Budget impact analysis of a digital monitoring platform for COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive debilitating condition with frequent exacerbations that have a high burden for patients and society. Digital tools may help to reduce the economic burden for patients and payers by improving outcomes. The Propeller platform is a digital self-management tool that facilitates passive monitoring of inhaler medication utilization, potentially assisting the healthcare team to identify patients at risk of a COPD exacerbation who may require further intervention. This study estimated the budget impact of Propeller from commercial payer and Medicare fee-for-service payer perspectives. METHODS: An Excel-based model was used to estimate the budget impact of Propeller for COPD patients in commercial and Medicare population sizes of 5 million members. Data on prevalence, baseline healthcare resource utilization (HCRU), and baseline use of rescue and controller inhaler medications with unit costs (adjusted to 2020 US dollars) were obtained from peer-reviewed literature. Data on reductions in HCRU during Propeller usage were based on direct evidence. Estimates for costs of remote monitoring were obtained from publicly available information. All patients were assumed to have insurance claims related to ongoing remote monitoring. RESULTS: The estimated number of annual eligible COPD patients for commercial and Medicare was 212,200 and 606,600, respectively. Propeller decreased costs by an estimated $2,475 (commercial) and $915 (Medicare) per enrolled patient. The greatest increase in expenditure was for remote monitoring related expenses. After accounting for estimated reductions in hospitalizations, emergency department visits and short-acting beta-agonist use, total net savings were approximately $1.60 and $1.70 per-member per-month for commercial and Medicare payers, respectively. CONCLUSION: Propeller is projected to be cost saving from both the commercial and Medicare payer perspectives.

Decreased Opioid Utilization and Cost at One Year in Chronic Low Back Pain Patients Treated with Transcutaneous Electric Nerve Stimulation (TENS).

INTRODUCTION: Chronic low back pain (CLBP) may be treated without opioids through the use of transcutaneous electrical nerve stimulation (TENS). However, no study has evaluated its clinical effect and economic impact as measured by opioid utilization and costs. The purpose of this study was to evaluate patients who were given TENS for CLBP compared to a matched group without TENS at one-year follow-up, to determine differences between opioid consumption. MATERIALS AND METHODS: Opioid utilization and costs in patients who did and did not receive TENS were extracted from a Medicare supplemental administrative claims database. Patients were selected if they had at least two ICD-9-CM coded claims for low back pain in a three-month period and were then propensity score matched at a 1:1 ratio between patients who received TENS and those who did not. There were 22,913 patients in each group who had a minimum follow-up of one year. There were no significant demographic or comorbidity differences with the exception that TENS patients had more episodes of back pain. RESULTS: Significantly fewer patients in the TENS group required opioids at final follow-up (57.7 vs. 60.3%). TENS patients also had significantly fewer annual per-patient opioid costs compared to non-TENS patients ($169 vs. $192). There were significantly lower event rates in TENS patients compared to non-TENS patients when measured by opioid utilization (characterized by frequency of prescription refills) (3.82 vs. 4.08, respectively) or pharmacy utilization (31.67 vs. 32.25). The TENS group also demonstrated a significantly lower cost of these utilization events ($44 vs. $49) and avoided more opioid events (20.4 events fewer per 100 patients annually). DISCUSSION: Treatment of CLBP with TENS demonstrated significantly fewer patients requiring opioids, fewer events where a patient required an opioid prescription, and lower per-patient costs. Since TENS is both non-invasive and a non-narcotic, it may potentially allow physicians to be more aggressive in treating CLBP patients.

Impact of Pseudomonas aeruginosa on resource utilization and costs in patients with exacerbated non-cystic fibrosis bronchiectasis.

AIMS: Non-cystic fibrosis bronchiectasis (NCFB) is a chronic progressive respiratory disorder occurring at a rate ranging from 4.2 to 278.1 cases per 100,000 persons, depending on age, in the United States. For many patients with NCFB, the presence of Pseudomonas aeruginosa (PA) makes treatment more complicated and typically has worse outcomes. Management of NCFB can be challenging, warranting a better understanding of the burden of illness for NCFB, treatments applied, healthcare resources used, and subsequent treatment costs. Comparing patients diagnosed with exacerbated NCFB, with or without PA on antibiotic utilization, treatments, and healthcare resources utilization and costs was the purpose of this study. MATERIALS AND METHODS: This was a retrospective cohort study of commercial claims from IQVIA's PharMetrics Plus database (January 1,2006-December 31, 2020). Study patients with a diagnosis of NCFB were stratified into two groups based on the presence or absence of PA, then followed to identify demographic characteristics, comorbid conditions, antibiotic treatment regimen prescribed, healthcare resources utilized, and costs of care. RESULTS: The results showed that patients with exacerbated NCFB who were PA+ had significantly more oral antibiotic fills per patient per year, more inpatient admissions with a longer length of stay, and more outpatient encounters than those who were PA-. For costs, PA+ patients also had significantly greater total healthcare costs per patient when compared to those who were PA-. CONCLUSION: Exacerbated NCFB with PA+ was associated with increased antibiotic usage, greater resource utilization, and increased costs. The major contributor to the cost differences was the use of inpatient services. Treatment strategies aimed at reducing the need for inpatient treatment could lessen the disparities observed in patients with NCFB.

