A cost-effectiveness analysis of lisdexamfetamine dimesylate in the treatment of adults with attention-deficit/hyperactivity disorder in the UK.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobehavioral disorder in children that may persist into adulthood. Lisdexamfetamine dimesylate (LDX) is approved in many countries for ADHD treatment in children, adolescents, and adults. OBJECTIVES: Estimate the cost-effectiveness of LDX as a first- or second-line treatment for adults with ADHD from the United Kingdom (UK) National Health Service (NHS) perspective compared with methylphenidate extended release (MPH-ER) and atomoxetine (ATX). METHODS: A 1-year decision-analytic model was developed. Health outcomes included response, non-response and inability to tolerate. Efficacy data were obtained from a mixed-treatment comparison (MTC). Response was a score of 1 or 2 on the Clinical Global Impression-Improvement scale. Tolerability was assessed by discontinuation rates due to adverse events. Utilities were identified via a systematic literature review. Health care resource use estimates were obtained via a survey of clinicians. Daily drug costs were estimated from mean doses reported in the trials used in the MTC. One-way and probabilistic sensitivity analyses (PSAs) were performed. RESULTS: LDX dominated MPH-ER and ATX; reducing mean per-patient annual cost by £5 and £200, and increasing mean quality-adjusted life years (QALYs) by 0.005 and 0.009, respectively. In the PSA, the probability of cost-effectiveness for LDX vs. MPH-ER and ATX at a threshold of £20,000 per QALY was 61% and 80%, respectively. CONCLUSIONS: From the perspective of the UK NHS, LDX is likely to provide a cost-effective treatment for adults with ADHD. This conclusion may be drawn with more certainty in comparison with ATX than with MPH-ER.

A Cost-Utility Analysis of Lisdexamfetamine Versus Atomoxetine in the Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder and Inadequate Response to Methylphenidate.

BACKGROUND: An economic analysis from the perspective of the UK National Health Service (NHS) evaluated the cost effectiveness of lisdexamfetamine dimesylate (LDX) compared with atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder who have had an inadequate response to methylphenidate. METHODS: A 1-year decision-analytic model was constructed, with the health outcomes "response", "nonresponse", and "unable to tolerate". Clinical data were taken from a head-to-head, randomized controlled trial in inadequate responders to methylphenidate. Response to treatment was defined as a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement subscale. Tolerability was assessed by discontinuation rates owing to adverse events. Utility weights were identified via a systematic literature review. Healthcare resource use estimates were obtained via a survey of clinicians. Daily drug costs were derived from British National Formulary 2012 costs and mean doses reported in the trial. One-way and probabilistic sensitivity analyses (PSAs) were performed. RESULTS: The comparison of LDX with atomoxetine resulted in an estimate of an incremental cost-effectiveness ratio of £1802 per quality-adjusted life-year (QALY). The result was robust in a wide range of sensitivity analyses; results were most sensitive to changes in drug costs and efficacy. In the PSA, assuming a maximum willingness to pay of £20,000 per QALY, LDX versus atomoxetine had an 86 % probability of being cost effective. In 38 % of PSA runs, LDX was more effective and less costly than atomoxetine. CONCLUSIONS: From the perspective of the UK NHS, LDX provides a cost-effective treatment option for children and adolescents who are inadequate responders to methylphenidate.

Cost effectiveness of darunavir/ritonavir combination antiretroviral therapy for treatment-naive adults with HIV-1 infection in Canada.

