Prospective Diabetes Study Outcomes Model Research Articles

Cost‐Effectiveness of an Electronic Medical Record Based Clinical Decision Support System

Medical groups have invested billions of dollars in electronic medical records (EMRs), but few studies have examined the cost-effectiveness of EMR-based clinical decision support (CDS). This study examined the cost-effectiveness of EMR-based CDS for adults with diabetes from the perspective of the health care system. Clinical outcome and cost data from a randomized clinical trial of EMR-based CDS were used as inputs into a diabetes simulation model. The simulation cohort included 1,092 patients with diabetes with A1c above goal at baseline. The United Kingdom Prospective Diabetes Study Outcomes Model, a validated simulation model of diabetes, was used to evaluate remaining life years, quality-adjusted life years (QALYs), and health care costs over patient lifetimes (40-year time horizon) from the health system perspective. Patients in the intervention group had significantly lowered A1c (0.26 percent, p=.014) relative to patients in the control arm. Intervention costs were $120 (SE=45) per patient in the first year and $76 (SE=45) per patient in the following years. In the base case analysis, EMR-based CDS increased lifetime QALYs by 0.04 (SE=0.01) and increased lifetime costs by $112 (SE=660), resulting in an incremental cost-effectiveness ratio of $3,017 per QALY. The cost-effectiveness of EMR-based CDS persisted in one-way, two-way, and probabilistic sensitivity analyses. Widespread adoption of sophisticated EMR-based CDS has the potential to modestly improve the quality of care for patients with chronic conditions without substantially increasing costs to the health care system.

COST EFFECTIVENESS OF PEER SUPPORT FOR TYPE 2 DIABETES

The aim of this study is to examine the cost-effectiveness of a group-based peer support intervention in general practice for patients with type 2 diabetes. Incremental cost utility analysis combining within trial and beyond trial components to compare the lifetime costs and benefits of alternative strategies: standardized diabetes care; group-based peer support in addition to standardized diabetes care. Within trial analysis was based on a cluster randomized controlled trial of 395 patients with type 2 diabetes in the east of Ireland. Beyond trial analysis was conducted using the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model. Uncertainty was explored using a range of sensitivity analyses and cost-effectiveness acceptability curves were generated. Compared with the control strategy, the intervention was associated with an increase of 0.09 (95 percent confidence interval [CI], -0.05 to 0.25) in mean quality-adjusted life-years per patient and savings of €637.43 (95 percent CI, -2455.19 to 1125.45) in mean healthcare cost per patient and €623.39 (95 percent CI, -2507.98 to 1298.49) in mean total cost per patient respectively. The likelihood of the intervention being cost-effective was appreciably higher than 80 percent for a range of potential willingness-to-pay cost-effectiveness thresholds. Our results suggest that while a group-based peer support intervention shows a trend toward improved risk factor management, we found no significant differences in final cost or effectiveness endpoints between intervention and control. The probabilistic results suggest that the intervention was more cost-effective, with probability values of higher than 80 percent across a range of potential cost-effectiveness threshold values.

Cost-effectiveness of second-line antihyperglycemic therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin

Metformin is widely accepted as first-line pharmacotherapy for patients with type 2 diabetes mellitus when glycemic control cannot be achieved by lifestyle interventions alone. However, uncertainty exists regarding the optimal second-line therapy for patients whose diabetes is inadequately controlled by metformin monotherapy. Increased use of newer, more costly agents, along with the rising incidence of type 2 diabetes, carries significant budgetary implications for health care systems. We conducted this analysis to determine the relative costs, benefits and cost-effectiveness of options for second-line treatment of type 2 diabetes. We used the United Kingdom Prospective Diabetes Study Outcomes Model to forecast diabetes-related complications, quality-adjusted life-years and costs of alternative second-line therapies available in Canada for adults with type 2 diabetes inadequately controlled by metformin. We obtained clinical data from a systematic review and mixed treatment comparison meta-analysis, and we obtained information on costs and utilities from published sources. We performed extensive sensitivity analyses to test the robustness of results to variation in inputs and assumptions. Sulphonylureas, when added to metformin, were associated with the most favourable cost-effectiveness estimate, with an incremental cost of $12 757 per quality-adjusted life-year gained, relative to continued metformin monotherapy. Treatment with other agents, including thiazolidinediones and dipeptidyl peptidase-4 inhibitors, had unfavourable cost-effectiveness estimates compared with sulphonylureas. These results were robust to extensive sensitivity analyses. For most patients with type 2 diabetes that is inadequately controlled with metformin monotherapy, the addition of a sulphonylurea represents the most cost-effective second-line therapy.

Are Population-Based Diabetes Models Useful for Individual Risk Estimation?

