Health-related quality of life (HRQL) for individuals with self-reported chronic physical and/or mental health conditions: panel survey of an adult sample in the United States.

BACKGROUND: In the US, approximately 53% of adults have at least one chronic condition. Comorbid physical and mental health conditions often have an incremental negative impact on health-related quality of life (HRQL). Primary study objectives were to quantify the impact on HRQL of a) ≥ 1 physical condition , b) ≥ 1 comorbid mental health conditions added to a physical one, c) ≥ 1 mental health condition, and d) ≥ 1 comorbid physical conditions added to at least one related to mental health. Decrements were based on a "Healthy" reference group reporting no chronic conditions. METHODS: Participants were sampled (n = 3877) from the US adult population as part of a 2009 normative survey. Demographics, number/ type of chronic conditions, and HRQL data were self-reported. HRQL was defined through SF-36v2® Physical Component Summary (PCS) scores and Mental Component Summary (MCS) scores. Participant "morbidity" groupings included Healthy; Physical Health Condition only, Mental Health Condition only, and Physical and Mental Health (Comorbid). PCS and MCS scores were also analyzed by physical disease clusters (e.g., cardiovascular, gastrointestinal). Multivariate regression models were used for all analyses. RESULTS: 81% of participants were Caucasian; 9% African American. Males and females were about equally represented; 63% were ≥ 45 years old. The average number of reported chronic conditions was 2.4 (SD = 2.4). Relative to the Healthy group, the Physical Condition group scored 6.4 (males) and 7.5 (females) points lower on PCS. The addition of a comorbid mental health condition resulted in a total reduction of 11 points in PCS and 15 points in MCS. Compared to the Healthy group, ≥ 1 mental health conditions was associated with MCS decrements of 11-12 points. A physical comorbidity led to additional decrements of 3-4 points for MCS, with a total of 15 points. Incremental HRQL burden defined by both MCS and PCS scores was relatively similar across the 5 defined physical disease clusters. CONCLUSION: Results provide quantitative information for US adults on specific PCS and MCS score decrements associated with a comorbid condition related to mental health, as well as a comorbid condition related to physical health.

Cost effectiveness of self-monitoring of blood glucose (SMBG) for patients with type 2 diabetes and not on insulin: impact of modelling assumptions on recent Canadian findings.

BACKGROUND: Canadian patients, healthcare providers and payers share interest in assessing the value of self-monitoring of blood glucose (SMBG) for individuals with type 2 diabetes but not on insulin. Using the UKPDS (UK Prospective Diabetes Study) model, the Canadian Optimal Prescribing and Utilization Service (COMPUS) conducted an SMBG cost-effectiveness analysis. Based on the results, COMPUS does not recommend routine strip use for most adults with type 2 diabetes who are not on insulin. Cost-effectiveness studies require many assumptions regarding cohort, clinical effect, complication costs, etc. The COMPUS evaluation included several conservative assumptions that negatively impacted SMBG cost effectiveness. OBJECTIVES: Current objectives were to (i) review key, impactful COMPUS assumptions; (ii) illustrate how alternative inputs can lead to more favourable results for SMBG cost effectiveness; and (iii) provide recommendations for assessing its long-term value. METHODS: A summary of COMPUS methods and results was followed by a review of assumptions (for trial-based glycosylated haemoglobin [HbA(1c)] effect, patient characteristics, costs, simulation pathway) and their potential impact. The UKPDS model was used for a 40-year cost-effectiveness analysis of SMBG (1.29 strips per day) versus no SMBG in the Canadian payer setting. COMPUS assumptions for patient characteristics (e.g. HbA(1c) 8.4%), SMBG HbA(1c) advantage (-0.25%) and costs were retained. As with the COMPUS analysis, UKPDS HbA(1c) decay curves were incorporated into SMBG and no-SMBG pathways. An important difference was that SMBG HbA(1c) benefits in the current study could extend beyond the initial simulation period. Sensitivity analyses examined SMBG HbA(1c) advantage, adherence, complication history and cost inputs. Outcomes (discounted at 5%) included QALYs, complication rates, total costs (year 2008 values) and incremental cost-effectiveness ratios (ICERs). RESULTS: The base-case ICER was $Can63 664 per QALY gained; approximately 56% of the COMPUS base-case ICER. SMBG was associated with modest risk reductions (0.10-0.70%) for six of seven complications. Assuming an SMBG advantage of -0.30% decreased the current base-case ICER by over $Can10 000 per QALY gained. With adherence of 66% and 87%, ICERs were (respectively) $Can39 231 and $Can54 349 per QALY gained. Incorporating a more representative complication history and 15% complication cost increase resulted in an ICER of $Can49 743 per QALY gained. CONCLUSIONS: These results underscore the importance of modelling assumptions regarding the duration of HbA(1c) effect. The current study shares several COMPUS limitations relating to the UKPDS model being designed for newly diagnosed patients, and to randomized controlled trial monitoring rates. Neither study explicitly examined the impact of varying the duration of initial HbA(1c) effects, or of medication or other treatment changes. Because the COMPUS research will potentially influence clinical practice and reimbursement policy in Canada, understanding the impact of assumptions on cost-effectiveness results seems especially important. Demonstrating that COMPUS ICERs were greatly reduced through variations in a small number of inputs may encourage additional clinical research designed to measure SMBG effects within the context of optimal disease management. It may also encourage additional economic evaluations that incorporate lessons learned and best practices for assessing the overall value of SMBG for type 2 diabetes in insulin-naive patients.

