Pharmacoeconomic considerations of multiple sclerosis therapy with the new disease-modifying agents

Multiple sclerosis (MS) represents the second most common cause of neurological disability in young adults. The introduction of treatments that can change the natural course of the disease has focused attention on the economic burden of MS. There have been fears that the newly approved treatments for MS will ruin healthcare systems. Other published economic evaluations stress that the economic burden of a disease should be seen in a global perspective and that new treatments offer an opportunity to reduce the burden of the disease in the long-term. This paper reviews a number of key health economic studies in MS, which reveal the burden of MS on society and the cost-effectiveness of the new disease-modifying drugs, and highlight some unresolved issues. All relevant costs, including indirect costs and costs of informal care, should be taken into account for a global estimation of the cost/benefit balance. Further rigorous economic evaluations, focusing on the comparison of different available alternatives, are necessary. A major task will be the collection of data on the impact of the new disease-modifying therapies in reducing disability progression over the long-term, outside clinical trials. Gathering this kind of information is of critical importance in order to improve the precision of cost-effectiveness estimates in the future.     

Economic evaluation in evidence-based practice

The economic evaluation of health care interventions and technologies is an essential part of any modern healthcare system. In recent years a growing demand for information about the economic benefits of healthcare technologies has seen a significant increase in the number of published economic evaluations of healthcare. Economic evaluation reviews have demonstrated considerable methodological flaws in a significant number of analyses in health care. Widely accepted guidance regarding the manner in which multinational economic evaluations should be designed, analysed and presented is still awaited. The main types of economic analyses are described in this article, providing a framework along which to evaluate them.     

Assessing the cost-effectiveness of pharmacogenomics

The use of pharmacogenomics to individualize drug therapy offers the potential to improve drug effectiveness, reduce adverse side effects, and provide cost-effective pharmaceutical care. However, the combinations of disease, drug, and genetic test characteristics that will provide clinically useful and economically feasible therapeutic interventions have not been clearly elucidated. The purpose of this paper was to develop a framework for evaluating the potential cost-effectiveness of pharmacogenomic strategies that will help scientists better understand the strategic implications of their research assist in the design of clinical trials, and provide a guide for health care providers making reimbursement decisions. We reviewed concepts of cost-effectiveness analysis and pharmacogenomics and identified 5 primary characteristics that will enhance the cost-effectiveness of pharmacogenomics: 1) there are severe clinical or economic consequence that are avoided through the use of pharmacogenomics, 2) monitoring drug response using current methods is difficult, 3) a well-established association between genotype and clinical phenotype exists, 4) there is a rapid and relatively inexpensive genetic test, and 5) the variant gene is relatively common. We use this framework to evaluate several examples of pharmacogenomics. We found that pharmacogenomics offers great potential to improve patients' health in a cost-effective manner. However, pharmacogenomics will not be applied to all currently marketed drugs, and careful evaluations are needed on a case-by-case basis before investing resources in research and development of pharmacogenomic-based therapeutics and making reimbursement decisions.     

Pricing and reimbursement of pharmaceuticals in Belgium

The Belgian healthcare system has a tradition of access and equity at affordable prices. As in other countries, the system becomes pressured by increasing healthcare costs. This paper describes the actual situation in Belgium with special focus on pharmaceutical products and the potential role of pharmacoeconomics in decision making on price and reimbursement. Nearly all people in Belgium are covered by compulsory health insurance. The system is paid for by social security, the patients and the federal and regional authorities. The part of the consumption of pharmaceuticals that is charged to insurance was about 62.1 billion Belgian francs (BeF), i.e. about 50% of the pharmaceutical market in 1994. Price setting in Belgium has been rather low due to the positive reimbursement list, where the price of a new drug is compared to existing drugs in a comparable therapeutic class (so-called reimbursement criteria). The expenditure on pharmaceuticals is increasing faster than global funding for public health. In order to control drug budgets, different cost-containment measures have been or are being taken, i.e. a mix of price, reimbursement and volume controls. These cost-containment measures are not necessarily in accordance with a health economic approach. This paper suggests the scope for better implementation of pharmacoeconomic evaluation, which can lead to more flexible reimbursement systems in specific indications. Therefore, a formal recognition of the role of objective economic evaluations is needed for both hospital and ambulatory care. This process should be proceeded by improving the understanding and robustness of pharmacoeconomic evaluations.     

