Pharmacoeconomic Guidelines Research Articles

Methodological Quality of Economic Evaluations of New Pharmaceuticals in the Netherlands

In the Netherlands, decisions about the reimbursement of new pharmaceuticals are based on cost effectiveness, as well as therapeutic value and budget impact. Since 1 January 2005, drug manufacturers are formally required to substantiate the cost effectiveness of drugs that have therapeutic added value in comparison with existing ones through pharmacoeconomic evaluations. Dutch guidelines for pharmacoeconomic research provide methods guidance, ensuring consistency in both the evidence and the decision-making process about drug reimbursement. This study reviewed the methodological quality of all 21 formally required pharmacoeconomic evaluations of new pharmaceuticals between 1 January 2005 and 1 October 2008, and verified whether these evaluations complied with pharmacoeconomic guidelines. Data on the quality of the pharmacoeconomic evaluations were extracted from the pharmacoeconomic reports published by the Dutch Health Care Insurance Board (CVZ). The Board's newsletters provided information on the advice to, and reimbursement decisions made by, the Dutch Minister of Health. All data extraction was carried out by two independent reviewers, and descriptive analyses were conducted. The methodological quality was sound in only 8 of the 21 pharmacoeconomic evaluations. In most cases, the perspective of analysis, the comparator drugs, and the reporting of both total and incremental costs and effects were correct. However, drug indication, form (i.e. cost utility/cost effectiveness) and time horizon of the evaluations were frequently flawed. Moreover, the costs and effects of the pharmaceuticals were not always analysed correctly, and modelling studies were often non-transparent. Twelve drugs were reimbursed, and nine were not. The compliance with pharmacoeconomic guidelines in economic evaluations of new pharmaceuticals can be improved. This would improve the methodological quality of the pharmacoeconomic evaluations and ensure consistency in the evidence and the decision-making process for drug reimbursement in the Netherlands.

Pharmacoeconomics and developing nations

The scarcity of resources within both industrialized and developing nations has catalyzed the adoption of more formalized approaches to support decisionmaking, particularly within healthcare. In many instances, however, the unique aspects present within developing countries may not permit the direct translation of pharmacoeconomic guidelines or recommendations from high-income economies. The purpose of this paper is to delineate the key attributes that differentiate pharmacoeconomics within developing nations, including the potential barriers to implementation and policy considerations involved. Through its approach to comprehensively assess costs and outcomes of technologies, pharmacoeconomic methodologies may help foster the optimal allocation of resources to improve the effectiveness, efficiency, and equity of healthcare delivery for societies worldwide.

The costs of urinary tract infection therapy with implementation of pharmacoeconomic guidelines at the clinic for infectious diseases of the Clinical center of Vojvodina

The Serbian health system does not have strict guidelines for the treatment of bacterial infections. The choice of treatment is empirical which is not necessarily the same compared to the treatment guidelines from countries with a developed pharmacotherapeutic practice. In this study we compared the difference between the current treatment and the treatment taking into account the latest pharmacotherapeutic and pharmacoeconomic guidelines in order to estimate clinical efficiency of antibacterial drugs that were given as a therapy of urinary tract infections and to evaluate pharmacoeconomic aspect of this therapy as well. Our study included 100 patients that were randomly chosen and divided into 2 groups. The first group was treated in an ordinary way, while the second one was treated strictly in accordance with the guidelines (British National Formulary - BNF, and Senford Guide). In both groups of the patients we compared length of hospitalization, combination of the used antibiotics, progress as a whole in clinical picture, laboratory analyses and the price of the whole treatment. Analyzing these values independently and according to statistical tests we proved that there were no significant differences between two groups with regard to the progress in a clinical picture as a whole and the length of hospitalization. According to this analysis, however suggested treatment based on guidelines showed a saving of 34.48% in comparison with the usual system of therapy. Efficacy of current treatment of urinary tract infection and the treatment according to foreign guidelines is the same, but the costs of the treatment are lower if the guidelines of developed health care systems are applied.