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.

Self-monitoring of blood glucose (SMBG) for type 2 diabetes patients treated with oral anti-diabetes drugs and with a recent history of monitoring: cost-effectiveness in the US.

OBJECTIVE: Stakeholders in the US and elsewhere are interested in country-specific and cohort-specific information with which to assess the long-term value of self-monitoring of blood glucose (SMBG) for patients with type 2 diabetes mellitus (T2DM) on oral anti-diabetes drugs (OADs). This study modeled the cost-effectiveness of SMBG at frequencies of once, twice, or three times per day for this population, and included those who had used SMBG in the prior year. RESEARCH DESIGN AND METHODS: Based on clinical findings of a longitudinal Kaiser Permanente study, a validated model was used to project 40-year clinical and economic outcomes for SMBG at (averages of) once, twice, or three times per day versus no SMBG. Baseline HbA1c (7.6%), age and gender represented the Kaiser study 'prevalent' SMBG users cohort. Unit costs came primarily from a 2003 published article; inflated to US$2006. Outcomes were discounted at 3% per annum, with sensitivity analyses on discount rates and time horizons. Analyses were conducted from a third-party payer perspective in the US, including only direct costs. MAIN OUTCOME MEASURES: Primary outcomes were differences in total costs, cumulative incidence of complications, quality-adjusted life years (QALYs); and incremental cost-effectiveness ratios (ICERs). RESULTS: For patients using SMBG once, twice, or three times per day, relative risks over 40 years were lower for 14 of 16 complications and slightly higher for 2 complications. Compared to 'no SMBG,' QALYs increased with SMBG frequency: 0.047, 0.116, and 0.132 QALYs for SMBG once, twice, and three times per day, respectively. Some increased costs with SMBG were offset by reductions in costs for several diabetes-related complications. Corresponding ICERs were $26,206, $18,572 and $25,436/QALY gained. Results were most sensitive to time horizon, with SMBG not cost-effective over a 5-year simulation period. CONCLUSIONS: Study limitations include the use of relatively short-term observational data, unknown levels of patient adherence, and assumptions regarding the duration of clinical effects. Results showed that compared to no SMBG, base case ICERs for each of the three SMBG frequencies examined were below $30,000, and that a portion of the increased costs associated with SMBG were offset by reductions in complication costs, and by modest increases in QALYs. Results add to the literature addressing the cost-effectiveness of SMBG as a component of care for T2DM patients on OADs, and in particular those with monitoring experience within the previous year.

Self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes on oral anti-diabetes drugs: cost-effectiveness in France, Germany, Italy, and Spain.

