Benchmarking the Cost-Effectiveness of Interventions Delaying Diabetes: A Simulation Study Based on NAVIGATOR Data.

OBJECTIVE: To estimate using the UK Prospective Diabetes Study Outcomes Model Version 2 (UKPDS-OM2) the impact of delaying type 2 diabetes onset on costs and quality-adjusted life expectancy using trial participants who developed diabetes in the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) study. RESEARCH DESIGN AND METHODS: We simulated the impact of delaying diabetes onset by 1-9 years, utilizing data from the 3,058 of 9,306 NAVIGATOR trial participants who developed type 2 diabetes. Costs and utility weights associated with diabetes and diabetes-related complications were obtained for the U.S. and U.K. settings, with costs expressed in 2017 values. We estimated discounted lifetime costs and quality-adjusted life years (QALYs) with 95% CIs. RESULTS: Gains in QALYs increased from 0.02 (U.S. setting, 95% CI 0.01, 0.03) to 0.15 (U.S. setting, 95% CI 0.10, 0.21) as the imposed time to diabetes onset was increased from 1 to 9 years, respectively. Savings in complication costs increased from $1,388 (95% CI $1,092, $1,669) for a 1-year delay to $8,437 (95% CI $6,611, $10,197) for a delay of 9 years. Interventions costing up to $567-$2,680 and £201-£947 per year would be cost-effective at $100,000 per QALY and £20,000 per QALY thresholds in the U.S. and U.K., respectively, as the modeled delay in diabetes onset was increased from 1 to 9 years. CONCLUSIONS: Simulating a hypothetical diabetes-delaying intervention provides guidance concerning the maximum cost and minimum delay in diabetes onset needed to be cost-effective. These results can inform the ongoing debate about diabetes prevention strategies and the design of future intervention studies.

Selecting the optimal risk threshold of diabetes risk scores to identify high-risk individuals for diabetes prevention: a cost-effectiveness analysis.

AIMS: Although risk scores to predict type 2 diabetes exist, cost-effectiveness of risk thresholds to target prevention interventions are unknown. We applied cost-effectiveness analysis to identify optimal thresholds of predicted risk to target a low-cost community-based intervention in the USA. METHODS: We used a validated Markov-based type 2 diabetes simulation model to evaluate the lifetime cost-effectiveness of alternative thresholds of diabetes risk. Population characteristics for the model were obtained from NHANES 2001-2004 and incidence rates and performance of two noninvasive diabetes risk scores (German diabetes risk score, GDRS, and ARIC 2009 score) were determined in the ARIC and Cardiovascular Health Study (CHS). Incremental cost-effectiveness ratios (ICERs) were calculated for increasing risk score thresholds. Two scenarios were assumed: 1-stage (risk score only) and 2-stage (risk score plus fasting plasma glucose (FPG) test (threshold 100 mg/dl) in the high-risk group). RESULTS: In ARIC and CHS combined, the area under the receiver operating characteristic curve for the GDRS and the ARIC 2009 score were 0.691 (0.677-0.704) and 0.720 (0.707-0.732), respectively. The optimal threshold of predicted diabetes risk (ICER < $50,000/QALY gained in case of intervention in those above the threshold) was 7% for the GDRS and 9% for the ARIC 2009 score. In the 2-stage scenario, ICERs for all cutoffs ≥ 5% were below $50,000/QALY gained. CONCLUSIONS: Intervening in those with ≥ 7% diabetes risk based on the GDRS or ≥ 9% on the ARIC 2009 score would be cost-effective. A risk score threshold ≥ 5% together with elevated FPG would also allow targeting interventions cost-effectively.

