aace/ace consensus statement · pdf file522 endocrine practice vol 21 no. 5 may 2015 aace/ace...

522 ENDOCRINE PRACTICE Vol 21 No. 5 May 2015

AACE/ACE Consensus Statement

George Grunberger, MD, FACP, FACE, Chair1; Timothy Bailey, MD, FACP, FACE, ECNU2; Pauline M. Camacho, MD, FACE3;

Daniel Einhorn, MD, FACP, FACE4; Alan J. Garber, MD, PhD, FACE5;Yehuda Handelsman, MD, FACP, FACE, FNLA6; R. Mack Harrell, MD, FACP, FACE, ECNU7;

Howard M. Lando, MD, FACP, FACE8; Bill Law Jr., MD, FACE, FACP9; Jonathan D. Leffert, MD, FACP, FACE, ECNU10; Eric A. Orzeck, MD, FACP, FACE11;

For the Glucose Monitoring Consensus Conference Writing Committee

From the 1Chair; Chairman, Grunberger Diabetes Institute; Clinical Professor, Internal Medicine and Molecular Medicine & Genetics, Wayne State University School of Medicine; Professor, Medicine, Oakland University William Beaumont School of Medicince. 2Director, AMCR Institute; Clinical Associate Professor, USCD School of Medicine. 3Professor of Medicine, Loyola University Medical Center; Director, Loyola University Osteoporosis and Metabolic Bone Disease Center, Maywood, IL. 4Immediate Past President, American College of Endocrinology; Past President, American Association of Clinical Endocrinologists; Medical Director, Scripps Whittier Diabetes Institute; Clinical Professor of Medicine, University of California, San Diego; Associate Editor, Journal of Diabetes; President, Diabetes and Endocrine Associates, La Jolla, CA. 5Professor, Departments of Medicine, Biochemistry, Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX. 6Medical Director & Principal Investigator, Metabolic Institute of America; President Elect, American College of Endocrinology. 7Clinical Assistant Professor, Nova Southeastern University School of Osteopathic Medicine, Davie, FL. 8Clinical Professor of Medicine, George Washington University, Alexandria, VA. 9Professor of Medicine, Chief, Section of Endocrinology, Univeristy of Tennessee Graduate School of Medicine of Knoxville; Past President, American Association of Clinical Endocrinologists; Past President, American College of Endocrinology. 10Managing Partner, North Texas Endocrine Center, Dallas, TX. 11Endocrinology Associates, Houston, TX.Address correspondence to American Association of ClinicalEndocrinologists, 245 Riverside Ave., Suite 200, Jacksonville, FL 32202.E-mail: [email protected]. DOI:10.4158/EP15653.CSTo purchase reprints of this article, please visit: www.aace.com/reprints.Copyright © 2015 AACE

This document represents the official position of the American Association of Clinical Endocrinologists and the AmericanCollege of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician.

AACE/ACE Consensus: Glucose Monitoring, Endocr Pract. 2015;21(No. 5) 523

Abbreviations:AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; A1C = glycated hemoglobin; BGM = blood glucose monitoring; CDC = Centers for Disease Control and Prevention; CGM = continuous glucose monitoring; CMS = Centers for Medicare and Medicaid Services; FDA = Food and Drug Administration; GM = glucose monitoring; MDR = medical device report; SMBG = self-monitoring of blood glucose

EXECUTIVE SUMMARY

The American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) held a Consensus Development Conference on September 28 and 29, 2014, to evaluate clinical science, utility, and access to blood and continuous glucose monitoring (BGM and CGM). Representatives from leading professional societies, government agencies, industry groups, public advocacy organizations, large employers, and healthcare payers met to consider the current state of knowledge regarding glucose monitoring (GM) and its implementa-tion in clinical practice. The following major conclusions were reached at the group discussions:

• GM has clearly upgraded the quality and safety of diabetes care. This is perhaps best appreciated in patients on intensive insulin therapy.

• The need for GM depends, in part, upon the antidiabetic therapies employed in each patient. Therapies using basal-only insulin require less frequent monitoring than those that incorporate prandial and/or basal insulin in the treatment pro-gram. Oral agent therapy may require less mon-itoring than insulin-based therapies; however, the use of sulfonylureas increases the need for GM due to the risks of hypoglycemia with these agents. CGM may be best for patients with type 1 diabetes on complex insulin regimens; however, it may also be useful in a select group of those with type 2 diabetes, especially those with a need for intensive insulin therapy and high risk of hypo-glycemia. Type 2 diabetes CGM candidates may also include patients with long-standing diabetes or severe kidney disease (chronic kidney disease stage 4 or 5).

• Monitoring with glucose oxidase-based systems shows unacceptably high failure rates to meet 2003 ISO standards (17-60%) and 2013 ISO stan-dards (33-85%).