OBJECTIVE: Stakeholders in Europe remain interested in assessments of country-specific value of self-monitoring of blood glucose (SMBG) for patients with type 2 diabetes treated with oral anti-diabetes drugs (OADs). This study used the IMS-CORE Diabetes Model to project the long-term (40-year) cost-effectiveness of SMBG at once, twice, or three times per day (vs. no SMBG) for this population from national reimbursement system perspectives in France, Germany, Italy, and Spain. METHODS: SMBG input costs (strips, lancets, meters, nurse training) were supplied by LifeScan in 2007 euro values and applied as appropriate for each country's reimbursement policy. Cohort characteristics and assumed Hb(A1c) effects came from a US Kaiser Permanente longitudinal analysis of new SMBG users. Country-specific estimations for use of screening programs and several concomitant medications, as well as mortality rates were used. Country-specific complication costs from published sources were inflated to 2007 euro. Base case outcomes were discounted at 3% per annum for France, Germany, and Italy; 6% for Spain. Sensitivity analyses varied time horizon and discount rates for each country. They also included a -0.036 dis-utility for SMBG in year 1. MAIN OUTCOME MEASURES: Primary outcomes included total direct costs, gains in quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) over 40 years. RESULTS: ICERs were largest in France (with meter costs included), and in Italy (with highest reimbursed costs for strips/lancets). ICERs for SMBG once, twice, and three times per day were 12,114 euros, 6282 euros, and 7958 euros (respectively) in France; and 12,694 euros, 11,934 euros, and 15,368 euros in Italy. ICERs for SMBG once or twice per day were <2000 euros in Germany and <4000 euros in Spain. ICERs for SMBG three times per day were <6000 euros/QALY in both countries. Results were most sensitive to the 5-year time horizon, although ICERs for SMBG once per day were below 50,000 euros/QALY in all countries but Italy (ICER = 77,064 euros). Five-year ICERs for SMBG twice per day were below 40,000 euros/QALY for all four countries, and those for SMBG three times per day were below 45,000 euros/QALY. With the SMBG dis-utility, ICERs increased modestly (321 euros- 2264 euros/QALY) in all scenarios except SMBG once per day in France (9578 euros increase) and Italy (5979 euros increase). Study limitations include the use of relatively short-term data from a single US observational study for SMBG clinical effects, unknown levels of patient adherence, and assumptions regarding the duration of clinical effects. CONCLUSIONS: With cost assumptions reflecting current reimbursement levels in France, Germany, Italy, and Spain, SMBG was found to be cost-effective across a 40-year time horizon, with all base case ICERs <16,000/QALY. This study adds to the literature on the country-specific, long-term value of SMBG for type 2 diabetes patients treated with OADs. Under current model assumptions, variations in cost-effectiveness results stemmed primarily from payer reimbursement practices for SMBG within each country.

A cost-effectiveness analysis to illustrate the impact of cost definitions on results, interpretations and comparability of pharmacoeconomic studies in the US.

BACKGROUND: There is a lack of a uniform proxy for defining direct medical costs in the US. This potentially important source of variation in modelling and other types of economic studies is often overlooked. The extent to which increased expenditures for an intervention can be offset by reductions in subsequent service costs can be directly related to the choice of cost definitions. OBJECTIVES: To demonstrate how different cost definitions for direct medical costs can impact results and interpretations of a cost-effectiveness analysis. METHODS: The IMS-CORE Diabetes Model was used to project the lifetime (35-year) cost effectiveness in the US of one pharmacological intervention 'medication A' compared with a second 'medication B' (both unspecified) for type 2 diabetes mellitus. The complications modelled included cardiovascular disease, renal disease, eye disease and neuropathy. The model had a Markov structure with Monte Carlo simulations. Utility values were derived from the published literature. Complication costs were obtained from a retrospective database study that extracted anonymous patient-level data from (primarily private payer) adjudicated medical and pharmaceutical claims. Costs for pharmacy services, outpatient services and inpatient hospitalizations were included. Cost definitions for complications included charged, allowed and paid amounts, and for medications included both wholesale acquisition cost (WAC) and average wholesale price (AWP). Costs were reported in year 2007 values. RESULTS: The cost-effectiveness results differed according to the particular combination of cost definitions employed. The use of charges greatly increased costs for complications. When the analysis incorporated WAC medication prices with charged amounts for complication costs, the incremental cost-effectiveness ratio (ICER) for medication A versus medication B was $US6337 per QALY. When AWP prices were used with charged amounts, medication A became a dominant treatment strategy, i.e. lower costs with greater effectiveness than medication B. For both allowed and paid scenarios, there was a difference in the ICER of over $US10,300 per QALY when medication prices were defined by WAC versus AWP. Ratios of medication costs to cardiovascular complication costs ranged from under 0.45 to over 1.7, depending upon the combination of costing definitions. CONCLUSIONS: Explicitly addressing the cost-definition issue can help provide meaningful cost-effectiveness data to payers for policy development and management of healthcare expenditures. It can also help move the pharmacoeconomics and outcomes research fields forward in terms of both methodology and practical application.

