Showing papers in "PharmacoEconomics in 2008"

Conducting discrete choice experiments to inform healthcare decision making: a user's guide.

Abstract: Discrete choice experiments (DCEs) are regularly used in health economics to elicit preferences for healthcare products and programmes. There is growing recognition that DCEs can provide more than information on preferences and, in particular, they have the potential to contribute more directly to outcome measurement for use in economic evaluation. Almost uniquely, DCEs could potentially contribute to outcome measurement for use in both cost-benefit and cost-utility analysis. Within this expanding remit, our intention is to provide a resource for current practitioners as well as those considering undertaking a DCE, using DCE results in a policy/commercial context, or reviewing a DCE. We present the fundamental principles and theory underlying DCEs. To aid in undertaking and assessing the quality of DCEs, we discuss the process of carrying out a choice study and have developed a checklist covering conceptualizing the choice process, selecting attributes and levels, experimental design, questionnaire design, pilot testing, sampling and sample size, data collection, coding of data, econometric analysis, validity, interpretation and welfare and policy analysis. In this fast-moving area, a number of issues remain on the research frontier. We therefore outline potentially fruitful areas for future research associated both with DCEs in general, and with health applications specifically, paying attention to how the results of DCEs can be used in economic evaluation. We also discuss emerging research trends. We conclude that if appropriately designed, implemented, analysed and interpreted, DCEs offer several advantages in the health sector, the most important of which is that they provide rich data sources for economic evaluation and decision making, allowing investigation of many types of questions, some of which otherwise would be intractable analytically. Thus, they offer viable alternatives and complements to existing methods of valuation and preference elicitation.

The NICE cost-effectiveness threshold: what it is and what that means.

Abstract: The National Institute for Health and Clinical Excellence (NICE) has been using a cost-effectiveness threshold range between 20,000 pound sterling and 30,000 pound sterling for over 7 years. What the cost-effectiveness threshold represents, what the appropriate level is for NICE to use, and what the other factors are that NICE should consider have all been the subject of much discussion. In this article, we briefly review these questions, provide a critical assessment of NICE's utilization of the incremental cost-effectiveness ratio (ICER) threshold to inform its guidance, and suggest ways in which NICE's utilization of the ICER threshold could be developed to promote the efficient use of health service resources. We conclude that it is feasible and probably desirable to operate an explicit single threshold rather than the current range; the threshold should be seen as a threshold at which 'other' criteria beyond the ICER itself are taken into account; interventions with a large budgetary impact may need to be subject to a lower threshold as they are likely to displace more than the marginal activities; reimbursement at the threshold transfers the full value of an innovation to the manufacturer. Positive decisions above the threshold on the grounds of innovation reduce population health; the value of the threshold should be reconsidered regularly to ensure that it captures the impact of changes in efficiency and budget over time; the use of equity weights to sustain a positive recommendation when the ICER is above the threshold requires knowledge of the equity characteristics of those patients who bear the opportunity cost. Given the barriers to obtaining this knowledge and knowledge about the characteristics of typical beneficiaries of UK NHS care, caution is warranted before accepting claims from special pleaders; uncertainty in the evidence base should not be used to justify a positive recommendation when the ICER is above the threshold. The development of a programme of disinvestment guidance would enable NICE and the NHS to be more confident that the net health benefit of the Technology Appraisal Programme is positive.

The burden of schizophrenia on caregivers: a review.

Abstract: Schizophrenia is a disabling, chronic psychiatric disorder that poses numerous challenges in its management and consequences. It extols a significant cost to the patient in terms of personal suffering, on the caregiver as a result of the shift of burden of care from hospital to families, and on society at large in terms of significant direct and indirect costs that include frequent hospitalizations and the need for long-term psychosocial and economic support, as well as life-time lost productivity. ‘Burden of care’ is a complex construct that challenges simple definition, and is frequently criticized for being broad and generally negative. Frequently, burden of care is more defined by its impacts and consequences on caregivers. In addition to the emotional, psychological, physical and economic impact, the concept of ‘burden of care’ involves subtle but distressing notions such as shame, embarrassment, feelings of guilt and self-blame. The early conceptualization of ‘burden of care’ into two distinct components (objective and subjective) has guided research efforts until the present time. Objective burden of care is meant to indicate its effects on the household such as taking care of daily tasks, whereas subjective burden indicates the extent to which the caregivers perceive the burden of care. Research contributions in later years (1980s to the present) have added more depth to understanding of the construct of burden of care by exploring important determinants and factors that likely contribute or mediate the caregiver’s perception of burden of care. Several studies examined the role of gender, and reported that relatives of male patients with schizophrenia frequently experience more social dysfunction and disabilities than those of female patients. Similarly, a number of other studies documented the contribution of ethnicity and cultural issues to subjective burden of care. Although there is no complete agreement on whether a specific cluster of psychotic symptoms has the most impact on a caregiver’s burden of care, there is agreement that the severity of symptoms increases it. An extensive literature concerning family interventions in schizophrenia has demonstrated the positive impact of various family interventions in improving family environment, reducing relapse and easing the burden of care. Although the evidence of such positive impact of family interventions in schizophrenia is well documented, such interventions are neither widely used nor appropriately integrated in care plans, and are frequently underfunded. Although the cost of caregiving is considered to be significant, there are no reliable estimates of the costs associated with such care. The majority of available literature categorized the cost of burden of care among the indirect costs of schizophrenia in general. In recent years, attempts to compare the costs of caregiving in several countries have been reported in the evolving literature on this topic. ‘Burden of care’ as a complex construct certainly requires the development of appropriate methodology for its costing. In achieving a balance between the patients’ and caregivers’ perspectives, caregivers have to be included in the care plan and adequate information and support extended to the family and caregivers. Access to better treatment for patients, including medications, psychosocial interventions and rehabilitation services, are important basic elements in easing the burden on caregivers. Other measures such as availability of crisis management, provision of legally mandated community treatment to avert hospitalization, and well informed and balanced advocacy are also important. Although research efforts have been expanded in the last 3 decades, an urgent need exists for enhancing such efforts, particularly in the development and evaluation of effective family interventions strategies. There is also a need for continued improvement in the delivery of psychiatric services to the severely psychiatrically ill and their families. As there is a lack of reliable cost information about the family burden of care specific to schizophrenia, there is an urgent need to develop reliable approaches that can generate data that can inform in policy making and organization of services.