OBJECTIVE: The AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects (ARTEMIS) clinical trial examined the efficacy and safety of two ritonavir-boosted protease inhibitors (PI/r), darunavir/r 800/100 mg once daily (QD) and lopinavir/r 800/200 mg daily, both used in combination with tenofovir disoproxil fumarate/emtricitabine. This study aimed to assess the cost effectiveness of the darunavir/r regimen compared with the lopinavir/r regimen in treatment-naive adults with HIV-1 infection in Canada. METHODS: A Markov model with a 3-month cycle time and six CD4 cell-count-based health states (>500, 351-500, 201-500, 101-200, 51-100, and 0-50 cells/mm(3)) followed a cohort of treatment-naive adults with HIV-1 infection through initial darunavir/r or lopinavir/r combination therapy and a common set of subsequent regimens over the course of their remaining lifetimes. Population characteristics and transition probabilities were estimated from the ARTEMIS clinical trial and other trials. Costs (in 2014 Canadian dollars), utilities, and mortality were estimated from Canadian sources and published literature. Costs and health outcomes were discounted at 5% per year. One-way and probabilistic sensitivity analyses were performed, including a simple indirect comparison of the darunavir/r initial regimen with an atazanavir/r-based regimen. RESULTS: In the base-case lifetime analysis, individuals receiving initial therapy with the darunavir/r regimen experienced 0.25 more quality-adjusted life-years (QALYs) with lower antiretroviral drug costs (-$14,246) and total costs (-$18,402) than individuals receiving the lopinavir/r regimen, indicating that darunavir/r dominated lopinavir/r. In an indirect comparison with an atazanavir/r-based regimen, the darunavir/r regimen remained the dominant choice, but with lower cost savings (-$2,303) and QALY gains (0.02). Results were robust to a wide range of other changes in input parameter values, population characteristics, and modeling assumptions. The probabilistic sensitivity analysis demonstrated that the darunavir/r regimen was cost effective compared with the lopinavir/r regimen in over 86% of simulations for willingness-to-pay thresholds between $0 and $100,000 per QALY gained. CONCLUSIONS: Darunavir/r 800/100 mg QD may be a cost-effective PI/r component of initial antiretroviral therapy for treatment-naive adults with HIV-1 infection in Canada.

Multicountry burden of chronic hepatitis C viral infection among those aware of their diagnosis: a patient survey.

BACKGROUND: The World Health Organization has called for global and regional assessments of the burden of hepatitis C (HCV) along with country-specific patient profiles to better inform healthcare policy. The present investigated the characteristics and burden of patients reporting a diagnosis of HCV infection in the US, France, Germany, Italy, Spain, the UK, urban China, and Japan using a consistent methodology of patient-reported surveys. METHODS: The 2010 5EU (N = 57,805), 2009 US (N = 75,000), 2008/2009 Japan (N = 37,683), and 2009/2010 urban China (N = 33,261) waves of the National Health and Wellness Survey were used as the data source. Within each country, patients with a self-reported diagnosis of HCV were compared with those who did not report a diagnosis of HCV on sociodemographics, health behaviors, comorbidities, and health outcomes (e.g., Short Form-12v2). The effect of HCV was examined using regression analysis applying sampling weights. RESULTS: The prevalence of HCV ranged from 0.26% (China) to 1.42% (Italy). Patients in Japan and Italy (61.60 and 61.02 years, respectively) were the oldest, while patients in the US were the most likely to be obese (39.31%) and have concomitant anxiety (38.43%) and depression (46.05%) compared with other countries. Pooling countries and adjusting for sociodemographics, health behaviors, and comorbidities, HCV was associated with significantly lower physical component summary scores (b = -2.51) and health utilities (b = -0.04) and greater overall work impairment (b = 8.79), physician visits (b = 2.91), and emergency department visits (b = 0.30) (all p<.05). The effects on health status were strongest in the US and UK while the effects on healthcare resource use were strongest in Japan. CONCLUSIONS: HCV was associated with a significant humanistic and economic burden. These results suggest that the manifestation of the HCV burden, and the profile of the patients themselves, varied dramatically by country. Successful disease management should be cognizant of region-specific unmet needs.

Budget impact analysis-principles of good practice: report of the ISPOR 2012 Budget Impact Analysis Good Practice II Task Force.

