think that Medicare is really interested in avoiding treatments that would potentially cause adverse effects, such as hypoglycemia, when and where this cost may outweigh the benefits. There may be more and more concern about avoiding adverse events such as hypoglycemia when it is less clear that there will be benefits from this intensive glucose control. There may be other benefits that other therapeutic approaches could provide that might be more appropriate.
Q: As a fellow person with type 1 diabetes, I have an A1c of 6.1%. I hate to think that one day, Medicare can decide what level of control I will be able to achieve. Why are there no payers in the room? CMS also affects private insurers…
Dr. Klonoff: It’s hard to get payers to come to this table. We have attempted and will continue to attempt it.
Comment: It is impossible to have one set of standards for patients with type 1 diabetes and a different set for patients with type 2 diabetes. Maybe you would like a standard for patients over 65 and one for patients younger than 65. Are we going to have one set for hypoglycemia and one set for hyperglycemia? What you need is one system to evaluate glucose meters using the best available standards. I think it would be premature to subdivide.
Session Six: Conclusions
Where Do We Go From Here?
Courtney Lias, PhD (Food and Drug Administration, Silver Spring, MD)
Dr. Lias’ final address to the audience summarized main points of the meeting and reassured the group that she had heard their concerns. After hearing the audience’s frustration over blood glucose meter regulation throughout the day, Dr. Lias seized the opportunity to demonstrate that she is dedicated to making a difference in the lives of people with diabetes. In applauding Dr. Klonoff’s efforts, she remarked that “a successful surveillance program would be a really valuable way for FDA to get more information.” She thanked the crowd for sharing thoughts, opinions, and insights, and summarized the meeting in three main points: 1) industry has positive responses to a proposed surveillance program; 2) there is a strong interest in it being a mandatory program; and 3) it is important to engage payers in this process. She also highlighted one major takeaway: patients are concerned about the quality of the products on the market. We agree that this was a major takeaway of this meeting, and we are very glad to see the FDA concerned about patient outcomes.
“From the patient community, it’s loud and clear to me that there is concern about the quality of some of the products that patients are being given access to…There is a fear that there are life and death consequences. I believe that. For someone with diabetes with a glucose of 50 mg/dl when the meter says 90 mg/dl – that is a problem. It motivates us every day to put a lot of our resources into those problems.” We were pleased to hear her understand the dire consequences of poor blood glucose monitors, and we hope that having the FDA hear patient, industry, and clinician concerns at this meeting will improve and increase the role of the FDA in ensuring safe devices for patients with diabetes.
Dr. Lias also acknowledged hearing about FDA’s “PR problem,” whereby many patients are concerned that the agency is not enforcing regulations against some companies. She repeatedly noted in Q&A that the public perception is often not true and not the full story of FDA’s dealings with companies in violation.
David Klonoff, MD (UCSF, San Francisco, CA)
Dr. David Klonoff closed the DTS meeting with his main conclusions from the day. He felt that the meeting’s discussion reinforced the need for a blood glucose monitor surveillance program, a problem that was first described at the May 25 meeting. Dr. Klonoff detected clear interest from the community in making such a program happen, though he also heard mixed feelings from many of the industry representatives. While such a program “won’t be 100% perfect for everybody,” Dr. Klonoff also believes that the diabetes community “will regret” not putting it in place. He made it abundantly clear that we need to act now, as there is a clear window of opportunity and interest from all the different communities (“The window does not stay open indefinitely, and diabetes does not go away”). Key next steps include: 1) convening the steering committee “soon”; 2) consulting with the FDA; and 3) seeking funding. Dr. Klonoff invited anyone interested in helping to contact him at firstname.lastname@example.org. He ended his talk as he began it – complementing the FDA on its willingness to talk openly, to move quickly on this front, and to throw around ideas.
DTS will be forming a steering committee and meeting soon. This committee will set rules and include different groups and industry (“Industry needs to feel comfortable with this”). While many in the audience called for payer representation, Dr. Klonoff was honest in stating that DTS doesn’t have good contacts with payers. CMS will be invited to participate.
Dr. Klonoff and colleagues will also be consulting with the FDA to organize the program and steering committee. It will be critical that the program has scientific and regulatory rigor.
DTS will be seeking funding for the BGMSP through “various channels.” (Dr. Klonoff joked, “There is a hat by the door. I hope you will be generous.”) Funding opportunities mentioned included talking to the FDA (“there maybe money”), industry, Congress (“if we have to”), and philanthropists. Said Dr. Klonoff, “I think this is important. I certainly heard from patients that this is important. Hopefully someone out there will be interested in helping.”
“It’s unheard of for a government agency to starting moving so quickly.” At the May 25 meeting, the FDA did not seem to have any plans in the works to create a surveillance program. Dr. Klonoff complemented the FDA on moving so fast to make this meeting happen in just a few months, a particularly speedy timeline for a government agency. He also found the day’s regulatory-diabetes community dynamic quite notable: “Who would think we’d be in a place where everyone was demanding the same thing and FDA is agreeing?”
-- by Adam Brown, Hannah Martin, and Kelly Close