Stated preferences of physicians and chronic pain sufferers in the use of classic strong opioids.

We conducted a two-stage study in France, Germany, Italy, Spain, Sweden, and the United Kingdom of the stated preferences of chronic pain sufferers treated with classic strong opioids and of physicians treating such patients. The qualitative stage identified attributes perceived important through focus groups with 84 pain sufferers and semistructured interviews with 11 physicians. The quantitative stage included online, discrete choice experiments (DCEs) in which respondents chose between hypothetical profiles or an opt-out in 15 choice tasks. The profile descriptions were based on the attributes elicited in the qualitative stage. DCEs were conducted for pain sufferers (N = 242) and physicians (N = 270) who passed a rationality test. Main-effects models were estimated by hierarchical Bayesian regression. Sufferers ranked nausea, pain impact, energy, alertness, and constipation; physicians ranked pain response, central nervous system (CNS) effects, nausea, dose form, and constipation in descending order of importance. Sufferers were unwilling to incur severe side effects to decrease pain and chose the opt-out in approximately one half of the choice tasks, whereas physicians were willing to trade between profiles. The models predicted physicians' choices better than those of pain sufferers. No age, sex, or country effects were seen, but stronger preferences were found among physicians treating noncancer (n = 40) than cancer pain and among the 55% of sufferers who had never discontinued long-term pain medication use. Sufferers' mean pain scores on an 11-point Likert scale were 4.0, 5.7, and 8.6 on their best, average, and worst days, respectively.

Cost-effectiveness of a recommendation of universal mass vaccination for seasonal influenza in the United States.

OBJECTIVES: We evaluated the cost-effectiveness of universal mass vaccination (UMV) against influenza compared with a targeted vaccine program (TVP) for selected age and risk groups in the United States. METHODS: We modeled costs and outcomes of seasonal influenza with UMV and TVP, taking a societal perspective. The US population was stratified to model age-specific (< 5, 5-17, 18-49, 50-64, and 65+ years) vaccine coverage and efficacy. Probability of influenza-related illness (ILI) and complications, health-care utilization, costs, and survival were estimated. For a season's intervention, ILI cases in that year, lifetime costs (2008 US$), and quality-adjusted life years (QALYs) lost (both discounted at 3% per annum) were calculated for each policy and used to derive incremental cost-effectiveness ratios. A range of sensitivity and alternative-scenario analyses were conducted. RESULTS: In base-case analyses, TVP resulted in 63 million ILI cases, 859,000 QALYs lost, and $114.5 billion in direct and indirect costs; corresponding estimates for UMV were 61 million cases, 825,000 QALYs lost, and $111.4 billion. UMV was therefore estimated to dominate TVP, saving $3.1 billion and 34,000 QALYs. In probabilistic sensitivity analyses, UMV was dominant in 82% and dominated in 0% of iterations. In alternative-scenario analyses, UMV dominated TVP when lower estimates of vaccine coverage were used. Lower estimates of ILI risk among unvaccinated, vaccine effectiveness, and risk of complications resulted in ICERs of $2800, $8100, and $15,900 per QALY gained, respectively, for UMV compared with TVP. CONCLUSIONS: UMV against seasonal influenza is cost saving in the United States under reasonable assumptions for coverage, cost, and efficacy.

Cost-effectiveness of maraviroc for antiretroviral treatment-experienced HIV-infected individuals in Mexico.