BACKGROUND: Budget impact analyses (BIAs) are an essential part of a comprehensive economic assessment of a health care intervention and are increasingly required by reimbursement authorities as part of a listing or reimbursement submission. OBJECTIVES: The objective of this report was to present updated guidance on methods for those undertaking such analyses or for those reviewing the results of such analyses. This update was needed, in part, because of developments in BIA methods as well as a growing interest, particularly in emerging markets, in matters related to affordability and population health impacts of health care interventions. METHODS: The Task Force was approved by the International Society for Pharmacoeconomics and Outcomes Research Health Sciences Policy Council and appointed by its Board of Directors. Members were experienced developers or users of BIAs; worked in academia and industry and as advisors to governments; and came from several countries in North America and South America, Oceania, Asia, and Europe. The Task Force solicited comments on the drafts from a core group of external reviewers and, more broadly, from the membership of the International Society for Pharmacoeconomics and Outcomes Research. RESULTS: The Task Force recommends that the design of a BIA for a new health care intervention should take into account relevant features of the health care system, possible access restrictions, the anticipated uptake of the new intervention, and the use and effects of the current and new interventions. The key elements of a BIA include estimating the size of the eligible population, the current mix of treatments and the expected mix after the introduction of the new intervention, the cost of the treatment mixes, and any changes expected in condition-related costs. Where possible, the BIA calculations should be performed by using a simple cost calculator approach because of its ease of use for budget holders. In instances, however, in which the changes in eligible population size, disease severity mix, or treatment patterns cannot be credibly captured by using the cost calculator approach, a cohort or patient-level condition-specific model may be used to estimate the budget impact of the new intervention, accounting appropriately for those entering and leaving the eligible population over time. In either case, the BIA should use data that reflect values specific to a particular decision maker's population. Sensitivity analysis should be of alternative scenarios chosen from the perspective of the decision maker. The validation of the model should include at least face validity with decision makers and verification of the calculations. Data sources for the BIA should include published clinical trial estimates and comparator studies for the efficacy and safety of the current and new interventions as well as the decision maker's own population for the other parameter estimates, where possible. Other data sources include the use of published data, well-recognized local or national statistical information, and, in special circumstances, expert opinion. Reporting of the BIA should provide detailed information about the input parameter values and calculations at a level of detail that would allow another modeler to replicate the analysis. The outcomes of the BIA should be presented in the format of interest to health care decision makers. In a computer program, options should be provided for different categories of costs to be included or excluded from the analysis. CONCLUSIONS: We recommend a framework for the BIA, provide guidance on the acquisition and use of data, and offer a common reporting format that will promote standardization and transparency. Adherence to these good research practice principles would not necessarily supersede jurisdiction-specific BIA guidelines but may support and enhance local recommendations or serve as a starting point for payers wishing to promulgate methodology guidelines.

Immunonutrition for patients undergoing elective surgery for gastrointestinal cancer: impact on hospital costs.

BACKGROUND: Oral or enteral dietary supplementation with arginine, omega 3 fatty acids and nucleotides (known as immunonutrition) significantly improve outcomes in patients undergoing elective surgery. The objective of the study was to determine the impact on hospital costs of immunonutrition formulas used in patients undergoing elective surgery for gastrointestinal cancer. METHODS: US hospital costs of stay with and without surgical infectious complications, and average cost per day in the hospital for patients undergoing elective surgery for gastrointestinal cancer were estimated using data from the Healthcare Cost and Utilization Project's 2008 Nationwide Inpatient Sample. These costs were then used to estimate the impact of perioperative immunonutrition on hospital costs using estimates of reduction in infectious complications or length of stay from a meta-analysis of clinical trials in patients undergoing elective surgery for gastrointestinal cancer. Sensitivity of the results to changes in baseline complication rates or length of stay was tested. RESULTS: From the meta-analysis estimates, use of immunonutrition resulted in savings per patient of $3,300 with costs based on reduction in infectious complication rates or $6,000 with costs based on length of hospital stay. Cost savings per patient were present for baseline complication rates above 3.5% or when baseline length of stay and infectious complication rates were reduced to reflect recent US data for those with upper and lower GI elective cancer surgery (range, $1,200 to $6,300). CONCLUSIONS: Use of immunonutrition for patients undergoing elective surgery for gastrointestinal cancer is an effective and cost-saving intervention.