Interpretation of modified prescription for pharmacoeconomic analysis of New Zealand

The Prescription for Pharmacoeconomic Analysis (PFPA) of New Zealand was firstly published in 1999. The original version was reviewed in 2004 and version 2, approved and published in 2007, is the living document. The main purpose for this guideline is to provide an overview of the methods PHARMAC (Pharmaceutical Management of Agency) uses when conducting cost-utility analysis. Compared with version 1, version 2 involved and discussed the most frequently mentioned issues in pharmacoeconomic guidelines around the world. This paper describes the distinguishes between version 1 and 2, the advantages of version 2 as well as the amendments that will be made in PHARMAC's future work, in order to provide meaningful advice for standardizing and documenting methods in China

Cost-effectiveness of cardiac resynchronisation therapy for patients with moderate-to-severe heart failure: a lifetime Markov model

ObjectiveTo assess the cost-effectiveness of cardiac resynchronisation therapy (CRT) both with CRT-P (biventricular pacemaker only) and with CRT-D (biventricular pacemaker with defibrillator) in patients with New York Heart Association (NYHA)...

What Do International Pharmacoeconomic Guidelines Say about Economic Data Transferability?

Objectives The objectives of this article were to assess the positions of the various national pharmacoeconomic guidelines on the transferability (or lack of transferability) of clinical and economic data and to review the methods suggested in the guidelines for addressing issues of transferability. Methods A review of existing national pharmacoeconomic guidelines was conducted to assess recommendations on the transferability of clinical and economic data, whether there are important differences between countries, and whether common methodologies have been suggested to address key transferability issues. Pharmacoeconomic guidelines were initially identified through the ISPOR Web site. In addition, those national guidelines not included in the ISPOR Web site, but known to us, were also considered. Results Across 27 sets of guidelines, baseline risk and unit costs were uniformly considered to be of low transferability, while treatment effect was classified as highly transferable. Results were more variable for resource use and utilities, which were considered to have low transferability in 63% and 45% of cases, respectively. There were some differences between older and more recent guidelines in the treatment of transferability issues. Conclusions A growing number of jurisdictions are using guidelines for the economic evaluation of pharmaceuticals. The recommendations in existing guidelines regarding the transferability of clinical and economic data are quite diverse. There is a case for standardization in dealing with transferability issues. One important step would be to update guidelines more frequently.

The Cost Utility of Autologous Chondrocytes Implantation Using ChondroCelect® in Symptomatic Knee Cartilage Lesions in Belgium

Knee cartilage lesions increase the risk of developing osteoarthritis (OA), and may eventually result in a total knee replacement (TKR). There is currently no consensus on the optimal treatment of cartilage lesions. ChondroCelect® (CC) is a cell-based therapy approved for use in autologous chondrocytes implantation (ACI) to treat symptomatic cartilage defects of the femoral condyle. Its capacity to safely restore good-quality cartilage was demonstrated in a randomized controlled trial (RCT) versus the surgical procedure microfracture (MFX). This study investigated the cost utility of CC used in ACI compared with MFX to treat symptomatic knee cartilage lesions in Belgium. A decision tree model comparing CC with MFX over a 40-year horizon was developed in TreeAge Pro™. The key timepoints of the model were (i) clinical assessment 5 years after initial intervention (success or no success, with or without re-operation); (ii) development of OA at 15 years (yes/no); (iii) need for TKR at 20 years (yes/no); and (iv) need for prosthesis revision at 35 years (yes/no). Clinical data provided by the RCT of CC versus MFX were the clinical success (response) rate based on the Knee injury and Osteoarthritis Outcome Score (KOOS) at 36 months (82.9% vs 62.0%; p = 0.048) and the proportion of good structural repair/presence of hyaline cartilage based on International Cartilage Repair Society (ICRS II) visual item at 12 months (44.9% vs 23.2%; p = 0.023). Utility scores by surgery outcome were derived from the SF-36 questionnaire responses collected in the RCT. Conservative assumptions related to the incidences of OA, TKR and prosthesis revision relied on a literature search. A patient chart review (n = 82) provided follow-up costs by surgery outcome. National tariffs were applied to direct medical resources used (healthcare payer perspective, year 2008 costs). Annual discounting was applied to costs (3%) and effects (1.5%) as recommended by the Belgian pharmacoeconomic guidelines. The incremental cost per QALY gained for CC compared with MFX was €16,229, with a difference in costs of €20,802 and 1.282 QALYs gained. Sensitivity analyses indicated that the key model drivers were the proportion of patients with hyaline cartilage and the correlation between hyaline cartilage formation and later avoidance of OA. Probabilistic sensitivity analyses showed robustness of the results, with 80% of the simulations below the usual UK National Institute for Health and Clinical Excellence (NICE) threshold of €22,000 per QALY. Assuming a good correlation between high-quality cartilage repair and avoidance of OA at a later stage, the benefits of the cell therapy CC over MFX in terms of QALYs gained and OA-related costs avoided appear real. Further research is required to explore long-term effects of cartilage repair and reduce uncertainty on quality of life of patients with OA before and after joint replacement.

