Showing papers in "PharmacoEconomics in 2006"

Good Practice Guidelines for Decision-Analytic Modelling in Health Technology Assessment: A Review and Consolidation of Quality Assessment

Abstract: The use of decision-analytic modelling for the purpose of health technology assessment (HTA) has increased dramatically in recent years. Several guidelines for best practice have emerged in the literature; however, there is no agreed standard for what constitutes a 'good model' or how models should be formally assessed. The objective of this paper is to identify, review and consolidate existing guidelines on the use of decision-analytic modelling for the purpose of HTA and to develop a consistent framework against which the quality of models may be assessed. The review and resultant framework are summarised under the three key themes of Structure, Data and Consistency. 'Structural' aspects relate to the scope and mathematical structure of the model including the strategies under evaluation. Issues covered under the general heading of 'Data' include data identification methods and how uncertainty should be addressed. 'Consistency' relates to the overall quality of the model. The review of existing guidelines showed that although authors may provide a consistent message regarding some aspects of modelling, such as the need for transparency, they are contradictory in other areas. Particular areas of disagreement are how data should be incorporated into models and how uncertainty should be assessed. For the purpose of evaluation, the resultant framework is applied to a decision-analytic model developed as part of an appraisal for the National Institute for Health and Clinical Excellence (NICE) in the UK. As a further assessment, the review based on the framework is compared with an assessment provided by an independent experienced modeller not using the framework. It is hoped that the framework developed here may form part of the appraisals process for assessment bodies such as NICE and decision models submitted to peer review journals. However, given the speed with which decision-modelling methodology advances, there is a need for its continual update.

Bayesian methods for evidence synthesis in cost-effectiveness analysis

Abstract: Recently, health systems internationally have begun to use cost-effectiveness research as formal inputs into decisions about which interventions and programmes should be funded from collective resources. This process has raised some important methodological questions for this area of research. This paper considers one set of issues related to the synthesis of effectiveness evidence for use in decision-analytic cost-effectiveness (CE) models, namely the need for the synthesis of all sources of available evidence, although these may not 'fit neatly' into a CE model. Commonly encountered problems include the absence of head-to-head trial evidence comparing all options under comparison, the presence of multiple endpoints from trials and different follow-up periods. Full evidence synthesis for CE analysis also needs to consider treatment effects between patient subpopulations and the use of nonrandomised evidence. Bayesian statistical methods represent a valuable set of analytical tools to utilise indirect evidence and can make a powerful contribution to the decision-analytic approach to CE analysis. This paper provides a worked example and a general overview of these methods with particular emphasis on their use in economic evaluation.

Generic health-related quality-of-life assessment in children and adolescents: methodological considerations.

Abstract: The health-related quality of life (HR-QOL) of children and adolescents is increasingly considered a relevant topic for research. Instruments to assess quality of life in children and adolescents of a generic as well as disease- or condition-specific nature are being developed and applied in epidemiological surveys, clinical studies, quality assurance and health economics. This paper attempts to give an overview on the state of the art of HR-QOL assessment in children as it relates to methodological and conceptual challenges. Instruments available in international or cross-cultural research to assess HR-QOL in generic terms were identified and described according to psychometric data provided and the width of application.

Using value of information analysis to prioritise health research: some lessons from recent UK experience.

Abstract: Decisions to adopt, reimburse or issue guidance on the use of health technologies are increasingly being informed by explicit cost-effectiveness analyses of the alternative interventions. Healthcare systems also invest heavily in research and development to support these decisions. However, the increasing transparency of adoption and reimbursement decisions, based on formal analysis, contrasts sharply with research prioritisation and commissioning. This is despite the fact that formal measures of the value of evidence generated by research are readily available. The results of two recent opportunities to apply value of information analysis to directly inform policy decisions about research priorities in the UK are presented. These include a pilot study for the UK National Co-ordinating Centre for Health Technology Assessment (NCCHTA) and a pilot study for the National Institute for Health and Clinical Excellence (NICE). We demonstrate how these results can be used to address a series of policy questions, including: is further research required to support the use of a technology and, if so, what type of research would be most valuable? We also show how the results can be used to address other questions such as, which patient subgroups should be included in subsequent research, which comparators and endpoints should be included, and what length of follow up would be most valuable.