Reconciliation of economic concerns and health policy: illustration of an equity adjustment procedure using proportional shortfall

Economic evaluations have become an important and much used tool in aiding decision makers in deciding on reimbursement or implementation of new healthcare technologies. Nevertheless, the impact of economic evaluations on reimbursement decisions has been modest; results of economic evaluations do not have a good record in predicting funding decisions. This is usually explained in terms of fairness; there is increasing awareness that valuations of QALYs may differ when the QALYs accrue to different patients. The problem, however, is that these equity concerns often remain implicit, and therefore frustrate explicitness and transparency in evidence-based decision making. It has been suggested that a so-called equity adjustment procedure may (partially) solve this problem. Typically this would involve the application of so-called equity weights, which can be used to recalculate the value of QALY gains for different patients. This paper explores such an equity adjustment procedure, using the equity concept of proportional shortfall. Proportional shortfall assumes that measurement of inequalities in health should concentrate on the fraction of QALYs that people lose relative to their remaining life expectancy, and not on the absolute number of QALYs lost or gained. It is the ratio of QALYs lost over the QALYs remaining. This equity concept combines elements of two popular but conflicting notions of equity: fair innings and severity-of-illness.We applied the concept of proportional shortfall to ten conditions and tentatively explored how an equity adjustment procedure using proportional shortfall might affect priority setting. Our equity adjustment procedure lowered the cost-effectiveness threshold when a condition was relatively mild. Because the proportional shortfall caused by the ten conditions differed considerably, the equity-adjustment procedure discriminated strongly between the ten conditions, and this experiment provided a good opportunity to explore the impact of equity adjustment for healthcare reimbursement decisions. In conclusion, our results suggest that equity can be measured and that integration of equity concerns into an economic evaluation improves the fit between economic models and reimbursement decisions. It is recommended that cost-effectiveness driven health policy systems consider equity adjustments.     

Pharmacoeconomic considerations of multiple sclerosis therapy with the new disease-modifying agents

Multiple sclerosis (MS) represents the second most common cause of neurological disability in young adults. The introduction of treatments that can change the natural course of the disease has focused attention on the economic burden of MS. There have been fears that the newly approved treatments for MS will ruin healthcare systems. Other published economic evaluations stress that the economic burden of a disease should be seen in a global perspective and that new treatments offer an opportunity to reduce the burden of the disease in the long-term. This paper reviews a number of key health economic studies in MS, which reveal the burden of MS on society and the cost-effectiveness of the new disease-modifying drugs, and highlight some unresolved issues. All relevant costs, including indirect costs and costs of informal care, should be taken into account for a global estimation of the cost/benefit balance. Further rigorous economic evaluations, focusing on the comparison of different available alternatives, are necessary. A major task will be the collection of data on the impact of the new disease-modifying therapies in reducing disability progression over the long-term, outside clinical trials. Gathering this kind of information is of critical importance in order to improve the precision of cost-effectiveness estimates in the future.     

Health economic evaluation of non-melanoma skin cancer and actinic keratosis

Non-melanoma skin cancer (NMSC) and actinic keratosis are becoming an increasingly important healthcare problem. There are approximately 1 million cases of NMSC in the US each year, primarily basal cell carcinomas, and the incidence is increasing. Although NMSC is significant in terms of both health risk and the resource implications for treatment within healthcare systems, our understanding of the health economics of NMSC is limited. The purpose of this article was to systematically review and assess published health economic studies of the treatment of NMSC and actinic keratosis, taking into consideration key aspects of guidelines set by drug purchasers and key reimbursement agencies, and to provide recommendations for appropriate modelling approaches and data collection for health economic studies of NMSC and actinic keratosis. We systematically reviewed the published literature from 1965 to 2003 for health economic evaluations of treatments of NMSC and actinic keratosis using the search terms: ('skin cancer' or 'non melanoma skin cancer' or 'basal cell carcinoma' or 'actinic keratosis') and ('decision model' or 'decision theoretic' or 'decision analytic' or 'health economic' or 'cost effective'). Studies using one of the following methodologies were included: cost-effectiveness, cost-benefit, cost-utility, cost-minimisation, cost-of-illness, cost-consequence, and treatment cost analysis. We identified eight studies evaluating NMSC. One of these studies also evaluated actinic keratosis. Although several studies satisfied some of the basic requirements of health economic evaluations, the majority had serious shortcomings that limit their usefulness. There are a few high-quality health economic evaluations assessing treatments for NMSC or actinic keratosis. However, our analysis suggests that additional data on treatment practice patterns and epidemiology need to be collected, and incorporated with efficacy and safety data in a formal decision-analytic framework to assist decision makers in allocating scarce healthcare resources.     