Use of indirect and mixed treatment comparisons for technology assessment.

Abstract: Indirect and mixed treatment comparison (MTC) approaches to synthesis are logical extensions of more established meta-analysis methods. They have great potential for estimating the comparative effectiveness of multiple treatments using an evidence base of trials that individually do not compare all treatment options. Connected networks of evidence can be synthesized simultaneously to provide estimates of the comparative effectiveness of all included treatments and a ranking of their effectiveness with associated probability statements. The potential of the use of indirect and MTC methods in technology assessment is considerable, and would allow for a more consistent assessment than simpler alternative approaches. Although such models can be viewed as a logical and coherent extension of standard pair-wise meta-analysis, their increased complexity raises some unique issues with far-reaching implications concerning how we use data in technology assessment, while simultaneously raising searching questions about standard pair-wise meta-analysis. This article reviews pair-wise meta-analysis and indirect and MTC approaches to synthesis, clearly outlining the assumptions involved in each approach. It also raises the issues that the National Institute for Health and Clinical Excellence (NICE) needed to consider in updating their 2004 Guide to the Methods of Technology Appraisal, if such methods are to be used in their technology appraisals.

An Overview of Methods and Applications to Value Informal Care in Economic Evaluations of Healthcare

Abstract: This paper compares several applied valuation methods for including informal care in economic evaluations of healthcare programmes: the proxy good method; the opportunity cost method; the contingent valuation method (CVM); conjoint measurement (CM); and valuation of health effects in terms of health-related quality of life (HR-QOL) and well-being. The comparison focuses on three questions: what outcome measures are available for including informal care in economic evaluations of healthcare programmes; whether these measures are compatible with the common types of economic evaluation; and, when applying these measures, whether all relevant aspects of informal care are incorporated. All types of economic evaluation can incorporate a monetary value of informal care (using the opportunity cost method, the proxy good method, CVM and CM) on the cost side of an analysis, but only when the relevant aspects of time costs have been valued. On the effect side of a cost-effectiveness or cost-utility analysis, the health effects (for the patient and/or caregiver) measured in natural units or QALYs can be combined with cost estimates based on the opportunity cost method or the proxy good method. One should be careful when incorporating CVM and CM in cost-minimization, cost-effectiveness and cost-utility analyses, as the health effects of patients receiving informal care and the carers themselves may also have been valued separately. One should determine whether the caregiver valuation exercise allows combination with other valuation techniques. In cost-benefit analyses, CVM and CM appear to be the best tools for the valuation of informal care. When researchers decide to use the well-being method, we recommend applying it in a cost-benefit analysis framework. This method values overall QOL (happiness); hence it is broader than just HR-QOL, which complicates inclusion in traditional health economic evaluations that normally define outcomes more narrowly. Using broader, non-monetary valuation techniques, such as the CarerQol instrument, requires a broader evaluation framework than cost-effectiveness/cost-utility analysis, such as cost-consequence or multi-criteria analysis.

Cost of epilepsy: a systematic review.

Abstract: The objective of this review was to overview published cost-of-illness (COI) studies of epilepsy and their methodological approaches. Epilepsy imposes a substantial burden on individuals and society as a whole. The mean prevalence of epilepsy is estimated at 0.52% in Europe, 0.68% in the US, and peaks up to 1.5% in developing countries. Estimation of the economic burden of epilepsy is of pivotal relevance to enable a rational distribution of healthcare resources. This is especially so with the introduction of the newer antiepileptic drugs (AEDs), the marketing of vagal-nerve stimulators and the resurgence of new surgical treatment options, which have the potential to considerably increase the costs of treating epilepsy.A systematic literature review was performed to identify studies that evaluated direct and indirect costs of epilepsy. Using a standardized assessment form, information on the study design, methodological framework and data sources were extracted from each publication and systematically reported. We identified 22 studies worldwide on costs of epilepsy. The majority of the studies reflected the costs of epilepsy in Europe (three studies each for the UK and Italy, one study each for Germany, the Netherlands, Switzerland, France and the EU) and the US (four studies), but studies were also available from India (two), Hong Kong, Oman, Burundi, Chile and Mexico. The studies utilized different frameworks to evaluate costs. All used a bottom-up approach; however, only 12 studies (55%) evaluated direct as well as indirect costs. The range for the mean annual direct costs lay between 40 International Dollar purchasing power parities (PPP-$) in rural Burundi and PPP-$4748 (adjusted to 2006 values) in a German epilepsy centre. Recent studies suggest AEDs are becoming the main contributor to direct costs. The mean indirect costs ranged between 12% and 85% of the total annual costs. Epilepsy is a cost-intensive disorder. A reliable comparison of the different COI studies in epilepsy is not easily feasible, as the evaluated studies show substantial methodological differences with respect to their patient selection criteria, diagnostic stratifications and evaluated costs. Therefore, there is an urgent need for studies that evaluate direct and indirect costs in a standardized fashion.