Costs of irritable bowel syndrome in the UK and US

Abstract: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, with an estimated prevalence rate in the general population of 10-15% in industrialised countries. Although IBS is not a life-threatening disease, it contributes significantly to a large segment of healthcare resource consumption. This review provides an overview of studies addressing the direct and indirect costs of IBS in the US and the UK. A systematic literature search was conducted in MEDLINE and the Cochrane library; additionally, all reference lists covering the years from 1960 to May 2004 were scanned. Twenty-four publications for the US and the UK, published between 1991 and 2003, were identified: 6 were excluded, 18 were included. Data for the UK, US and UK + US were reported in 5, 11 and 2 publications, respectively. Total direct cost estimates per patient per year ranged from US 348 dollars to US 8750 dollars (calculated for year 2002). The average number of days off work per year because of IBS was between 8.5 and 21.6; indirect costs ranged from US 355 dollars to US 3344 dollars. The total costs and cost components of IBS are influenced by several factors: features of the investigated patient group (age, limitation to healthcare seekers or all IBS patients, comorbidity, severity of symptoms), database used, method of data collection (retrospective or prospective, varying cost components, time-point of data collection in relation to index-date of IBS diagnosis, method of cost calculation [incidence or prevalence based]) and different healthcare systems in the US and the UK. These factors led to the incomparability of published data, thus no comprehensive picture can be drawn of the total costs related to IBS in the UK and US. Data underline the magnitude of the economic impact of IBS in the UK and US, which is increased by a factor of 1.1-6.0, compared with matched non-IBS control groups. IBS contributes both direct and indirect costs to the total healthcare bill. Further studies should take influencial factors into account and report related data carefully in order to provide useful and comparable published cost data. Additionally, further research on the cost effectiveness of diagnostic procedures and therapies in IBS is required to define strategies to help IBS patients improve their quality of life and reduce related costs.

Cost-of-illness studies : a review of current methods.

Abstract: The number of cost-of-illness (COI) studies has expanded considerably over time. One outcome of this growth is that the reported COI estimates are inconsistent across studies, thereby raising concerns over the validity of the estimates and methods. Several factors have been identified in the literature as reasons for the observed variation in COI estimates. To date, the variation in the methods used to calculate costs has not been examined in great detail even though the variations in methods are a major driver of variation in COI estimates. The objective of this review was to document the variation in the methodologies employed in COI studies and to highlight the benefits and limitations of these methods.

Recent developments in decision-analytic modelling for economic evaluation.

Abstract: The past few years have seen rapid changes in the methods of decision-analytic modelling of healthcare programmes for the purposes of economic evaluation. This paper focuses on four developments in modelling that have emerged over the past few years or have become more widely used. First, no one optimal method for extrapolating outcomes from clinical trials has yet been established. Modellers may draw from a set of varied assumptions about survival extrapolation that encompass a range of possibilities from highly optimistic to extremely cautious. Secondly, the practicality and appeal of microsimulation as a method for analysing healthcare decision problems has increased dramatically with the speed of computing technology. Individual instantiations of a system are generated by using a random process to draw from probability distributions a large number of times (also known as Monte Carlo or probabilistic simulation). Microsimulation is moving in new directions, such as discrete-event simulations that simulate sequences of events by drawing directly from probability distributions of event times; this approach is now being broadly applied to model situations where populations of patients interact with healthcare delivery systems. Microsimulation modelling of transmission systems at the population level is also rapidly developing. Thirdly, model calibration is emerging as a new tool that may offer health scientists a means of generating important fundamental knowledge about disease processes. Model calibration allows evidence synthesis in which observations on observable quantities are used to draw inferences about unobservable quantities. The methodology of model calibration has advanced considerably, drawing on theories of numerical analysis and mathematical programming such as gradient methods, intelligent grid search algorithms, and many more. As a fourth issue, an area of extraordinary activity is in the use of transmission models to analyse interventions for infectious diseases, including population-wide effects of vaccination. Transmission models use differential equations to simulate, deterministically for the most part, transitions among infection-related health states. Only recently have modelling methodologies been combined so that cost-effectiveness analyses can consider explicitly not only the patient-level benefits of interventions but also the secondary benefits through transmission dynamics. Advances in technology allow more realistic and complex healthcare models to be simulated more rapidly. However, decision makers will not readily accept results from models unless they can understand them intuitively and explain them to others in relatively simple terms. The challenge for the next generation of modellers is not only to harness the power available from these newly accessible methods, but also to extract from the new generation of models the insights that will have the power to influence decision makers.

A comparative review of health-related quality-of-life measures for use in HIV/AIDS clinical trials.

Abstract: With the advent of highly active antiretroviral therapy (HAART), HIV-infected patients are living longer and are concerned not only with a treatment’s ability to extend their life but also with the quality of the life they are able to lead. Regulatory authorities are also paying closer attention to the use of health-related quality-of-life (HR-QOL) measures in clinical trials and to the subsequent claims that are made based on the results. This paper reviews existing HR-QOL measures reported in the HIV/AIDS literature since 1990 and identifies those most worthy of consideration for use in future clinical trials.