• A proliferation of unbranded and often inac-curate GM systems has occurred in the market-place, driven by mail-order diabetes suppliers

under the Centers for Medicare and Medicaid Services (CMS)-mandated competitive bidding process. Patients typically gain no real savings benefits from unbranded meter use, and safety risks imposed by GM inaccuracies are reported and well known. Switching from branded to unbranded meters and glucose strips is frequently initiated by intermediary profit-driven durable medical equipment (DME) suppliers. Such behav-ior should be prohibited by regulators and should not be tolerated by prescribers. The U.S. Food and Drug Administration (FDA) needs to enforce existing regulations, during both the approval and the postmarketing surveillance processes. It appears that some manufacturers obtain FDA approval for prototype strips and then later modify their production practices, which no longer meet the initially approved quality. The inability of the FDA to remove these previously approved but now inaccurate strips from the market is a flaw in the regulatory system.

• Although CGM has been shown to be beneficial, it has still not been fully accepted as the stan-dard of care in type 1 diabetes by all insurers and prescribers. Many insurance carriers also do not reimburse for adequate quantities of CGM test-ing supplies for patients with either type 1 or 2 diabetes, despite the recent findings of the Centers for Disease Control and Prevention (CDC) show-ing that hypoglycemia from antidiabetic medica-tions is the second most common cause of emer-gency department visits and hospitalizations due to adverse drug reactions in the United States.

• Providing more accurate GM systems and insur-ing that these systems are appropriately used in patients with diabetes mellitus will improve the risk-benefit ratio for diabetes treatment. (Endocr Pract. 2015;21:522-533)

BACKGROUND

Glucose monitoring (GM) is mandatory for mod-ern diabetes care. While GM is essential, it is not ade-quate by itself to promote optimal diabetes management. Appropriate action based on GM data is required to effect change. An educated patient collaborating with healthcare professionals can prevent or delay debilitating, and even deadly, complications of this disease. GM is complex and costly and further complicated by issues of access, reim-bursement, and durable medical equipment (DME) quality. Cost control measures implemented throughout the health-care system in the United States have created a renewed interest in the most efficient and effective uses of blood GM (BGM) and continuous GM (CGM) technology to optimize outcomes for patients with diabetes.

524 AACE/ACE Consensus: Glucose Monitoring, Endocr Pract. 2015;21(No. 5)

Recognizing the need to address these issues and build consensus on GM, the AACE/ACE convened a con-ference to debate these points on September 28 and 29, 2014, at the Hyatt Regency at Capitol Hill in Washington, DC. Participants included members of healthcare associa-tions, insurance companies, government, patient advocacy groups, pharmaceutical and equipment manufacturing companies, healthcare systems, physicians, educators, and allied healthcare professionals.

Specifically, 4 questions were asked:

1. Which data support GM (as distinct from glycemic control) as a means to prevent diabetic macro- and microvascular complications?a) Does the frequency of GM correlate with better

outcomes?b) Which patients benefit most from structured GM? c) Do glucose strip and CGM accuracies correlate

with better outcomes? 2. Should the U.S. Food and Drug Administration (FDA)

improve postapproval surveillance of glucose strip, glucose meter, and CGM quality?a) Does substandard GM technology harm patients?

If so, which data support such a claim? Are all manufacturers required to report this data to the FDA?

b) What is the current state of affairs at the FDA in postmarketing meter and CGM surveillance?

c) What enforcement options are available to the FDA, and how are they implemented?

3. Do current private insurance and Medicare policies bal-ance the need to provide patient access to high-quality care and effective GM and, if not, what policy changes are needed with respect to:a) Patient Access to BGM supplies

i. Competitive Bidding Program ii. Limiting glucose strip brand or meter

typeb) Patient access to CGM technology c) Limited or lack of coverage for sensor-augmented

insulin pump therapy and emerging semi-auto-mated CGM/pump combinations

4. What are the most effective ways for the key stake-holders (physicians, allied healthcare professionals, patients, professional associations, educators, inves-tigators, payers, industry, employers, healthcare sys-tems, regulators) to achieve appropriate, evidence-based, cost-effective regulation of GM (BGM and CGM) technology?

METhODS AND SCOPE OF CONFERENCE

The goal of the AACE/ACE Glucose Monitoring Consensus Conference was to develop the evidence base

for a comprehensive regulatory action plan for healthcare insurance providers and to identify points of consensus along with alternative interpretations among diverse con-stituencies representing the major stakeholders in GM in the United States. The intention was to have the broad range of stakeholders jointly examine the evidence from different perspectives. Thus, the conference offered an opportunity for “emergent thinking” and joint discov-ery with a highly diverse set of viewpoints. The organiz-ers viewed this approach as critical since the action plan will ultimately require concerted action and cooperation among stakeholders based on a consensus interpretation of evidence.

The AACE/ACE Glucose Monitoring Consensus Conference pillars and the constituencies that comprise each pillar are listed in Table 1. The Medical, Scientific, Professional, and Educational Societies pillar included professional organizations representing multidisciplinary healthcare professionals participating in the care of patients with diabetes. The Government, Regulatory, Payers, and Employers pillar comprised groups that set policy for healthcare and disease prevention, large employers con-cerned with the adverse health impact of diabetes among their employees, and major payers or healthcare insurance companies. The Industry pillar encompassed pharmaceuti-cal companies developing GM devices and testing strips. The Patient and Lay Organizations pillar included lay and professional organizations advocating for diabetes patients.