Screening for type 2 diabetes: a short report for the National Screening Committee.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) has been increasing, owing to increases in overweight and obesity, decreasing physical activity and the changing demographic structure of the population. People can develop T2DM without symptoms and up to 20% may be undiagnosed. They may have diabetic complications, such as retinopathy, by the time they are diagnosed, or may suffer a heart attack, without warning. Undiagnosed diabetes can be detected by raised blood glucose levels. AIM: The aim of this review was to provide an update for the UK National Screening Committee (NSC) on screening for T2DM. METHODS: As this review was undertaken to update a previous Health Technology Assessment review published in 2007, and a more recent Scottish Public Health Network review, searches for evidence were restricted from 2009 to end of January 2012, with selected later studies added. The databases searched were MEDLINE, EMBASE, MEDLINE-in-Process & Other Non-Indexed Citations, Science Citation Index and Conference Proceedings Citation Index. The case for screening was considered against the criteria used by the NSC to assess proposed population screening programmes. RESULTS: Population screening for T2DM does not meet all of the NSC criteria. Criterion 12, on optimisation of existing management, has not been met. A report by the National Audit Office (NAO) gives details of shortcomings. Criterion 13 requires evidence from high-quality randomised controlled trials that screening is beneficial. This has not been met. The Ely trial of screening showed no benefit. The ADDITION trial was not a trial of screening, but showed no benefit in cardiovascular outcomes from intensive management in people with screen-detected T2DM. Criterion 18 on staffing and facilities does not appear to have been met, according to the NAO report. Criterion 19 requires that all other options, including prevention, should have been considered. A large proportion of cases of T2DM could be prevented if people avoided becoming overweight or obese. The first stage of selection would use risk factors, using data held on general practitioner computer systems, using the QDiabetes Risk Score, or by sending out questionnaires, using the Finnish Diabetes Risk Score (FINDRISC). Those at high risk would have a measure of blood glucose. There is no perfect screening test. Glycated haemoglobin (HbA1c) testing has advantages in not requiring a fasting sample, and because it is a predictor of vascular disease across a wider range than just the diabetic one. However, it lacks sensitivity and would miss some people with diabetes. Absolute values of HbA1c may be more useful as part of overall risk assessment than a dichotomous 'diabetes or not diabetes' diagnosis. The oral glucose tolerance test is more sensitive, but inconvenient, more costly, has imperfect reproducibility and is less popular, meaning that uptake would be lower. CONCLUSIONS: When considered against the NSC criteria, the case for screening is less strong than it was in the 2007 review. The main reason is the absence of cardiovascular benefit in the two trials published since the previous review. There is a case for selective screening as part of overall vascular risk assessment. Population screening for T2DM does not meet all of the NSC criteria. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Cost-effectiveness of screening strategies for identifying pediatric diabetes mellitus and dysglycemia.

OBJECTIVE: To conduct a cost-effectiveness analysis of screening strategies for identifying children with type 2 diabetes mellitus and dysglycemia (prediabetes/diabetes). DESIGN: Cost simulation study. SETTING: A one-time US screening program. STUDY PARTICIPANTS: A total of 2.5 million children aged 10 to 17 years. INTERVENTION: Screening strategies for identifying diabetes and dysglycemia. MAIN OUTCOME MEASURES: Effectiveness (proportion of cases identified), total costs (direct and indirect), and efficiency (cost per case identified) of each screening strategy based on test performance data from a pediatric cohort and cost data from Medicare and the US Bureau of Labor Statistics. RESULTS: In the base-case model, 500 and 400 000 US adolescents had diabetes and dysglycemia, respectively. For diabetes, the cost per case was extremely high ($312 000-$831 000 per case identified) because of the low prevalence of disease. For dysglycemia, the cost per case was in a more reasonable range. For dysglycemia, preferred strategies were the 2-hour oral glucose tolerance test (100% effectiveness; $390 per case), 1-hour glucose challenge test (63% effectiveness; $571), random glucose test (55% effectiveness; $498), or a hemoglobin A1c threshold of 5.5% (45% effectiveness; $763). Hemoglobin A1c thresholds of 5.7% and 6.5% were the least effective and least efficient (ranges, 7%-32% and $938-$3370) of all strategies evaluated. Sensitivity analyses for diabetes revealed that disease prevalence was a major driver of cost-effectiveness. Sensitivity analyses for dysglycemia did not lead to appreciable changes in overall rankings among tests. CONCLUSIONS: For diabetes, the cost per case is extremely high because of the low prevalence of the disease in the pediatric population. Screening for diabetes could become more cost-effective if dysglycemia is explicitly considered as a screening outcome.

Screening for type 2 diabetes and dysglycemia.