Cost effectiveness of insulin glargine plus oral antidiabetes drugs compared with premixed insulin alone in patients with type 2 diabetes mellitus in Canada.

BACKGROUND: Several treatment options are available for patients with type 2 diabetes mellitus who are making the transition from oral antidiabetes drugs (OADs) to insulin. Two options currently recommended by the Canadian Diabetes Association for initiating insulin therapy in patients with type 2 diabetes who are no longer responsive to OADs alone are insulin glargine plus OADs, and premixed insulin therapy only. Because of differences in efficacy, adverse events (such as hypoglycaemia) and acquisition costs, these two treatment options may lead to different long-term clinical and economic outcomes. OBJECTIVE: To determine the cost effectiveness of insulin glargine plus OADs compared with premixed insulin without OADs in insulin-naive patients with type 2 diabetes in Canada. METHODS: Using treatment effects taken from a published clinical trial, the validated IMS-CORE Diabetes Model was used to simulate the long-term cost effectiveness of insulin glargine with OADs, versus premixed insulin. Input treatment effects for the two therapeutic approaches were based on changes in glycosylated haemoglobin A(1c) (HbA(1c)) at clinical trial endpoint, and hypoglycaemia rates. The analysis was conducted from the perspective of the Canadian Provincial payer. Direct treatment and complication costs were obtained from published sources (primarily from Ontario) and reported in $Can, year 2008 values. All base-case costs and outcomes were discounted at 5% per year. Sensitivity analyses were conducted around key parameters and assumptions used in the study. Outcomes included direct medical costs associated with both treatment and diabetes-related complications. Cost-effectiveness outcomes included total average lifetime (35 years) costs, life expectancy (LE), QALYs and incremental cost-effectiveness ratios (ICERs). RESULTS: Base-case analyses showed that, compared with premixed insulin only, insulin glargine in combination with OADs was associated with a 0.051-year increase in LE and a 0.043 increase in QALYs. Insulin glargine plus OADs showed a very slight increase in total direct costs ($Can 343 +/- 2572), resulting in ICERs of $Can 6750 per life-year gained (LYG) and $Can 7923 per QALY gained. However, considerable uncertainty around the ICERs was demonstrated by insulin glargine having a 50% probability of being cost effective at a willingness-to-pay threshold of $Can 10,000 per QALY, and a 54% probability at a $Can 20,000 threshold. Base-case results were most sensitive to assumed disutilities for hypoglycaemic events, to the assumed effect of insulin glargine plus OADs on HbA(1c), and to its assumed acquisition costs. CONCLUSIONS: These findings should be interpreted within the context of a large degree of uncertainty and of several study limitations that include a single clinical trial as the source for primary treatment assumptions and a single province as the source for most cost inputs. Under current study assumptions and limitations, insulin glargine plus OADs was projected to be a cost-effective option, compared with premixed insulin only, for the treatment of insulin-naive patients with type 2 diabetes unresponsive to OADs. Additional work is needed to examine the generalizability of the findings to individual jurisdictions of the Canadian healthcare system.

Objective measurement in Parkinson's disease: a descriptive analysis of Parkinson's symptom scores from a large population of patients across the world using the Personal KinetiGraph®.

BACKGROUND: The Personal KinetiGraph® (PKG®) Movement Recording System provides continuous, objective, ambulatory movement data during routine daily activities and provides information on medication compliance, motor fluctuations, immobility, and tremor for patients with Parkinson's disease (PD). Recent evidence has proposed targets for treatable symptoms. Indications for PKG vary by country and patient selection varies by physician. METHODS: The analyses were based upon 27,834 complete and de-identified PKGs from January 2012 to August 2018 used globally for routine clinical care. Median scores for bradykinesia (BKS) and dyskinesia (DKS) as well as percent time with tremor (PTT) and percent time immobile (PTI) were included as well as proportions of PKGs above published PKG summary score target values (BKS > 25, DKS > 9, PTT > 1%, PTI > 10%). Two sub-analyses included subjects who had 2+ PKG records and scores above proposed BKS and DKS targets, respectively, on their first PKG. Median BKS and DKS scores for subsequent PKGs (1st, 2nd, etc.) were summarized and limited to those with 100+ subsequent PKGs for each data point. RESULTS: Significant differences between countries were found for all 4 PKG parameter median scores (all p < 0.0001). Overall, 54% of BKS scores were > 25 and ranged from 46 to 61% by country. 10% of all DKS scores were > 9 and ranged from 5 to 15% by country. Sub-analysis for BKS showed global median BKS and DKS scores across subsequent PKGs for subjects who had 2+ PKGs and had BKS > 25 on their first PKG. There were significant changes in BKS from 1st to 2nd-6th PKGs (all p < 0.0001). Sub-analysis for DKS showed global median BKS & DKS scores across subsequent PKGs for subjects who had 2+ PKGs and had DKS > 9 on their first PKG. There were significant changes in DKS from 1st to 2nd and 3rd PKGs (both p < 0.0001). CONCLUSIONS: This analysis shows that in every country evaluated a meaningful proportion of patients have sub-optimal PD motor symptoms and substantial variations exist across countries. Continuous objective measurement (COM) in routine care of PD enables identification and quantification of PD motor symptoms, which can be used to enhance clinical decision making, track symptoms over time and improve PD symptom scores. Thus, clinicians can use these PKG scores during routine clinical management to identify PD symptoms and work to move patients into a target range or a more controlled symptom state.