Predictive models are increasingly used in guidelines and informed decision-making interventions. We compared predictions from 2 prominent models for diabetes: the United Kingdom Prospective Diabetes Study (UKPDS) outcomes model and the Archimedes-based Diabetes Personal Health Decisions (PHD) model. Ours was a simulation study comparing 10-year and 20-year model predictions for risks of myocardial infarction (MI), stroke, amputation, blindness, and renal failure for representative test cases. The Diabetes PHD model predicted substantially higher risks of MI and stroke in most cases, particularly for stroke and for 20-year outcomes. In contrast, the UKPDS model predicted risks of amputation and blindness ranging from 2-fold to infinitely higher than the Diabetes PHD model. Predictions for renal failure all differed by more than 2-fold but in a complicated pattern varying by time frame and specific risk factors. Relative to their predictions for white men, the UKPDS model predicted much lower MI and stroke risks for women and Afro-Caribbean men than the Diabetes PHD model did for women and black men. A substantial majority of the Diabetes PHD point estimates fell outside of the UKPDS outcomes model's 95% CIs. These models produced markedly different predictions. Patients and providers considering risk estimates from such models need to understand their substantial uncertainty and risk of misclassification.

Use of the UKPDS Outcomes Model to predict all-cause mortality in U.S. adults with type 2 diabetes mellitus: Comparison of predicted versus observed mortality

Aims The applicability of the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model is unknown in populations with type 2 diabetes mellitus (T2DM) outside the United Kingdom. We compared all-cause mortality predicted from the UKPDS model with observed mortality among T2DM subjects in the U.S. Methods We studied participants with T2DM from the National Health and Nutrition Examination Survey 1988–1994 with characteristics comparable to the UKPDS cohort. The 10-year observed all-cause mortality was compared to the UKPDS model-predicted mortality. The Lifetable method was used to estimate the probability of mortality for 10 years following diagnosis. Results Among 156 subjects with characteristics comparable to the UKPDS cohort, mean age was 49.6 years, age at T2DM diagnosis was 47.1 years, and T2DM duration averaged 2.6 years, with follow-up for 10.4 years. The UKPDS model-predicted 10-year mortality was 15.7%, similar to the observed mortality of 14.2%. Corresponding 10-year predicted versus observed mortality was 32.7% versus 32.4% including subjects >age 65, 17.0% versus 19.3% including individuals with pre-existing CVD, and 31.1% versus 20.9% including individuals with diabetes duration ≥6 years. Conclusion All-cause mortality predicted by the UKPDS model was comparable to observed mortality in U.S. NHANES participants with characteristics similar to the UKPDS.

Life Expectancy in Individuals With Type 2 Diabetes: Implications for Annuities

Insurance companies often offer people with diabetes ''enhanced impaired life annuity'' at preferential rates, in view of their reduced life expectancy. To assess the appropriateness of ''enhanced impaired life annuity'' rates for individuals with type 2 diabetes. Patients. There were 4026 subjects with established type 2 diabetes (but not known cardiovascular or other life-threatening diseases) enrolled into the UK Lipids in Diabetes Study. Measurements. Estimated individual life expectancy using the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model. Subjects were a mean (SD) age of 60.7 (8.6) years, had a blood pressure of 141/83 (17/10) mm Hg, total cholesterol level of 4.5 (0.75) mmol/L, HDL cholesterol level of 1.2 (0.29) mmol/L, with median (interquartile range [IQR]) known diabetes duration of 6 (3-11) years, and HbA(1c) of 8.0% (7.2-9.0). Sixty-five percent were male, 91% white, 4% Afro-Caribbean, 5% Indian-Asian, and 15% current smokers. The UKPDS Outcomes Model median (IQR) estimated age at death was 76.6 (73.8-79.5) years compared with 81.6 (79.4-83.2) years, estimated using the UK Government Actuary's Department data for a general population of the same age and gender structure. The median (IQR) difference was 4.3 (2.8-6.1) years, a remaining life expectancy reduction of almost one quarter. The highest value annuity identified, which commences payments immediately for a 60-year-old man with insulin-treated type 2 diabetes investing 100,000, did not reflect this difference, offering 7.4K per year compared with 7.0K per year if not diabetic. The UK Government Actuary's Department data overestimate likely age at death in individuals with type 2 diabetes, and at present, ''enhanced impaired life annuity'' rates do not provide equity for people with type 2 diabetes. Using a diabetes-specific model to estimate life expectancy could provide valuable information to the annuity industry and permit more equitable annuity rates for those with type 2 diabetes.

Development of life-expectancy tables for people with type 2 diabetes.