OBJECTIVE: Maraviroc is the first approved drug in a new class of antiretrovirals, the CCR5 antagonists. The objective of this study was to predict the long-term clinical impact and cost-effectiveness of maraviroc in treatment-experienced adults with HIV/AIDS in Mexico. METHODS: The AntiRetroviral Analysis by Monte Carlo Individual Simulation (ARAMIS) model was adapted to the Mexican context to predict clinical and economic outcomes of treating with optimized background therapy (OBT) versus testing for viral tropism status and treating with OBT ± maraviroc accordingly in treatment-experienced adults in Mexico. Baseline characteristics and efficacy were from the MOTIVATE trials' screening cohort. Costs and population mortality data were specific to Mexico. Results were reported from the perspective of health care payers in 2008 Mexican pesos (converted to 2008 US$ in parentheses). RESULTS: Compared to treatment with OBT alone, treatment with OBT ± maraviroc contingent on tropism test result increased projected undiscounted life expectancy and discounted quality-adjusted life expectancy from 7.54 to 8.71 years and 4.42 to 4.92 quality-adjusted life years (QALYs), respectively, at an incremental cost of $228,215 (US$21,329). The resultant incremental cost-effectiveness ratio (ICER) was $453,978 (US$42,429) per QALY gained. The ICER was somewhat lower when maraviroc was modeled in individuals susceptible to ≤ 2 components of OBT ($407,329; US$38,069), while the ICER was higher in individuals susceptible to ≥3 OBT components ($718,718; US$67,171). CONCLUSION: In treatment-experienced individuals with HIV/AIDS in Mexico, maraviroc may be cost-effective, particularly in individuals with limited options for active antiretroviral therapy (ART).

A microsimulation of the cost-effectiveness of maraviroc for antiretroviral treatment-experienced HIV-infected individuals.

PURPOSE: Maraviroc (MVC) is the first approved CCR5 antagonist. The aim of this study was to explore the cost-effectiveness of MVC in treatment-experienced or treatment-resistant HIV-infected adults. METHODS: The validated HIV microsimulation model ARAMIS was used to predict clinical and economic outcomes of treating patients with optimized background therapy (OBT) alone, as compared to a strategy of testing for the patient's viral tropism and treating with OBT with or without (+/-) MVC in a cohort corresponding to the MOTIVATE screening cohort. RESULTS: Compared to treatment with OBT alone, a treatment strategy of OBT +/- MVC (twice daily) according to tropism test result was predicted to increase CD4+ cell count after 5 years (from mean 249 to 360 cells/microL), undiscounted life expectancy (7.6 to 8.9 years), and quality-adjusted life years (QALYs; from 4.99 to 5.71) for an additional $40,500, giving an incremental cost-effectiveness ratio of $56,400 per QALY gained. The result was relatively insensitive to alternative clinical and cost assumptions within reasonable ranges, but for individuals with HIV susceptible to only two or fewer components of OBT, the ICER decreased to $52,000 per QALY gained. CONCLUSION: MVC is cost-effective, especially among individuals with few remaining options for active antiretroviral therapy.

Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain.

BACKGROUND: Few direct head-to-head comparisons have been conducted between drugs for the treatment of diabetic peripheral neuropathic pain (DPNP). Approved or recommended drugs in this indication include duloxetine (DLX), pregabalin (PGB), gabapentin (GBP) and amitriptyline (AMT). We conducted an indirect meta-analysis to compare the efficacy and tolerability of DLX with PGB and GBP in DPNP, using placebo as a common comparator. METHODS: We searched PubMed, EMBASE, CENTRAL databases and regulatory websites for randomized, double-blind, placebo-controlled, parallel group or crossover clinical trials (RCTs) assessing DLX, PGB, GBP and AMT in DPNP. Study arms using approved dosages with assessments after 5-13 weeks were eligible. Efficacy criteria were: reduction in 24-hour pain severity (24 h PS) for all three drugs, and response rate (>or= 50% pain reduction) and Patient Global Impression of Improvement/Change (PGI-I/C) for DLX and PGB only. Tolerability criteria included: discontinuation, diarrhoea, dizziness, headache, nausea and somnolence. Direct comparisons versus placebo were conducted with pooled fixed - and random-effects analyses on endpoints reported in at least two studies of each drug. Indirect comparisons were performed between DLX and each of PGB and GBP using Bayesian simulation. RESULTS: Three studies of DLX, six of PGB, two of GBP and none of AMT met the inclusion criteria. In random-effects and fixed-effects analyses of DLX, PGB and GBP, all were superior to placebo for all efficacy parameters, with some tolerability trade-offs. Indirect comparison of DLX with PGB found no differences in 24 h PS, but significant differences in PGI-I/C, favouring PGB, and in dizziness, favouring DLX were apparent. Comparing DLX and GBP, there were no statistically significant differences. CONCLUSION: From the few available studies suitable for indirect comparison, DLX shows comparable efficacy and tolerability to GBP and PGB in DPNP. Duloxetine provides an important treatment option for this disabling condition.

