Psychometric evaluation of the hepatitis C virus patient-reported outcomes (HCV-PRO) instrument: validity, responsiveness, and identification of the minimally important difference in a phase 2 clinical trial.

PURPOSE: To describe the psychometric properties and identify the minimally important difference (MID) of the hepatitis C virus patient-reported outcomes (HCV-PRO) instrument. Chronic HCV infection and associated treatments negatively affect PROs of function and well-being. METHODS: In a phase 2 trial, HCV-infected patients received direct-acting antivirals (DAAs) for 12 weeks with peg-interferon/ribavirin (peg-IFN/RBV) for 48 weeks, or placebo plus peg-IFN/RBV. The HCV-PRO total score, SF-36 PCS and MCS scores, EQ-5D-3L, and EQ VAS were measured at baseline, week 8, end of DAA treatment (EODT), end of peg-IFN/RBV treatment (EOT), and posttreatment week 24 (SVR24). Convergent validity of the HCV-PRO was assessed by Pearson's correlation coefficients. Discriminant validity was assessed by analyzing mean HCV-PRO total scores by EQ-5D anxiety/depression and pain/discomfort domain scores (none vs. some) and presence/absence of depression or fatigue adverse events. MID was identified through effect size (ES) and receiver-operating characteristic (ROC) curve analyses (HCV-PRO response vs. SF-36 PCS/MCS and EQ VAS MID thresholds). RESULTS: In 74 patients (22 % female; 81 % White; 51 % ≥50 years), correlations (0.64-0.96) between HCV-PRO total scores, SF-36 PCS/MCS scores, and EQ VAS scores at all time points supported convergent validity. HCV-PRO total scores were reduced to 10-30 points in patients impaired by depression, pain, or fatigue symptoms. Impact of peg-IFN/RBV regimen on HCV-PRO ES increased over time (EODT -0.76; EOT -0.93). ES and ROC curve analyses indicated an MID of -10 points. CONCLUSION: The HCV-PRO was valid and responsive in the population studied. An MID of -10 points represented a threshold of clinical significance for the HCV-PRO.

Development and initial psychometric evaluation of the hepatitis C virus-patient-reported outcomes (HCV-PRO) instrument.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is an important public health issue owing to its worldwide prevalence and its profound effects on patients' well-being and function. We developed a new patient self-report tool, the HCV patient-reported outcomes (HCV-PRO) instrument, to assess patients' function and well-being reflecting both HCV disease and treatment burdens. METHODS: Items were developed through a qualitative phase including scientific literature review, expert appraisal, and semi-structured patient interviews. The item pool was initially psychometrically tested in 60 adult HCV patients, 18 years of age or older at a university hepatology clinic. A final psychometric test was conducted in 241 members of the online Harris International Panel to examine scale reliability, confirm factor structure, and assess convergent and discriminant validity. RESULTS: A single-factor 16-item HCV-PRO instrument demonstrated good model fit. The HCV-PRO items and total score (range 0-100) showed excellent item response (few floor and ceiling effects) and reliability (alpha > 0.90). Convergent validity was established from moderate to high (r > 0.50) correlation with symptom burden, life satisfaction (ladder of life), and SF-36v2 scales scores. Mean HCV-PRO scores differentiated between currently treated patients, those previously treated, and patients never treated (p < 0.01), suggesting strong known-groups validity. CONCLUSIONS: The results provide initial evidence that the HCV-PRO can yield reliable and valid measurement of the effects of HCV and its treatment on the well-being and function of HCV-infected patients.

Economics of switching to second-line antiretroviral therapy with lopinavir/ritonavir in Africa: estimates based on DART trial results and costs for Uganda and Kenya.