To develop tables that report the life expectancy associated with levels of major modifiable risk factors for patients with type 2 diabetes. A set of tables reporting life-expectancy stratified by age-sex groups for combinations of modifiable risk was constructed based on predictions from the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model. This model is based on a system of parametric proportional hazards risk equations for estimating mortality and vascular complications of diabetes that have been estimated from 3642 patients from the UKPDS. The tables show substantial potential gains in life expectancy within every age group from modifying major risk factors. The estimated life expectancy of men at age of 55 years with type 2 diabetes, 5 years after diagnosis, varies between 13.2 years for a patient who smokes, has systolic blood pressure of 180 mmHg, a total:HDL cholesterol ratio of 8, and HbA(1c) of 10%, and 21.1 years for a non-smoker with SBP of 120 mmHg, total/HDL ratio of 4, and HbA(1c) of 6%. Life expectancy tables provide a potentially useful tool of conveying prognostic information to people with type 2 diabetes and suggest substantial scope for increasing longevity by improving modifiable risk factors.

Development of a diabetes treatment simulation model: with application to assessing alternative treatment intensification strategies on survival and diabetes‐related complications

The objective of this analysis is to project the long-term impacts on life expectancy and occurrence over 5, 10, and 40 years of microvascular and macrovascular complications of diabetes when using different haemoglobin A1c (HbA1c) thresholds for intensifying treatment of type 2 diabetes. A flexible, discrete-event simulation model has been developed to evaluate alternative treatment strategies based on the United Kingdom Prospective Diabetes Study Outcomes Model. In the present analysis, the model is used to investigate the impact of alternative HbA1c thresholds for treatment intensification ranging from 7.0 to 9.0%. For each intensification strategy, the model is run using 80 simulated patients for each of 1224 patient profiles from the Real-Life Effectiveness and Care Patterns of Diabetes Management study (for a total of 97,920 simulated patients) to project the number of patients who will experience diabetes-related complications over time. The use of lower HbA1c thresholds for intensifying treatment is associated with improved long-term outcomes. When the HbA1c threshold for intensifying therapy from oral treatment to basal insulin (T1) is 7.0% and the threshold for intensifying basal insulin to multiple-dose insulin (T2) is 7.0%, simulated patients spend 54% of their time with HbA1c >7.0%, but 95% of their time with HbA1c >7.0% if T1 and T2 are set to 9.0%. More aggressive or proactive treatment postures are projected to reduce clinical events, including diabetes-related deaths and diabetes-related complications, particularly myocardial infarctions (MIs). When T1 and T2 are set to 7.0%, there are 592 fewer diabetes-related deaths in the first 5 years of the simulation and 3740 fewer deaths over 40 years compared with the results when T1 and T2 are set to 9.0%. These decreases in deaths were also associated with a 0.35 year gain in projected life expectancy. Compared with an aggressive strategy with both T1 and T2 being 7%, 644 more patients are projected to experience at least one episode of MI in the first 5 years if treatment intensification is delayed until HbA1c reaches 9.0%. This number increases over time, reaching 2906 additional patients experiencing at least one MI over a 40-year time period. We report results from a discrete-event simulation model to explore the impact of alternative treatment strategies for patients with type 2 diabetes. Strategies that intensify therapy (in response to rising HbA1c levels) at lower HbA1c thresholds (e.g. 7.0%) are associated with enhanced projected long-term health outcomes.

Cost‐effectiveness of sitagliptin‐based treatment regimens in European patients with type 2 diabetes and haemoglobin A1c above target on metformin monotherapy

Sitagliptin is a novel oral incretin enhancer that acts by inhibiting the dipeptidyl peptidase 4 enzyme and is indicated in Europe as a treatment adjunct to metformin (MF), sulphonylurea (SU), MF plus SU and diet and exercise, in the management of type 2 diabetes mellitus. The objective of the current analysis was to evaluate the cost-effectiveness of adding sitagliptin to the regimens of patients with haemoglobin A1c (HbA1C) above the International Diabetes Federation goal (6.5%) while on MF in six European countries: Austria, Finland, Portugal, Scotland (United Kingdom), Spain and Sweden. A discrete event simulation model, which employed the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model risk equations for predicting risks of diabetes-related complication, was used. Lifetime costs and benefits were projected for alternative treatment strategies of adding sitagliptin, compared with adding rosiglitazone or a SU to MF in patients not at HbA1C goal on MF monotherapy. Changes in HbA1C as well as side effects associated with these different treatment strategies were based on clinical trial data. Mean baseline values from local epidemiologic studies involving patients with type 2 diabetes not at HbA1C goal on MF monotherapy were included in the current analysis. Costs of medications, side effects and direct costs of diabetes-related complications were based on country-specific data. UKPDS-based disutility weights associated with diabetes complications were incorporated. Disutilities associated with medication side effects were based on published data. All future costs and benefits were discounted according to local guidelines on cost-effectiveness analysis. One-way sensitivity analyses were conducted by varying key input parameters. The discounted incremental cost-effectiveness ratios (ICER) associated with the addition of sitagliptin to MF, compared with adding rosiglitazone, in the different countries analysed ranged from treatment with sitagliptin being dominant (cost saving with improved health outcome) to its being cost-effective [4,766 euros per quality-adjusted life year (QALY)]. Treatment with sitagliptin added to MF was cost-effective compared with adding a SU, with discounted ICER values ranging from 5949 euros/QALY to 20,350 euros/QALY across countries. Sensitivity analyses showed that these results were robust to changes in input parameters, including clinical efficacy, costs and utility weights for both diabetes-related complications and hypoglycaemia. Compared with adding rosiglitazone or a SU to MF, adding sitagliptin to MF is projected to be either cost saving or cost-effective for patients with type 2 diabetes who are not at HbA1C goal on MF.