Preferences of patients with diabetes mellitus for inhaled versus injectable insulin regimens.

BACKGROUND: In clinical trials, patients have expressed greater satisfaction with inhaled human insulin (EXUBERA, Pfizer) than with injectable insulin. No studies to date have attempted to quantify the strength of preferences for these alternative routes of administration. OBJECTIVE: To elicit health state preference values from people with diabetes mellitus for treatment with inhaled human insulin compared with injectable insulin. STUDY DESIGN: A patient preference study. METHODS: Written descriptions were developed for five clinical scenarios: two for type 1 diabetes and three for type 2 diabetes. Each scenario required adjustment or initiation of insulin treatment because of poor glycaemic control. Two alternative insulin regimens were described for each scenario: injectable-only or inhaled human insulin to replace or reduce the number of daily injections. Equal efficacy was assumed within each of these scenario pairs.A total of 344 UK adults (66% male), 132 (mean age 49 years) with type 1 diabetes and 212 (mean age 63 years) with type 2 diabetes, rated scenario pairs corresponding to their own type of diabetes and rated their own health by time trade-off (TTO), by correspondence with EQ-5D health descriptions and on the EQ-5D visual analogue scale. Respondents stated their preference for, or indifference between, the injection-only or inhalation variant comprising each scenario pair. TTO utilities and EQ-5D utilities by UK community tariff were compared within each scenario pair, for the total sample rating, each scenario pair, and by subgroups of stated preference for each variant. RESULTS: A majority, ranging from 63% to 81% across the scenarios, preferred inhalation. Mean differences in TTO scores were 0.074, 0.076, 0.088, 0.053 and 0.043 for the five scenarios, respectively (p < 0.005 for all). Mean EQ-5D differences were 0.043, 0.029, 0.037, 0.020 and 0.021 for the five scenarios, respectively (p < 0.05 for scenarios 1 and 3), driven mainly by differences on the pain/discomfort dimension of the EQ-5D. Differences in favour of inhalation among those preferring inhalation, were greater than differences in favour of injections among those preferring injections. Mean self-rated health was similar between respondents with type 1 and type 2 diabetes, at 0.83 (TTO) and 0.75 (EQ-5D). The TTO was more sensitive than EQ-5D. Self-rated health by EQ-5D compared closely with reported values from the UK Prospective Diabetes Study (UKPDS). CONCLUSIONS: This study highlights the utility differences that people with diabetes perceive between the prospect of inhaled and injected routes of insulin administration, even under the assumption of no difference in efficacy. These differences are magnified when the comparison in utility scores is between the majority who prefer the inhaled route and the minority who prefer the injectable route.

The cost effectiveness of influenza vaccination for adults aged 50 to 64 years: a model-based analysis for Spain.

An economic evaluation of reducing the age threshold for routine influenza vaccination in Spain from 65 to 50 years was performed. A probabilistic model was used to compare a policy based on a recommendation to vaccinate all adults aged 50-64 with the existing vaccination policy for that age group, during interpandemic periods. Two perspectives were considered: third-party payer (TPP) and societal. Model inputs were obtained primarily from the published literature and validated through expert opinion. From TPP perspective, incremental cost-effectiveness ratios were estimated at euro14,919 per quality-adjusted life-year (QALY) gained and euro9731 per life-year gained. From societal perspective, the corresponding results were euro4149 per QALY and euro2706 per life-year gained. Extending routine influenza vaccination to people over 50 years of age is likely to be cost-effective.

The cost-effectiveness of influenza vaccination for people aged 50 to 64 years: an international model.