Updating and confirming an industry-sponsored pharmacoeconomic model: comparing two antipsychotics in the treatment of schizophrenia.

OBJECTIVE: This study updated a 2001 decision economic model that used indirect data and confirmed its findings by developing a new cost-effectiveness model by using now available head-to-head data. The models compared olanzapine with ziprasidone in the treatment of schizophrenia in the United States. METHODS: A decision analytic modeling approach was used to estimate annual health-care costs and health outcomes, incorporating events such as response, relapse, and suicide. Patients without response to first-line treatment switched to the other comparator. Decision tree probabilities were extracted from head-to-head studies and other published clinical literature. Direct health-care costs and quality-adjusted life-years (QALYs) were estimated on the basis of resource use and utility weights for initial and relapse episodes, maintenance therapy, and extended episodes of illness. Disutilities associated with treatment-emergent adverse events were included. RESULTS: Consistent with the 2001 model, this model found that first-line treatment with olanzapine is associated with fewer hospital days, fewer days with extrapyramidal symptoms, and higher QALYs than is first-line treatment with ziprasidone. Total costs were lower for the olanzapine pathway ($70,232-$72,776 vs. $73,086-$73,310 in the Positive and Negative Syndrome Scale analysis) due to the cost savings associated with reduced health-care resource use. The incremental cost per QALY gained indicated that the olanzapine pathway dominated the ziprasidone pathway. CONCLUSIONS: Decision analytic models should be continuously assessed against new data. This case study shows that incorporating new data confirmed results of a previously published model in which olanzapine was associated with better expected health outcomes and lower total health-care costs than was ziprasidone.

Cost-effectiveness of prasugrel in a US managed care population.

OBJECTIVE: Decision-makers in the US may be interested in the applicability to their populations of cost-effectiveness results generated from clinical trial populations. METHODS: An economic model estimating the cost-effectiveness of prasugrel plus aspirin relative to clopidogrel plus aspirin for patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) was developed from a managed care organization (MCO) perspective. The model estimated 15-month cardiovascular events or bleeding-related outcomes, life expectancy, and costs for patients who received thienopyridine treatment during and after a PCI following a diagnosis of ACS. Post-ACS event rates for patients treated with clopidogrel were from an MCO. The relative risks of these events with prasugrel compared with clopidogrel were from a head-to-head clinical trial. RESULTS: The results of the base-case analysis indicated that, in an MCO population, use of prasugrel-based therapy rather than clopidogrel-based therapy at current prices resulted in cost-savings and fewer clinical events over the 15 months after an ACS diagnosis followed by PCI. At possible lower prices for generic clopidogrel-based therapy, the cost-effectiveness ratio for prasugrel-based therapy compared with clopidogrel-based therapy was between $6643 and $13,906 per life-year gained. The results were most sensitive to the relative costs of the two treatments and the cost for hospital stays. LIMITATIONS: Limitations of the study included lack of follow-up of patients disenrolling from the MCO before the end of the 15-month observation period, the assumption of equal relative risks of events in an MCO as in the clinical trial, and the lack of information on the ratio of cost to charges in the MCO database. CONCLUSIONS: Use of prasugrel-based therapy compared with clopidogrel-based therapy in ACS patients having a PCI resulted in cost-savings at current prices and favorable cost-effective ratios at likely generic prices for clopidogrel-based therapy because of offsetting savings in the costs of rehospitalization.

Cost effectiveness of tiotropium for chronic obstructive pulmonary disease: a systematic review of the evidence.