The Cost Effectiveness of Anticoagulation Management Services for Patients with Atrial Fibrillation and at High Risk of Stroke in the US

Abstract: Background Anticoagulation therapy with warfarin is widely considered the standard of care for stoke prophylaxis in patients with atrial fibrillation who are at high risk of stroke. Community-based studies in the US have reported that the effectiveness of anticoagulation varies by management approach and that patients receiving warfarin have international normalised ratio (INR) values within the target therapeutic range less than half the time.

Costs of Inflammatory Bowel Disease in Germany

Abstract: Introduction: Inflammatory bowel disease (IBD) is a chronic condition that afflicts young adults in their economically productive years. The goal of this study was to determine the costs of IBD in Germany from a societal perspective, using cost diaries. Methods: Members of the German Crohn’s Disease and Ulcerative Colitis Association who had IBD were recruited by post, and those who agreed to participate documented their IBD-associated costs prospectively in a diary over 4 weeks. They documented their use of healthcare facilities, medications, sick leave and out-of-pocket expenditures, as well as general demographic information, the status and history of their IBD, and long-term disability. Item costs were calculated according to national sources. Cost data were calculated using non-parametric bootstrapping and presented as mean costs (year 2004) over 4 weeks. Results: The cost diaries were returned by 483 subjects (Crohn’s disease: n = 241, ulcerative colitis: n = 242) with a mean age of 42 years and an average disease duration of 13 years (SD ± 8.09). The cost diaries were regarded as ‘easy to complete’ by 89% of participants. The mean 4-week costs per subject were €1425 (95% CI 1201, 1689) for Crohn’s disease and €1015 (95% CI 832, 1258) for ulcerative colitis. Of the total costs for Crohn’s disease, 64% were due to indirect costs such as early retirement or sick leave and 32% were due to direct medical costs. In contrast, of the total costs for ulcerative colitis, 41% were due to direct medical costs and 54% to indirect costs. Conclusions: This is the first comprehensive cost study for Crohn’s disease and ulcerative colitis in Germany. The most important economic factors that influenced the cost profiles of both diseases were the long-term productivity losses due to an ongoing inability to work and the cost of medications. Results indicate significant cost differences between Crohn’s disease and ulcerative colitis. This data provides initial cost estimates that can be analysed further with respect to cost determinants and disease-specific costs in the future.

Economic evaluation and decision making in the UK.

Abstract: This article reviews the development of economic evaluation of health technologies in the UK and its impact on decision making. After a long period of limited impact from studies mainly carried out as academic exercises, the advent of the National Institute for Health and Clinical Excellence (NICE) in 1999 provided a transparent decision-making context where economic evaluation plays a central role. This article reviews some of the key characteristics about the way NICE works, for example, the way NICE has defined the form of analysis that it requires, reflecting its objective of maximising health gain (QALYs) from the predetermined and limited UK NHS budget.

Information Created to Evade Reality (ICER): Things We Should Not Look to for Answers

Abstract: Cost-effectiveness analysis has been advocated in the health economics methods literature and adopted in a growing number of jurisdictions as an evidence base for decision makers charged with maximising health gains from available resources. This paper critically appraises the information generated by cost-effectiveness analysis, in particular the incremental cost-effectiveness ratio (ICER). It is shown that this ratio is used as comparative information on what are non-comparable options and hence evades the reality of the decision-maker's problem. The theoretical basis for the ICER approach is the simplification of theoretical assumptions that have no relevance to the decision maker's context. Although alternative, well established methods can be used for addressing the decision maker's problem, faced with the increasing evidence of the theoretical and empirical failures of the cost-effectiveness approach, some proponents of the approach now propose changing the research question to suit the approach as opposed to adopting a more appropriate method for the prevailing and continuing problem. As long as decision makers are concerned with making the best use of available healthcare resources, cost-effectiveness analysis and the ICER should not be where we look for answers.

Pharmacoeconomic analyses of azathioprine, methotrexate and prospective pharmacogenetic testing for the management of inflammatory bowel disease.

Abstract: Objectives: To compare the cost effectiveness of azathioprine (AZA), methotrexate (MTX) and no immunosuppression for maintaining remission of moderate to severe inflammatory bowel disease (IBD) in New Zealand Caucasians, and to determine whether prospective testing for poor metabolisers of AZA by genotype or phenotype is cost effective.

Functional impairment, healthcare costs and the prevalence of institutionalisation in patients with Alzheimer's disease and other dementias.