Following the Conference, the writing committee developed this consensus statement, based on participant responses to the 4 key questions, presentations of keynote speakers, and open discussions among the pillars.

I. GM AND COMPLICATIONS

Several modern studies have demonstrated the impor-tance of glucose control to reduce both short- and long-term complications. One of the major tools to improve gly-cemic control is GM. With the advancement of technology, many meters are now available that allow SMBG through-out the day. We now have advanced technology that allows CGM. Emergent technology now enables GM to interface with insulin administration. Although experts favor fre-quent GM in most patients with diabetes, many insurance payers, including the CMS, deny appropriate monitoring access due to the cost of possibly an open-ended policy. Understanding the need to form consensus on these issues, participant experts evaluated the available evidence to sup-port GM in people with diabetes.

Consensus participants emphasized that GM is only reasonable if it is actionable. Most major diabetes stud-ies have focused on the long-term outcomes of glucose control, in particular micro- and macrovascular disease. However, an equally important aspect of diabetes care involves prevention of short-term complications, including


Table 1Glucose Monitoring Consensus Conference Pillar Participants

Pillar Pillar ParticipantsMedical, Scientific, Professional, and Educational Societies

Irl B. Hirsch, MD Keynote Speaker University of Washington

David C. Klonoff, MD, FACP, FRCP (Edin), Fellow AIMBEKeynote Speaker

Mills-Peninsula Health Services

Jo Jo Dantone, MS, RDN, LDN, CDE Diabetes Care and Education Practice Group, Academy of Nutrition and Dietetics

Helena Duncan College of American PathologistsMarion Franz, MS, RDN, CDE Academy of Nutrition and Dietetics

Guido Freckmann, MD Institut für Diabetes-Technologie Forschungsund Entwicklungsgesellschaft mbH an der Universität Ulm

Barry Ginsberg, MD, PhD Diabetes Technology ConsultantsLouis C. Haenel IV, DO, FACE, FACOI American Osteopathic AssociationAaron J. Kowalski, PhD JDRF

Betty A. Krauss, RDN, CDE Diabetes Care and Education Practice Group, Academy of Nutrition and Dietetics

David Marrero, PhD Diabetes Translational Research Center, Indiana UniversityMolly McElwee-Malloy, RN, CDE American Association of Diabetes EducatorsGerardo Moreno, MD, MSHS American Geriatrics SocietyJerry Penso, MD, MBA American Medical Group AssociationGary Puckrein, PhD National Minority Quality ForumRobert Ratner, MD, FACP, FACE American Diabetes AssociationDavid Sacks, MB, ChB, FRCPath American Association for Clinical Chemistry Mitchel Scott, PhD Clinical Chemistry, Washington UniversityKrishnaswami Vijayaraghavan, MD, MS, FACP, FACC, FNLA American College of Cardiology

Phyllis Zimmer, MN, FNP, FAANP, FAAN Nurse Practitioner Healthcare FoundationGovernment, Regulatory, Payers, and Employers

Kimberly Jinnett, PhD, MSPH Keynote Speaker Integrated Benefits InstituteCourtney H. Lias, PhD Keynote Speaker

U.S. Food & Drug Administration, Division of Chemistry and Toxicology Devices

Kenneth Snow, MD, MBA Keynote Speaker Aetna

Pamela Allweiss, MD, MPH Centers for Disease Control and Prevention, Division of Diabetes Translation

Guillermo Arreaza, MD National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health

Sanford Cohen, MD United Healthcare

Alberto Gutierrez, PhD U.S. Food & Drug Administration, Division of Chemistry and Toxicology Devices

Todd Prewitt, MD HumanaWilliam Rogers, MD, FACEP Centers for Medicare and Medicaid Services

Industry Chris Arapoff Medtronic DiabetesAlan Cariski, MD, JD, FACP, FACE LifeScan, IncNathan Carrington, PhD Roche Diabetes CareJacob Drapkin J & J Diabetes Solutions CompaniesClaudia Graham, PhD, MPH Dexcom, IncBrian Levy, MD, FACE J & J Diabetes Solutions CompaniesRobert Morin, MD, FACE Bayer HealthCare, LLCDavid Price, MD Dexcom, IncMelissa Dodson Schooley, JD MedtronicSteve Scott Abbott Diabetes CareMark Swinton, MBA Abbott Diabetes CareBruce T. Taylor Roche Diagnostics Diabetes CareRamakrishna Venugopalan, PhD, MBA Animas Corporation, a J&J CompanyDuncan Williams Abbott Diabetes Care

Patient and Lay Organizations Kelly Close Keynote Speaker diatribe.org

Bennet Dunlap, MSHC StripSafelyLarry Ellingson, RPh National Diabetes Volunteer Leadership CouncilManny Hernandez Diabetes Hands FoundationJeff Hitchcock Children with DiabetesCynthia Rice, MPP JDRFLarry Smith National Diabetes Volunteer Leadership Council


hypoglycemia and diabetic ketoacidosis (DKA). Available data support GM, CGM, and advanced technologies to reduce and prevent hypoglycemia. Management plans should be developed by the patient and their diabetes clini-cian to optimize glucose control and should be based on individual patient preferences and lifestyle. Isolated stud-ies have failed to demonstrate value for GM in achieving glucose control due to poor design and a lack of clinical intervention related to results of GM. More recent trials using structured GM coupled with clinical decision-mak-ing demonstrate clear-cut benefits in improving glucose control (1-3).