Health Technology Assessment and Economic Evaluation: Arguments for a National Approach

141/2000 of the European Parliament and the Council of 16 December 1999 on orphan medicinal products. Official Journal of the European Union, January 22, 2000, L18. 6 Drummond M, Barbieri M, Cook J, et al. Transferability of economic evaluations across jurisdictions: ISPOR Good Research Practices Task Force Report. Value Health 2009;12: 409–18. 7 ISPOR. Pharmacoeconomic guidelines around the world. Available from: http://www.ispor.org/PEguidelines/index.asp [Accessed April 13, 2009]. 8 Manca A. Economic data transferability for HTA: are we there yet? Value Health 2009;12:407. 9 O’Sullivan A, Thompson D, Bekker D. Country-to-country adaptation of pharmacoeconomic research: methodologic challenges and potential solutions. ISPOR Connect 2009;15:6–8. 10 European Commission. Health Programme 2008–2013: Together for Health. Brussels: European Commission, 2007. Available from: http://ec.europa.eu/health/ph_programme/pgm2008-2013_ en.htm [Accessed April 14, 2009]. 11 European Network for Health Technology Assessment. About EUnetHTA. Available from: http://www.eunethta.net/ [Accessed April 14, 2009]. 12 European Network for Health Technology Assessment. HTA core model handbook. Available from: https://fio.stakes.fi/htacore/ handbook.html [Accessed April 14, 2009].

The Transferability of Valuing Lost Productivity across Jurisdictions. Differences between National Pharmacoeconomic Guidelines

For at least two decades, there has been an intense debate on whether and how to include the value of lost productivity in economic evaluations. This debate is often reflected in pharmacoeconomic guidelines, which have been developed to indicate the methods and requirements for the design, execution, and reporting of economic evaluations in a particular country. Objective To examine what various national pharmacoeconomic guidelines recommend regarding the identification, measurement, and valuation of lost productivity. Methods First, the theoretical framework on how lost productivity can be identified, measured, and valued is described. Second, a summary sheet has been used to identify various pharmacoeconomic guidelines recommendations regarding the value of lost productivity. Results Twenty-two of the 30 guidelines identified recommend performing economic evaluations using the societal perspective. Nevertheless, even if the societal perspective is recommended, it is not always clear how the value of lost productivity should be taken into account. Most guidelines recommend including the costs of absenteeism from paid and/or unpaid work. In addition, although no agreement exists on how lost productivity should be valued, none of the guidelines recommended using the US panel approach for the valuation of lost productivity. Discussion The different recommendations hinder international transferability of the value of lost productivity. This difficulty is mainly caused by different recommendations regarding identification and valuation. These differences result from the debate and lack of consensus on including the value of lost productivity losses in economic evaluations. It will become easier to transfer data across jurisdictions if all data are reported transparently.

Translation and cross-cultural adaptation into Brazilian Portuguese of the Measure of Parental Style (MOPS) - a self-reported scale - according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) recommendations

To describe the translation and adaptation methodology for the Measure of Parental Style, a self-report instrument developed originally in English, following the International Society for Pharmacoeconomics and Outcomes Research guidelines, comparing this to other methodologies used for the same purposes. Translation and Cultural Adaptation group International Society for Pharmacoeconomics and Outcomes Research guidelines were followed (preparation, first forward translation, reconciliation, back translation, revision of back translation, harmonization, cognitive debriefing, revision of debriefing results, syntax and orthographic revision, final report). A careful and qualified cross-cultural translation and adaptation of an instrument contribute for measuring what it is designed to measure across cultures. Presenting this process, besides its final product, provides the opportunity that this experience could be replicated for adaptation of other instruments.