Abstract: The progressive decline in functional status for patients with Alzheimer’s disease and other dementias (ADOD) is well documented However, there is limited information on the economic benefits of interventions improving functional status in an ADOD population This study estimated the relationship between the degree of functional impairment in patients with ADOD and their healthcare costs and prevalence of institutionalisation Retrospective cross-sectional analyses of the Medicare Current Beneficiary Survey (MCBS) were performed A nationally representative sample of Medicare beneficiaries with ADOD was identified from the 1995–8 waves of the MCBS (n = 3138): 34% in the community, 57% institutionalised and 9% residing in both settings during the year Three measures of functioning were used: the number of activities of daily living (ADLs) and independent ADLs (IADLs) impaired; an index summarising number and severity of ADL and IADL impairments; and the Katz Index of ADLs Healthcare costs included costs for all healthcare services received in all settings, regardless of whether they were covered by insurance or paid out of pocket The relationships between each measure of impairment and healthcare costs and prevalence of institutionalisation were estimated using linear and logistic regression Healthcare costs (1995–8 values) for all ADOD patients increased by $US1958 (p < 0001) for each additional ADL impairment and $US549 (p = 0073) for each additional IADL impairment For community-dwelling ADOD patients, healthcare costs increased by $US1541 (p < 0001) for each additional ADL and $US714 (p = 0022) for each additional IADL Costs also increased by severity on the summary index and the Katz Index Odds of institutionalisation also increased by the three measures of functional impairment Although relationships between function and costs have been described previously, the exact nature of these relationships has not been investigated solely in patients with dementia The data from this study suggest a strong relationship between functional impairment and healthcare costs, specifically in patients with dementia Even IADL impairments, which are common in mild to moderate dementia, may significantly raise costs The results suggest that therapies and care management that improve functioning may possibly reduce other healthcare costs

Usefulness of the Audit of Diabetes-Dependent Quality-of-Life (ADDQoL) Questionnaire in Patients with Diabetes in a Multi-Ethnic Asian Country

Abstract: Introduction: Asia will be at the forefront of the current epidemic of diabetes mellitus. Quality of life (QOL) is an important outcome measure in the assessment of diabetes care. However, few QOL instruments are culturally suitable for use in Asian countries. The Audit of Diabetes-Dependent Quality-of-Life (ADDQoL) questionnaire is a third-generation individualised QOL instrument. Individualised instruments such as the ADDQoL have the potential to be useful and less costly alternatives to computerised adaptive testing (CAT), which may not be practical in developing countries. Objective: To evaluate and validate the ADDQoL questionnaire in Englishspeaking patients with diabetes in Singapore, a multi-ethnic Asian country. Methods: The ADDQoL and EQ-5D were administered to English-speaking respondents with type 1 or 2 diabetes (aged ≥18 years) recruited from a tertiary acute-care referral hospital by convenience sampling. The usefulness of the key design features of the ADDQoL were assessed by measuring the number of zeroimportance responses, the change in item ranking with and without weighting for importance, and the frequency of utilisation of the ‘not applicable’ (NA) options. The acceptability, factor structure and internal consistency (Cronbach’s α) of the ADDQoL were also assessed. Data were subjected to unforced factor analysis with oblimin rotation and then the condition was set to force a one-factor solution. The validity of the ADDQoL was tested with the following hypotheses: those with moderate or severe problems on the EQ-5D would have worse ADDQoL average weighted impact (AWI) scores than those with a perfect health rating on the EQ-5D; those with better Present QOL scores on the ADDQoL would have better EQ-5D utility and visual analogue scale (VAS) scores; on the ADDQoL, AWI scores would correlate better with diabetes-dependent QOL than with Present QOL scores; and female respondents, those who required insulin or had longer duration of known diabetes would have worse ADDQoL AWI scores (known-group validity). Results: We analysed data from 152 respondents (49% Chinese, 34% Indian; 45% female; mean age 52 years, range 18–80; mean duration of known diabetes 10 years, range 0–62). There were few missing data. Weighted scoring and NA options were shown to be necessary, thus supporting the usefulness of individualised health-related QOL measures. Factor structure of the ADDQoL was supported and internal consistency was high (α = 0.94). All hypotheses were fulfilled except for one that was partially fulfilled; respondents with longer duration of known diabetes did not report worse ADDQoL AWI scores. Conclusions: The ADDQoL is culturally appropriate, valid, reliable and well accepted among Singaporean patients with diabetes. Individualised measures such as the ADDQoL allow one to obtain precise score estimates and may offer developing countries a useful alternative to CAT.

Impacts of cost containment strategies on pharmaceutical expenditures of the National Health Insurance in Taiwan, 1996-2003.