Type 2 diabetes mellitus (T2DM) and dysglycemia (impaired glucose tolerance and/or impaired fasting glucose) are increasingly contributing to the global burden of diseases. The authors reviewed the published literature to critically evaluate the evidence on screening for both conditions and to identify the gaps in current understanding. Acceptable, relatively simple, and accurate tools can be used to screen for both T2DM and dysglycemia. Lifestyle modification and/or medication (e.g., metformin) are cost-effective in reducing the incidence of T2DM. However, their application is not yet routine practice. It is unclear whether diabetes-prevention strategies, which influence cardiovascular risk favorably, will also prevent diabetic vascular complications. Cardioprotective therapies, which are cost-effective in preventing complications in conventionally diagnosed T2DM, can be used in screen-detected diabetes, but the magnitude of their effects is unknown. Economic modeling suggests that screening for both T2DM and dysglycemia may be cost-effective, although empirical data on tangible benefits in preventing complications or death are lacking. Screening for T2DM is psychologically unharmful, but the specific impact of attributing the label of dysglycemia remains uncertain. Addressing these gaps will inform the development of a screening policy for T2DM and dysglycemia within a holistic diabetes prevention and control framework combining secondary and high-risk primary prevention strategies.

Treatment recommendations for prediabetes.

A variety of definitions and diagnostic cutpoints have been promulgated for prediabetes without universal agreement. Professional organizations agree that current scientific evidence justifies intervention in high-risk populations for the delay or prevention of progression to diabetes. Lifestyle intervention is universally accepted as the primary intervention strategy. Secondary intervention is advocated in high-risk individuals or in the absence of a clinical response to lifestyle modification.

Potential savings in Mexico from screening and prevention for early diabetes and hypertension.

This study analyzes the potential economic benefits of identifying and treating patients with so-called prediabetes and prehypertension through the Mexican prevention program known by its Spanish acronym PREVENIMSS. The results show that for each US dollar invested in prevention, $84-$323 would be saved over a twenty-year period. For this and other reasons, providing preventive care for prediabetes and prehypertension patients is better than the current routine care model, in which care is provided in most cases when the disease has progressed substantially. Yet data show that screening and preventive care services are still not being used widely enough in Mexico, are provided too late, or are not sufficiently targeted to the most at-risk individuals. Investing in preventive care for patients with prediabetes and prehypertension is cost saving.

Stem cell approaches for the treatment of type 1 diabetes mellitus.

Type 1 diabetes is characterized by near total absence of pancreatic b cells. Current treatments consisting of insulin injections and islet transplantation are clinically unsatisfactory. In order to develop a cure for type 1 diabetes, we must find a way to reverse autoimmunity, which underlies b cell destruction, as well as an effective strategy to generate new b cells. This article reviews the different approaches that are being taken to produce new b cells. Much emphasis has been placed on selecting the right non-b cell population, either in vivo or in vitro, as the starting material. Different cell types, including adult stem cells, other types of progenitor cells in situ, and even differentiated cell populations, as well as embryonic stem cells and induced pluripotent stem cells, will require different methods for islet and b cell induction. We discussed the pros and cons of the different strategies that are being used to re-invent the pancreatic b cell.

Screening adults for pre-diabetes and diabetes may be cost-saving.

OBJECTIVE: The economic costs of hyperglycemia are substantial. Early detection would allow management to prevent or delay development of diabetes and diabetes-related complications. We investigated the economic justification for screening for pre-diabetes/diabetes. RESEARCH DESIGN AND METHODS: We projected health system and societal costs over 3 years for 1,259 adults, comparing costs associated with five opportunistic screening tests. All subjects had measurements taken of random plasma and capillary glucose (RPG and RCG), A1C, and plasma and capillary glucose 1 h after a 50 g oral glucose challenge test without prior fasting (GCT-pl and GCT-cap), and a subsequent diagnostic 75 g oral glucose tolerance test (OGTT). RESULTS: Assuming 70% specificity screening cutoffs, Medicare costs for testing, retail costs for generic metformin, and costs for false negatives as 10% of reported costs associated with pre-diabetes/diabetes, health system costs over 3 years for the different screening tests would be GCT-pl $180,635; GCT-cap $182,980; RPG $182,780; RCG $186,090; and A1C $192,261; all lower than costs for no screening, which would be $205,966. Under varying assumptions, projected health system costs for screening and treatment with metformin or lifestyle modification would be less than costs for no screening as long as disease prevalence is at least 70% of that of our population and false-negative costs are at least 10% of disease costs. Societal costs would equal or exceed costs of no screening depending on treatment type. CONCLUSIONS: Screening appears to be cost-saving compared to no screening from a health system perspective, and potentially cost-neutral from a societal perspective. These data suggest that strong consideration should be given to screening-with preventive management-and that use of GCTs may be cost-effective.