One of the most commonly used measures to monitor glucose control is glycated hemoglobin (A1c). However, in a large subgroup of people with diabetes, an estimated 15% of A1c values might be misleading. Specifically, cer-tain ethnic groups, people with sickle cell anemia, and patients with severe kidney disease have A1c levels that do not correlate with average glycemia (4). Additionally, in patients with widely variable glucose levels, the A1c will not provide a true picture of detrimental recurrent hypo- and hyperglycemic episodes. For these patients, frequent GM or continuous GM is virtually the only way to assess glucose control over time (5).

FrequencyParticipant experts suggested engaged people with

type 1 diabetes should perform GM at least 8 times daily. The American Diabetes Association recommends that patients on intensive insulin regimens conduct self-moni-toring of blood glucose (SMBG) prior to meals and snacks, occasionally postprandially, at bedtime, prior to exercise, when they suspect low blood glucose, after treating low blood glucose, and prior to critical tasks (e.g., driving) (6). Frequent GM reduces frequency of hypoglycemia. In a study of people with type 1 diabetes, increased fre-quency of GM decreased mean A1c across all age groups (7). Although there was no upper limit to the frequency of daily monitoring that offered the most benefit to A1c control, the effect appears to begin to plateau around 7 to 8 times per day (8).

Epidemiologic observational data indicate that SMBG correlates with decreased diabetes-related complications and with all-cause mortality in people with type 2 diabetes (9). Patients with type 2 diabetes and high hypoglycemia risk such as those on multiple daily injections (MDI) of insulin should have glucose monitored at frequency similar to patients with type 1 diabetes. In addition, people with type 2 diabetes who are treated with medications that can cause hypoglycemia (e.g., basal insulin and sulfonylurea), especially the elderly, are more prone to hypoglycemia and should have more frequent monitoring. Although there is a lack of robust data, the consensus of expert opinion sug-gested GM from 3 to 5 times per day in this population. Because controlled trials in people with type 2 diabetes

managed with lifestyle modification or medications with low risk of hypoglycemia are lacking, participant expert opinion suggested that such patients should monitor glu-cose as clinically indicated, from 1 to 4 times per day. Experts suggested that pregnant, insulin-treated patients should monitor their glucose at least 8 times daily, while those managed with lifestyle modifications or low-hypo-glycemia risk medications need less frequent monitoring, perhaps 4 to 6 times per day. Large, randomized trials are needed to validate these expert clinical opinions. There was considerable discussion about the fre-quency of GM in all patient populations, but the consensus was that clinical usage must be driven by clinician-patient collaborative agreement on the optimal level of GM.

CGMCGM usage has improved clinical diabetes outcomes

by reducing hypoglycemia (1). CGM is recommended in all patients with type 1 diabetes and should be available to all type 2 diabetes on multiple insulin injections, basal insulin, or sulfonylureas. CGM should also be used in all patients who are at risk for hypoglycemia and/or have hypoglycemia unawareness (10).

While studies using CGM in type 2 diabetes are lim-ited, experts in clinical practice realize that it can be useful in identifying and correcting postprandial glycemic excur-sions (11,12). It was the participant expert opinion that intermittent use of CGM (usually 1-2 weeks) in patients with type 2 diabetes might be more effective than daily glucose fasting glucose in guiding the need for medication adjustment or advancing to new medications.

Accuracy The existing data indicate that accuracy of GM cor-relates with increased patient confidence in using GM devices, resulting in better adherence, more confident insulin adjustments, and improved quality of life (13). Recognizing this fact, participants expressed a concern that increased accuracy may affect upfront cost and lead insurers to view accurate GM as cost prohibitive. The par-ticipant experts identified the 2013 ISO standards for accu-racy, precision, and bias as a step in the right direction, with the realization that the standard applied at low glucose levels may need to be more stringent to avoid clinically inappropriate decisions. Participants also noted that values that are far out of range are more problematic than inherent meter bias, as these can affect immediate decision making if confirmatory testing is not performed (14). In particular, the importance of errors in or around the hypoglycemic range was emphasized.

KNOwLEDGE GAPS

More data are needed on the long-term efficacy of fre-quent monitoring and the effect of glucose meters, strips,


and CGM accuracies on outcomes. Participants agreed that much future research is needed on effective and efficient ways to upload, analyze, and visualize glucose data in a standard manner and then effectively use those data to make clinical decisions. Thus, the availability of accurate glucose meters and established ways to effectively use the data to avoid wasting resources are both important factors. Cost is a major issue in GM, particularly as technol-ogy advances. The cost-effectiveness of GM in patients with type 2 diabetes who are managed with lifestyle modi-fication or low-risk medications needs to be investigated. Published studies addressing outcomes related to GM lag far behind ongoing technological advances, and more research is needed. Although there is a dire need to col-lect more data regarding GM accuracy, it would be unethi-cal to conduct large randomized trials using inaccurate meters. Thus, it is hoped that registry-based postmarket-ing data may help answer clinical questions that cannot be addressed in controlled trials.