Exploring Uncertainty in Cost-Effectiveness Analysis

Abstract: This paper describes the key principles of why an assessment of uncertainty and its consequences are critical for the types of decisions that a body such as the UK National Institute for Health and Clinical Excellence (NICE) has to make. In doing so, it poses the question of whether formal methods may be useful to NICE and its advisory committees in making such assessments. Broadly, these include the following: (i) should probabilistic sensitivity analysis continue to be recommended as a means to characterize parameter uncertainty; (ii) which methods should be used to represent other sources of uncertainty; (iii) when can computationally expensive models be justified and is computation expense a sufficient justification for failing to express uncertainty; (iv) which summary measures of uncertainty should be used to present the results to decision makers; and (v) should formal methods be recommended to inform the assessment of the need for evidence and the consequences of an uncertain decision for the UK NHS?

Economic burden of heart failure in the elderly.

Abstract: Heart failure (HF) ranks among the most costly chronic diseases in developed countries. At present these countries devote 1–2% of all healthcare expenditures towards HF. In the US, these costs are estimated at $US30.2 billion for 2007. The burden of HF is greatest among the elderly, with 80% of HF hospitalizations and 90% of HF-related deaths in this cohort. As a result, approximately three-quarters of the resources for HF care are consumed by elderly patients. As demographic shifts increase the number of elderly individuals in both developed and developing nations, the resources devoted to HF care will likely further increase. Hospitalization accounts for roughly two-thirds of HF costs, but procedures, outpatient visits and medications also consume significant financial resources. HF also adversely impacts patient quality of life, and these relevant effects may not be captured in pure cost analyses. The cost effectiveness of several pharmacological interventions has been explored. In general, neurohormonal antagonists used for outpatient treatment of chronic HF are relatively cost effective, in part by reducing hospitalizations. Because HF poses such an enormous financial burden, efficient resource allocation for its management is a major societal and governmental challenge. In order to make informed decisions and allocate resources for HF care rationally, detailed data regarding costs and resource use will be essential. Further studies are needed to examine the impact of pharmacological and non-pharmacological interventions on costs and resource use in elderly individuals with HF.

The impact of influenza on working days lost: a review of the literature.

Abstract: Seasonal influenza is a prevalent and highly contagious acute respiratory disease that, year on year, results in increased morbidity and mortality on a global scale. Because of the widespread and debilitating nature of the disease, annual influenza epidemics result in substantial workplace absenteeism, and the associated cost of lost productivity is a significant component of the substantial financial burden of the disease to society. The objective of this review was to identify studies that had attempted to quantify the impact of influenza upon otherwise healthy adults in terms of working days lost associated with an episode of influenza.

Modelling methods for pharmacoeconomics and health technology assessment: an overview and guide.

Abstract: This paper provides an overview of, and guidance as to when, why and how to choose and use, different simulation modelling methods as applied to healthcare. What simulation is and why it is necessary in addressing healthcare problems are discussed. In addition, key criteria for choosing an appropriate method (project type, population resolution, interactivity, treatment of time and space, resource constraints, autonomy and how knowledge is embedded) are covered. Key concepts for each method, moving from the simplest to most complex methods, are reviewed in some detail.

Perspectives on patient-reported outcomes : content validity and qualitative research in a changing clinical trial environment.

Abstract: Patient-reported outcomes (PROs) represent the voice of the patient in drug and device evaluation. As such, the outcomes selected for evaluation must be relevant to the patient, and the instruments used to capture them must have sound measurement properties. This paper discusses the role of qualitative research methods in assuring PRO clarity and content validity in a clinical trial environment characterized by evolving regulatory policy, new advances in technology and increasingly diverse samples within global clinical trials. Three important PRO measurement issues influenced by these changes are addressed: (i) endpoint selection and instrument development; (ii) the adaptation of instruments for electronic administration; and (iii) conceptual equivalence of measures across diverse samples. These are viewed as interrelated issues of content validity that can be addressed through the appropriate and rigorous application of qualitative research methods. Focus groups, cognitive debriefing, user acceptance testing and translation methodologies are discussed as ways to address and document the content validity of PRO instruments and ensure the empirical data representing the voice of the patient is sound.

Cost-effectiveness analyses of vaccination programmes : a focused review of modelling approaches.