Good Research Practices for Measuring Drug Costs in Cost Effectiveness Analyses: Issues and Recommendations: The ISPOR Drug Cost Task Force Report—Part I

Objectives The assignment of prices or costs to pharmaceuticals can be crucial to results and conclusions that are derived from pharmacoeconomic cost effectiveness analyses (CEAs). Although numerous pharmacoeconomic practice guidelines are available in the literature and have been promulgated in many countries, these guidelines are either vague or silent about how drug costs should be established or measured. This is particularly problematic in pharmacoeconomic studies performed from the “societal” perspective, because typically the measured cost of a brand name pharmaceutical is not a true economic cost but also includes transfer payments from some members of society (patients and third party payers) to other members of society (pharmaceutical manufacturer stockholders) in large part as a reward for biomedical innovation. Moreover, there are numerous and complex institutional factors that influence how drug costs should be measured from other CEA perspectives, both internationally and within the domestic US context. The objective of this report is to provide guidance and recommendations on how drug costs should be measured for CEAs performed from a number of key analytic perspectives. Methods ISPOR Task Force on Good Research Practices—Use of Drug Costs for Cost Effectiveness Analysis (Drug Cost Task Force [DCTF]) was appointed with the advice and consent of the ISPOR Board of Directors. Members were experienced developers or users of CEA models, worked in academia, industry, and as advisors to governments, and came from several countries. Because how drug costs should be measured for CEAs depend on the perspectives, five Task Force subgroups were created to develop drug cost standards from the societal, managed care, US government, industry, and international perspective. The ISPOR Task Force on Good Research Practices—Use of Drug Costs for Cost Effectiveness Analysis (DCTF) subgroups met to develop core assumptions and an outline before preparing six draft reports. They solicited comments on the outline and drafts from a core group of 174 external reviewers and more broadly from the membership of ISPOR at two ISPOR meetings and via the ISPOR web site. Results Drug cost measurements should be fully transparent and reflect the net payment most relevant to the user's perspective. The Task Force recommends that for CEAs of brand name drugs performed from a societal perspective, either 1) CEA analysts use a cost that more accurately reflects true societal drug costs (e.g., 20–60% of average sales price), or when that is too unrealistic to be meaningful for decision-makers, 2) refer to their analyses as from a “limited societal perspective.” CEAs performed from a payer perspective should use drug prices actually paid by the relevant payer net of all rebates, copays, or other adjustments. When such price adjustments are confidential, the analyst should apply a typical or average discount that preserves this confidentiality. Conclusions Drug transaction prices not only ration current use of medication but also ration future biomedical research and development. CEA researchers should tailor the appropriate measure of drug costs to the analytic perspective, maintain clarity and transparency on drug cost measurement, and report the sensitivity of CEA results to reasonable drug cost measurement alternatives.

Good Research Practices for Measuring Drug Costs in Cost-Effectiveness Analyses: An International Perspective: The ISPOR Drug Cost Task Force Report—Part VI

Objective The pharmacoeconomic guidelines available in the literature or promulgated in many countries are either vague or silent about how drug costs should be established or measured so an international comparison of cost-effectiveness analysis (CEA) results can be made. The objective of this report is to provide guidance and recommendations on how drug costs should be measured for CEAs done from an internationally comparative perspective. Methods Members of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force on Good Research Practices—Use of Drug Costs for Cost Effectiveness Analysis (Drug Cost Task Force [DCTF]) subgroup from several countries were experienced developers or users of CEA models, and worked in academia, industry, and as advisors to governments. They solicited comments on drafts from a core group of 174 external reviewers and more broadly, from the members of the ISPOR at the ISPOR 12th Annual International meeting and via the ISPOR Web site. Results Drug units should be standardized in terms of volume of active ingredient, regardless of packaging and dosing strength variations across countries. Drug costs should be measured in local currency per unit of active ingredient and should be converted to other currencies using sensitivity analyses of purchasing power parities (PPP) and exchange rates, whichever is more appropriate. When using drug prices from different years, the consumer price index for the local currency should be applied before the PPP and/or exchange rate conversion. Conclusion CEA researchers conducting international pharmacoeconomic analysis should tailor the appropriate measure of drug costs to the international perspective, to maintain clarity and transparency on drug cost measurement in the context of international drug comparison and report the sensitivity of CEA results to reasonable cost conversions.

Belgian Methodological Guidelines for Pharmacoeconomic Evaluations: Toward Standardization of Drug Reimbursement Requests