Economic evaluation of drugs and its potential uses in policy making

Interest in the economic evaluation of drug treatments is steadily increasing, but the impact of such evaluations on decisions concerning the use of drugs is unclear. In this article I examine different decision and policy situations where economic evaluations of drug treatments could potentially be used. Economic evaluations may be used as an aid to the development of treatment guidelines, decisions within healthcare organisations, and decisions relating to approval, reimbursement and pricing. Economic evaluations appear to be most useful in the development of treatment guidelines and as an aid to reimbursement decisions. The incentive to use economic evaluations embodied in the healthcare system is also important. It is argued that it is too early to introduce regulations that require the use economic evaluations in, for example, reimbursement decisions. A more cautious approach might be preferred, where economic evaluations are used more selectively until the methodology and the field have developed further.     

The Cost-Effectiveness and Cost-Benefit of Screening and Brief Intervention for Unhealthy Alcohol Use in Medical Settings

SUMMARY

Economic evaluation can be a valuable tool for assessing the efficiency and value of health care programs. To examine the literature on the economic evaluation of alcohol screening and brief intervention in medical settings, relevant studies were identified in the MEDLINE database (1966 through November 2006) and by hand-searching the references of identified articles and relevant journals. The 15 identified studies used a range of economic evaluation methods, including cost analysis, cost-benefit, cost-effectiveness, and cost-utility. Nearly all of the studies supported the use of alcohol screening and brief intervention. The studies that prospectively collected cost and effect data and/or conformed closely to methodological guidelines demonstrated a strong economic benefit of alcohol screening and brief intervention when compared to usual care. Overall, the reviewed studies support alcohol SBI in medical settings as a wise use of health care resources and illustrate the usefulness of economic evaluation for assessing alcohol prevention and treatment programs.     

Principles of pharmacoeconomic analysis of drug therapy

Economic analyses have become increasingly important in healthcare in general and with respect to pharmaceuticals in particular. If economic analyses are to play an important and useful role in the allocation of scarce healthcare resources, then such analyses must be performed properly and with care. This article outlines some of the basic principles of pharmacoeconomic analysis. Every analysis should have an explicitly stated perspective, which, unless otherwise justified, should be a societal perspective. Cost minimisation, cost-effectiveness, cost-utility and cost-benefit analyses are a family of techniques used in economic analyses. Cost minimisation analysis is appropriate when alternative therapies have identical outcomes, but differ in costs. Cost-effectiveness analysis is appropriate when alternative therapies differ in clinical effectiveness but can be examined from the same dimension of health outcome. Cost-utility analysis can be used when alternative therapies may be examined using multiple dimensions of health outcome, such as morbidity and mortality. Cost-benefit analysis requires the benefits of therapy to be described in monetary units and is not usually the technique of choice. The technique used in an analysis should be described and explicitly defended according to the problem being examined. For each technique, the method of determining costs is the same; direct, indirect, and intangible costs can be considered. The specific costs to be used depend on the analytical perspective; a societal perspective implies the use of both direct and indirect economic costs. A modelling framework such as a decision tree, influence diagram, Markov chain, or network simulation must be used to structure the analysis explicitly. Regardless of the choice of framework, all modelling assumptions should be described. The mechanism of data collection for model inputs must be detailed and defended. Models must undergo careful verification and validation procedures. Following baseline analysis of the model, further analyses should examine the role of uncertainty in model assumptions and data.     