Health economic comparison between continuous subcutaneous insulin infusion and multiple daily injections of insulin for the treatment of adult type 1 diabetes in Canada.

BACKGROUND: Patients with type 1 diabetes mellitus (DM) may be treated with insulin via multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). OBJECTIVE: The purpose of this study was to evaluate the projected long-term cost-effectiveness of CSII compared with MDI by modeling a simulated sample of adult patients with type 1 DM in Canada. METHODS: A health economic model was used to determine the incremental cost-effectiveness ratio (ICER) of CSII compared with MDI from the perspective of a Canadian provincial government. The primary input variable was change in glycosylated hemoglobin (HbA(1c)). A series of Markov constructs also simulated the progression of disease-related complications. Annual acquisition costs for CSII and MDI were year-2006 Can $6347.18 and Can $4649.69, respectively. A 60-year time horizon and a discount rate of 5.0% per annum on costs and clinical outcomes were used. RESULTS: Mean direct lifetime costs were Can $15,591 higher with CSII treatment than MDI. Treatment with CSII was associated with an improvement in discounted life expectancy of 0.655 quality-adjusted life-years (QALYs) over a 60-year time horizon, compared with MDI (mean [SD], 10.029 [0.133] vs 9.374 [0.076] QALYs). ICERs were Can $27,264 per life-year gained and Can $23,797 per QALY for CSII compared with MDI. The results were most sensitive to HbA(1c) assumptions. CONCLUSION: Based on this analysis, CSII may be a cost-effective treatment option when compared with MDI in adult patients with type 1 DM in Canada.

A cost-effectiveness analysis of continuous subcutaneous insulin injection versus multiple daily injections in type 1 diabetes patients: a third-party US payer perspective.

OBJECTIVE: To estimate the long-term cost-effectiveness of using continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) of insulin in adult and child/young adult type 1 diabetes mellitus (T1DM) patients from a third-party payer perspective in the United States. METHOD: A previously validated health economic model was used to determine the incremental cost-effectiveness ratio (ICER) of CSII compared with MDI using published clinical and cost data. The primary input variable was change in HbA(1c), and was assumed to be an improvement of -0.9% to -1.2% for CSII compared with MDI for child/young adult and adults, respectively. A series of Markov constructs simulated the progression of diabetes-related complications. RESULTS: CSII was associated with an improvement in quality-adjusted life-years (QALYs) gained of 1.061 versus MDI for adults and 0.799 versus MDI for children/young adults. ICERs were $16,992 and $27,195 per QALY gained for CSII versus MDI in adults and children/young adults, respectively. Improved glycemic control from CSII led to a lower incidence of diabetes complications, with the most significant reduction in proliferative diabetic retinopathy (PDR), end stage renal disease (ESRD), and peripheral vascular disease (PVD). The number needed to treat (NNT) for PDR was nine patients, suggesting that only nine patients need to be treated with CSII to avoid one case of PDR. The NNT for ESRD and PVD was 19 and 41, respectively. CONCLUSIONS: Setting the willingness to pay at $50,000/QALY, the analysis demonstrated that CSII is a cost-effective option for patients with T1DM in the United States.

Long-term cost-effectiveness of pioglitazone versus placebo in addition to existing diabetes treatment: a US analysis based on PROactive.

OBJECTIVE: To estimate the long-term cost-effectiveness of adding pioglitazone versus placebo to standard treatment in high-risk patients with type 2 diabetes. METHODS: The validated CORE Diabetes Model was modified to project long-term clinical and cost outcomes associated with pioglitazone versus placebo, based on results from PROactive. The model retained basic structure and functionality, with interdependent Markov submodels, Monte Carlo simulation and user interface. Adjustments to submodels were made to accommodate the PROactive primary end points. The analysis was from the perspective of a third party US health-care payer perspective, projected over a lifetime horizon using a 3% annual discount. RESULTS: Over a lifetime horizon, addition of pioglitazone was associated with increased life expectancy (0.237 life-years) and quality-adjusted life expectancy (QALE) [0.166 quality-adjusted life-years (QALYs)] versus placebo. Estimated long-term complication rates showed that pioglitazone reduced the number of events versus placebo for most outcomes. Lifetime total direct costs were marginally higher with pioglitazone versus placebo ($272,694 vs. $265,390, difference $7,305). The incremental cost-effectiveness ratio for pioglitazone versus placebo was $44,105 per QALY gained. Probabilistic sensitivity analysis indicated a 55% likelihood that pioglitazone would be considered cost-effective in the United States, with a willingness to pay of $50,000 per QALY gained. CONCLUSIONS: The addition of pioglitazone to existing therapy in high-risk patients with type 2 diabetes was projected to improve life expectancy, QALE and complication rates compared with placebo. Addition of pioglitazone was in the range generally considered acceptable.