BACKGROUND: Substantial immunological improvement has been reported for HIV-infected patients who switch from a failing regimen to a protease inhibitor regimen with Lopinavir/ritonavir (LPV/r). We use decision analysis modeling to estimate health and economic consequences expected from this switch. METHODS: A Markov model combined best evidence for CD4(+) T-cell response, infectious disease events, death rates, and quality of life for African populations with Kenyan and Ugandan data on drug and medical care costs. We estimate the incremental cost-effectiveness ratio of switching to an LPV/r-based regimen versus remaining on a failed first antiretroviral (ARV) regimen or discontinuing all ARV drugs. The model assumes concurrent use of cotrimoxazole, and 4% annual loss to follow-up. Local effects due to prevalence of malaria and tuberculosis are included in the model. Sensitivity analysis examines the effects of varying disease, ARV therapy and CD4(+) T-cell cost, and ART discontinuation assumptions. RESULTS: The base model estimates an improvement of 20 months in average survival for the LPV/r group. The respective LPV/r ICER for Kenya is $1483 per quality-adjusted life year (QALY) compared to $1673/QALY for Uganda. The ICERs increase to $1517 and $1707, respectively, if CD4(+) T-cell tests cost $25. The model comparing switching to LPV/r to discontinuing all ARV drugs decreases both costs and benefits proportionally for the treatment groups. CONCLUSION: The estimates are clearly below the most stringent World Health Organization benchmark for cost-effectiveness for Kenya and within the acceptable range of cost-effectiveness for Uganda. Thus, the switch to second-line therapy with LPV/r in these countries appears to be a cost-effective use of resources.

Economic modeling of the combined effects of HIV-disease, cholesterol and lipoatrophy based on ACTG 5142 trial data.

BACKGROUND: This study examines the cost and consequences of initiating an ARV regimen including Lopinavir/ritonavir (LPV/r) or Efavirenz (EFV), using data from a recent clinical trial in a previously published model of HIV-disease. METHODS: We populated the Markov model of HIV-disease with data from ACTG 5142 study to estimate the economic outcomes of starting ARV therapy with a PI-containing regimen as compared to an NNRTI-containing regimen, given their virologic and immunologic efficacy and effects on cholesterol and lipoatrophy. CNS toxicities and GI tolerability were not included in the model because of their transient nature or low cost remedies, and therefore lack of economic impact. CD4+ T-cell counts and the HIV-1 RNA (viral load) values from the study were used to assign a specific health state (HS) to each patient for each quarter year. The resulting frequencies used as "raw" data directly into the model obviate the reliance on statistical tests, and allow the model to reflect actual patient behavior in the clinical trial. An HS just below the last observed HS was used to replace a missing value. RESULTS: The modeled estimates (undiscounted) for the LPV/r-based regimen resulted in 1.41 quality-adjusted life months (QALMs) gained over a lifetime compared to the EFV-based regimen. The LPV/r-based regimen incurred $7,458 (1.8%) greater cost over a lifetime due to differences in drug costs and survival. The incremental cost effectiveness ratio using the discounted cost and QALYs was $88,829/QALY. Most of the higher costs accrue before the 7th year of treatment and were offset by subsequent savings. The estimates are highly sensitive to the effect of lipoatrophy on Health-related Quality of Life (HRQOL), but not to the effect of cholesterol levels. CONCLUSIONS: The cost effectiveness of ARV regimens may be strongly affected by enduring AEs, such as lipoatrophy. It is important to consider specific AE effects from all drugs in a regimen when ARVs are compared. TRIAL REGISTRATION: (ClinicalTrials.gov number, NCT00050895http://[ClinicalTrials.gov]).

Psychometric development and validation of the chronic constipation treatment satisfaction questionnaire (CTSAT-Q).

OBJECTIVES: To develop and validate the constipation treatment satisfaction questionnaire (CTSAT-Q) for use in patients with chronic constipation and irritable bowel syndrome with constipation (IBS-c). METHODS: Questionnaire development included item representation from the reviewed literature, focus groups, and pretesting. Dimensions related to treatment satisfaction were identified with exploratory factor analysis, verified with confirmatory factor analysis (CFA), and tested with structural equation modeling. RESULTS: A total of 31,988 email invitations were disseminated to obtain 311 qualified respondents with diagnoses for chronic constipation and IBS-c using ROME II criteria, which required that two of the following symptoms: fewer than 3 bowel movements per week, hard or lumpy stools, straining with defecation, and a sensation of incomplete evacuation, a sensation of anorectal obstruction, and the use of manual maneuvers to assist defecation be present 25% of the time during the last year. Approximately 84% of the sample was female. Item-to-total correlations were 0.66 for activities, ranged from 0.60 to 0.67 for expectations, from 0.59 to 0.69 for value, from 0.56 to 0.60 for effectiveness, and 0.68 to 0.79 for treatment satisfaction. All standardized parameter estimates from CFA were significant (P < 0.01). The chi-square was 46.98, df = 41, P = 0.241, comparative fit index = 0.996, Tucker-Lewis Index = 0.994, root mean square error of approximation = 0.022, indicating an excellent fit between the sample data and proposed model. Treatment satisfaction was a strong and significant predictor of effectiveness, activities, and value (P < 0.001). CONCLUSIONS: The CTSAT-Q was demonstrated to be reliable and valid, and appears to assess treatment satisfaction for patients with chronic constipation and patients with IBS-c.