Abstract: Introduction: Pharmaceutical expenditure (PE) of the National Health Insurance (NHI) programme in Taiwan grew from 62.2 billion Taiwan new dollars ($NT) in 1996 to $NT94.5 billion in 2003.The government has been introducing many strategies to control PE since the inception of NHI including price adjustment based on the prices of international products or existing products (inter-brands comparison), or market price and volume survey; delegation of financial responsibility to regional bureaux; co-payment for outpatient drugs; generic grouping (the reference pricing scheme based on chemical equivalence); a global budget payment system for clinics and hospitals; and reduction in the flat daily payment rate of the drugs for clinics. The aim of this study was to evaluate the impact of these cost containment strategies on the PE of the NHI programme from 1996 to 2003. Methods: To take the growth and seasonal trends of monthly PE into consideration, Box and Tiao’s time-series event intervention analysis based on the Box-Jenkins auto-regressive integrated moving-average model was applied to evaluate the impact of various cost containment strategies on total and subsector (outpatient, inpatient, clinic and hospital sectors) PE. Monthly data of PE of the NHI programme from 1996 to 2003 (the dependent variables) were obtained from the Bureau of the NHI. Drugs prescribed by dentists and Chinese medical doctors at outpatient departments were excluded. Results: After fitting the patterns of time series and controlling for the calendar effect of the Chinese New Year and the severe acute respiratory syndrome outbreak in 2003, three strategies (generic grouping, delegation of financial responsibility and reduction of the flat payment rate of clinics) were significantly associated with a reduction in PE. However, the hospital global budget strategy offset partial savings from these three strategies. Cumulative savings during the study period were estimated to be $NT25.442 billion ($US0.80 billion). Of all the strategies, generic grouping was the most effective although it had less effect on the clinic subsector. Neither drug co-payment nor price adjustment based on the international or inter-brand price comparison had significant impacts on PE. Conclusion: Generic grouping, reduction of the flat payment rate and delegation of financial responsibility were effective in controlling PE. A global budget alone would be unable to control PE without other direct financial incentives. Neither drug co-payment nor brand-specific price adjustment based on prices of international/ existing products had a significant impact on PE.

Incorporating carer effects into economic evaluation

Abstract: Background: Despite great interest in the development of methods used in the economic evaluation of health technologies, the effects of carer costs and quality of life (QOL) on the cost effectiveness of treatments has not been widely explored. Yet carer effects are clearly evident in the literature and relevant to the perspective of many published economic evaluations. Objective: To examine whether patient QOL is associated with carer time and carer QOL. Methods: We used two datasets to investigate carer effects. Firstly, we used 40 312 cases from the Health Outcomes Data Repository (HODaR) to assess the relationship between patient utility, using the EuroQoL (EQ)-5D, and the number of days care needed from friends and relatives. The stability of the relationship across patient subgroups was assessed by replicating the analysis in ten disease groups. Secondly, we used 64 cases from a study of patients with Alzheimer's disease and their primary carer. These data allowed us to estimate the relationships between patient and carer utility, using the EQ-5D, and patient utility and carer burden using the Community Dementia Quality of Life Profile (CDQLP). Results: For carer time, a linear model showed that each 0.1-point reduction in patient utility was associated with a 2.5-day increase in carer time over a 6-week period. A more general model, based on EQ-5D domain scores, was better specified and showed that decreased functioning within each domain is associated with increased carer time. Problems with self-care and usual activities have the greatest impact on carer time. These models do not appear to be stable across different disease groups. For carer utility, the relationships between carer and patient utility have low explanatory power and are poorly specified. A clearer relationship is shown between carer burden and utility, such that when sociodemographic covariates are introduced, the relationship reaches conventional levels of statistical significance (p < 0.05). Conclusions: The preliminary work described here shows that improving patient QOL may reduce the need for carer time and improve carer QOL. Incorporating such effects into economic evaluations will change cost-per-QALY estimates, with the size of reduction dependent on the domains of health affected by treatment. Clinical studies need to capture carer data so that we can better understand these effects, and how they impact on economic evaluation.

Evaluation of Non-Medical Costs Associated with Visual Impairment in Four European Countries

Abstract: Introduction Visual impairment is a severe disability that puts a heavy burden on individuals, families and society. In developed countries, the two major diseases leading to irreversible visual impairment are glaucoma and age-related macular degeneration. Their prevalence will increase dramatically with population aging. The economic consequences of visual impairment are considerable, but have rarely been documented, apart from some ‘top-down’ estimates based on national statistics. We estimated the non-medical costs related to visual impairment in four European countries: France, Italy, Germany and the UK.

Hepatitis C: cost of illness and considerations for the economic evaluation of antiviral therapies.