Long-Term Cost-utility Analysis of a Multidisciplinary Primary Care Diabetes Management Program in Ontario

ABSTRACT OBJECTIVES To estimate the cost-effectiveness of a multidisciplinary diabetes management program using the Ontario Diabetes Economic Model (ODEM). METHODS Using an Ontario-specific United Kingdom Prospective Diabetes Study Outcomes Model, changes in risk factors (e.g. glycosylated hemoglobin) were used to predict event rates for diabetes-related complications, costs and expected quality-adjusted life years (QALYs). Incremental costeffectiveness ratios were calculated based on the cost of the program, projected cost and effectiveness over a lifetime. The base case assumed a 1-year treatment effect, 3% discount rate and 40-year time horizon. RESULTS The ODEM estimated that improvements in risk factors prevented 16.2/1000 deaths and 15.5/1000 myocardial infarctions, and led to a 50% relative risk reduction in first amputations.The lifetime incremental cost per QALY gained in the base case was $5992. CONCLUSION Short-term outcomes were improved, translating into avoidance of downstream complications; thus, the increased costs of program implementation were partly offset. Overall, the program represents a cost-effective method for managing type 2 diabetes.

Reassessment of cardiovascular risk in diabetes

To review recent trials and reassess cardiovascular risk in people with diabetes. Recent clinical trials have tended to focus on lower-risk participants with diabetes who have had event rates considerably lower than participants in the early lipid trials. Statin studies have generally shown benefit in those without cardiovascular disease and at lower levels of low-density lipoprotein cholesterol. Results of fibrate and glitazone studies have been mixed; the question of benefit among statin-treated patients remains unanswered. Investigators failed to confirm the benefits of glucose control observed in the original Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction study possibly due to study design issues. Epidemiologic follow-up of the Diabetes Control and Complications Trial showed sustained benefit of glucose control. A number of studies have shown the benefit of inpatient control of blood glucose. We await the results of ongoing blood pressure trials and other ongoing trials, which should provide much new information. A conceptual model of cardiovascular risk for people with diabetes mellitus based on the UK Prospective Diabetes Study outcomes model is discussed. The majority of adults with diabetes have a substantially greater risk compared with those without diabetes and a small percentage has very high risk. A minority of individuals may have considerably lower 10-year risk.

A model to estimate the lifetime health outcomes of patients with Type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model (UKPDS no. 68)

The aim of this study was to develop a simulation model for type 2 diabetes that can be used to estimate the likely occurrence of major diabetes-related complications over a lifetime, in order to calculate health economic outcomes such as quality-adjusted life expectancy. Equations for forecasting the occurrence of seven diabetes-related complications and death were estimated using data on 3642 patients from the United Kingdom Prospective Diabetes Study (UKPDS). After examining the internal validity, the UKPDS Outcomes Model was used to simulate the mean difference in expected quality-adjusted life years between the UKPDS regimens of intensive and conventional blood glucose control. The model's forecasts fell within the 95% confidence interval for the occurrence of observed events during the UKPDS follow-up period. When the model was used to simulate event history over patients' lifetimes, those treated with a regimen of conventional glucose control could expect 16.35 undiscounted quality-adjusted life years, and those receiving treatment with intensive glucose control could expect 16.62 quality-adjusted life years, a difference of 0.27 (95% CI: -0.48 to 1.03). The UKPDS Outcomes Model is able to simulate event histories that closely match observed outcomes in the UKPDS and that can be extrapolated over patients' lifetimes. Its validity in estimating outcomes in other groups of patients, however, remains to be evaluated. The model allows simulation of a range of long-term outcomes, which should assist in informing future economic evaluations of interventions in type 2 diabetes.