BACKGROUND: Tiotropium has been shown to reduce exacerbations and improve quality of life for patients with chronic obstructive pulmonary disease (COPD), a lung disease characterized by a persistent and progressive airflow limitation. OBJECTIVES: To present a systematic literature review of the cost effectiveness of treatment with tiotropium compared with other currently used treatments for COPD. METHODS: A systematic search was performed via PubMed, the Cochrane database, and EMBASE from 2002 to 2009. Methods and results by study design and by country were compared. RESULTS: Seventeen studies were included in the review. Study designs were characterized as follows: modeling based on clinical trial data, and empirical analysis based on either clinical trial or observational data. Comparing monotherapy regimens (12 studies), all study designs found that treatment with tiotropium was associated with lower costs for hospitalisation and other non-drug services. Total costs, including the costs of maintenance drugs, were lower with tiotropium in some, but not all, of the studies. Tiotropium was shown to be cost effective based on commonly accepted benchmark values. Limitations of the review included the wide variety of outcome measures used in different studies, the limited number of observational database studies for monotherapy, and limited data for combination therapy regimens. CONCLUSIONS: The main conclusions of the economic evaluations derived from clinical trial data at the time of product approval and from later observational data reflecting clinical use are similar: use of tiotropium monotherapy is associated with lower hospital and other non-drug costs and better health outcomes and is either cost saving or cost effective compared with other maintenance monotherapies.

Adherence to guidelines for sensitivity analysis: cost-effectiveness analyses of dual oral antiplatelet therapy.

OBJECTIVE: Cost-effectiveness analyses of new treatments for cardiovascular disease frequently require input parameters whose values are known with uncertainty due to limited data. The objective of this paper is to examine the extent to which published sensitivity analyses addressing this uncertainty adhere to Health Technology Assessment (HTA) guidelines. RESEARCH DESIGN AND METHODS: A systematic review of published cost-effectiveness analyses was performed for an example drug treatment scenario, dual oral antiplatelet therapy compared with aspirin alone following acute coronary syndromes and/or percutaneous coronary intervention. The following medical literature databases were searched for articles published from January 1997 to June 2007: PubMed, Cochrane Collaboration, EMBASE and the Health Economic Evaluation Database (HEED). Evidence tables were created to show the sensitivity of the cost-effectiveness estimates to changes in the input parameter values, as well as the data sources used for the reference-case and sensitivity analysis input parameter values. The extent to which the sensitivity analyses adhered to HTA guidelines were also examined. RESULTS: Cost-effectiveness ratios were most sensitive to changes in the efficacy of dual antiplatelet therapy and reference-case model assumptions about costs beyond the trial period. Although alternative values tested in the sensitivity analysis for some input parameters were based on observed ranges or distributions, alternative values tested for many other input parameters were assumed without justification. CONCLUSIONS: Sensitivity analyses in the cost-effectiveness studies of dual oral antiplatelet therapy were not fully adherent with HTA guidelines. In particular, long-term costs and benefits were not always included in the sensitivity estimates, the impact of differential effects on death and myocardial infarction was not explored, and justification for the alternative parameter values tested was not always provided.

Rate, type, and cost of pelvic organ prolapse surgery in Germany, France, and England.

OBJECTIVE: To estimate the rate, type and costs of surgical interventions for pelvic organ prolapse (POP) in Germany, France, and England. STUDY DESIGN: We identified the number, rate, and type of hospital admissions for pelvic floor surgery in 2005 from national hospital activity databases in each country: the German Hospital Episode, the French Medical Care Program Information System, and the National Health Service England Hospital Episode Statistics. Costs to the payer were estimated using the Diagnosis-Related Group reimbursement rates for each country. RESULTS: In 2005, the number (rate) of admissions for POP surgery was 36,854 (0.87 per 1000 women) in Germany, 36,679 (1.14 per 1000 women) in France, and 28,959 (1.13 per 1000 women) in England. Admissions for POP surgery constituted 10.4%, 16.7% and 16.9% of all admissions for female genital tract therapeutic interventions in Germany, France and England, respectively. At least 20% of hysterectomies were performed for the primary indication of POP. 57.4%, 45.0%, and 40.1% of all admissions for POP surgery included a hysterectomy. The costs to payers were 144,236,557 euro, 83,067,825 euro, and 81,030,907 euro in Germany, France, and England, respectively. CONCLUSION: Burden and costs associated with POP surgery are substantial in the three countries studied. Thus, programs aimed at reducing the burden of this disease are desirable.

Rate, type, and cost of invasive interventions for uterine myomas in Germany, France, and England.