Abstract: Chronic hepatitis C virus (HCV) infection affects 170 million individuals worldwide. As it is detected incidentally through the evaluation of liver function tests or at the time of blood donor testing, it is usually clinically silent until the advanced stages of liver disease have occurred, when treatment is less effective and shortages of donor liver organs limit the therapeutic options. Combination therapy with ribavirin and pegylated interferon has resulted in sustained viral negative response rates of 54-61%. Because treatment is expensive and not uniformly effective, and because not all chronically infected patients will develop complications, concerns have arisen regarding the cost effectiveness of combination therapy. This paper reviews the public health and individual implications of HCV infections. Because of the latency of infection, numerous country-specific population analyses suggest that HCV will cause an increasing number of liver-related deaths over the next 10 years, despite the dramatic drop in incidence over the past 10-15 years. These deaths will be related to prevalent HCV infection from transfusion and injection drug use prior to identification of the virus and availability of screening tests in the late 1980s and early 1990s. HCV can reduce life expectancy and impair quality of life, yet not all patients will develop progressive liver disease, and antiviral treatment may have associated adverse effects. Finally, to assess the value of antiviral drugs for HCV infection, this paper reviews studies examining the costs of antiviral drugs and of the disease itself along with response to antiviral therapy and the cost effectiveness of antiviral therapy. Although antiviral therapy appears to be expensive, when also considering the likelihood of sustained viral response to therapy, and the cost savings, quality-of-life improvement and prolongation of life expectancy from the prevention of HCV complications, antiviral treatment for HCV appears to be cost effective when compared with other well accepted medical interventions.

QALYs: are they helpful to decision makers?

Abstract: The QALY is the product of life expectancy (estimated in years) and its quality over that time (estimated in utilities or QOL units). It theoretically enables direct comparison of the costs of obtaining different health outcomes through cost utility analysis (CUA). In this review, we argue that, at present, the problems related to the use of utilities preclude the use of cost per QALY as a major determinant of policy decisions on the acquisition and use of health technologies. Those who use CUA can be divided into (i) those who inform the process of decision making through CUA and (ii) those who make the decisions. The former have no direct budgetary responsibility for the decisions that are taken, while the decision makers must pay for those decisions from their budgets. Use of CUA rests on the assumption that all QALYs are of equivalent value in the eyes of society. However, the value accorded to them varies with circumstances. The utilities or QOL indices required to compute QALYs can be measured in different ways, which give different answers, and have been shown to be unreliable. Thus, the QALY is not sufficiently accurate or reliable to be used by decision makers as a basis for comparison of the costs of different technologies. Until the theoretical and practical problems of determining health preferences are resolved and the methods of their measurement are standardised, it is necessary to estimate the cost effectiveness of health interventions by relating their cost to their primary health outcomes.

Interstitial Cystitis: Cost, treatment and co-morbidities in an employed population.

Abstract: of women and a smaller proportion of men, although many individuals with IC may be misdiagnosed or remain undiagnosed. Factors that can contribute to the cost of IC include medical and drug utilisation related to treatment and diagnosis of IC and associated conditions (e.g. depression), as well as employee work loss. This study assesses the direct medical cost and indirect cost of work loss for IC patients in the first year after diagnosis, and evaluates IC treatment patterns and prevalence of co-morbidities. Methods: Data for patients under the age of 65 years with at least one diagnosis of IC (n = 749) were drawn from a de-identified, administrative database of approx- imately 2 million beneficiaries that included medical, drug and disability claims for 1999-2002. A 2 : 1 matched control sample of patients without an IC diagno- sis (non-IC sample) was randomly selected based on patient characteristics. Indirect costs were calculated from a subgroup of 152 IC patients (plus their matched controls) who had disability information available. Costs incurred in the first year after IC diagnosis and co-morbidities were compared between IC patients and the non-IC sample, with the difference in costs defined as 'excess costs' of IC patients. Treatment patterns were profiled in the 2 months following initial diagnosis of IC. Descriptive statistics are presented. A multivariate two-part model was applied to estimate the IC direct medical cost, indirect cost and total cost to adjust for observed patient demographics and co- morbidities. Statistical significance was evaluated by the bootstrap method. Results: The average IC patient had 130% higher direct costs (p < 0.05) and the average IC employee patient had 84% higher indirect costs than the average non- IC control individual. IC patients also had a higher diagnostic prevalence of prostatitis (relative risk (RR) = 40.0), endometriosis (RR = 7.4), vulvodynia (RR = 6.9), chronic pelvic pain (RR = 5.8) and urinary tract infections (RR = 5.1) (all p < 0.05). IC patients were also more likely to report depression (RR = 2.8) and anxiety (RR = 4.5 ) than non-IC controls (all p < 0.05). Seventeen percent of IC patients received pentosan polysulfate therapy, the only US FDA-approved oral drug therapy indicated for treating IC, within the first 2 months after diagnosis. Of these patients, 69% received at least one 'other' drug from the non-approved oral medications studied. Approximately one-third of IC

'Lost in translation': accounting for between-country differences in the analysis of multinational cost-effectiveness data.