Estimating the long-term cost-effectiveness of exenatide in the United States: an adjunctive treatment for type 2 diabetes mellitus.

OBJECTIVES: This analysis provides an early estimate of the cost-effectiveness of adjunctive exenatide in treating type 2 diabetes mellitus in the United States. Data from pivotal phase III 30-week clinical trials and 52 weeks of their subsequent open-label extension studies (i.e., 82 weeks total) were used to project the effects of 30 years of adjunctive exenatide treatment. METHODS: This analysis utilized a published and validated Markov model incorporating Monte Carlo simulation with tracker variables to estimate the clinical and cost outcomes of adding exenatide to a background of metformin and/or sulfonylurea treatment, with the effects of 30 years of adjunctive exenatide treatment (projected from data from 82 weeks of exenatide treatment) compared with no additional treatment beyond metformin and/or a sulfonylurea. Sensitivity analyses were performed on key clinical assumptions, discount rates, and shorter time horizons. RESULTS: The base-case scenario (30 years of exenatide) yielded an incremental cost-effectiveness ratio (ICER) of $35,571. We found that shortening the time horizons and removing the lipid effects of exenatide had the greatest negative impact on ICERs when performing sensitivity analysis. CONCLUSIONS: Our analysis demonstrated that exenatide used for 20 or 30 years compared with no additional treatment beyond metformin and/or a sulfonylurea is cost-effective in the adjunctive treatment of type 2 diabetes with an ICER less than $50,000 per life-year gained. Sensitivity analyses suggest that, in addition to sustained reduction in HbA(1c), the added clinical effects of improved lipid values, systolic blood pressure, and reduced body mass index all positively contributed to the cost-effectiveness of exenatide.

The impact of clinical trial design on cost-effectiveness analyses: illustration from a published study of the one-touch ultrasmart blood glucose meter for insulin-using diabetes patients.

One source of variation in cost-effectiveness analyses stems from the characteristics of the study upon which each is based. This report provides cost-effectiveness analyses using data from a recently published randomized clinical trial (RCT) comparing an integrated glucose meter/electronic logbook to a conventional glucose meter/paper logbook in helping to control hemoglobin A1c in type 1 or type 2 diabetes. RCT participants and health care professionals (HCPs) were "blinded" to results of meter downloads until week 16, when participants chose systems. They returned to "usual care" and could obtain meter results and share them with their HCPs. Those eligible returned 26-65 weeks later for an observational visit. The CORE Diabetes Model was used to estimate the 60-year cost-effectiveness of the electronic (vs. conventional) meter. With no price premium, the newer technology represented a dominant strategy (greater effectiveness/lower costs) based on the RCT alone or on the RCT + observational visit. With a $100.00/year premium, the incremental cost-effectiveness ratio was $28,053 based on the RCT, but the electronic monitor was dominant when simulations included observational visit results. One plausible reason for the greater benefits of the electronic monitor with the observational period included was the ability of patients and HCPs to make better clinical and lifestyle modifications based on fully available, formatted data. Because the advantages of the electronic meter are based on timely access to accurate feedback, the importance of naturalistic, unblinded studies for technology assessments can be appreciated. Addressing the methodological issues discussed here can help integrate clinical and economic outcomes for diabetes care innovations.

Direct medical costs for type 2 diabetes mellitus complications in the US commercial payer setting: a resource for economic research.

BACKGROUND: Medical complications are the key drivers of the direct medical costs of treating patients with type 2 diabetes mellitus. However, the published literature shows great variability across studies in the number and type of sources from which these costs for diabetes are obtained. OBJECTIVE: To provide to researchers a set of costs for type 2 diabetes complications, originally developed for input into an established diabetes model, that are empirically based, clearly and consistently defined and applicable to a large segment of managed care patients in the US. METHODS: Patients with 1 of 24 diabetes-related complications between 1 January 2003 and 31 December 2004 and with evidence of type 2 diabetes were identified using a nationally representative US commercial insurance claims database. Therapy utilization and complication cost data were extracted for all patients for the 12 months following the first identified complication; data for months 13-24 were obtained for a subset of patients with at least 24 months of follow-up enrollment. Medical costs included both the amounts charged by medical providers and the health plan contracted allowed amounts. Costs were expressed as $US, year 2007 values. RESULTS: A total of 44 021 patients with a minimum of 12 months of continuous follow-up enrollment were identified, with a mean age of 56 years; a subset of 32 991 patients with at least 24 months of continuous health-plan enrollment was also identified. Among the aggregate sample, 74% of patients were receiving oral antidiabetics, 26% were receiving insulin, 43% were receiving ACE inhibitors and 50% were receiving antihyperlipidaemics/HMG-CoA reductase inhibitors (statins) during the first 12 months following the index complication. The majority of patients had at least one physician office visit (99.8%), laboratory diagnostic test (96.2%) and other outpatient visit (97.5%). Six complications (angina pectoris, heart failure, peripheral vascular disease, renal disease, nonproliferative retinopathy and neuropathy) had a prevalence of at least 10%. Allowed amounts for most complications were 30-45% of charges. Myocardial infarction, heart failure and renal disease had the greatest fiscal impact because of the total number of patients experiencing them (7.2%, 14.0% and 11.0%, respectively) and their associated costs; 12-month mean allowed amounts were $US 14,853, $US 11,257 and $US 13,876, respectively, and 12-month mean charged amounts were $US 41,695, $US 30, 066 and $US 34,987, respectively. Similarly, in the subset of 32 991 patients, these three complications had higher allowed and charged amounts over months 13-24 compared with the majority of other complications of interest. CONCLUSION: These costing results provide an important resource for economic modelling and other types of costing research related to treating diabetes-related complications within the US managed care system.