Psychometric evaluation of the Osteoporosis Patient Treatment Satisfaction Questionnaire (OPSAT-Q), a novel measure to assess satisfaction with bisphosphonate treatment in postmenopausal women.

BACKGROUND: The Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) is a new measure of patient satisfaction with bisphosphonate treatment for osteoporosis. The objective of this study was to evaluate the psychometric characteristics of the OPSAT-Q. METHODS: The OPSAT-Q contains 16 items in four subscales: Convenience, Confidence with Daily Activities, Side Effects, and Overall Satisfaction. All four subscale scores and an overall composite satisfaction score (CSS) can be computed. The OPSAT-Q, Osteoporosis Targeted Quality of Life (OPTQoL), and sociodemographic/clinical questionnaires, including 3 global items on convenience, functioning and side effects, were self-administered to women with osteoporosis or osteopenia recruited from four US clinics. Analyses included item and scale performance, internal consistency reliability, reproducibility, and construct validity. Reproducibility was measured using the intraclass correlation coefficient (ICC) via a follow-up questionnaire completed by participants 2 weeks post baseline. RESULTS: 104 women with a mean age of 65.1 years participated. The majority were Caucasian (64.4%), living with someone (74%), and not currently employed (58.7%). 73% had osteoporosis and 27% had osteopenia. 80% were taking weekly bisphosphonates and 18% were taking daily medication (2% missing data). On a scale of 0-100, individual patient subscale scores ranged from 17 to 100 and CSS scores ranged from 44 to 100. All scores showed acceptable internal consistency reliability (Cronbach's alpha > 0.70) (range 0.72 to 0.89). Reproducibility ranged from 0.62 (Daily Activities) to 0.79 (Side Effects) for the subscales; reproducibility for the CSS was 0.81. Significant correlations were found between the OPSAT-Q subscales and conceptually similar global measures (p < 0.001). CONCLUSION: The findings from this study confirm the validity and reliability of the OPSAT-Q and support the proposed composition of four subscales and a composite score. They also support the use of the OPSAT-Q to examine the impact of bisphosphonate dosing frequency on patient satisfaction.

Patient health utility, work productivity, and lifestyle impairment in chronic hepatitis C patients in France.

BACKGROUND: France has a high prevalence of patients with chronic hepatitis C virus (HCV). Clinical consequences of HCV are well-recognized, while health-related quality of life (HRQoL) and productivity impacts remain less understood. This study evaluates how HCV disease severity and HCV treatment outcomes impact HRQoL and productivity among patients in France. METHODS: From October 2012 to January 2013, physicians treating HCV patients in France completed Patient Record Forms, which included information on patient demographics, disease stage, and treatment status. Subsequently, these HCV patients completed the EQ-5D-3L health-state instrument and the HCV-specific Work Productivity and Activity Impairment (WPAI:HepC) Questionnaire. Results are reported in descriptive and stratified analyses by disease stage and treatment status. Linear regression analyses were performed to determine independent associations between disease severity and treatment status with EQ-5D and WPAI:HepC. RESULTS: There were 297 matched physician and patient response forms completed. Mean EQ-5D Index score was 0.764, and mean EQ-VAS score was 65.85. Regression analyses showed that older age and worse disease severity were significantly associated with lower EQ-5D Index and EQ-VAS scores. Stratification of EQ-5D Index and EQ-VAS scores showed significantly better scores for HCV treatment responders compared to non-responders. Stratification of WPAI:HepC questions by disease stage revealed greater productivity impact on HCV patients with more severe disease. CONCLUSIONS: In a cross-sectional sample of HCV patients in France, worsening HRQoL and productivity/activity impairment was significantly associated with disease progression and increasing age. This information provides insight into the benefits of treating HCV patients and preventing disease progression.