An overview of methods and applications to value informal care in economic evaluations of healthcare

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.     

Methodological issues in economic assessments of new therapies. The case of colony-stimulating factors

Pharmacoeconomic evaluations estimate the value of medical interventions by comparing their clinical consequences and costs. Economic analyses, based on resource use data collected during 3 clinical trials of lenograstim, were performed as part of a lenograstim economic evaluation programme. Undertaking economic evaluations alongside clinical trials presents a number of methodological challenges, since the trials may be performed in atypical settings, have inappropriate follow-up, or use end-points that are not useful for economic evaluation. This paper reports on how these challenges were met in the lenograstim economic evaluation programme. In particular, it was decided that the evaluations would be based on an intent-to-treat perspective, with the same period of follow-up (for costs) for both lenograstim and vehicle groups.     

Economics of atypical antipsychotics in bipolar disorder: a review of the literature

Economic evaluations are increasingly being used by policy makers to evaluate the relative costs and benefits of healthcare interventions. These analyses provide economic and clinical evidence to decision makers seeking to make recommendations on treatment alternatives for patients. This article describes the economic evidence on the atypical antipsychotics currently approved for the treatment of bipolar disorder. This area remains under-researched. A literature search identified only six relevant studies of atypical antipsychotics in bipolar disorder: two retrospective database analyses, three economic analyses alongside clinical trials and one cost-effectiveness analysis. Based on the limited available studies, there appears to be no significant difference in healthcare resource use between olanzapine, quetiapine, risperidone and valproate semisodium (divalproex sodium; an antiepileptic drug and a standard treatment for mania associated with bipolar disorder). While a cost-effectiveness study for the UK found haloperidol (a conventional antipsychotic) to be more cost effective than atypical antipsychotics, these results must be considered with caution because of the non-inclusion of adverse effects in the model. No economic data are available for aripiprazole, clozapine or ziprasidone in bipolar disorder. Until more economic evidence becomes available, the economic implications of atypical antipsychotic treatment in patients with bipolar disorder are unlikely to significantly impact on prescribing and treatment patterns. Future economic studies evaluating atypical antipsychotics in bipolar disorder should address the issue of long-term costs and effectiveness to reflect the chronic nature of the disease, the variety of health states that patients may experience and the range of treatments they may receive. A better understanding of the complex interplay between effectiveness, safety, quality of life, adherence and resource use should ultimately contribute to improving the treatment of bipolar disorder.     

Recommended structure for reporting economic evaluation on pharmaceuticals in Belgium

Pharmacoeconomic evaluations become more important for the reimbursement of pharmaceuticals, and will be obligatory for new pharmaceutical drugs for which an added therapeutic value is claimed and a price premium is proposed by the manufacturer. Therefore, it is important to guide purchasers and providers of pharmaceutical care in their efforts related to the evaluation process. Standard Report Format can support the quality, transparency and exhaustiveness of the data submitted. A multidisciplinary task force developed a Standard Report Format for pharmacoeconomic evaluations in Belgium.     

Handling uncertainty in cost-effectiveness models

The use of modelling in economic evaluation is widespread, and it most often involves synthesising data from a number of sources. However, even when economic evaluations are conducted alongside clinical trials, some form of modelling is usually essential. The aim of this article is to review the handling of uncertainty in the cost-effectiveness results that are generated by the use of decision-analytic-type modelling. The modelling process is split into a number of stages: (i) a set of methods to be employed in a study are defined, which should include a 'reference case' of agreed methods to enhance the comparability of results; (ii) the clinical and demographic characteristics of the patients the model relates to should be specified as carefully as in any experimental study; and (iii) the data requirements of the model should be estimated using the principles of Bayesian statistics, such that prior distributions are specified for unknown model parameters. Monte Carlo simulation can then be employed to sample from these prior distributions to obtain a distribution of the cost effectiveness of the intervention. Such probabilistic analyses are related to parameter uncertainty. In addition, modelling uncertainty is likely to add a further layer of uncertainty to the results of particular analyses.     