Abstract: Cost effectiveness is becoming an increasingly important factor for stakeholders faced with decisions about adding a new vaccine into national immunization programmes versus alternative use of resources. Evaluating cost effectiveness, taking into account the relevant biological, clinical, epidemiological and economic factors of a vaccination programme, generally requires use of a model. This review examines the modelling approaches used in cost-effectiveness analyses (CEAs) of vaccination programmes. After overviewing the key attributes of models used in CEAs, a framework for categorising theoretical models is presented. Categories are based on three main attributes: static/dynamic; stochastic/deterministic; and aggregate/individual based. This framework was applied to a systematic review of CEAs of all currently available vaccines for the period of 1976 to May 2007. The systematic review identified 276 CEAs of vaccination programmes. The great majority (83%) of CEAs were conducted in the setting of high-income countries. Only a few vaccines were widely studied, with 57% of available CEAs being focused on the varicella, influenza, hepatitis A, hepatitis B or pneumococcal vaccine. Several time trends were evident, indicating that the number of vaccine CEAs being published is increasing; the main health outcome measures are moving away from the number of cases prevented towards quality-adjusted and unadjusted life-years gained, and more complex models are beginning to be used. The modelling approach was often not adequately described. Of the 208 CEAs that could be categorized according to the framework, around 90% were deterministic, aggregate-level static models. Although a dynamic transmission model is required to account for herd-immunity effects, only 23 of the CEAs were dynamic. None of the CEAs were individual based. To improve communication about the cost effectiveness of vaccination programmes, we believe the first step is for analysts to be more transparent with each other. A clear description of the model type using consistent terminology and justification for the model choice must begin to accompany all CEAs. As a minimum, we urge modellers to provide an explicit statement about the following attributes: static/dynamic; stochastic/deterministic; aggregate/individual based; open/closed. Where relevant, time intervals (discrete/continuous) and (non)linearity should also be described. Enhanced methods of assessing model performance and validity are also required. Our results emphasize the need to improve modelling methods for CEAs of vaccination programmes; specifically, model choice, construction, assessment and validation.

Subgroups and heterogeneity in cost-effectiveness analysis.

Abstract: The National Institute for Health and Clinical Excellence (NICE) is required to consider cost effectiveness when issuing guidance about the use of health technologies within the UK NHS. Cost effectiveness is a means of supporting a system objective of maximizing population health gain from the available budget. There is a range of sources of variation between individuals in disease prognosis, and in the costs and effects of health technologies. It is often possible to explain some of this variation on the basis of the clinical and sociodemographic characteristics of patients. This facilitates subgroup-specific estimates of parameters in decision analytic models and provides a means of assessing heterogeneity in cost effectiveness between different types of patient. Given the objective of the NHS, there is a clear need for NICE, and similar decision makers in other systems, to reflect this heterogeneity by being as specific as possible about the characteristics of the recipients of new treatments. The use of subgroup analysis in cost-effectiveness analysis raises a number of methodological questions that have been given little consideration in the literature. They include a need to define the possible sources of heterogeneity that exist, which extends beyond relative treatment effect (which is the focus of clinical trial analysis) to include, for example, sources relating to baseline event rates. There is also the issue of how heterogeneity in model parameters should be estimated and how uncertainty should be appropriately quantified. A major issue also exists concerning the appropriateness, in terms of equity, of using all or some of the subgroup analyses as a basis of decision making. NICE needed to consider these and other issues when updating its methods guidance.

Non-traditional settings for influenza vaccination of adults: costs and cost effectiveness

Abstract: Influenza vaccination rates remain far below national goals in the US. Expanding influenza vaccination in non-traditional settings such as worksites and pharmacies may be a way to enhance vaccination coverage for adults, but scant data exist on the cost effectiveness of this strategy. The aims of this study were to (i) describe the costs of vaccination in non-traditional settings such as pharmacies and mass vaccination clinics; and (ii) evaluate the projected health benefits, costs and cost effectiveness of delivering influenza vaccination to adults of varying ages and risk groups in non-traditional settings compared with scheduled doctor’s office visits. All analyses are from the US societal perspective. We evaluated the costs of influenza vaccination in non-traditional settings via detailed telephone interviews with representatives of organizations that conduct mass vaccination clinics and pharmacies that use pharmacists to deliver vaccinations. Next, we constructed a decision tree to compare the projected health benefits and costs of influenza vaccination delivered via non-traditional settings or during scheduled doctor’s office visits with no vaccination. The target population was stratified by age (18–49, 50–64 and ≥65 years) and risk status (high or low risk for influenza-related complications). Probabilities and costs (direct and opportunity) for uncomplicated influenza illness, outpatient visits, hospitalizations, deaths, vaccination and vaccine adverse events were derived from primary data and from published and unpublished sources. The mean cost (year 2004 values) of vaccination was lower in mass vaccination ($US17.04) and pharmacy ($US11.57) settings than in scheduled doctor’s office visits ($US28.67). Vaccination in non-traditional settings was projected to be cost saving for healthy adults aged ≥50 years, and for high-risk adults of all ages. For healthy adults aged 18–49 years, preventing an episode of influenza would cost $US90 if vaccination were delivered via the pharmacy setting, $US210 via the mass vaccination setting and $US870 via a scheduled doctor’s office visit. Results were sensitive to assumptions on the incidence of influenza illness, the costs of vaccination (including recipient time costs) and vaccine effectiveness. Using non-traditional settings to deliver routine influenza vaccination to adults is likely to be cost saving for healthy adults aged 50–64 years and relatively cost effective for healthy adults aged 18–49 years when preferences for averted morbidity are included.

Economic burden of bilateral neovascular age-related macular degeneration: multi-country observational study.