Costs and absence of HCV-infected employees by disease stage.

OBJECTIVES: Quantify the costs and absenteeism associated with stages of the Hepatitis C virus (HCV). STUDY DESIGN: Retrospective analysis of the HCMS integrated database from multiple geographically diverse, US-based employers with employee information on medical, prescription, and absenteeism claims. METHODS: Employee data were extracted from July 2001-March 2013. Employees with HCV were identified by ICD-9-CM codes and classified into disease severity cohorts using diagnosis/procedure codes assigning the first date of most severe claim as the index date. Non-HCV employees (controls) were assigned random index dates. Inclusion required 6-month pre-/post-index eligibility. Medical, prescription, and absenteeism cost and time were analyzed using two-part regression (logistic/generalized linear) models, controlling for potentially confounding factors. Costs were inflation adjusted to September 2013. RESULTS: All direct costs comparisons were statistically significant (p ≤ 0.05) with mean medical costs of $1813 [SE = $3] for controls (n = 727,588), $4611 [SE = $211] for non-cirrhotic (n = 1007), $4646 [SE = $721] for compensated cirrhosis (CC, n = 87), $12,384 [SE = $1122] for decompensated cirrhosis (DCC, n = 256), $33,494 [SE = $11,753] for hepatocellular carcinoma (HCC, n = 17) and $97,724 [SE = $32,437] for liver transplant (LT, n = 19) cohorts. Mean short-term disability days/costs were significantly greater for the non-cirrhotic (days = 2.03 [SE = 0.36]; $299 [SE = $53]), DCC (days = 6.20 [SE = 1.36]; $763 [SE = $169]), and LT cohorts (days = 21.98 [SE = 8.21]; $2537 [SE = $972]) compared to controls (days = 1.19 [SE = 0.01]; $155 [SE = $1]). Mean sick leave costs were significantly greater for non-cirrhotic ($373 [SE = $22]) and DCC ($460 [SE = $54]) compared to controls ($327 [SE = $1]). CONCLUSIONS: Employees with HCV were shown to have greater direct and indirect costs compared to non-HCV employee controls. Costs progressively increased in the more severe HCV disease categories. Slowing or preventing disease progression may avert the costs of more severe liver disease stages and enable employees with HCV to continue as productive members of the workforce.

Cost-minimization comparison of darunavir plus ritonavir and lopinavir/ritonavir in HIV-1 infected treatment-naïve women of childbearing age.

BACKGROUND: Guidelines from the Department of Health and Human Services in the US recommend ritonavir-boosted lopinavir (LPV/r) as a preferred protease inhibitor (PI) for HIV-positive antiretroviral-naїve pregnant women. These guidelines also cite ritonavir-boosted darunavir (DRV + RTV) as an alternative PI in this clinical scenario. The purpose of this analysis was to compare economic outcomes for regimens based on these two treatments. STUDY DESIGN: An existing discrete event simulation (DES) model was adapted to conduct a cost-minimization analysis comparing the two regimens in HIV-infected women of childbearing age (WOCBA), from the perspective of a healthcare payer in the US. METHODS: The DES model was used to represent disease states, health events, healthcare encounters, pregnancy, and treatment choices in HIV-infected WOCBA starting treatment with regimens based on either LPV/r or DRV + RTV. It also incorporated parameters for individual patient characteristics, and for antiretroviral (ARV) treatment effectiveness, treatment sequencing, clinical progression, and resource use. Potential events included scheduled physician visits; viral suppression; viral rebound; AIDS-related complications; CHD events; treatment discontinuation and switching; ARV treatment side-effects (SE); and death. The primary outcomes were discounted 5-year and 10-year healthcare costs. Alternative scenarios considered different rates of switching from DRV + RTV to LPV/r upon conception. RESULTS: Compared with DRV + RTV, LPV/r was associated with similar clinical outcomes while offering savings at the 5- and 10-year horizons (of $24,904 and $43,502 per patient, respectively), and in extensive sensitivity analyses. The main driver of the savings was the difference in cost between PIs. CONCLUSIONS: Starting HIV-infected ARV-treatment-naїve WOCBA on an LPV/r-based regimen is cost-saving and provides similar patient outcomes compared to a DRV + RTV-based regimen.