ObjectiveTo develop methodological guidelines for pharmacoeconomic evaluation (PE) submitted to the Belgian Drug Reimbursement Committee as part of a drug reimbursement request. MethodsIn 2006, preliminary pharmacoeconomic guidelines were developed by a multidisciplinary research team. Their feasibility was tested and discussed with all stakeholders. The guidelines were adapted and finalized in 2008. ResultsThe literature review should be transparent and reproducible. PE should be performed from the perspective of the health-care payer, including the governmental payer and the patient. The target population should reflect the population identified for routine use. The comparator to be considered in the evaluation is the treatment most likely to be replaced. Cost-effectiveness and cost–utility analyses are accepted as reference case techniques, under specific conditions. A final end point—as opposed to a surrogate end point—should be used in the incremental cost-effectiveness ratio (ICER). For the calculation of quality-adjusted life-years (QALYs), a generic quality-of-life measure should be used. PE should in principle apply a lifetime horizon. Application of shorter time horizons requires appropriate justification. Uncertainty around the ICER should always be assessed. Costs and outcomes should be discounted at 3% and 1.5%, respectively. ConclusionThe current guidelines are the result of a constructive collaboration between the Belgian Health Care Knowledge Centre, the National Institute for Health and Disability Insurance and the pharmaceutical industry. A point of special attention is the accessibility of existing Belgian resource use data for PE. As PE should serve Belgian health-care policy, they should preferably be based on the best available data.

Sampling Uncertainty in the Cost-Effectiveness Evaluations and Guidance Given by the Existing Pharmacoeconomic Guidelines: A Question to Be Considered

The objective of this study is to analyze the guidance given by the existing pharmacoeconomic guidelines up to the sampling uncertainty. The aim is to focus on the existing degree of vagueness of guidelines in order to facilitate the tasks of those who must base their choices on studies of this kind. After the grouping of methods in an appropriate way so that there would be a relative correspondence with the guidelines, a selection of 22 guidelines was made to study the precision given to sampling uncertainty and the preferred methods of handling this uncertainty. The methods of handling uncertainty have plainly evolved in recent years. However, the differentiations in the guidelines concerning this field are considerable. Consequently, the tasks of submitters, evaluators, and decision makers become very difficult.

Impact of patient sample on costs of events in pharmacoeconomic models

Pharmacoeconomic guidelines have focused on improving the measurement of effectiveness, but have largely ignored the assessment of cost inputs. We explored differences in adverse event cost estimates derived from three different sources in a case study of selective COX2 NSAIDs. We found substantial differences in costs of adverse events across data sources. We also determined that treatment costs associated with adverse events differed substantially based upon inclusion/exclusion criteria. Health services researchers should be deliberate in the choice of adverse event treatment costs that are used in decision analytic models. Future guidelines should seek to delineate best practices for cost calculations.

Pharmacoeconomic Evaluations of Pharmacogenetic and Genomic Screening Programmes

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.

Providing Systematic Guidance in Pharmacoeconomic Guidelines for Analysing Costs

Despite the considerable amount of work that has gone into the standardisation of costs, a recent survey indicated that there is still a wide variation in methods used in costing studies in the published literature. Part of the answer to the lack of standardisation may lie in pharmacoeconomic guidelines themselves. The purpose of this paper is to categorise the current recommendations for the analysis of costs within an economic evaluation, and to use these categories to assess variations in guidelines. Based on identified costing methodology, we developed a detailed categorisation. We then surveyed existing guidelines to determine similarities and differences in the guidelines. Our framework had five categories: general design items; resource identification and classification; resource measurement; resource valuation; and overall reporting. We noted differences in perspective, some of which were due to methodological uncertainty and differences in the purposes of the studies covered by the guidelines. There was very little guidance in how to put the basic cost measure into operation. In addition, the preferred concept for resource utilisation was that of resource use under actual (rather than experimental) conditions, and there was very little guidance as to how to achieve this measure. There are still large variations, as well as gaps, in guidelines in the costing area. This is due, in part, to wide-ranging objectives for studies, methodological uncertainty and a neglect of the fundamentals of costing. We recommend that the contents of the basic measure of 'average cost' should be explained in more detail, with recurring, capital and allocated overhead costs being reported separately. A target capacity level (e.g. 80%) should be reported, even if in a sensitivity analysis. More guidance should be provided regarding the translation of utilisation under experimental care to that under routine care. For resource valuation, adjustments to the 'average cost' measure should be made explicit. There should be more guidance on how to project system-wide costs from the costs of one hospital. The manner in which overall results are reported should be addressed, including the identification of how costs should be categorised.