An introduction to the methods of cost-effectiveness analysis

The comparative cost-effectiveness of interventions is a fundamental consideration of health technology assessment (HTA) in the UK.(1) The use of modelling to extrapolate benefits to patients and costs over a specified time period is a common technique in cost-effectiveness analyses. All modelling techniques, by their nature, are subject to different levels of uncertainty. Assessment and understanding of the level and impact of this uncertainty is a fundamental part of the decision-making process. In this article, we build on our previous article A guide to health economic evaluations and discuss different modelling approaches to cost-effectiveness analysis and the importance of uncertainty.(2)     

Review of the cost-effectiveness of interventions to improve seamless care focusing on medication

Aim of the review This review of the international literature aims to assess the evidence and its methodological quality relating to the cost-effectiveness of interventions to improve seamless care focusing on medication. Method Studies were identified by searching Medline, EMBASE, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews, and EconLit up to March 2011 using search terms related to health economics and to seamless care. To be included, economic evaluations had to explore the costs and consequences of an intervention to improve seamless care focusing on medication as compared with usual care. Methodological quality of studies was assessed by considering perspective; design; source of clinical and economic data; cost and consequence measures; allowance for uncertainty; and incremental analysis. Costs were actualized to 2007 values. Results Eight studies on medication interventions for hospitalized patients in the transition between ambulatory and hospital care were included in the review. A variety of types of medication interventions and target populations have been assessed, but the evidence is limited to one economic evaluation for each particular intervention type and each specific target population. Most studies demonstrated an impact of interventions on compliance and (re)hospitalization rates and costs. The studies did not find an impact on quality of life or symptoms. Economic evaluations suffered from methodological limitations related to the narrow perspective; restriction to health care costs only; exclusion of costs of the intervention; use of intermediate consequence measures; no allowance for uncertainty; and absence of incremental analysis. Conclusion In light of the small number of economic evaluations and their methodological limitations, it is not possible to recommend a specific intervention to improve seamless care focusing on medication on health economic grounds.     

The RTOG Outcomes Model: economic end points and measures

Recognising the value added by economic evaluations of clinical trials and the interaction of clinical, humanistic and economic end points, the Radiation Therapy Oncology Group (RTOG) has developed an Outcomes Model that guides the comprehensive assessment of this triad of end points. This paper will focus on the economic component of the model. The Economic Impact Committee was founded in 1994 to study the economic impact of clinical trials of cancer care. A steep learning curve ensued with considerable time initially spent understanding the methodology of economic analysis. Since then, economic analyses have been performed on RTOG clinical trials involving treatments for patients with non-small cell lung cancer, locally-advanced head and neck cancer and prostate cancer. As the care of cancer patients evolves with time, so has the economic analyses performed by the Economic Impact Committee. This paper documents the evolution of the cost-effectiveness analyses of RTOG from performing average cost-utility analysis to more technically sophisticated Monte Carlo simulation of Markov models, to incorporating prospective economic analyses as an initial end point. Briefly, results indicated that, accounting for quality-adjusted survival, concurrent chemotherapy and radiation for the treatment of non-small cell lung cancer, more aggressive radiation fractionation schedules for head and neck cancer and the addition of hormone therapy to radiation for prostate cancer are within the range of economically acceptable recommendations. The RTOG economic analyses have provided information that can further inform clinicians and policy makers of the value added of new or improved treatments.     

Economic evaluation in healthcare. A brief history and future directions

Over the last decade there has been tremendous interest in economic evaluations of healthcare programmes, especially in the pharmaceutical field. Economic evaluations started about 30 years ago as rather crude analyses, in which the value of improved health was measured in terms of increased labour production. Now, more refined methods are available to measure health changes in terms of quality-adjusted life-years gained or willingness to pay. It is important to continue this development, and major fields for future work include the incorporation of quality-of-life measurements into economic evaluations and the linking of cost-effectiveness and cost-benefit analyses into a unified framework of economic evaluation. How to incorporate distributional issues is another important area. Finally, it seems crucial to further explore the link between economic evaluation and decision making, since the purpose of economic evaluations is to affect decision making.