Continuous subcutaneous insulin infusion versus multiple daily injections of insulin: economic comparison in adult and adolescent type 1 diabetes mellitus in Australia.

BACKGROUND: Recent meta-analyses in the published medical literature have found improved glycaemic control with continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) of insulin for patients with diabetes mellitus. In Australia, CSII is predominantly used in type 1 diabetes mellitus (T1DM) patient populations. OBJECTIVE/INTERVENTION: To project long-term costs and outcomes of CSII (Novorapid or Humalog) compared with MDI (NPH insulin plus Novorapid or Humalog) in adult and adolescent T1DM patients in Australia. METHODS: The study was a modelling analysis utilising a lifetime horizon in adult and adolescent specialty care T1DM patient populations from Australia. Published Australian diabetes complication costs (adjusted to Australian dollars [$A], year 2006 values), treatment costs and discount rates of 5.0% per annum were applied to costs and clinical outcomes. A lifetime horizon was taken, considering only direct medical costs and excluding indirect and non-medical costs. The validated CORE diabetes model employs standard Markov/Monte Carlo simulation techniques. It was used to simulate diabetes progression in Australian adult (mean age 43 years, duration of diabetes 17 years, mean glycosylated haemoglobin [HbA(1c)] 8.2%) and adolescent (mean age 17 years, duration of diabetes 6 years, mean HbA(1c) 8.9%) patients with baseline characteristics taken predominantly from Australian National Diabetes Information Audit and Benchmarking (ANDIAB) in Australia. The main outcome measures were incremental costs and effectiveness of CSII compared with MDI in Australian adult and adolescent patients with T1DM. RESULTS: Mean direct lifetime costs were $A34,642 higher with CSII treatment than with MDI for adult patients and $A41,779 higher for adolescent patients. Treatment with CSII was associated with an improvement in life expectancy of 0.393 years for adults compared with MDI and 0.537 years for adolescents. The corresponding gains in QALYs were 0.467 QALYs and 0.560 QALYs for adults and adolescents, respectively. This produced incremental cost effectiveness ratios (ICERs) of $A88,220 and $A77,851 per life-year gained for CSII compared with MDI for adult and adolescent T1DM patients, respectively, in Australia. These data also produced corresponding ICERs of $A74,147 per QALY and $A74,661/QALY for adult and adolescent T1DM patients, respectively. Sensitivity analyses suggested that our base-case assumptions were mostly robust with improvements in ICERs for reduction in hypoglycaemic events with CSII treatment and worse ICERs for lower HbA(1c) changes associated with CSII treatment compared with MDI. CONCLUSIONS: Our analysis suggests that CSII is associated with ICERs in the range of $A53,022-259,646 per QALY gained, with most ICERs representing good value for money in Australia under the majority of scenarios explored.

Application of economic analyses in U.S. managed care formulary decisions: a private payer's experience.