CONCLUSION

GM is essential to diabetes care, particularly for reduc-ing hypoglycemia, provided that it is performed in a struc-tured fashion and acted upon appropriately. Implementing clinical actions based on data gained during GM is criti-cal for diabetes control. There seems to be a relationship between higher GM frequency and better glycemic control. The consensus of the participant experts calls for wider use of GM and CGM and emphasizes the need for studies that can address efficacy and cost.

II. POSTAPPROVAL SURVEILLANCE AND QUALITY

INTRODUCTION

Shortcomings in the pre- and postmarketing surveil-lance of glucose strip, glucose meter, and CGM quality have been widely recognized. Patients and healthcare pro-fessionals are seeking guidance from the FDA regarding accuracy of testing and meter standards, along with clearer labels to help consumers understand the results. What con-stitutes “substandard” monitoring, however, is not clearly defined. Further, companies producing GM devices are currently permitted to advertise improved clinical out-comes to patients, even if those outcomes have not been demonstrated for their specific technology. Participants described a lack of consistency in the way that FDA post-market surveillance (which relies heavily on self-reporting by manufacturers) is applied across all manufacturers. Another major concern related to the volume of data to be analyzed is that the FDA is operating under significant budgetary restraints.

Importantly, both stand-alone CGM devices and sen-sor-augmented insulin pumps are FDA approved as Class III devices. There are clear differences between Class III (premarket Approval [PMA]) and Class II (Premarket Notification [501K]) devices in terms of FDA notifica-tions, manufacturing quality, audits, and documenta-tion. In addition, Unlike Class II manufacturers, Class III device manufacturers are not permitted to develop generic devices. Given the flooding of the U.S. market with generic devices, Class II BGM device manufacturers require addi-tional FDA efforts to assure quality in the postmarketing arena (15,16). The 2003 ISO standard for blood glucose monitors requires that 95% of blood glucose results be within 15 mg/dL of reference for glucose <75 mg/dL and within 20% of reference for glucose ≥75 mg/dL (17). The 2013 ISO stan-dard requires that 95% of glucose results <100 mg/dL be within 15 mg/dL of reference and within 15% of reference for glucose ≥100 mg/dL (18). However, at least 6 studies evaluating the performance of blood GM devices published between 2010 and 2014 have demonstrated that only 40 to 83% met ISO 2003 standards, and only 14 to 67% met ISO 2013 standards (19-24). Many of the less accurate meters are manufactured outside the U.S. and sold at a lower cost. Because DME providers receive fixed reimbursement from insurers, they are financially incentivized to promote these low-cost meters.

The FDA agrees that glucose meters that do not perform as designed pose a risk to patients. The agency receives at least 30,000 reports/year of cases of patient harm including suspected device-associated deaths, seri-ous injuries, and malfunctions for glucose meters and CGMs (25). Despite a requirement to report data on pos-sible patient harm, some lesser known brands report sig-nificantly less data than the branded multinational manu-facturers. Diabetes Technology Society public meetings have highlighted substantial accuracy issues observed in currently available systems (26). The FDA states that they have tools to effectively ensure that meters and strips per-form within labeled levels, including adverse events reports and intermittent inspections of manufacturing facilities. The FDA also has multiple enforcement options including recalls, seizures, safety alerts, warning letters, injunctions, and civil money penalties. Although the FDA can prevent distribution of underperforming meters, they do not have the ability to desanction previously cleared meters on the market, and there is no formal policy at the CMS for the handling of FDA warning letters.

Among FDA options are collaborating with manu-facturers to improve AE reporting, development of new methods to analyze medical device report (MDR) data, and the drafting of new guidance for manufacturer reporting.


In the long view, intelligent deployment of harmo-nized diabetes registries with device numbers, strip lot codes, glucose download data, and hospital encounters could provide a comprehensive “big data” alternative to the expensive postmarketing field testing of BGM and CGM devices.

KNOwLEDGE GAPS

• The data to support patient harm from errant BGM are inadequate due to lack of reporting and difficulty in accurately attributing responsibility for adverse events to the strip manufacturer, pharmaceutical com-pany, patient error, or disease progression.

• Reporting of adverse events through the MDR mech-anism is erratic and not standardized.

• Information regarding postapproval quality of BGM strips is lacking, particularly data from manufacturers of mail order strips and devices.

CONCLUSIONS

• The FDA is to be commended for their recognition of the need for independent and ongoing pre- and post-marketing testing of BGM devices. Funding for such surveillance could be derived from manufacturer revenues or government programs including registry development subsidies based on a percentage of total strip sales or other methodology.

• The AACE believes that the FDA should rigorously apply existing enforcement options and expeditiously prohibit the sale and marketing of devices that do not meet acceptable quality standards, including product embargo, if necessary.