Abstract: Cost-effectiveness analysis has gained status over the last 15 years as an important tool for assisting resource allocation decisions in a budget-limited environment such as healthcare. Randomised (multicentre) multinational controlled trials are often the main vehicle for collecting primary patient-level information on resource use, cost and clinical effectiveness associated with alternative treatment strategies. However, trial-wide cost effectiveness results may not be directly applicable to any one of the countries that participate in a multinational trial, requiring some form of additional modelling to customise the results to the country of interest. This article proposes an algorithm to assist with the choice of the appropriate analytical strategy when facing the task of adapting the study results from one country to another. The algorithm considers different scenarios characterised by: (a) whether the country of interest participated in the trial; and (b) whether individual patient-level data (IPD) from the trial are available. The analytical options available range from the use of regression-based techniques to the application of decision-analytic models. Decision models are typically used when the evidence base is available exclusively in summary format whereas regression-based methods are used mainly when the country of interest actively recruited patients into the trial and there is access to IPD (or at least country-specific summary data). Whichever method is used to reflect between-country variability in cost-effectiveness data, it is important to be transparent regarding the assumptions made in the analysis and (where possible) assess their impact on the study results.

Cost Effectiveness of Tumour Necrosis Factor-α Inhibitors as First-Line Agents in Rheumatoid Arthritis

Abstract: Background and objective Rheumatoid arthritis (RA) is an autoimmune disease with an unknown aetiology that results in >9 million physician visits and >250 000 hospitalisations per year in the US. Tumour necrosis factor-a (TNFa) inhibitors are effective agents in treating RA; however, their cost effectiveness as first-line agents has not been investigated. This study aimed to examine the cost effectiveness of using TNFa inhibitors (both as monotherapy and in combination with methotrexate) as first-line agents versus methotrexate (monotherapy) from a payer perspective.

Using discrete choice experiments within a cost-benefit analysis framework : Some considerations

Abstract: A great advantage of the stated preference discrete choice experiment (SPDCE) approach to economic evaluation methodology is its immense flexibility within applied cost-benefit analyses (CBAs). However, while the use of SPDCEs in healthcare has increased markedly in recent years there has been a distinct lack of equivalent CBAs in healthcare using such SPDCE-derived valuations. This article outlines specific issues and some practical suggestions for consideration relevant to the development of CBAs using SPDCE-derived benefits. The article shows that SPDCE-derived CBA can adopt recent developments in cost-effectiveness methodology including the cost-effectiveness plane, appropriate consideration of uncertainty, the net-benefit framework and probabilistic sensitivity analysis methods, while maintaining the theoretical advantage of the SPDCE approach. The concept of a cost-benefit plane is no different in principle to the cost-effectiveness plane and can be a useful tool for reporting and presenting the results of CBAs. However, there are many challenging issues to address for the advancement of CBA methodology using SPCDEs within healthcare. Particular areas for development include the importance of accounting for uncertainty in SPDCE-derived willingness-to-pay values, the methodology of SPDCEs in clinical trial settings and economic models, measurement issues pertinent to using SPDCEs specifically in healthcare, and the importance of issues such as consideration of the dynamic nature of healthcare and the resulting impact this has on the validity of attribute definitions and context.

Analysis sans frontières: can we ever make economic evaluations generalisable across jurisdictions?

Abstract: Over the last decade or so, a number of healthcare systems have used economic evaluations as a formal input into decisions about the coverage or reimbursement of new healthcare interventions. This change in the policy landscape has placed some important demands on the design and characteristics of economic evaluation and these are increasingly evident in studies being presented to decision makers. One challenge has been to make studies specific to the context in which the decision is being taken. This is because of the inevitable geographical variation in many of the parameters within an analysis. There has been a series of important contributions to the published literature in recent years on how to quantify geographical heterogeneity within economic analyses based on randomised controlled trials. However, there are good reasons for economic evaluation for decision making to be undertaken using methods of evidence synthesis and decision analytical modelling, but issues of geographical variation still need to be handled appropriately. The key requirements of economic evaluations for decision making within healthcare systems can be defined as follows: (i) a design that meets the objectives and constraints of the healthcare system; (ii) coherent and complete specification of the decision problem; (iii) inclusion of all relevant evidence; and (iv) recognition and appropriate handling of uncertainty. In satisfying these requirements, it is important to be aware of variation between jurisdictions, and this imposes some important analytical requirements on economic studies. While many agencies have produced guidelines on preferred methods for healthcare economic evaluation, these exhibit considerable variation. Some of this variation can be justified by genuine differences between systems in clinical practice, objectives and constraints, while some of the variation relates to differences of opinion about appropriate analysis given methodological uncertainty. However, some of the variation in guidance is difficult to justify and is inconsistent with the aims and objectives of the systems the analyses are seeking to inform. Decision makers and analysts need to work together to streamline and where possible harmonise guidelines on methods for economic evaluations, whilst recognising legitimate variation in the needs of different healthcare systems. Otherwise, there is the risk that scarce resources will be wasted in producing country-specific analyses in situations where these are not justified. Expected value of information analyses are also emerging as a tool that could be considered by decision makers to guide their policy on the acceptance or non-acceptance of data from other jurisdictions.