OBJECTIVES: Routine influenza vaccination is currently recommended in several countries for people aged more than 60 or 65 years or with high risk of complications. A lower age threshold of 50 years has been recommended in the United States since 1999. To help policymakers consider whether such a policy should be adopted more widely, we conducted an economic evaluation of lowering the age limit for routine influenza vaccination to 50 years in Brazil, France, Germany, and Italy. METHODS: The probabilistic model was designed to compare in a single season the costs and clinical outcomes associated with two alternative vaccination policies for persons aged 50 to 64 years: reimbursement only for people at high risk of complications (current policy), and reimbursement for all individuals in this age group (proposed policy). Two perspectives were considered: third-party payer (TPP) and societal. Model inputs were obtained primarily from the published literature and validated through expert opinion. The historical distribution of annual influenza-like illness (ILI) incidence was used to simulate the uncertain incidence in any given season. We estimated gains in unadjusted and quality-adjusted life expectancy, and the cost per quality-adjusted life-year (QALY) gained. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Comparing the proposed to the current policy, the estimated mean costs per QALY gained were R$4,100, EURO 13,200, EURO 31,400 and EURO 15,700 for Brazil, France, Germany, and Italy, respectively, from a TPP perspective. From the societal perspective, the age-based policy is predicted to yield net cost savings in Germany and Italy, whereas the cost per QALY decreased to R$2800 for Brazil and EURO 8000 for France. The results were particularly sensitive to the ILI incidence rate, vaccine uptake, influenza fatality rate, and the costs of administering vaccination. Assuming a cost-effectiveness threshold ratio of EURO 50,000 per QALY gained, the probabilities of the new policy being cost-effective were 94% and 95% for France, 72% and near 100% for Germany, and 89% and 99% for Italy, from the TPP and societal perspectives, respectively. CONCLUSIONS: Extending routine influenza vaccination to people more than 50 years of age is likely to be cost-effective in all four countries studied.

Cost-effectiveness analysis of oxaliplatin compared with 5-fluorouracil/leucovorin in adjuvant treatment of stage III colon cancer in the US.

BACKGROUND: The MOSAIC trial demonstrated that oxaliplatin/5-fluorouracil/leucovorin (FU/LV) (FOLFOX4) as adjuvant treatment of TNM stage II and III colon cancer significantly improves disease-free survival compared with 5-FU/LV alone. For stage III patients the 4-year disease-free survival (DFS) was 69% in the FOLFOX4 arm vs 61% in the LV5FU2 arm, P = .002). The cost-effectiveness of FOLFOX4 in stage III patients was evaluated from a US Medicare perspective. METHODS: By using individual patient-level data from the MOSAIC trial (median follow-up: 44.2 months), DFS and overall survival (OS) were estimated up to 4 years from randomization. DFS was extrapolated from 4 to 5 years by fitting a Weibull model and subsequent survival was estimated from life tables. OS beyond 4 years was predicted from the extrapolated DFS estimates and observed survival after recurrence. Costs were calculated from trial data and external estimates of resources to manage recurrence. RESULTS: Patients on FOLFOX4 were predicted to gain 2.00 (95% confidence interval [CI]: 0.63, 3.37) years of DFS over those on 5-FU/LV. The predicted life expectancy of stage III patients on FOLFOX4 and 5-FU/LV was 17.61 and 16.26 years, respectively. Mean total lifetime disease-related costs were $56,300 with oxaliplatin and $39,300 with 5-FU/LV. Compared with 5-FU/LV, FOLFOX4 was estimated to cost $20,600 per life-year gained and $22,800 per quality-adjusted life-year (QALY) gained, discounting costs and outcomes at 3% per annum. CONCLUSIONS: FOLFOX4 is likely to be cost-effective compared with 5-FU/LV in the adjuvant treatment of stage III colon cancer. The incremental cost-effectiveness ratio compares favorably with other funded interventions in oncology.

Variability of cost-effectiveness estimates for pharmaceuticals in Western Europe: lessons for inferring generalizability.