Lopinavir/ritonavir versus darunavir plus ritonavir for HIV infection: a cost-effectiveness analysis for the United States.

BACKGROUND: The ARTEMIS trial compared first-line antiretroviral therapy (ART) with lopinavir/ritonavir (LPV/r) to darunavir plus ritonavir (DRV + RTV) for HIV-1-infected subjects. In order to fully assess the implications of this study, economic modelling extrapolating over a longer term is required. OBJECTIVE: The aim of this study was to simulate the course of HIV and its management, including the multiple factors known to be of importance in ART. METHODS: A comprehensive discrete event simulation was created to represent, as realistically as possible, ART management and HIV outcomes. The model was focused on patients for whom clinicians believed that LPV/r or DRV + RTV were good options as a first regimen. Prognosis was determined by the impact of initial treatment on baseline CD4+ T-cell count and viral load, adherence, virological suppression/failure/rebound, acquired resistance mutations, and ensuing treatment changes. Inputs were taken from trial data (ARTEMIS), literature and, where necessary, stated assumptions. Clinical measures included AIDS events, side effects, time on sequential therapies, cardiovascular events, and expected life-years lost as a result of HIV infection. The model underwent face, technical and partial predictive validation. Treatment-naive individuals similar to those in the ARTEMIS trial were modelled over a lifetime, and outcomes with first-line DRV + RTV were compared with those with LPV/r, both paired with tenofovir and emtricitabine. Up to three regimen changes were permitted. Drug prices were based on wholesale acquisition cost. Outcomes were lifetime healthcare costs (in 2011 US dollars) from the US healthcare system perspective and quality-adjusted life-years (QALYs) (discounted at 3 % per annum). RESULTS: Choice of LPV/r over DRV + RTV as initial ART resulted in nearly identical clinical outcomes, but distinctly different economic consequences. Starting with an LPV/r regimen potentially results in approximately US$25,000 discounted lifetime savings. Accumulated QALYs for LPV/r and DRV + RTV were 12.130 and 12.083, respectively (a 19-day difference). In sensitivity analyses, net monetary benefit ranged from US$12,000 to US$31,000, favouring LPV/r (base case US$27,762). CONCLUSIONS: A comprehensive simulation of lifetime course of HIV in the USA indicated that using LPV/r as first-line therapy compared with DRV + RTV may result in cost savings, with similar clinical outcomes.

All-cause health care charges among managed care patients with constipation and comorbid irritable bowel syndrome.

OBJECTIVE: Chronic idiopathic constipation and irritable bowel syndrome (IBS) are common gastrointestinal conditions with potentially significant burden on managed care systems. Our objective was to examine all-cause resource utilization and charges associated with constipation alone (C-only) and with IBS with comorbid constipation (IBS+C). METHODS: Administrative claims from a US health plan between January 1, 2003 and December 31, 2005 were analyzed. Patients with C-only (n = 48 585) and IBS+C (n = 10 952) were identified using International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes. Outcomes were compared with demographically matched controls and with a benchmark group of patients with migraine (N = 48 759). An index date was defined as the date 3 months prior to first observed diagnosis of the condition of interest. Outcomes were evaluated over a 12-month period before and after the index date. RESULTS: The pre-to-post increase in total charges for subjects with C-only was substantially higher than that for the comparison group ($8837 vs $1717; P < 0.001) or the migraine group ($8837 vs $ 4804; P < 0.001). Subjects with IBS+C also had a greater pre-to-post increase in total charges than did comparison group members ($6192 vs $1319; P < 0.001) and subjects with migraine ($6192 vs $4804; P = 0.0120). CONCLUSIONS: Both C-only and IBS+C impose substantial economic burden on third-party payers.

Insomnia medication use and the probability of an accidental event in an older adult population.