• The AACE recommends that requirements and report-ing formats for reporting adverse events to the FDA through MDR mechanisms be harmonized and that distribution pathways to insurers be standardized.

• Studies to demonstrate comparative effectiveness should be required and may be facilitated by invest-ment in standardized diabetes data registries.

• Contemporary accuracy standards (e.g., ISO 15197:2013) should be adopted by the FDA and applied to all BGM devices available on the U.S. market to promote accurate SMBG.

• Accuracy results should be part of the product label-ing, and manufacturers should be held to the standard on their labeling.

• More education of patients and healthcare profes-sionals is necessary for optimal use of the MedWatch Reporting System.

III. BALANCING PATIENT ACCESS AND QUALITY OF CARE

Medicare Patient Access to BGM SuppliesThe number of patients with diabetes and their medical

expenses continue to escalate (27). Two studies have shown positive associations between mandated coverage of strips, meters, or services and more SMBG (28,29). Currently, the CMS views all FDA-approved BGM devices to be of equivalent quality based on 1976 standards, despite the fact that technology has improved dramatically over the last 40 years. In January 2014, the FDA issued draft guidance for BGM and SMBG devices to set standards for quality (30,31). Both draft guidance documents outline stricter standards than previously described with tighter glucose accuracy requirements.

Using the Competitive Bidding Program, Medicare restricts patient access to potentially more expensive, improved technology devices and limits choice for patients and healthcare professionals, based primarily on cost (32). This policy may inhibit patient access to clinically indicated SMBG. A report by the Office of the Inspector General described a 22% reduction in Medicare claims for blood glucose strips, implying that patients may no longer be testing blood glucose as often as recommended, and in some instance, stopping testing completing (33).

Balancing cost with access to SMBG is a challenge that is likely to increase in the future as the overall spend-ing on diabetes care increases. A population-level model recently projected that future direct spending on diabetes care is likely to at least double over the next 25 years. Without changes in public and private insurance cover-age, such spending will put our healthcare system and our patients in peril (27).

Over the next quarter century, technologic inno-vation will be instrumental in minimizing glycemia-related hospitalizations and diabetes complication costs. Unfortunately, device manufacturers view the current Competitive Bidding Process as a barrier to innovation. To the extent that GM accuracy is enhanced by new tech-nology, limiting access to innovation may increase patient risk for adverse glycemic events. Additionally, quarterly attestation documentation requirements for patients and healthcare professionals discourage GM utilization and increase the potential for serious health events in patients with diabetes. Clearly, research studies on optimal ways to efficiently document glucose data, along with their review and appropriate action being taken, are urgently needed. Attestations without clinically relevant purpose do not result in improved care and outcomes and only add to healthcare professionals’ frustration.


Patient Access to CGM TechnologyCGM technology is not covered as a benefit under

the current Medicare program because, at present, there is no benefit category for these devices (34). Successful CGM users with type 1 diabetes under commercial insur-ance are categorically denied coverage for this technology upon enrollment in Medicare, despite data that showed improved glycemic control in patients with type 1 diabe-tes mellitus compared to SMBG (35). Hypoglycemia is especially risky in the Medicare population with associ-ated emergency department visits, accidents, seizures, and cardiac events (36). Several prospective studies have shown improved glycemic control with fewer hypoglyce-mic events in patients with type 1 or 2 diabetes using CGM technology (2,12,37-40). In a contradictory meta-analysis by Langendam et al, there was no difference in hypoglyce-mic events between CGM and SMBG, although the over-all number of hypoglycemic events for all groups in the study was quite small (40). The weight of current evidence suggests that arbitrary Medicare/Medicaid denial of cover-age for CGM devices is imprudent in high-risk patients on intensive insulin regimens with a history of hypoglycemic seizures, high cardiac risk, or frequent hospitalizations due to glycemic fluctuations.

Limited or Lack of Coverage for Sensor-Augmented Insulin Pump Therapy

The FDA has approved threshold suspend CGM/insu-lin pump systems. While several private health plans offer coverage, there a few notable exceptions of large payers still debating this issue while patients continue to suffer dangerous hypoglycemic events. A small number of pri-vate health plans have developed language specific to artificial pancreas systems to address continually advanc-ing technology that is essential to patient care. In the Langendam meta-analysis, glycemic control as measured by A1c level was improved with sensor-augmented insulin pump therapy compared to MDI. There were few hypo-glycemic events in this meta-analysis, which prevents con-clusions about the hypoglycemia prevention benefit of the sensor augmented insulin pump technology (40). As with CGM devices, Medicare does not have a benefit category for emerging algorithm-based, feedback loop-closing treat-ment technologies (34).

RECOMMENDATIONS

• Contemporary quality standards for glucose measure-ment need to be incorporated into the BGM competi-tive bidding process. This process should be modified to assure the availability of the highest quality prod-ucts at the best price.