Abstract: There is limited previous research examining the healthcare costs of neovascular age-related macular degeneration (NV-AMD), which constrains our understanding of the economic impact of this condition. With aging populations, this leading cause of rapid vision loss in Western countries is expected to become a pressing health predicament, requiring decision makers to evaluate alternative treatment strategies for AMD. To document the economic burden of bilateral NV-AMD, the late stage of AMD, in elderly patients, from a societal perspective. Study design, setting and participants: A cross-sectional, observational study surveyed 401 patients with bilateral NV-AMD and 471 non-AMD subjects in Canada, France, Germany, Spain and the UK. Physicians’ records and subjects’ standardized telephone interviews were used to record medical resource utilization, assistance with daily living and social benefits. Annual bilateral NV-AMDrelated socioeconomic costs were calculated in €, year 2005 values. Main outcome measures: Societal costs including direct vision-related medical costs (e.g. treatment of AMD and vision-related equipment), direct non-vision-related medical costs (e.g. medications) and direct non-medical-related costs (e.g. home healthcare and social services) were the main outcome measures. The demographic profile of NV-AMD patients was similar across countries; however, co-morbid condition profiles varied. NV-AMD patients reported substantial health-related problems and associated health resource utilization (HRU). In the previous 12 months, 12–22% of patients fell, and half of these patients required medical treatments. More than 20% (range 21–59%) of patients were prescribed vision-enhancing equipment. More than half of the patients (54–81%) were living with a spouse or family member and 19–41% reported receiving assistance for activities of daily living. The average annual societal cost per bilateral NV-AMD patient treated was estimated to be €7879 in Canada, €7349 in France, €12 445 in Germany, €5732 in Spain and €5300 in the UK, and direct vision-related medical costs accounted for 23–63% of the total cost. Half of the patients were diagnosed with bilateral NV-AMD for <1 year, with an average length of 5 months; there were no statistically significant differences in total annual costs per patient between these patients and those who were diagnosed with bilateral disease for ≥1 year. Estimated annual societal costs of bilateral NV-AMD patients in these countries ranged from €268 to €1311 million. Estimated annual societal costs of all NV-AMD patients in these countries ranged from €671 to €3278 million. Bilateral NV-AMD imposes significant functional impairment on patients, leading to increased HRU and a high societal cost burden. Differences in national healthcare systems and NV-AMD treatment patterns were reflected in the wide variation of NV-AMD costs across the five surveyed countries. Even though the prevalence rates and per-patient costs varied by country, the societal costs of NV-AMD patients were substantial in each country. Earlier intervention with effective therapies is expected to reduce disease burden and disability associated with NV-AMD and, thus, decrease the overall societal cost.

A Multicentre, Prospective Study to Evaluate Costs of Septic Patients in Brazilian Intensive Care Units

Abstract: Background Sepsis has a high prevalence within intensive care units, with elevated rates of morbidity and mortality, and high costs. Data on sepsis costs are scarce in the literature, and in developing countries such as Brazil these data are largely unavailable.

Multiple sclerosis in the UK: service use, costs, quality of life and disability.

Abstract: Background: Multiple sclerosis (MS) is a chronic condition that affects quality of life (QOL), leads to disability and requires ongoing care inputs. Few studies have examined the impact of QOL, disability and demographic characteristics on treatment costs. Objective: To investigate the links between service use, costs, QOL and disability for people with MS. Methods: A cross-sectional study was conducted in people with MS who were members of the Multiple Sclerosis Society of Great Britain and Northern Ireland. A questionnaire, consisting of sociodemographic questions, the Client Service Receipt Inventory, EQ-5D and Guy’s Neurological Disability Scale (GNDS), was sent to 4000 members of the Society. Service and lost employment costs were calculated. Regression models were developed to identify the participant characteristics that were associated with costs, QOL and disability. All costs are presented in year 2006–7 values. Results: Questionnaires were returned by 1942 members (48.9%). The mean (SD) EQ-5D QOL score was 0.41 (0.34), whilst the GNDS disability score was 20.8 (8.9). The mean (SD) service cost over the preceding 6 months was £8397 (£10 404), and most of this (71.6%) was due to informal care. Only a small amount of cost (8.1%) was due to the use of disease-modifying drugs and drugs for spasticity. Lost employment costs amounted to a mean of £4240. Higher costs were associated with higher levels of disability and lower levels of health-related QOL. Conclusions: This study showed that MS participants had high levels of service use, and that QOL was low in comparison with other conditions. There were significant associations between costs, QOL and disability.

Valuing Health States for Use in Cost-Effectiveness Analysis

Abstract: This article reviews the general issues in valuing health states for use in cost-effectiveness analysis and the specific issues considered by the National Institute for Health and Clinical Excellence (NICE) in its recent review of the methods of technology appraisal. The general issues are how to describe health, how to value health and who should provide the values for health. The specific issues considered by NICE included whether and what should be the reference-case instrument, what to do when there are no data using the reference-case measure, what to do when the reference-case measure is not suitable and how to judge when it is not suitable, how to review and synthesize data, and how to incorporate health-state utility values into cost-effectiveness models.

Estimating ‘Costs’ for Cost-Effectiveness Analysis

Abstract: Since 1999, the National Institute for Health and Clinical Excellence (NICE) Technology Appraisal Programme has been charged with producing guidance for the NHS in England and Wales on the appropriate use of new and existing healthcare programmes. Guidance is based on an assessment of a number of factors, including cost effectiveness. The identification, measurement and valuation of costs are important components of any cost-effectiveness analysis. However, working through these steps raises a number of important methodological questions. For example, how should 'future' resource use be estimated, and is there a need to consider all 'future' costs? Given that NICE produces national guidance, should national unit cost data be used to value resources or should local variations in negotiated prices be taken into account? This paper was initially prepared as a briefing paper as part of the process of updating NICE's 2004 Guide to the Methods of Technology Appraisal for a workshop on 'costs'. It outlines the issues that were raised in the original briefing paper and the subsequent questions that were discussed at the workshop.

Recent national and regional drug reforms in Sweden: implications for pharmaceutical companies in Europe.