BACKGROUND: Promoting use of pharmaco-economic models by formulary reviewers is a goal of the Academy of Managed Care Pharmacy (AMCP) Format for Formulary Submissions, but relatively few decision makers use such models, and many doubt that they provide meaningful input. OBJECTIVE: To demonstrate how sophisticated disease-based pharmaco-economic models can aid formulary decision makers when long-term outcomes data are lacking. METHODS: The Center for Outcomes Research (CORE) Diabetes Model (CDM), a published, validated Markov pharmaco-economic model that projects clinical and economic endpoints, was used to model the cost-effectiveness of exenatide, a new injectable antidiabetic agent that enhances glucose-dependent insulin secretion, in a standard cohort of type 2 diabetes patients (mean body mass index [BMI] = 27.5 3 kg/m2), compared with a modified obese cohort (mean BMI = 35 3 kg/m2) that was otherwise demographically identical at baseline to the standard cohort. The standard cohort was assumed to maintain baseline weight during treatment, and the modified obese cohort was assumed to experience weight loss of approximately 9% (mean = 3 kg/m2), with corresponding improvements in blood pressure, low density lipoprotein cholesterol, and triglycerides. We selected a 30-year time horizon because it was the time interval during which the CDM predicted most of the subjects would have died, and the costs obtained thus reasonably projected lifetime total direct medical costs for these cohorts. While treatment options certainly will change over a 30-year period, our goal was to estimate the incremental effect of exenatide over other available therapies. RESULTS: The model predicted reduced long-term treatment costs in obese patients, driven by an 11% decrease in cardiovascular disease burden and derived from the presumed weight loss. The incremental cost-effectiveness ratio (ICER) for adding exenatide over 3 years was 35,000 dollars/quality-adjusted life-year (QALY). Using a 30-year horizon, ICER values were 13,000 dollars/QALY versus insulin, 32,000 dollars versus generic glyburide, and 16,000 dollars versus no additional treatment. Exenatide dominated pioglitazone. By comparison, the 30-year ICER for exenatide versus insulin in the nonobese cohort was 33,000 dollars. These results were presented to the pharmacy and therapeutics (P&T) committee and influenced its decision to add exenatide to the drug formulary. While our modeling assumed certain patient characteristics (e.g., obesity, need of further A1c reduction at baseline, motivation to lose weight), the P&T committee imposed only a step-therapy requirement to try either metformin or a sulfonylurea before trying exenatide and did adopt a nonspecific requirement for physician reauthorization of refills before the fourth pharmacy claim for exenatide. CONCLUSIONS: Disease-based pharmaco-economic models may help third party payers project costs and be particularly useful when only data from short-term clinical trials are available. In the present case, the pharmacy staff of a health plan used a pharmaco-economic model for drug treatment of type 2 diabetes provided by the manufacturer as part of the AMCP Format dossier process to project cost outcomes for exenatide, adjunct injectable therapy for patients taking metformin and/or sulfonylurea. The P&T committee approved the drug for inclusion in the drug formulary based in part on the results of the pharmaco-economic model produced from the cost inputs entered into the model by the health plan pharmacists.

Treating diabetes to accepted standards of care: a 10-year projection of the estimated economic and health impact in patients with type 1 and type 2 diabetes mellitus in the United States.

OBJECTIVE: The aim of this study was to investigate the health-economic impact of maintaining glycosylated hemoglobin (HbA(1c)) values in all US patients with currently uncontrolled type 1 or type 2 diabetes mellitus at the American Diabetes Association (ADA) standard of 7.0% and the American Association of Clinical Endocrinologists (AACE) target of 6.5% compared with maintenance at current population-based values. METHODS: The CORE-Center for Outcomes Research Diabetes Model was used to predict costs and outcomes for patients with uncontrolled type 1 and type 2 diabetes who remain at established population mean HbA(1c) values in comparison with those for patients who maintain the standard value of 7.0% or the target value of 6.5%. The analysis was run from a societal perspective over a 10-year time horizon. The costs of treating complications and medication costs were retrieved from published sources. Costs and clinical outcomes were discounted at 3% per annum. Sensitivity analyses were performed on the discount rate and time horizon. RESULTS: This analysis found that maintaining HbA(1c) at the ADA standard value of 7.0% and the AACE target value of 6.5% in patients with uncontrolled type 1 and type 2 diabetes could achieve total direct medical cost savings of nearly 35 US dollars and 50 billion US dollars , respectively, over 10 years. When indirect cost savings were included, the total savings increased to between nearly 50 billion US dollars and 72 billion US dollars for these respective HbA(1c) targets, corresponding to 4% and 6% of the total annual US health care costs of 1.3 trillion US dollars. Reduced savings were observed with a higher discount rate and shorter time horizon, but savings increased as the time horizon became longer. These cost savings must be weighed against the cost of reaching the HbA(1c) goals and the likelihood of achieving the clinical objectives. CONCLUSIONS: Efficient targeting of financial resources toward the goal of lowering HbA(1c) in line with published guidelines could lead to financial savings in the range from nearly 35 billion US dollars to 72 billion US dollars over the next 10 years.

The CORE Diabetes Model: Projecting long-term clinical outcomes, costs and cost-effectiveness of interventions in diabetes mellitus (types 1 and 2) to support clinical and reimbursement decision-making.

OBJECTIVES: We have developed an Internet-based, interactive computer model to determine the long-term health outcomes and economic consequences of implementing different treatment policies or interventions in type 1 and type 2 diabetes mellitus. The model projects outcomes for populations, taking into account baseline cohort characteristics and past history of complications, current and future diabetes management and concomitant medications, screening strategies and changes in physiological parameters over time. The development of complications, life expectancy, quality-adjusted life expectancy and total costs within populations can be calculated. METHODS: The model is based on a series of sub-models that simulate important complications of diabetes (cardiovascular disease, eye disease, hypoglycaemia, nephropathy, neuropathy, foot ulcer, amputation, stroke, ketoacidosis, lactic acidosis and mortality). Each sub-model is a Markov model using Monte Carlo simulation incorporating time, state, time-in state, and diabetes type-dependent probabilities derived from published sources. Analyses can be performed on cohorts with type 1 or type 2 diabetes. Cohorts, defined in terms of age, gender, baseline risk factors and pre-existing complications, can be modified or new cohorts defined by the user. Economic and clinical data in the model can be edited, thus ensuring adaptability by allowing the inclusion of new data as they become available; creation of country- or provider-specific versions of the model; and allowing the investigation of new hypotheses. CONCLUSIONS: The CORE Diabetes Model allows the calculation of long-term outcomes, based on the best data currently available. Diabetes management strategies can be compared in different patient populations in a variety of realistic clinical settings, allowing the identification of efficient diabetes management strategies.