Assessing the cost-effectiveness of drug and lifestyle intervention following opportunistic screening for pre-diabetes in primary care.

AIMS/HYPOTHESIS: This study aims to evaluate the cost-effectiveness of a screening programme for pre-diabetes, which was followed up by treatment with pharmaceutical interventions (acarbose, metformin, orlistat) or lifestyle interventions (diet, exercise, diet and exercise) in order to prevent or slow the onset of diabetes in those at high risk. METHODS: To approximate the experience of individuals with pre-diabetes in the Australian population, we used a microsimulation approach, following patient progression through diabetes, cardiovascular disease and renal failure. The model compares costs and disability-adjusted life years lived in people identified through an opportunistic screening programme for each intervention compared with a 'do nothing' scenario, which is representative of current practice. It is assumed that the effect of a lifestyle change will decay by 10% per year, while the effect of a pharmaceutical intervention remains constant throughout use. RESULTS: The most cost-effective intervention options are diet and exercise combined, with a cost-effectiveness ratio of AUD 22,500 per disability-adjusted life year (DALY) averted, and metformin with a cost-effectiveness ratio of AUD 21,500 per DALY averted. The incremental addition of one intervention to the other is not cost-effective. CONCLUSIONS/INTERPRETATION: Screening for pre-diabetes followed by diet and exercise, or metformin treatment is cost-effective and should be considered for incorporation into current practice. The number of dietitians and exercise physiologists needed to deliver such lifestyle change interventions will need to be increased to appropriately support the intervention.

Pharmaco-economic issues for diabetes therapy.

A systematic review was undertaken to analyse pharmaco-economic issues in diabetes, with evidence selected on the basis of relevance and immediacy. Pharmaco-economics in diabetes primarily relates to making choices about antidiabetic pharmaceuticals, and this is being influenced by global trends. Trends include increasing numbers of patients with diabetes, with increasing costs of caring for people with diabetes, and an ever-present focus on the costs of pharmaceuticals which are predicted to increase as the pace of development of new medications parallels the increasing incidence of the condition. These developments have influenced the demand for health care in diabetes in the last decade, and will continue to determine this in the coming decade. Recent national experiences are cited to illustrate current issues and to focus specifically upon the challenges facing a raft of new diabetes treatment options now hitting the marketplace, although supported by fewer completed long-term trials. It can be anticipated that these newer agents will be appraised for their cost-effectiveness or value for money. Economic analyses for some of the new technologies are summarized; in general, the peer-reviewed publications using well-accepted and validated models have reported that these technologies are cost-effective. Endorsement of any technology in a national setting is not awarded simply because the incremental cost-effectiveness ratio (ICER) falls below the threshold regarded as value for money. In most national observations the reviewers expressed concerns about assumptions used in economic modelling which resulted in the ICERs being deemed optimistic at best, generally highly uncertain, and resulting in the cost-effectiveness appearing better than it really would be in clinical practice. This has often led to the authorities concluding that the price advantage of new technologies over comparators could not be justified, essentially leading to restrictions in use compared to their licence. In general, a paucity of robust evidence on longer-term outcome data together with a lack of health-related quality of life (HRQOL) data collected in a reliable manner in appropriate patients and amenable to utility (and hence quality adjusted life year or QALY) estimation have resulted in problems for these new drugs at the so-called fourth (cost-effectiveness) hurdle. In the light of these findings, the implications for generating credible fit-for-purpose cost-effectiveness analyses of new technologies in diabetes are discussed. Throughout this chapter, the interested reader is referred to a number of excellent review articles for further details.

Cost-effectiveness of screening for pre-diabetes among overweight and obese U.S. adults.