Abstract: With an aging population and increased prevalence of chronic diseases, such as obesity and diabetes mellitus, drug reforms are needed across Europe to ensure the continued provision of comprehensive healthcare. It is also a challenge, with the limited resources available, to fund new innovative drugs that significantly improve patient health. Recent national and regional reforms in Sweden have moderated the rate of increase in drug expenditure, despite increased volumes of drug use and the launch of new, expensive drugs. National reforms include the adoption of economic principles when assessing the value and subsequent reimbursement of new and existing drugs, as well as reforms to obtain low prices for generic drugs. Regional reforms aim to encourage the rational use of medicines through the establishment of drug and therapeutic committees, development of guidelines, academic detailing, continuous benchmarking of prescribing patterns, and financial incentives. Some of these reforms provide examples to other European countries, whilst others duplicate existing measures. As such, we believe other European countries can benefit from an analysis of the Swedish reforms. We believe the pharmaceutical industry can also benefit from this analysis by working with key regional payers involved with developing and implementing the reforms as they moderate and refine their future activities, including finding acceptable ways of introducing new expensive drugs.

Cost-utility analysis of varenicline versus existing smoking cessation strategies using the BENESCO Simulation model: application to a population of US adult smokers.

Abstract: Background Of 1 346 700 total deaths each year in the US, an estimated 440 100 are smoking related, making it the leading preventable cause of premature death in the US. Despite the health and economic benefits of smoking cessation being well documented, reimbursement coverage for smoking cessation therapies is generally limited in the US and elsewhere.

Cost-Effectiveness Analyses of Natalizumab (Tysabri®) Compared with Other Disease-Modifying Therapies for People with Highly Active Relapsing-Remitting Multiple Sclerosis in the UK

Abstract: Natalizumab (Tysabri®) is a new disease-modifying therapy that has been shown to be clinically effective in patients with relapsing-remitting multiple sclerosis (RRMS) and has been licensed for use in patients with highly active RRMS (HARRMS). These patients are those who experience higher relapse rates and faster disability progression than the general RRMS population. To estimate the cost effectiveness of natalizumab compared with interferon-s, glatiramer acetate and best supportive care from various UK cost perspectives. A 30-year Markov model was developed, based on previously published models for multiple sclerosis, to estimate transition between disability states and the probability of relapse within disability states. The model was parameterized with data from the UK Multiple Sclerosis (MS) Survey 2005 and data from the AFFIRM study, a 2-year multicentre, randomized, double-blind, placebo-controlled trial of natalizumab in RRMS patients. Additional data were sourced from the literature. A UK societal cost perspective was used in the base case, with additional cost perspectives considered in the sensitivity analysis. The baseline characteristics for the patient group were taken from the patient population in the AFFIRM study (mean age 36 years, mean time since diagnosis 5 years and a mean Kurtzke Extended Disability Status Scale [EDSS] score of 2.5). The model and its parameterization were designed and developed to support a reimbursement application for natalizumab submitted to the UK National Institute for Health and Clinical Excellence (NICE). Efficacies for natalizumab and glatiramer acetate were taken from clinical trial data, and for interferon-s from a meta-analysis of clinical trial data. Disutilities from adverse events for each comparator were also included in the model. Outcomes and costs were discounted at 3.5% per anum. Costs for interferon-s and glatiramer acetate were based on published prices (year 2006 values) under the UK Risk Sharing Scheme, and for natalizumab the UK NHS list price was used. Diagnostic, administration and adverse event costs were also included. The incremental cost-effectiveness ratios (ICERs) were calculated for the base case, and a probabilistic sensitivity analysis was performed to assess the probability of cost effectiveness at different willingness-to-pay thresholds. The ICER for natalizumab compared with interferon-s was £2300 per QALY. Compared with glatiramer acetate, it was £2000 per QALY, and compared with best supportive care it was £8200 per QALY. From a health and social care cost perspective, the ICERs were £18 700, £20 400 and £25 500 per QALY, respectively. At a willingness-to-pay threshold of £30 000 per QALY, the probability of natalizumab being cost effective against any comparator from a societal perspective was >89%. If UK society is willing to pay more than £8200 per QALY, or Health and Social Services are willing to pay more than £26 000 per QALY, this analysis suggests that natalizumab is likely to be a cost-effective treatment for all patients with HARRMS.

Pharmacoeconomic evaluations of pharmacogenetic and genomic screening programmes: A systematic review on content and adherence to guidelines

Abstract: The fields of pharmacogenetics and pharmacogenomics have become important practical tools to progress goals in medical and pharmaceutical research and development As more screening tests are being developed, with some already used in clinical practice, consideration of cost-effectiveness implications is important A systematic review was performed on the content of and adherence to pharmacoeconomic guidelines of recent pharmacoeconomic analyses performed in the field of pharmacogenetics and pharmacogenomics Economic analyses of screening strategies for genetic variations, which were evidence-based and assumed to be associated with drug efficacy or safety, were included in the review The 20 papers included cover a variety of healthcare issues, including screening tests on several cytochrome P450 (CYP) enzyme genes, thiopurine S-methyltransferase (TMPT) and angiotensin-converting enzyme (ACE) insertion deletion (ACE I/D) polymorphisms Most economic analyses reported that genetic screening was cost effective and often even clearly dominated existing non-screening strategies However, we found a lack of standardization regarding aspects such as the perspective of the analysis, factors included in the sensitivity analysis and the applied discount rates In particular, an important limitation of several studies related to the failure to provide a sufficient evidence-based rationale for an association between genotype and phenotype Future economic analyses should be conducted utilizing correct methods, with adherence to guidelines and including extensive sensitivity analyses Most importantly, genetic screening strategies should be based on good evidence-based rationales For these goals, we provide a list of recommendations for good pharmacoeconomic practice deemed useful in the fields of pharmacogenetics and pharmacogenomics, regardless of country and origin of the economic analysis