A cost-effectiveness analysis of pioglitazone plus metformin compared with rosiglitazone plus metformin from a third-party payer perspective in the US.

OBJECTIVE: The long-term cost-effectiveness of using pioglitazone plus metformin (Actoplusmet dagger) compared with rosiglitazone plus metformin (Avandamet double dagger) in treating type 2 diabetes (T2DM) was assessed from a US third-party payer perspective. RESEARCH DESIGN AND METHODS: Clinical efficacy (change in HbA(1c) and lipids) and baseline cohort parameters were extracted from a 12-month, randomized clinical trial (Derosa et al., 2006) evaluating the efficacy and tolerability of pioglitazone versus rosiglitazone, both in addition to metformin, in adult T2DM patients with insufficient glucose control (n = 96). A Markov-based model was used to project clinical and economic outcomes over 35 years, discounted at 3% per annum. Costs for complications were taken from published sources. Base-case assumptions were assessed through several sensitivity analyses. MAIN OUTCOME MEASURES: Outcomes included incremental life-years, quality-adjusted life-years (QALYs), total direct medical costs, cumulative incidence of complications and associated costs, and incremental cost-effectiveness ratios (ICERs). RESULTS: Compared to rosiglitazone plus metformin, pioglitazone plus metformin was projected to result in a modest improvement in 0.187 quality-adjusted life-years. Over patients' lifetimes, total direct medical costs were projected to be marginally lower with pioglitazone plus metformin (difference -$526.), largely due to reduced CVD complication costs. While costs were higher among renal, ulcer/amputation/neuropathy, and eye complications in the pioglitazone plus metformin group, the cost savings for CVD complications outweighed their economic impact. Pioglitazone plus metformin was found to be a dominant long-term treatment strategy in the US compared to rosiglitazone plus metformin. Sensitivity analyses showed findings to be robust under almost all scenarios, including short-term time horizons, 6% discounting, removal of individual lipid parameters, and modifications of patient cohort to more closely represent a US T2DM population. Pioglitazone plus metformin was no longer dominant with 0% discounting, with 25% reduction in its HbA(1c) effects, or with a 15% increase in its acquisition price. CONCLUSIONS: Under a range of assumptions and study limitations around cohorts, clinical effects, and treatment patterns, this long-term analysis showed that pioglitazone plus metformin, when compared to rosiglitazone plus metformin, was a dominant treatment strategy within the US payer setting. Results were driven by the combination of modest differences in QALYs and modest savings in total complication costs over 35 years.

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.

Cost-effectiveness of insulin detemir compared to NPH insulin for type 1 and type 2 diabetes mellitus in the Canadian payer setting: modeling analysis.