Penny and Pound Wise

Because of growing pressure on the healthcare budget in The Netherlands, appropriate justification of current expenditures and future investments in public healthcare are becoming increasingly important. Therefore, the Dutch Ministry of Health, Welfare and Sport is expanding its use of pharmacoeconomic evaluation in informed reimbursement decision-making of new pharmaceuticals. Since June 2002, pharmaceutical companies have been invited to submit a pharmacoeconomic dossier with their reimbursement applications of innovative drugs. As of January 2005 submission of a pharmacoeconomic dossier is mandatory for all drugs claiming to have therapeutic value. Currently, several European governmental and non-governmental organisations are making efforts to harmonise pharmacoeconomic research guidelines at the EU level. Ultimately, this may facilitate a more efficient way of conducting pharmacoeconomic research and encourage the use of pharmacoeconomic data by national assessment agencies and governments. It is anticipated that international pharmaceutical companies will increasingly invest in pharmacoeconomics while government staff will become more experienced in appraising the dossiers, thus resulting in an upward momentum in the quality and usability of pharmacoeconomic data. From the Dutch government's perspective, the use of pharmacoeconomic evaluation in reimbursement decision-making should offer a true opportunity for pharmaceutical companies to present the added value for money of new drugs. Using pharmacoeconomic data, costs, benefits and effects of pharmaceuticals are increasingly being considered from a societal perspective, thus going beyond the sole consideration of the impact on the pharmaceutical budget.

PHP1 ASSESSMENT OF PROPOSED GUIDELINES FOR PHARMACOECONOMIC SUBMISSIONS IN GREECE: OVERVIEW AND IMPLEMENTATION PROBLEMS

OBJECTIVES: Greek authorities have proposed draft pharmacoeconomic (PE) guidelines for reimbursement submissions. Our objective is to compare these to guideline documents in the EU countries, Australia and Canada in terms of purpose and methodology and identify potential implementation problems. METHODS: We reviewed and compared the proposed guidelines along the following criteria: purpose of PE analysis, responsibility and conduct, type of analysis, comparator choice, perspective, resource use and cost assessment, outcome measurement and validation of results. Based on the above as well as current Greek literature we assessed potential problems in implementing the proposed guidelines. RESULTS: In terms of comparison, pharmacoeconomic submissions in Greece aim at reimbursement. PE studies can be conducted either by the pharmaceutical industry, CROs or academia. Cost-minimization analysis is sufficient when effectiveness of the alternatives is equal. Otherwise, cost consequence analysis is mandatory followed by costeffectiveness, cost-benefit or cost-utility analyses. Standard and least costly existing therapies are mandatory comparators. The perspective of analysis is not clearly stated. Cost outcomes should reflect detailed resource use description. Effectiveness measures should be based on RCTs or meta-analysis results. No explicit reference is made of naturalistic studies. Modeling is accepted. QoL outcomes are accepted. Discounting and sensitivity analyses are obligatory. As a result of our comparative analysis, the following issues should be investigated in the transition phase. Applying monetary values is difficult given the absence of official price lists and concurrent use of public and private providers. Epidemiological data and databases regarding clinical practice are scant. Extensive modeling assumptions are required to transfer international clinical data to the Greek environment. Experience with PE is rare among researchers and government. CONCLUSIONS: Proposed guidelines are similar with published ones, with minor country-specific differences. The implementation problems identified require a transition phase to establish methodological grounds and generate experience.

Design, Analysis and Presentation of Multinational Economic Studies

Over the last decade, there has been a proliferation in the number of economic evaluations of pharmaceuticals to meet the growing demand for information about the economic benefits of healthcare technologies. The majority of these studies have been commissioned by pharmaceutical companies for the purposes of drawing attention to the resource and quality-of-life aspects of new or existing products. Such information has become important in overcoming a new obstacle, namely the demonstration of cost effectiveness (the so-called 'fourth hurdle'), in addition to the three well-established criteria of quality, tolerability and efficacy. To ensure the maintenance of standards, guidance for economic evaluations has emerged lately in the form of guidelines, regulations, principles, policies and positions. Drummond outlined three purposes of these guidelines, as follows: as a requirement prior to reimbursement, as statements of methodological standards, and as a statement of ethical standards. Such guidelines are designed to assist both the economic analyst and the decision-maker. In laying out the state of the art regarding the methodology of economic evaluation, guidelines assist the analyst in performing high-quality, scientifically valid studies, and assist the decision-maker in properly interpreting and assessing their quality. In response to these growing requirements for cost-effectiveness data globally, it has become increasingly common for economic evaluations to be conducted on an international scale. However, the recommendations in pharmacoeconomics guidelines regarding the manner in which these multinational economic evaluations should be designed, analysed and presented are too limited to be of any real value. This article examines the various issues that must be taken into consideration when conducting multinational studies, and provides a review of the techniques and approaches that have been suggested to date. It concludes with recommendations for potential inclusion in future sets of pharmacoeconomic guidelines.