STUDY OBJECTIVE: The objective of our study was to quantify the rate, type, and cost of interventions for uterine myomas to payers in Germany, France, and England. DESIGN: Computations using data from national hospital activity databases. DESIGN CLASSIFICATION: II-3. SETTING: Hospital admissions in Germany, France, and England. PATIENTS: Women admitted for a surgical or radiologic intervention for uterine myomas. INTERVENTIONS: Surgical or radiologic interventions for uterine myomas. MEASUREMENTS AND MAIN RESULTS: We identified the number and type of hospital admissions involving surgical or radiologic interventions for uterine myomas, through the analysis of national hospital activity databases from each country. We calculated the costs of these hospitalizations to payers in these countries using the diagnosis-related group reimbursement rates. In 2005, the number (rate) of hospital admissions involving interventions for uterine myomas was 64 299 (1.53/1000 women) in Germany, 37 787 (1.17/1000 women) in France, and 18 274 (0.71/1000 women) in England. The annual costs of these interventions to payers were euro212 313 090 in Germany, euro73 278 270 in France (excluding surgeon and anesthetist fees for interventions in the private sector), and euro52 674 672 in England. The percentage of interventions for uterine myomas that included a hysterectomy was 84.9% in Germany, 59.7% in France, and 64.1% in England. CONCLUSION: The number of admissions and costs associated with interventions for uterine myomas are substantial in the 3 European countries studied. Hysterectomy is the most frequent surgical intervention used to treat uterine myomas. The results in this article provide useful information for policy makers wishing to evaluate the cost effectiveness and budget impact of new, less invasive interventions.

Nonresponse, partial response, and failure to achieve remission: humanistic and cost burden in major depressive disorder.

OBJECTIVE: To characterize the spectrum of clinical outcomes achieved with depression treatment and the associated impact on quality of life (QOL), functional status, overall well-being, health-care costs, and productivity. SOURCES: Electronic databases including Medline were searched for English language sources between 1995 and 2007 using key words of depression, nonresponse, partial response, and remission and QOL, functional status, utility, cost, and productivity. STUDY SELECTION: Relevant abstracts were obtained for 488 references and full-text articles were reviewed that included primary data and compared outcomes by treatment response. Data were abstracted from 26 full-text articles. DATA ABSTRACTION: Detailed evidence tables were prepared with the relevant data as well as information on the study design. All data abstracted were checked for accuracy. synthesis: Treatment remitters and partial responders reported clinically and statistically significant improvements in QOL, functional status, and overall well-being compared to nonresponders. Annual health-care costs and productivity losses were significantly lower for remitters and partial responders compared to nonresponders. CONCLUSIONS: The reduced disease burden for remitters and partial responders compared to nonresponders indicates that new treatment strategies that improve the rates of response/remission with initial treatment might have value to patients and to society.

Principles of good practice for budget impact analysis: report of the ISPOR Task Force on good research practices--budget impact analysis.