Utility measurement in healthcare: the things I never got to.

Abstract: The present article provides a brief historical background on the development of utility measurement and cost-utility analysis in healthcare. It then outlines a number of research ideas in this field that the author never got to.

Cost Effectiveness of Budesonide/Formoterol for Maintenance and Reliever Therapy versus Salmeterol/ Fluticasone plus Salbutamol in the Treatment of Asthma

Abstract: Introduction: Budesonide/formoterol (Symbicort®) Maintenance And Reliever Therapy (SMART) is an effective and well tolerated treatment option for patients with asthma. We compared the cost effectiveness from a societal perspective of this one-inhaler regimen with that of maintenance salmeterol/fluticasone propionate (Seretide®) plus salbutamol (albuterol) as needed (Seretide® Fixed Combination [SFC]). Study design: A cost-effectiveness analysis was performed based on effectiveness and resource-utilisation data collected prospectively in a randomised, 12-month study performed in 2143 patients in 16 countries. Resource utilisation data were pooled and unit costs (€, year 2003 values) from Italy, France, the UK and Germany were used to generate estimates of direct and total costs per patient per year and cost per severe exacerbation avoided. Methods: Adolescents and adults with asthma (n = 2143; mean forced expiratory volume in 1 second [FEV1] 73% predicted; mean inhaled corticosteroid [ICS] dose 884 µg/day) were randomised to SMART or SFC. The effectiveness measure used was the number of severe exacerbations per patient per year. Direct costs included medication use (budesonide/formoterol 160µg/4.5µg or salmeterol/fluticasone 50µg/100µg, 50µg/250µg or 50µg/500µg plus salbutamol) and nonmedication-related resource use, including days in hospital, emergency room visits, specialist or primary care physician visits and other healthcare provider contacts. Indirect costs, including the number of days when the patient or their carer was unable to attend to their normal daily activities, were also assessed. The study assumed a European societal perspective (i.e. including direct and indirect costs). Results: Treatment with SMART resulted in significantly fewer severe exacerbations per patient per year compared with SFC (0.24 vs 0.31 events per patient per year; p = 0.0025). Resource use was low in both groups. Medication costs accounted for the majority of the total costs. The increased effectiveness of SMART was achieved at a reduced or similar cost compared with SFC. SMART dominated when German unit costs were applied (i.e. there was a statistically significant reduction in both costs and number of exacerbations). In all other countries, the incremental cost-effectiveness ratios showed that there was a reduction in mean total cost per exacerbation avoided; however, this difference was not statistically significant. Conclusion: This analysis demonstrates that, compared with SFC, SMART may be cost effective from a societal perspective for the treatment of patients with asthma in Italy, Germany, France and the UK. SMART provided a reduction in the number of severe exacerbations per patient per year, at no statistically significant increase in cost — or even at a lower cost — compared with SFC plus as-needed reliever salbutamol.

Cost effectiveness of preventive interventions in type 2 diabetes mellitus: a systematic literature review.

Abstract: A systematic review of the literature was conducted to give an overview of economic evaluations of preventive interventions in type 2 diabetes mellitus. The interventions were sorted by type of preventive intervention (primary, secondary or tertiary) and by category (e.g. education, medication for hypertension). Several databases were searched for studies published between January 1990 and May 2004 on the three types of preventive intervention. For each study selected, inclusion of specific components from a standardised list of items, including quality, was recorded in a database. Summary tables were generated based on the database. A number of conclusions were drawn from this review. The most important was that strict blood pressure control was a more cost-effective intervention than less strict control, as shown by six studies reporting cost savings to very low costs per life-year gained. Primary and secondary prevention of type 2 diabetes were also highly cost effective, but these results were based on very few studies. Medications to reduce weight and hyperglycaemia together were cost effective compared with conventional interventions. Finally, the separate results regarding medications to reduce weight, hyperglycaemia and hypercholesterolaemia varied enormously, thus no conclusion could be drawn and further economic analysis is required.

The impact of incremental innovation in biopharmaceuticals: drug utilisation in original and supplemental indications.

Abstract: Background: The apparent decrease in the rate of approval of new molecular entities has provoked extensive discussion and fears that the productivity of biopharmaceutical research and development has severely declined in recent years.