OBJECTIVE: This study was conducted to quantify the long-term cost-effectiveness of insulin detemir (Levemir) versus intermediate-acting neutral protamine Hagedorn (NPH) insulin for the treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in Canada, and to assess the sensitivity of results to dis-utilities for hypoglycemic events. dagger Levemir is a trade name of Novo Nordisk, Princeton, NJ, USA RESEARCH DESIGN AND METHODS: The web-based IMS-CORE diabetes model has a menu-driven interface programmed in hypertext markup language (HTML). It was used to project lifetime (60 years for T1DM and 35 years for T2DM) clinical and economic outcomes for patients on detemir vs. NPH. Cohort characteristics, utilities, and costs were derived from published literature. For T1DM, clinical trial data for HbA(1c) improvement (detemir -0.94% +/- 1.07; NPH -0.82% +/- 1.01) from baseline, and rates of hypoglycemic events (major events: 0.20 vs. 0.80 per patient-year for detemir vs. NPH, respectively) were modeled. For T2DM, observational study data for HbA(1c) improvement (detemir -0.18%) from baseline, and reductions in hypoglycemic events (major events: 0.0995 vs. 1.33 per patient-year for detemir vs. NPH, respectively) were modeled. Base-case hypoglycemia dis-utilities were -0.0118 for major and -0.0035 for minor events. Sensitivity analyses were conducted on discount rate and hypoglycemia dis-utility. OUTCOME MEASURES: Outcomes included costs of treatment/management and costs (and incidence) of diabetes-related complications. Incremental cost-effectiveness ratios (ICERs) were calculated from differences in total costs and quality-adjusted life-years (QALYs). RESULTS: Average total costs for T1DM were $CAN 83 622 +/- 4585 for detemir and $CAN 72 016 +/- 4593 for NPH. QALYs increased by 0.475 years with detemir, with an ICER of $CAN 24 389/QALY. Average direct costs for T2DM were $CAN 74 919 +/- 6391 (detemir) and $CAN 69 230 +/- 6840 (NPH). QALYs increased by 0.305 years. The ICER was $CAN 18 677. Although detemir was associated with slightly lower costs for most complications, results were driven by the differences in rates and costs for hypoglycemic events, and their assumed dis-utility. Study limitations include the use of single trials for clinical assumptions and the lack of analyses for patient risk sub-groups. CONCLUSIONS: Findings provide evidence for the cost-effectiveness of detemir vs. NPH in treating T1 and T2DM in Canada, and support the key role of assumptions regarding the impact of hypoglycemic events. Additional work is needed to determine the extent to which results are robust for different sub-groups of patients and for variation in assumptions around HbA(1c) improvements and hypoglycemic event rates.

Pioglitazone versus rosiglitazone treatment in patients with type 2 diabetes and dyslipidemia: cost-effectiveness in the US.

OBJECTIVES: Pioglitazone hydrochloride (Actos † ) and rosiglitazone maleate (Avandia ‡ ) are members of the thiazolidinedione (TZD) class of oral anti-diabetic drugs (OADs) and are used to treat type 2 diabetes mellitus (T2DM). Greater beneficial effects on lipids have been demonstrated with pioglitazone, however. Study objectives were to evaluate the long-term cost-effectiveness of pioglitazone compared to rosiglitazone in treating patients with T2DM and dyslipidemia, and determine the extent to which reported beneficial lipid effects of pioglitazone would improve clinical and economic outcomes through reduced macrovascular complications. † Actos is a trade name of Takeda Pharmaceuticals Co. Ltd., Deerfield, IL, US ‡ Avandia is a trade name of GlaxoSmithKline, Research Triangle, NC, US. RESEARCH DESIGN AND METHODS: The validated CORE Diabetes Model (CDM) was used to simulate changes in glycosylated hemoglobin (HbA(1c)), complications, and direct medical costs. Baseline parameters came from a multi-center, double-blind trial comparing lipid and glycemic effects of pioglitazone (n = 400) and rosiglitazone (n = 402) among individuals with T2DM and untreated dyslipidemia. Sensitivity analyses examined the impact of cohort, clinical, and cost inputs on incremental cost effectiveness ratios (ICERs). RESULTS: In the base case, pioglitazone was associated with mean (standard deviation [SD]) quality-adjusted life years (QALYs) of 7.476 (0.123) vs. 7.326 (0.128) for rosiglitazone. Pioglitazone had $3038 higher total direct costs, but $580 lower complication costs. Risks of four cardiovascular complications were reduced with pioglitazone (relative risks 0.860-0.942), while risks of 17 other complications were slightly higher (relative risks 1.001-1.056). The ICER for pioglitazone treatment was $20 171/QALY. Results were most sensitive to the effects of HbA(1c), high-density lipoprotein-cholesterol, overall lipid effects, and pioglitazone acquisition costs. CONCLUSIONS: Study limitations include issues of generalizability of the trial patient population, as well as inability to capture non-adherence and variation in 'real-world' treatment patterns. Nevertheless, pioglitazone (when compared to rosiglitazone) was found to have long-term value as a treatment option for T2DM patients with dyslipidemia treated within the US payer setting.

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.