OBJECTIVES: There is growing recognition that a comprehensive economic assessment of a new health-care intervention at the time of launch requires both a cost-effectiveness analysis (CEA) and a budget impact analysis (BIA). National regulatory agencies such as the National Institute for Health and Clinical Excellence in England and Wales and the Pharmaceutical Benefits Advisory Committee in Australia, as well as managed care organizations in the United States, now require that companies submit estimates of both the cost-effectiveness and the likely impact of the new health-care interventions on national, regional, or local health plan budgets. Although standard methods for performing and presenting the results of CEAs are well accepted, the same progress has not been made for BIAs. The objective of this report is to present guidance on methodologies for those undertaking such analyses or for those reviewing the results of such analyses. METHODS: The Task Force was appointed with the advice and consent of the Board of Directors of ISPOR. Members were experienced developers or users of budget impact models, worked in academia, industry, and as advisors to governments, and came from several countries in North America, Oceana, Asia, and Europe. The Task Force met to develop core assumptions and an outline before preparing a draft report. They solicited comments on the outline and two drafts from a core group of external reviewers and more broadly from the membership of ISPOR at two ISPOR meetings and via the ISPOR web site. RESULTS: The Task Force recommends that the budget impact of a new health technology should consider the perspective of the specific health-care decision-maker. As such, the BIA should be performed using data that reflect, for a specific health condition, the size and characteristics of the population, the current and new treatment mix, the efficacy and safety of the new and current treatments, and the resource use and costs for the treatments and symptoms as would apply to the population of interest. The Task Force recommends that budget impact analyses be generated as a series of scenario analyses in the same manner that sensitivity analyses would be provided for CEAs. In particular, the input values for the calculation and the specific cost outcomes presented (a scenario) should be specific to a particular decision-maker's population and information needs. Sensitivity analysis should also be in the form of alternative scenarios chosen from the perspective of the decision-maker. The primary data sources for estimating the budget impact should be published clinical trial estimates and comparator studies for efficacy and safety of current and new technologies as well as, where possible, the decision-maker's own population for the other parameter estimates. Suggested default data sources also are recommended. These include the use of published data, well-recognized local or national statistical information and in special circumstances, expert opinion. Finally, the Task Force recommends that the analyst use the simplest design that will generate credible and transparent estimates. If a health condition model is needed for the BIA, it should reflect health outcomes and their related costs in the total affected population for each year after the new intervention is introduced into clinical practice. The model should be consistent with that used for the CEA with regard to clinical and economic assumptions. CONCLUSIONS: The BIA is important, along with the CEA, as part of a comprehensive economic evaluation of a new health technology. We propose a framework for creating budget impact models, guidance about the acquisition and use of data to make budget projections and a common reporting format that will promote standardization and transparency. Adherence to these proposed good research practice principles would not necessarily supersede jurisdiction-specific budget impact guidelines, but may support and enhance local recommendations or serve as a starting point for payers wishing to promulgate methodology guidelines.

Optimal assignment of treatments to health states using a Markov decision model: an introduction to basic concepts.

Assessing the cost effectiveness of a new health intervention often requires modelling to estimate the impact of the intervention on cost, survival and quality of life over the lifetime of a cohort of patients. Markov modelling is a methodology that is commonly employed to estimate these long-term costs and benefits. As commonly used, these models assume that the patients continue to get the treatments assigned regardless of the change in health states. In this paper, we describe an extension to the Markov modelling approach, called Markov decision modelling. Such a model starts with a set of health states and treatments and optimally assigns treatments to each of the health states. A Markov decision model can be used to identify the optimal treatment strategy not just for the initial disease state, but also as the disease state changes over time. We present a dynamic programming approach to identifying the optimal assignment of treatments, and illustrate this methodology using an example. The Markov decision modelling approach provides an efficient way of identifying optimal assignment of treatments to health states, but, like the standard Markov model, may be of limited use when probabilities of future events depend on past history in a complex fashion. Even with its limitations, Markov decision models offer an opportunity for health economists to inform healthcare decision-makers on how to modify current treatment pathways to incorporate new treatments as they become available.

Minimizing resistance consequences after virologic failure on initial combination therapy: a systematic overview.

OBJECTIVE: To identify optimal first-line therapies based on the rate of virologic success (VS) and the preservation of future treatment options in antiretroviral therapy (ART)-naive subjects. DESIGN: Systematic overview of genotypic resistance mutations from clinical trials of combination ART. METHODS: Various sources were searched for studies in ART-naive subjects providing virologic response rates and genotypes from subjects with virologic failure. The International AIDS Society-USA genotypic resistance guidelines were used to calculate regimen resistance cost (RCreg) and number of active drug (AD) scores for each regimen and to rank the regimens. RESULTS: Intra- and interstudy comparisons showed higher VS rates for nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens (range: 51%-76%) and boosted protease inhibitor (boosted PI) regimens (range: 55%-79%). Boosted PI failures had the lowest RCreg (range: 0.12-0.21) and the highest AD (range: 19.80-20.18) scores. NNRTI failures had higher RCreg (range: 0.00-1.22) and lower AD (range: 16.83-21) scores. CONCLUSIONS: NNRTI and boosted PI regimens provide the highest rates of VS in treatment-naive HIV-infected persons. Treatment option scores were higher in subjects who failed boosted PI- containing regimens versus NNRTI-containing regimens, however.