OBJECTIVE: This study examined the risk of accidental events in older adults prescribed a sedating antidepressant, long-acting benzodiazepine, short-acting benzodiazepine, and nonbenzodiazepine, relative to a reference group (selective melatonin receptor agonist). METHODS: This was a retrospective cohort analysis of older adults (≥65 years) with newly initiated pharmacological treatment of insomnia. Data were collected from the Thomson MarketScan(®) Medicare Supplemental and Coordination of Benefits databases (January 1, 2000, through June 30, 2006). Probit models were used to evaluate the probability of an accidental event. RESULTS: Data were analyzed for 445,329 patients. Patients taking a long-acting benzodiazepine (1.21 odds ratio [OR]), short-acting benzodiazepine (1.16 OR), or nonbenzodiazepine (1.12 OR) had a significantly higher probability of experiencing an accidental event during the first month following treatment initiation compared with patients taking the reference medication (P < 0.05 for all). A significantly higher probability of experiencing an accidental event was also observed during the 3-month period following the initiation of treatment (1.62 long-acting benzodiazepine, 1.60 short-acting benzodiazepine, 1.48 nonbenzodiazepine, and 1.56 sedating antidepressant; P < 0.05). CONCLUSIONS: Older adults taking an SAD or any of the benzodiazepine receptor agonists appear to have a greater risk of an accidental event compared with a reference group taking an MR.

Association of insomnia with quality of life, work productivity, and activity impairment.

PURPOSE: To assess the association of insomnia with health-related quality of life (HRQOL), work productivity, and activity impairment. METHODS: Data were obtained from the 2005 US National Health and Wellness Survey. Subjects were assigned to the insomnia group (diagnosed insomnia experienced at least a few times a month) or the noninsomnia group (no insomnia or sleep symptoms). HRQOL was assessed using the short form 8 (SF-8) (mental and physical scores). The work productivity and activity impairment questionnaire (WPAI) assessed absenteeism (work time missed), presenteeism (impairment at work), work productivity loss (overall work impairment), and activity impairment. Linear regression models were used to control for potential confounders. RESULTS: A total of 19,711 adults were evaluated (5,161 insomnia, 14,550 noninsomnia). Subjects in the insomnia group had significantly lower SF-8 physical (-5.40) and mental (-4.39) scores and greater activity impairment scores (+18.04) than subjects in the noninsomnia group (P < 0.01 for all). Employed subjects in the insomnia group had greater absenteeism (+6.27), presenteeism (+13.20), and work productivity loss (+10.33) scores than those in the noninsomnia group (P < 0.01 for all). CONCLUSIONS: Insomnia is significantly associated with poorer physical and mental quality of life and work productivity loss and activity impairment.

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 benefit costs and absenteeism due to insomnia from the employer's perspective: a retrospective, case-control, database study.

OBJECTIVE: To objectively assess the economic impact of insomnia on direct medical and prescription costs and indirect absence-related salary replacement costs and on absences and to compare the prevalence and costs of comorbidities in employees with and without insomnia. METHOD: A retrospective analysis was performed on employee data from the Human Capital Management Services Research Reference Database (January 2001-September 2007). Employees were identified as having insomnia (ICD-9 criteria) based on history of receiving medications used to treat insomnia or physician's diagnosis of insomnia. Control employees had no history of medications used to treat insomnia and no insomnia diagnosis. Annual costs and number of absences were compared using 2-part regression models, controlling for demographics, job information, geographic region, comorbid disorders, and the Charlson Comorbidity Index score. Comorbidity prevalence, costs, and services were compared. RESULTS: Data were collected for 299,188 employees (17,230 employees with insomnia and 281,958 control employees). Annual mean incremental costs were $2,053 greater (in total) for employees with insomnia compared with controls (specific increments: medical $751, drug $735, sick leave $208, short-term disability $179, long-term disability $10, and workers' compensation $170). Employees with insomnia missed a mean of 3.10 more workdays annually than those without insomnia. Nearly all comorbid conditions were more prevalent, were more costly, and resulted in a greater utilization of services in employees with insomnia compared to those without. All of the above comparisons were significant (P < .05). CONCLUSION: Insomnia was associated with increased costs, greater absenteeism, and an increased number of comorbid conditions in an employed population. Consistent with other analyses based on these data, the study estimated the annual cost of insomnia in the US civilian labor force to be approximately $15.0-17.7 billion (US dollars).

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.