OBJECTIVE: To estimate the cost-effectiveness of screening overweight and obese individuals for pre-diabetes and then modifying their lifestyle based on the Diabetes Prevention Program (DPP). RESEARCH DESIGN AND METHODS: A Markov simulation model was used to estimate disease progression, costs, and quality of life. Cost-effectiveness was evaluated from a health care system perspective. We considered two screening/treatment strategies for pre-diabetes. Strategy 1 included screening overweight subjects and giving them the lifestyle intervention included in the DPP if they were diagnosed with both impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Strategy 2 included screening followed by lifestyle intervention for subjects diagnosed with either IGT or IFG or both. Each strategy was compared with a program of no screening. RESULTS: Screening for pre-diabetes and treating those identified as having both IGT and IFG with the DPP lifestyle intervention had a cost-effectiveness ratio of $8,181 per quality-adjusted life-year (QALY) relative to no screening. If treatment was also provided to subjects with only IGT or only IFG (strategy 2), the cost-effectiveness ratio increased to $9,511 per QALY. Changes in screening-related parameters had small effects on the cost-effectiveness ratios; the results were more sensitive to changes in intervention-related parameters. CONCLUSIONS: Screening for pre-diabetes in the overweight and obese U.S. population followed by the DPP lifestyle intervention has a relatively attractive cost-effectiveness ratio.

Efficient cutoff points for three screening tests for detecting undiagnosed diabetes and pre-diabetes: an economic analysis.

OBJECTIVE: Opportunistic screening for undiagnosed type 2 diabetes and pre-diabetes (either impaired glucose tolerance or impaired fasting glucose) is recommended by the American Diabetes Association. The aim of this study was to determine efficient cutoff points for three screening tests for detecting undiagnosed diabetes alone or both undiagnosed diabetes and pre-diabetes. RESEARCH DESIGN AND METHODS: We estimated the number of individuals with undiagnosed diabetes alone or with both undiagnosed diabetes and pre-diabetes that could be detected by using different cutoff points for each screening test as the product of the prevalence of each condition, the sensitivity of the tests at each cutoff point for identifying each condition, and the number of individuals who would be eligible for screening in the U.S. We estimated the total cost of opportunistic screening by multiplying the cost for screening one person by the number of individuals screened. RESULTS: The most efficient cutoff points for both detecting pre-diabetes and undiagnosed diabetes (100 mg/dl for the fasting plasma glucose test, 5.0% for the HbA(1c) test, and 100 mg/dl for the random capillary blood glucose test) were less than those for detecting undiagnosed diabetes alone (110 mg/dl for the fasting plasma glucose test, 5.7% for the HbA(1c) test, and 120 mg/dl for the random capillary blood glucose test). CONCLUSIONS: A lower cutoff value should be used when screening for pre-diabetes and undiagnosed diabetes together than when screening for undiagnosed diabetes alone.

Costs of screening for pre-diabetes among US adults: a comparison of different screening strategies.

OBJECTIVE: We evaluated various strategies to identify individuals aged 45-74 years with pre-diabetes (either impaired glucose tolerance or impaired fasting glucose). RESEARCH DESIGN AND METHODS: We conducted a cost analysis to evaluate the effectiveness (proportion of cases identified), total costs, and efficiency (cost per case identified) of five detection strategies: an oral glucose tolerance test (OGTT), a fasting plasma glucose (FPG) test, an HbA(1c) test, a capillary blood glucose (CBG) test, and a risk assessment questionnaire. For the first strategy, all individuals received an OGTT. For the last four strategies, only those with a positive screening test received an OGTT. Data were from the Third U.S. National Health and Nutrition Examination Survey, 2000 census, Medicare, and published literature. One-time screening costs were estimated from both a single-payer perspective and a societal perspective. RESULTS: The proportion of pre-diabetes and undiagnosed diabetes identified ranged from 69% to 100% (12.1-17.5 million). The cost per case identified ranged from US dollars 176 to US dollars 236 from a single-payer perspective and from US dollars 247 to US dollars 332 from a societal perspective. Testing all with OGTT was the most effective strategy, but the CBG test and risk assessment questionnaire were the most efficient. If people are substantially less willing to take an OGTT than a FPG test, then the FPG testing strategy was the most effective strategy. CONCLUSIONS: There is a tradeoff between effectiveness and efficiency in choosing a strategy. The most favorable strategy depends on if the goal of the screening program is to identify more cases or to pursue the lowest cost per case. The expected percentage of the population willing to take an OGTT is also a consideration.