Drug persistency patterns for patients treated with rivastigmine or donepezil in usual care settings.

OBJECTIVE: To compare levels of persistency with 2 cholinesterase (ChE) inhibitors--rivastigmine and donepezil--for the treatment of Alzheimer's disease (AD) through the use of administrative claims data. METHODS: This retrospective cohort study identified treatment-naive, community-based AD patients having an initial prescription (index event) for rivastigmine or donepezil between June and December 2000, in the United States, from pharmacy claims in a proprietary administrative claims database. Patients were excluded if they received either drug during the 180 days prior to their index prescription or if they did not have continuous plan enrollment during this period and for at least 90 days following the index date. The probability of treatment discontinuation within the first 60 days of treatment was estimated. Time to treatment discontinuation was analyzed for the cohort of patients that remained on therapy > or =60 days as well as for subgroups of the cohort reaching either approved or maximum recommended doses of donepezil or rivastigmine. Treatment discontinuation was defined as either a stop of therapy (no prescription refill within 60 days of estimated completion of prior prescription) or a switch to an alternative AD drug. Kaplan-Meier survival and proportional hazard model analyses were performed. Proportion of days covered (PDC) by an AD therapy was also evaluated in each quarter during the first year of follow-up. RESULTS: Of the newly treated AD study population, 30.4% (171/563) of rivastigmine patients and 31.2% (583/1,871) of donepezil patients discontinued treatment within 60 days of starting therapy (P = 0.72). For the cohort of patients that remained on therapy > or =60 days, the mean time to treatment discontinuation was 331 days (95% confidence interval [CI], 307-355) for rivastigmine patients (n = 392) versus 337 days (95% CI, 322-352) for donepezil patients (n = 1288). The proportion of patients with a PDC > or =80% after 12 months of follow-up was 23% for the donepezil group and 19% for the rivastigmine group (P = 0.34). For the cohort subgroup that reached an approved dose, the mean time to treatment discontinuation was 346 days (95% CI, 318-374) for rivastigmine patients (n = 282) versus 338 days (95% CI, 323-353) for donepezil patients (n = 1,283). For the cohort subgroup that reached the maximum recommended dose, the mean time to treatment discontinuation was 396 days (95% CI, 343-449) for rivastigmine patients (n = 61) versus 364 days (95% CI, 344-384) for donepezil patients (n = 712). CONCLUSION: Newly treated AD patients in a usual care setting who initiate therapy with either rivastigmine or donepezil have similar levels of persistency with treatment.

Budget impact analysis: review of the state of the art.

A budget impact analysis for a new pharmaceutical product provides estimates of the likely impact of the new drug on a healthcare decision maker's short- and longer-term annual budgets. Budget impact analysis are an essential part of a comprehensive economic assessment of a new pharmaceutical product and are increasingly required, along with cost-effectiveness analyses, before national or local formulary approval or reimbursement. Standards for the development, content and presentation of the results of a budget impact analysis have recently been proposed but detailed guidance on alternative methods for estimating budget impacts are not yet available. Methods for performing these analyses require either static or dynamic analysis techniques depending on the type of health condition and health impact of the new drug. Several factors, that are not generally needed for cost-effectiveness analysis, should be part of a comprehensive budget impact analysis including the size of the treated population, second-order costs, market diffusion rates for the new drug, and off-label use. A review of the recent literature indicates that there is only a limited number of published budget impact analyses and these vary greatly in the methods used. Instead of publication in peer-reviewed journals, budget impact analyses are more frequently presented directly to decision makers as interactive computer programs designed to compute the budget impact for specific health plans using plan-specific inputs. It is recommend that a comprehensive approach to budget impact estimation be adopted, with the results being presented from both a societal perspective as well as from more limited perspectives depending on the needs of the decision maker.