Pharmaceutical Risk-Sharing Agreements

Abstract: Increased spending on pharmaceuticals continues to foster debate over healthcare policy The increasing costs of bringing products to the market, as well as increased utilization of pharmaceuticals contribute to increased pharmaceutical expenditure; however, appropriate pharmaceutical use can, in certain cases, reduce overall healthcare costs Nevertheless, the perception of high drug prices still puts pressure on pharmaceutical companies to build confidence in the proposition that their products are worth the additional expense One potential approach to building this confidence, and maintaining investment incentives, is for the pharmaceutical company to share the risk of a situation in which there is uncertainty about whether the product is effective for the consumer and payer Such risk-sharing arrangements for pharmaceuticals, like warranties, can be used to signal high quality when product quality is not fully observable While there may be difficulties in devising such schemes for every product, such risk-sharing plans may become a staple feature of the market in the future

Unrelated medical costs in life-years gained: should they be included in economic evaluations of healthcare interventions?

Abstract: Which costs and benefits to consider in economic evaluations of healthcare interventions remains an area of much controversy. Unrelated medical costs in life-years gained is an important cost category that is normally ignored in economic evaluations, irrespective of the perspective chosen for the analysis. National guidelines for pharmacoeconomic research largely endorse this practice, either by explicitly requiring researchers to exclude these costs from the analysis or by leaving inclusion or exclusion up to the discretion of the analyst. However, the inclusion of unrelated medical costs in life-years gained appears to be gaining support in the literature. This article provides an overview of the discussions to date. The inclusion of unrelated medical costs in life-years gained seems warranted, in terms of both optimality and internal and external consistency. We use an example of a smoking-cessation intervention to highlight the consequences of different practices of accounting for costs and effects in economic evaluations. Only inclusion of all costs and effects of unrelated medical care in life-years gained can be considered both internally and externally consistent. Including or excluding unrelated future medical costs may have important distributional consequences, especially for interventions that substantially increase length of life. Regarding practical objections against inclusion of future costs, it is important to note that it is becoming increasingly possible to accurately estimate unrelated medical costs in life-years gained. We therefore conclude that the inclusion of unrelated medical costs should become the new standard.

Having your cake and eating it: office of fair trading proposal for funding new drugs to benefit patients and innovative companies.

Abstract: There are insufficient resources in the UK to fund all new technologies and new indications approved by the National Institute for Health and Clinical Excellence (NICE). Diverting funding from existing sources will have a detrimental effect on the provision of other priority services. The UK Office of Fair Trading (OFT) recently suggested a value-based pricing approach that appears workable but has generated considerable debate. Their proposal of a 25% premium for the originator product once generics are available is more generous than seen in a number of other European countries, where typically only the lowest priced product is reimbursed. The OFT proposal for a maximum 50% premium for patent-protected products, versus the prices of generics in a class or related classes, is also more generous than the proposed reforms for the pricing of proton pump inhibitors in Sweden or current reforms in Germany. In our opinion, the OFT proposals are persuasive and in accordance with the reforms seen in other European countries, and therefore should be adopted. The alternatives to fully funding new drugs or new indications as approved by NICE are either tightening the cost per QALY threshold, giving NICE an annual notional budget to fund its advice alongside suggested areas for disinvestment, proactively switching patients from high-cost brand-name drugs to generics, or further delaying funding for new drugs and new indications approved by NICE. The majority of these suggestions are not in the best interests of patients or innovative pharmaceutical companies seeking to reap the rewards of their efforts.

Guidelines for conducting pharmaceutical budget impact analyses for submission to public drug plans in Canada.

Abstract: Until now, there has been no standardized method of performing and presenting budget impact analyses (BIAs) in Canada. Nevertheless, most drug plan managers have been requiring this economic data to inform drug reimbursement decisions. This paper describes the process used to develop the Canadian BIA Guidelines; describes the Guidelines themselves, including the model template; and compares this guidance with other guidance on BIAs. The intended audience includes those who develop, submit or use BIA models, and drug plan managers who evaluate BIA submissions. The Patented Medicine Prices Review Board (PMPRB) initiated the development of the Canadian BIA Guidelines on behalf of the National Prescription Drug Utilisation Information System (NPDUIS). The findings and recommendations from a needs assessment with respect to BIA submissions were reviewed to inform guideline development. In addition, a literature review was performed to identify existing BIA guidance. The detailed guidance was developed on this basis, and with the input of the NPDUIS Advisory Committee, including drug plan managers from multiple provinces in Canada and a representative from the Canadian Agency for Drugs and Technologies in Health. A Microsoft® Excel-based interactive model template was designed to support BIA model development. Input regarding the guidelines and model template was sought from each NPDUIS Advisory Committee member to ensure compatibility with existing drug plan needs. Decisions were made by consensus through multiple rounds of review and discussion. Finally, BIA guidance in Canadian provinces and other countries were compared on the basis of multiple criteria. The BIA guidelines consist of three major sections: Analytic Framework, Inputs and Data Sources, and Reporting Format. The Analytic Framework section contains a discussion of nine general issues surrounding BIAs (model design, analytic perspective, time horizon, target population, costing, scenarios to be compared, the characterisation of uncertainty, discounting, and validation methods). The Inputs and Data Sources section addresses methods for market size estimation, comparator selection, scenario forecasting and drug price estimation. The Reporting Format section describes methods for BIA reporting. The new Canadian BIA Guidelines represent a significant departure from the limited guidance that was previously available from some of the provinces, because they include specific details of the methods of performing BIAs. The Canadian BIA Guidelines differ from the Principles of Good Research Practice for BIAs developed by the International Society for Pharmacoeconomic and Outcomes Research (ISPOR), which provide more general guidance. The Canadian BIA Guidelines and template build upon existing guidance to address the specific requirements of each of the participating drug plans in Canada. Both have been endorsed by the NPDUIS Steering Committee and the PMPRB for the standardization of BIA submissions.