Validation of the CORE Diabetes Model against epidemiological and clinical studies.

OBJECTIVES: The aim of this study was to assess the validity of the CORE Diabetes Model by comparing results from model simulations with observed outcomes from published epidemiological and clinical studies in type 1 and type 2 diabetes. METHODS: A total of 66 second- (internal) and third- (external) order validation analyses were performed across a range of complications and outcomes simulated by the CORE Diabetes Model (amputation, cataract, hypoglycaemia, ketoacidosis, macular oedema, myocardial infarction, nephropathy, neuropathy, retinopathy, stroke and mortality). Published studies were reproduced in the model by recreating cohorts in terms of demographics, baseline risk factors and complications, treatment patterns and patient management strategies, and simulating the progress of the cohort to an equivalent time horizon. RESULTS: Correlation analysis on results from 66 validation simulations produced an R2 value of 0.9224 (perfect fit = 1). A correlation plot of published study data versus values simulated by the CORE Diabetes Model had a trend line with a gradient of 1.0187 (perfect fit = 1). Validation analyses in type 1 and type 2 diabetes were associated with R2 values of 0.9778 and 0.8861 respectively. Correlation of second-order validation analyses (model predictions versus observed outcomes in studies used to construct the model) produced an R2 value of 0.9574, and the value for third-order analyses (model predictions versus observed outcomes in studies not used to construct the model) was 0.9023. CONCLUSIONS: The CORE Diabetes Model provides an accurate representation of patient outcomes when compared to 66 studies of diabetes and its complications. Model flexibility ensures it can be used to compare diabetes management strategies in different cohorts across a variety of clinical settings.

Comparing the long-term cost-effectiveness of repaglinide plus metformin versus nateglinide plus metformin in type 2 diabetes patients with inadequate glycaemic control: an application of the CORE Diabetes Model in type 2 diabetes.

OBJECTIVES: As an example application of the CORE Diabetes Model in type 2 diabetes, we simulated the cost-effectiveness of repaglinide/metformin combination therapy versus nateglinide/metformin for treatment of individuals with type 2 diabetes with an inadequate response to sulphonylurea, metformin, or fixed dose glyburide/metformin. METHODS: The CORE Diabetes Model was used to simulate long-term outcomes for a cohort of individuals with type 2 diabetes treated with either repaglinide/metformin or nateglinide/metformin. HbA1c changes for each regimen were taken from a comparative study. At the end of the study, changes in HbA1c from baseline were -1.28% points and -0.67% points for repaglinide/metformin and nateglinide/metformin, respectively. Median final doses were 5.0 mg/day for repaglinide, 360 mg/day for nateglinide and 2000 mg/day metformin in each treatment arm. Costs were calculated as the annual costs for drugs plus costs of complications (US Medicare perspective) over a 30-year period. Life expectancy (LE) and quality-adjusted life expectancy (QALE) were calculated. Outcomes and costs were discounted at 3% annually. RESULTS: With repaglinide/metformin, improved glycaemic control led to projected decreases in complication rates, improvement of LE and QALE by 0.15 and 0.14 years respectively, and total cost savings of 3,662 dollars/person over the 30-year period. Repaglinide/metformin had a 96% probability that the incremental costs per quality-adjusted life year gained would be 20,000 dollars or less, and a 66% probability that repaglinide/metformin would be cost-saving compared to nateglinide/metformin. Sensitivity analyses supported the validity and reliability of the results. CONCLUSIONS: In the health economic context, repaglinide/metformin combination was dominant to nateglinide/metformin. The CORE Diabetes Model is a tool to help third-party reimbursement payers identify treatments for type 2 diabetes that are good value for money.

Impact of changes in HbA1c, lipids and blood pressure on long-term outcomes in type 2 diabetes patients: an analysis using the CORE Diabetes Model.