OBJECTIVES: It has long been suggested that, whereas the results of clinical studies of pharmaceuticals are generalizable from one jurisdiction to another, the results of economic evaluations are location dependent. There has been, however, little study of the causes of variation, whether differences in study results among countries are systematic, or whether they are important for decision making. METHODS: A literature search was conducted to identify economic evaluations of pharmaceuticals conducted in two or more European countries. The studies identified were then classified by methodological type and analyzed to assess their level of variability and to identify the main causes of variation. Assessments were also made of the extent to which differences in study results among countries were systematic and whether they would lead to a different decision, assuming a range of values of the threshold willingness-to-pay for a life-year or quality-adjusted life-year (QALY). RESULTS: In total 46 intercountry drug comparisons were identified, 29 in multicountry studies and 17 in comparable single country studies that were considered to be sufficiently similar in terms of methodology. The type of study (i.e., trial-based or modeling study) had some impact on variability, but the most important factor was the extent of variation across countries in effectiveness, resource use or unit costs, allowed by the researcher's chosen methodology. There were few systematic differences in study results among countries, so a decision maker in country B, on seeing a recent economic evaluation of a new drug in country A, would have little basis on which to predict whether the drug, if evaluated, would be more or less cost-effective in his or her country. Given the extent of variation in cost-effectiveness estimates among countries, the importance of this for decision making depends on decision makers' thresholds in willingness-to-pay for a QALY or life-year. If a cost-effectiveness threshold (i.e., willingness-to-pay) for a life-year or QALY of dollar 50,000 were assumed, the same conclusion regarding cost-effectiveness would be reached in most cases. CONCLUSION: This review shows that cost-effectiveness results for pharmaceuticals vary from country to country in Western Europe and that these variations are not systematic. In addition, constraints imposed by analysts may reduce apparent variability in the estimates. The lessons for inferring generalizability are not straightforward, although the implications of variation for decision making depend critically on the cost-effectiveness thresholds applying in Western Europe.

An economic evaluation of sequential i.v./po moxifloxacin therapy compared to i.v./po co-amoxiclav with or without clarithromycin in the treatment of community-acquired pneumonia.

STUDY OBJECTIVE: To evaluate costs, clinical consequences, and cost-effectiveness from a German and French health-care system perspective of sequential i.v./po moxifloxacin monotherapy compared to co-amoxiclav with or without clarithromycin (AMC +/- CLA) in patients with community-acquired pneumonia (CAP) who required parenteral treatment. METHODS: Costs and consequences over 21 days were evaluated based on clinical cure rates 5 to 7 days after treatment and health resource use reported for the TARGET multinational, prospective, randomized, open-label trial. This trial compared sequential i.v./po monotherapy with moxifloxacin (400 mg qd) to i.v./po co-amoxiclav (1.2 g i.v./625 mg po tid) with or without clarithromycin (500 mg bid) for 7 to 14 days in hospitalized patients with CAP. Since no country-by-treatment interaction was found in spite of some country differences for length of hospital stays, resource data (antimicrobial treatment, hospitalization, and out-of-hospital care) from all centers were pooled and valued using German and French unit prices to estimate CAP-related cost to the German Sickness Funds and French public health-care sector, respectively. RESULTS: Compared to AMC +/- CLA, treatment with moxifloxacin resulted in 5.3% more patients achieving clinical cure 5 to 7 days after therapy (95% confidence interval [CI], 1.2 to 11.8%), increased speed of response (1 day sooner for median time to first return to apyrexia, p = 0.008), and a reduction in hospital stay by 0.81 days (95% CI, - 0.01 to 1.63) within the 21-day time frame. Treatment with moxifloxacin resulted in savings of 266 euro and 381 euro for Germany and France respectively, primarily due to the shorter length of hospital stay. Cost-effectiveness acceptability curves show moxifloxacin has a > or = 95% chance of being cost saving from French and German health-care perspectives, and higher probability of being cost-effective at acceptability thresholds up to 2,000 euro per additional patient cured. CONCLUSION: i.v./po monotherapy with moxifloxacin shows clinical benefits including increased speed of response and is cost-effective compared to i.v./po AMC +/- CLA in the treatment of CAP.