Self-monitoring of blood glucose in type 2 diabetes: cost-effectiveness in the united states.

OBJECTIVE: This study was designed to model the cost-effectiveness of self-monitoring of blood glucose (SMBG) at frequencies of 1 or 3 times per day for patients with type 2 diabetes mellitus (T2DM) who are treated with oral antidiabetic (OAD) medications within the United States. STUDY DESIGN: Based on a Kaiser Permanente study showing glycosylated hemoglobin (HbA1C) improvements related to SMBG frequency, a validated model was used to project 40-year clinical and economic outcomes for SMBG at 1 or 3 times per day vs no SMBG. METHODS: Baseline mean HbA1C (8.6%), age, and sex of the simulated cohort came from the Kaiser analysis of new SMBG users of OAD agents for T2DM. Other cohort characteristics, transition probabilities, utilities, and direct costs (from a US public payer perspective) were derived from relevant literature. Outcomes were discounted at 3% per annum, with sensitivity analyses performed on discount rates and time horizons. RESULTS: Compared with no SMBG, quality-adjusted life expectancy increased with SMBG frequency. Increases were 0.103 and 0.327 quality-adjusted life-years (QALYs) for SMBG at 1 and 3 times per day, respectively. Corresponding incremental cost-effective ratios (ICERs) were $7856 and $6601 per QALY gained. Results indicate that SMBG at both 1 and 3 times per day in this cohort of patients with T2DM taking OADs would represent good value for money in the United States, with ICERs being most sensitive to the time horizon. CONCLUSIONS: Longer time horizons generally led to greater SMBG cost-effectiveness. The ICER for SMBG 3 times per day was $518 per QALY over a 10-year time horizon, indicating very good value.

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.

An examination of factors affecting persistence with initial antipsychotic treatment in patients with schizophrenia.

OBJECTIVES: During a schizophrenia treatment episode, persistence with the initial antipsychotic may indicate optimal pharmacotherapy and be a precursor to longer-term effectiveness and other positive outcomes. The objective of this study was to examine the ability of selected variables to predict antipsychotic persistence among patients receiving olanzapine or risperidone as initial treatment. RESEARCH DESIGN AND METHODS: Data for this analysis, which was not defined in the original study protocol, came from a naturalistic, randomized, open-label trial comparing costs and effectiveness of first-line antipsychotic treatment options in schizophrenia. Predictor variables were as follows: (1) patients' initial antipsychotic (olanzapine [n = 222] or risperidone [n = 218]); (2) current (within 30 days) comorbid diagnosis of substance abuse; and (3) nine self-report items from the Rating of Medication Influence (ROMI) scale, including an item assessing patients' perceptions of the role of their therapeutic alliance in their adherence. MAIN OUTCOME MEASURES: For the primary analysis, a stepwise logistic regression was used in predicting antipsychotic persistence of at least 180 days. Variables found to be significantly predictive were included in a second analysis that assessed persistence at additional thresholds (> 90 days, > 270 days, and completion of the 1-year study). RESULTS: Four variables predicted longer antipsychotic persistence; olanzapine as initial antipsychotic (p = 0.004), absence of comorbid substance abuse (p = 0.025), and two of the ROMI items representing patients' subjective response to treatment--positive relationship with clinical staff (p = 0.048) and fulfillment of life goals (p = 0.050). CONCLUSIONS: Within a randomized trial design, this study corroborated the influence of several factors on antipsychotic persistence in schizophrenia. Results support the importance of the initial antipsychotic treatment option, presence of a comorbid substance abuse diagnosis, and the role of patients' subjective responses. Additional research is needed to further explore these and other factors as predictors of antipsychotic persistence, and of subsequent treatment outcomes.

Cost-effectiveness of olanzapine as first-line treatment for schizophrenia: results from a randomized, open-label, 1-year trial.