• Diabetes care requires a highly individualized treat-ment plan. As part of this planning, selection of GM technology demands close collaboration between

patients and healthcare professionals. BGM and CGM coverage decisions by payers should place a higher priority on avoidance of long-term complication and hospital costs than on minimizing near-term GM costs. The optimal long-term health needs of the patient are best judged by the treating healthcare professionals.

• Unfettered access to GM technology is not currently provided by many payers. FDA approval of the tech-nology and healthcare professional recommendations should be necessary and sufficient for benefit cover-age. Ongoing randomized controlled trials, compara-tive effectiveness studies, and/or registry follow-up studies should be performed to further elucidate the details of appropriate technology use, including cost-effective approaches to capturing, analyzing, visualiz-ing, and using glucose data to optimize glucose control and quality of life.

IV. COST-EFFECTIVE USAGE OF GM TEChNOLOGY

Participants were in general agreement that the ideal health system would provide just the right amount of GM for a given individual as determined by the individual and their healthcare professional. Unfortunately, the current system creates distortions in which some people who need more monitoring are denied access, while others may be sent supplies in excess of need in the absence of sufficient controls to prevent fraud and abuse. It is not likely that we will have randomized clinical trials to answer the question in the near future, so we must create a consensus based on current data, clinical experience, and expert opinion. Underlying all of these considerations is the recognition of the reality of finite resources and the need to make hard choices among competing interests.

It is extremely important to address diabetes-related processes at the Federal government level because the gov-ernment is the largest payer, and its actions affect every other payer. The sheer number of agencies within the exec-utive branch, each with their own agendas and complex reporting structure, makes it difficult to effect significant change.

An example of a focused response to this challenge is the National Diabetes Clinical Care Commission Act cur-rently under consideration in the House and Senate, which seeks to coordinate actions of agencies related to diabetes and assist them with direction by clinical experts from a sanctioned advisory body (Fig. 1). All stakeholders would benefit from streamlining of regulatory processes involved in access to GM technology. A simple innovation that will ease the current regulatory burden would be a single form for the prescription of GM and documentation of its medi-cal necessity.

One of the most egregious examples of diabetes care distortions occurs when people with type 1 diabetes who


are glycemically stable on CGM are forced to discontinue CGM when they join Medicare, leaving them more vulner-able to hypoglycemia at the stage of life when it is most dangerous. Participants in the consensus conference agreed that Medicare needs to establish a benefit category for CGM and a benefit structure for advanced diabetes tech-nologies to come.

Communicating best practices of GM to both patients with diabetes and those caring for them is challenging. Telemedicine technology to wirelessly transfer glucose data from patients’ meters to care providers has been avail-able for some time. It is also possible to send therapeutic advice to patients based on computerized algorithms or digitized human interpretation of the transmitted glucose data. Such advice could include further guidance on moni-toring and changes to therapy. However, there is currently

no reimbursement mechanism for such technologic inter-action, and the legal status of transmitting computerized advice across state lines is not well defined. There is lim-ited reimbursement for some types of telemedicine, which may include reviewing glucose data, but these programs are still in their infancy and not generally available. With the epidemic increase in diabetes prevalence, a new and more cost-effective approach to disseminate and dispense expert diabetes advice is needed.

In the future, we are hopeful that government-driven funding and informatics protocols can be developed to promote effective use of electronic health record data via large national diabetes registries. Federally mandated tech-nology and strip lot identifiers could then be used to pro-vide informatic links between diabetes technology use and clinically pertinent outcomes. With the implementation of

Fig. 1. The proposed National Diabetes Clinical Care Commission coordinating stakeholders involved in the care of patients living with diabetes and recommending action to U.S. Congress and Secretary of Health and Human Services. AHRQ = Agency for Healthcare Research and Quality; CDC = Centers for Disease Control and Prevention; CMS = Centers for Medicare and Medicaid Services; DOD = Department of Defense; FDA = Food and Drug Administration; HRSA = Health Resources and Services Administration; IHS = Indian Health Service; NIH = National Institutes of Health; VHA = Veterans Health Administration.


effective registries, the strategies to achieve appropriate, evidence-based, cost-effective usage of GM technology should become more apparent.

CONCLUSION

The responses from experts representing government, regulatory, payers, and employers; the pharmaceutical industry; medical, scientific, and professional societies; and patient advocacy and lay organizations were gratify-ing, with participants providing written answers and data to the 4 questions posed prior to the consensus conference. They had all been provided with the summaries of these materials in advance. This strategy enhanced the quality of open discussions during the conference, and the format offered a unique opportunity for representatives from a broad continuum of patient care fields to discuss different perspectives and form consensus. This conference proved to be a valuable forum for promoting diabetes patient care improvements in future iterations.

The consensus conference provided opportunities to review state-of-the-art GM technology, highlight missing data, and problem-solve among groups with varied, and sometimes competing, perspectives but with the common motivation of improving diabetes patient care. Published guidelines from medical societies constitute an additional source of consensus regarding the best data available at a point in time. Consensus conference-driven education for the public and professionals raises awareness and may gen-erate political will to make improvements in GM regula-tory processes.