OBJECTIVES: Various factors influence the risk of complications in type 2 diabetes patients. The isolated impact of single risk factors on long-term outcomes is unclear. The aim of this study was to calculate the projected effects on life expectancy (LE), quality-adjusted LE (QALE) and total costs of complications (TC) of 10% improvements in baseline levels of either total cholesterol (T-CHOL), high-density lipoprotein cholesterol (HDL), systolic blood pressure (SBP), glycosylated haemoglobin (HbA1c), and all four parameters combined. METHODS: A cohort of newly diagnosed patients (baseline age 52 years, HbA1c 9.1%, SBP 137 mmHg, T-CHOL 212 mg/dL, and HDL 39 mg/dL) was defined. The CORE Diabetes Model was used to simulate LE, QALE and TC (US third-party payer perspective discounted at 3% annually) over patients' lifetimes, assuming no change in risk factors, an isolated 10% improvement in each parameter, or a 10% improvement in all parameters simultaneously. RESULTS: Improved HbA1c led to increases in LE and QALE of 1.00 and 0.81 years respectively, and decreased TC of (US) 10,800 dollars/patient. Improved SBP led to improvements in LE and QALE of 0.67 and 0.55 years respectively and decreased TC of 7,049 dollars. Decreased T-CHOL led to improvements in LE and QALE of 0.29 and 0.20 years, respectively, and increased TC of 1,923 dollars. Increased HDL led to improvements in LE and QALE of 0.28 and 0.18 years respectively, and increased TC of 2,162 dollars. Simultaneous improvements in all parameters led to projected improvements in LE and QALE of 2.17 and 1.72 years respectively, and decreased TC of 14,533 dollars. CONCLUSIONS: Combined improvements in HbA1c, lipid levels and SBP produced the greatest benefits in terms of LE, QALE and TC. A 10% improvement in HbA1c had the greatest impact on these three outcomes.

What impact would pancreatic beta-cell preservation have on life expectancy, quality-adjusted life expectancy and costs of complications in patients with type 2 diabetes? A projection using the CORE Diabetes Model.

OBJECTIVE: Type 2 diabetes is characterised by progressive failure of pancreatic beta-cell function against a background of insulin resistance. Multifactorial interventions, including intensive glycaemic and blood pressure control, reduce the risk of onset and progression of complications. However, current management of type 2 diabetes focuses on treatment of signs and symptoms of disease instead of targeting underlying causes. A number of newer pharmacological interventions, including thiazolidinediones and glucagon-like peptides, have shown early promise in preserving pancreatic beta-cell function. The aim of this study was to investigate the impact of stabilising beta-cell function on long-term outcomes in patients with type 2 diabetes. METHODS: The CORE Diabetes Model was used to project life expectancy (LE), quality-adjusted LE (QALE) and total lifetime complication costs (TC) for a cohort of newly-diagnosed patients with type 2 diabetes, either with a typical increase of HbA1c over time as observed in the UKPDS, or assuming stabilisation of HbA1c after diagnosis with a hypothetical new treatment, representing beta-cell function stabilisation. Costs due to diabetes-related complications (from a US third-party payer perspective), were discounted at 3% annually. Both non-discounted and discounted (at 3% annually) LE and QALE were calculated. Sensitivity analyses were performed to test the robustness of results. RESULTS: Over a time period of 50 years, in a cohort with no increase of HbA1c over time, LE and QALE were improved by mean (SD) 1.02 (0.36) and 0.96 (0.25) years, and total costs of complications were reduced by 6,377 dollars (2,568) per patient compared to the cohort with a typical increase in HbA1c over time. Results were robust under a wide range of plausible assumptions. CONCLUSIONS: New interventions that stabilise pancreatic betacell function may have an important impact on length and quality of life, and lead to reduced costs of complications in patients with type 2 diabetes.

Deleterious effects of increased body weight associated with intensive insulin therapy for type 1 diabetes: increased blood pressure and worsened lipid profile partially negate improvements in life expectancy.

OBJECTIVE: Weight gain is an unwanted side effect of improved glycaemic control in type 1 diabetes, associated with increased blood pressure (BP) and worsening lipid profiles. While improved glycaemic control per se should improve long-term patient outcomes, increases in BP and worsening lipid profiles may counteract these benefits. The aim of this modelling study was to assess whether the increased body weight and associated worsening of lipid profile and blood pressure would negate the improvements in glycaemic control seen with intensive therapy in patients with type 1 diabetes. METHODS: A validated diabetes model projected life expectancy (LE), quality-adjusted LE (QALE) and total lifetime costs of complications in type 1 diabetes cohorts with the characteristics of patients from the Diabetes Control and Complications Trial (DCCT). The following four cohorts (A-D) were created based on increased body weight under either conventional or intensive therapy: A) conventional glycaemic control in the subgroup with lowest weight-gain quartile after 6.5 years (HbA1c increased by 11% from baseline); B) conventional control in the highest weight-gain quartile (no change in HbA1c from baseline); C) intensive control in the lowest quartile of weight gain (with 16.1% decrease in HbA1c, but no increase in weight or associated BP, and improved lipid profile); D) intensive control in the highest quartile of weight gain (with 21% decrease in HbA1c, increased systolic BP of 6 mmHg, and worsened lipid profile). Data were derived from DCCT and other published sources. RESULTS: Intensive control, even with weight gain, led to major improvements in LE and QALE, and reduction in costs of complications versus conventional therapy. Intensive therapy with no weight increase led to a higher LE (increased by 0.57 years) and higher QALE (increased by 0.28 years) and lower costs of complications (reduced by 523 dollars/patient), compared to intensive therapy with the highest quartile of weight gain. CONCLUSIONS: Concerns about weight gain should not deter intensive insulin therapy. However, the value of improving glycaemic control without increasing body weight (and associated increased BP and worsening of lipid profile) has been confirmed.