OBJECTIVES: This randomized, open-label trial was designed to help inform antipsychotic treatment policies. It compared the 1-year cost-effectiveness of initial treatment with olanzapine (OLZ) (n = 229) versus a "fail-first" algorithm on conventional antipsychotics (then olanzapine if indicated) (CON) (n = 214); and versus initial treatment with risperidone (RIS) (n = 221). METHODS: Individuals with schizophrenia or schizoaffective disorder were recruited from May 1998 to September 2001. Clinical, functioning, and resource utilization data were collected at baseline and five postbaseline visits. Brief Psychiatric Rating Scale scores defined "clinical effectiveness;" Lehman Quality of Life Scale social relations scores defined "social effectiveness." RESULTS: Requiring failure on less expensive antipsychotics before use of olanzapine did not result in total cost savings, despite significantly higher antipsychotic costs with OLZ. Total 1-year mean costs were 21,283 dollars for CON; 20,891 dollars for OLZ; and 21,347 dollars for RIS (pair-wise comparisons nonsignificant). Intent-to-treat effectiveness comparisons (nonsignificant) were augmented by analyses that adjusted for duration on initial antipsychotic treatment, and by comparisons of patients remaining on initial antipsychotic treatment versus those who required switching. When accounting for differential switching rates (OLZ 0.14 vs. CON 0.53, P < 0.0001; vs. RIS 0.31, P < 0.0001), OLZ was significantly more effective than CON on clinical (P = 0.025) and social (P = 0.043) measures, and significantly more effective than RIS on the social (P = 0.002) measure. Further, patients initiated on an antipsychotic from which they needed to switch required additional resources for hospitalization (P = 0.036) and crisis services (P = 0.029). CONCLUSIONS: Approaches that integrate costs, effectiveness, and treatment patterns are important for providing optimal information regarding the value of first-line antipsychotic options for schizophrenia.

Service utilization and costs of olanzapine versus divalproex treatment for acute mania: results from a randomized, 47-week clinical trial.

OBJECTIVE: This study examined direct treatment costs based on medication and service use data collected in a 47-week multi-center, double-blind, randomized clinical trial of olanzapine versus divalproex for patients with bipolar disorder and and experiencing acute mania. RESEARCH DESIGN AND METHODS: Patients who completed the 3-week acute phase and entered into the 44-week maintenance phase (n = 147) of the trial were included. Service use data were collected at weeks 3, 7, 15, 23, 31, 39 and 47 of the maintenance phase. Analyses were conducted to address potential biases from discontinuation patterns and use of this patient sub-sample. RESULTS: Overall, per patient yearly costs were similar for olanzapine- and divalproex-treated patients ($14 967 vs. $15 801). Psychiatric-related costs accounted for 95.4% and 93.6% of the total costs for olanzapine- and divalproextreated patients, respectively. Study medication costs were significantly higher for olanzapine than for divalproex ($4662 vs. $1755, p < 0.01). However, this was offset by the combined effects of numerically lower costs for several other services with olanzapine treatment. Some of the savings associated with olanzapine treatment compared with divalproex treatment resulted from differences in costs associated with emergency room services ($432 vs. $1346, p < 0.05). CONCLUSIONS: Overall per-patient treatment costs were similar for olanzapine and divalproex. Recognizing challenges in analyzing and generalizing cost outcomes from a clinical trial setting, results provide some much-needed comparative economic information regarding these two medication options for treating mania in bipolar disorder.

Economic outcomes associated with switching individuals with schizophrenia between risperidone and olanzapine: findings from a large US claims database.

OBJECTIVES: To assess the impact of switching atypical antipsychotic treatment [from (i) risperidone to olanzapine or (ii) olanzapine to risperidone] on medication use patterns and treatment costs for individuals with schizophrenia. METHODS: Using a large, integrated medical service and pharmacy claims database, 244 individuals diagnosed with schizophrenia (International Classification of Diseases [9th revision]: 295.xx) who switched treatment from risperidone to olanzapine (n = 202) or from olanzapine to risperidone (n = 42) were identified. Changes in medication use patterns and treatment costs (1999 values) per patient from the pre- to the post-switch period were evaluated. McNemar's tests were used to compare changes in use of antiparkinsonian, antidiabetic and antihyperlipidaemic agents and typical antipsychotics, while the Wilcoxon signed rank tests were applied to examine changes in treatment costs. RESULTS: After switching from risperidone to olanzapine, the percentage of patients using concomitant antiparkinsonian agents and typical antipsychotics decreased significantly from 30.20% to 21.29% (p = 0.0094) and from 30.69% to 18.32% (p = 0.0006), respectively. There was no significant change in the use of antidiabetic or antihyperlipidaemic drugs. For mental health-related treatment, annualised pharmaceutical costs increased by $US1761 (from $US1829 to $US3590, p < 0.0001) but medical service costs decreased by $US3511 (from $US11 292 to $US7781, p = 0.0036), driven primarily by significantly lower emergency room care and hospital outpatient costs. This resulted in no significant change in overall mental healthcare costs. Similar results were observed with total healthcare costs. In contrast, after switching from olanzapine to risperidone there was no significant change in treatment patterns for any of the medications assessed or in healthcare costs (mental healthcare-related or total), despite a significant decrease in mental health-related pharmaceutical costs. CONCLUSIONS: Switching from risperidone to olanzapine was associated with improved medication use patterns for antiparkinsonian and typical antipsychotic agents. While both mental health and total healthcare pharmaceutical costs increased significantly, this was not associated with a significant increase in overall mental health and total healthcare costs. These outcomes, however, were not evidenced in patients switched from olanzapine to risperidone.