Management and Prevention of Diabetic Foot Ulcers and Infections

Abstract: Diabetic foot ulcers and infections are common and incur substantial economic burden for society, patients and families We performed a comprehensive review, on a number of databases, of health economic evaluations of a variety of different prevention, diagnostic and treatment strategies in the area of diabetic foot ulcers and infections We included English-language, peer-reviewed, cost-effectiveness, cost-minimization, cost-utility and cost-benefit studies that evaluated a treatment modality against placebo or comparator (ie drug, standard of care), regardless of year Differences were settled through consensus The search resulted in 1885 potential citations, of which 20 studies were retained for analysis (3 cost minimization, 13 cost effectiveness and 4 cost utility) Quality scores of studies ranged from 708% (fair) to 875% (good); mean = 784% ± 533% In diagnosing osteomyelitis in patients with diabetic foot infection, magnetic resonance imaging (MRI) showed 82% sensitivity and 80% specificity MRI cost less than 3-phase bone scanning + Indium (In)-111/Gallium (Ga)-67; however, when compared with prolonged antibacterials, MRI cost $US120 (year 1993 value) more without additional quality-adjusted life-expectancy Prevention strategies improved life expectancy and QALYs and reduced foot ulcer rates and amputations Ampicillin/sulbactam and imipenem/cilastatin were both 80% successful in treating diabetic foot infections but the latter cost $US2924 more (year 1994 value) Linezolid cure rates were higher (977%) than vancomycin (860%) and cost $US873 less (year 2004 value) Ertapenem costs were significantly lower than piperacillin/tazobactam ($US356 vs $US503, respectively; year 2005 values) Becaplermin plus good wound care may be cost effective in specific populations Bioengineered living-skin equivalents increased ulcer-free months and ulcers healed, but costs varied between countries Promogran® produced more ulcer-free months than wound care alone (375 vs 341 months, respectively) Treatment with cadexomer iodine resulted in higher rates of healed ulcer (29% vs 11%) and lower weekly treatment costs (Swedish krona [SEK]903 vs SEK1421; year 1993 values) than standard care Filgrastim decreased hospital stays, time to resolution and costs (36% lower) compared with usual care Adjunctive hyperbaric oxygen produced an incremental cost per QALY at year 1 of $US27 310 and $US2255 at year 12 (year 2001 values) Overall, preventive strategies were shown to be cost effective and potentially cost saving Various antibacterial regimens are cost effective but empiric choices should be based on local resistance patterns MRI was cost effective compared with three-phase bone scanning + In-111/Ga-67 but not against prolonged antibacterial therapy Other innovations (becaplermin, bioengineered living-skin equivalents, filgrastim, cadexomer iodine ointment, hyperbaric oxygen, Promogran®) may be cost effective in this population but more studies are needed to confirm these findings

Economic evaluation of interventions to treat opiate dependence : a review of the evidence.

Abstract: Opiate dependence imposes a significant economic burden on society in terms of treatment-related costs and prevention services, other healthcare costs, the work absenteeism of patients, productivity loss arising from premature death of patients, costs associated with crime, and social welfare expenditure. The objective of this research is to review the literature on economic evaluation of treatment of opiate dependence (including detoxification, maintenance and psychosocial support). A literature review was performed on several electronic databases, including MEDLINE (Ovid), Cochrane Database of Systematic Reviews, NHS Economic Evaluation Library Database (via Cochrane Library), Web of Science, Social Science Citations Index, EMBASE and PsycINFO. A sensitive approach was used in order to maximize the number of articles retrieved; no language or publication year limitations were applied to the searches. A combination of subject heading term searches and natural word searches were used. The Drummond checklist was applied to assess the quality of economic evaluations. A total of 259 articles were considered relevant, with eight review studies identified. The treatment spectrum ranged from detoxification to maintenance treatments involving the use of agonist and/or antagonist treatments. The evidence suggests that, although the quality of economic evaluations is reasonably good, there is a dearth of knowledge about the cost effectiveness of treatments for opiate dependence. The majority of the literature reporting the results of cost-effectiveness analyses used surrogate outcome measures and adopted a narrow treatment provider perspective. Studies that have conducted cost-benefit analyses, in spite of methodological divergences, generally adopted a societal perspective and consistently demonstrated positive economic returns from opiate treatment. A paucity of research examined the extent to which psychosocial or behavioural interventions support or replace conventional pharmacological approaches. Economic evaluation provides a useful framework to assist policy makers in allocating resources across competing needs. Opiate dependence is a considerable burden on society's resources, and treatment provides a cost-beneficial solution to address these consequences. However, to better inform the decision-making process, researchers must continue to produce high-quality, methodological, comparable and scientifically credible economic evaluations.