ACKNOwLEDGMENT

The Glucose Monitoring Consensus Conference Writing Committee would like to thank Glenn Sebold, director of public/media relations and creative services for the AACE, and Amy Johnson, public and media rela-tions coordinator for the AACE, for their expert assistance in planning and executing the consensus conference and developing the consensus statement following the confer-ence. The Committee would also like to thank the following AACE staff members for their work in planning the con-sensus conference and their assistance at the conference: Mary Green, assistant director for public and corporate communications; Stephanie Spatola, director of meetings and event services; Alysia Tampkin, legislative coordina-tor; and Michael Williams, JD, healthcare policy coordi-nator and Health Insurance Portability and Accountability Act compliance officer.

The Committee acknowledges editorial assistance pro-vided by Renée Kashuba, medical writer. The Committee would like to thank Sara Cintron Milo, director of legisla-tion and government affairs, for her assistance in develop-ing graphics for this consensus statement.

DISCLOSURES

Dr. George Grunberger (chair) reports he has received speaker’s honoraria from Novo Nordisk; Salix Pharmaceuticals, Inc; AstraZeneca; Valeritas, Inc; Janssen Pharmaceuticals, Inc; Merck & Co, Inc; sanofi-aventis U.S. LLC; Takeda Pharmaceutical Company Limited; VIVUS Inc; Eisai Co, Ltd; Boehringer Ingelheim GmbH; and Eli Lilly and Company. He has received research support as an investigator for Eli Lilly and Company; AstraZeneca; Novo Nordisk; and Medtronic, Inc.

Dr. Timothy Bailey reports he has received honoraria as a speaker and consultant from Novo Nordisk and as a consultant from Bayer AG; BD (Becton, Dickinson and Company); Medtronic, Inc; and sanofi-aventis U.S. LLC. He has received research support from Abbott; ACON Laboratories, Inc; Alere; Animas Corporation; Bayer AG; BD (Becton, Dickinson and Company); Cebix; Bristol-Myers Squibb Company; Dexcom, Inc; GlaxoSmithKline; Halozyme Therapeutics; Insulet Corporation; LifeScan, Inc; Eli Lilly and Company; MannKind Corporation; Medtronic, Inc; Merck & Co, Inc; Orexigen Therapeutics, Inc; sanofi-aventis U.S. LLC; and Tandem Diabetes Care.

Dr. Pauline M. Camacho reports she has received research grants as a principal investigator from Eli Lilly and Company and Amgen Inc and honoraria for advisory board participation from Mission Pharmacal Company and Intarcia Therapeutics, Inc.

Dr. Daniel Einhorn reports he has received honoraria as a consultant for Halozyme Therapeutics, Novo Nordisk, Bristol-Myers Squibb Company/AstraZeneca/Amylin Pharmaceuticals, Inc, and Eli Lilly and Company; research grants from sanofi-aventis U.S. LLC, AstraZeneca, Eli Lilly and Company, Takeda Pharmaceutical Company Limited, and MannKind Corporation; research, consulting, and speaking grants from Janssen Pharmaceuticals, Inc; and options as a consultant for GlySens Incorporated and Freedom-Meditech Inc.

Dr. Alan J. Garber reports he has received honoraria from Halozyme Therapuetics as an advisory board mem-ber and from Janssen Pharmaceuticals, Inc as an advisory board member and as speaker. He has received consulting fees from Lexicon Pharmaceuticals, Inc and honoraria and consulting fees from Novo Nordisk (speaker, consultant, and advisory board); Merck & Co, Inc (speaker, consultant, and advisory board); Salix Pharmaceuticals, Inc (speaker and consultant); and VIVUS Inc (speaker, consultant, and advisory board).

Dr. Yehuda Handelsman reports that he has received research grants from Boehringer Ingelheim GmbH; Amgen Inc; Intarcia Therapeutics, Inc; GlaxoSmithKline; Lexicon Pharmaceuticals, Inc; Merck & Co, Inc; Novo Nordisk; sanofi-aventis U.S. LLC; and Takeda Pharmaceutical Company Limited. He has received consultant fees from Amgen Inc; Merck & Co, Inc; sanofi-aventis U.S. LLC; and


Halozyme Therapuetics, as well as consultant and speaker fees from Boehringer Ingelheim GmbH, GlaxoSmithKline, and Novo Nordisk.

Dr. R. Mack Harrell reports no relevant financial rela-tionships with any commercial interests.

Dr. Howard M. Lando reports he has received hono-raria as a speaker for Daiichi-Sankyo Company, Limited; Abbott; Santarus, Inc; and AbbVie Inc and owns stock in Abbott, AbbVie Inc, Pfizer Inc, and Proctor & Gamble.

Dr. Bill Law Jr. reports no relevant financial relation-ships with any commercial interests.

Dr. Jonathan D. Leffert reports he has received a speaker’s honorarium from Abbott Pharmaceuticals and research grants as an investigator for Novo Nordisk; Boehringer Ingelheim GmbH; Eli Lilly and Company; Merck & Co, Inc; Bristol-Myers Squibb Company; and AbbVie Inc.

Dr. Eric A. Orzeck reports no relevant financial rela-tionships with any commercial interests.

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