Assessing the value of antipsychotics for treating schizophrenia: the importance of evaluating and interpreting the clinical significance of individual service costs.

Schizophrenia is a serious and complex disorder, with treatment requiring a large number and wide range of health and social service resources. This paper addresses one challenge for assessing the direct costs of antipsychotic treatments - that of interpreting both cost and effectiveness implications of specific components of service use. Information collected on direct component costs has frequently been analysed and reported only in total. Results of several published studies provide evidence that the total direct medical costs associated with atypical antipsychotics appear to be at least equivalent to, and in some cases lower than, those associated with conventional agents. An important implication of this cost-equivalency finding is that treatment involving higher medication costs have led to offsets in certain medical service costs. Results from several studies demonstrate a shift of cost components, primarily from more expensive inpatient to less expensive outpatient care. Although the common inpatient versus outpatient dichotomy is useful, the complexities of schizophrenia and the heterogeneity of outpatient service provision are likely to warrant greater specificity. Published schizophrenia treatment guidelines can assist researchers to more fully understand and meaningfully interpret the possible relationship of antipsychotic effectiveness to the use of particular outpatient services. Because the disease requires comprehensive and continuous care, outpatient treatment costs may be better conceptualised as baseline or expectable costs necessary in the maintenance phase of treatment. Lack of expectable costs may represent poor patient outcomes and increased intangible costs. In contrast, reductions in acute outpatient service costs may provide important markers of treatment effectiveness. A small number of studies have examined the use of crisis services, but additional work is needed to differentiate treatments vis-à-vis the need for intensive (acute) interventions. The assessment and clinical interpretation of individual cost components may offer an important opportunity to build upon initial results focusing on total costs and tailor analyses to the complexities of the disorder and the treatment process. Research able to incorporate clinical acumen into cost analyses will enhance the ability of healthcare policy makers to make informed decisions regarding the value of different antipsychotic medications for the treatment of schizophrenia.

Assessing antipsychotic effectiveness in dementia with the factor structure of the Psychogeriatric Dependency Rating Scale (PGDRS).

OBJECTIVE: Behavioral and psychological symptoms of dementia (BPSD) impact patient functioning, caregiver burden, and transition to structured living environments. The purpose of this study was to use the derived factor structure of the Psychogeriatric Dependency Rating Scale (PGDRS) to retrospectively assess short-term antipsychotic effectiveness. SETTING AND MEASUREMENT: A principal components factor analysis was conducted with PGDRS admission ratings for a large national sample of hospitalized dementia patients (N = 2747). Changes in calculated factor scores (admission to discharge) were used to compare effectiveness for a subset of patients treated with one of three antipsychotic agents: haloperidol, olanzapine, or risperidone. RESULTS: A four-factor solution accounted for almost 60% of rating variance. Factors were interpreted as disruptive overactivity, thought/communication disorder, interpersonal aggressiveness, and destructiveness. Medication effects (adjusting for group differences) were found for only the Interpersonal Aggressiveness factor. Improvement in this factor score was significantly greater in the olanzapine group. CONCLUSIONS: Findings suggest that these four PGDRS factors can provide a useful framework for symptom assessment and for targeted treatment.