Current Trends in the Use of Pharmacoeconomics and Outcomes Research in Europe
Article first published online: 5 JAN 2002
Value in Health
Volume 2, Issue 5, pages 323–332, September 1999
How to Cite
Drummond, M., Dubois, D., Garattini, L., Horisberger, B., Jönsson, B., Kristiansen, I. S., Le Pen, C., Pinto, C. G., Poulsen, P. B., Rovira, J., Rutten, F., Von Der Schulenburg, M. G. and Sintonen, H. (1999), Current Trends in the Use of Pharmacoeconomics and Outcomes Research in Europe. Value in Health, 2: 323–332. doi: 10.1046/j.1524-4733.1999.25003.x
- Issue published online: 5 JAN 2002
- Article first published online: 5 JAN 2002
In recent years there has been a large increase in the number of economic evaluations of pharmaceuticals . Many of these studies have been commissioned by individual pharmaceutical companies, in support of new or existing products. Europe, particularly the countries of the European Union, represents one of the world's largest pharmaceutical markets. Therefore there is considerable interest in whether the activities of companies, in commissioning and undertaking pharmacoeconomics or outcomes research studies, are having any impact.
The experience in Europe was reviewed earlier by Drummond et al. . It was pointed out that the situation in Europe is characterized by its diversity. First, a wide range of health care systems exist, including both “socialized” national health services, such as those in Scandinavia and the United Kingdom, and “liberal” systems, involving a wide range of insurers and providers, more common in southern and central Europe.
Secondly, European countries differ widely in their approaches to the pricing and reimbursement of pharmaceuticals. Drummond et al.  discussed four different approaches. For example, some countries such as the United Kingdom allow free pricing of drugs by companies but regulate profits. Other countries such as France operate a two-stage administered system where an assessment of the therapeutic equivalence (to other existing products) is made first and then price is negotiated depending on the classification of the product.
There is also a growing interest in Europe in reference-based pricing, in which drugs are assigned to groups or “clusters” depending on assessments of pharmacological or therapeutic equivalence. A reference price (or reimbursement level) is then set for the cluster as a whole, although the manufacturer is free to set the price at or above the reference price. This approach exists in Denmark, Norway, Germany, Sweden, and The Netherlands; only in Germany and The Netherlands has clustering been extended beyond pharmacological equivalence.
By contrast, in some countries such as Italy prices are set according to comparison with those existing in a group of other countries, and the level of reimbursement is set according to the clinical importance of the drug.
At the time of the earlier article, Drummond et al.  reported that no European jurisdiction formally required economic evaluation as a basis for pricing or reimbursement decisions. Recently, however, a number of European Countries have indicated that formal requirements will be introduced or are under consideration. Also, in a number of countries, guidelines for undertaking pharmaeconomics studies have been proposed either by the authorities or by academic researchers.
Therefore the purpose of this paper is to revisit the earlier analysis of Drummond et al. , given the changes that have taken place. It considers the following issues:
- • Are economic evaluations officially required in any country?
- • Are there any other statements or guidance from the authorities (e.g., government, sickness funds, or insurers) relating to the need for economic evaluation of health technologies?
- • Do any published guidelines exist for economic evaluation in European countries?
- • What is the current practice of economic evaluation of pharmaceuticals in the various countries, and what are the major trends?
- • What are the major uses of studies: price negotiation, reimbursement decisions, local formulary decisions, developing practice guidelines, communicating to prescribers?
The study concentrated on 13 western European countries, including 11 countries of the European Union. Together these represented most, if not all, of the major pharmaceutical markets outside the United States and Japan and included all countries where we expected any substantial activity in pharmacoeconomics and outcomes research. The focus was on full economic evaluations, that is, studies comparing the costs and outcomes of drug therapies in terms of improved health . The broader range of outcomes research studies, including quality of life studies, burden of disease studies, and analyses of databases was not considered. Such studies are often included in company submissions to pricing or reimbursement agencies. However, while containing relevant information, they do not address value for money directly and do not comply with the guidelines for economic evaluations currently being promulgated by reimbursement authorities.
In each country, the study coordinators (the coauthors of this paper) completed a questionnaire covering the issues outlined above. No guidance was given on the sources to be consulted when completing the questionnaire, but it was expected that the coordinators would rely heavily on the published literature and their own local knowledge. Each coordinator was a prominent health economist in the country concerned.
No comprehensive surveys of decision-makers or users of pharmacoeconomics and outcomes research studies were carried out for this study, although some coordinators were able to make use of surveys recently conducted as part of the European Union Concerted Action on the Methodology of Economic Evaluation of Health Technology (EUROMET Project—Project Leader, Professor Graf von der Schulenburg). Where such surveys were available (in Finland, Germany, The Netherlands, Portugal, Spain, Sweden, and the United Kingdom), the results were able to provide some validation of the findings presented here. Other coordinators relied on informal discussions with colleagues and key officials to validate their findings.
To determine the current practice of economic evaluation in the various countries, study coordinators were asked to give examples of up to five landmark studies of economic evaluations of pharmaceuticals conducted since 1993. In addition the OHE-HEED database  was searched in order to determine the total number of economic evaluations conducted and the analytic methods used.
All the responses were collated and analyzed by the first author and the report produced. No external funding was sought and the views expressed are solely those of the authors.
Official Requirements for Economic Studies
A number of the countries included have now indicated that studies are required, or may be required, in the future. In The Netherlands the Sickness Insurance Fund Council (Ziekenfondsraad) has announced that from mid-1999, economic evaluations will be required for new drugs not covered by the reference price system. In practice this means innovative new compounds for which there is no near equivalent, or compounds for which the manufacturer claims better effectiveness and hence a premium price.
In Portugal, a new decree law (305/98) states that Infarmed, the drug reimbursement agency, may request economic evaluations whenever it deems these necessary for decisions about the reimbursement of pharmaceuticals.
In Finland, from the beginning of 1998 an official requirement came into effect that an application to the Pharmaceuticals Pricing Board (PPB) by a company for a “reasonable wholesale price” must be accompanied by an economic evaluation of the product. This evaluation should provide a detailed and credible assessment of the costs and benefits attainable by treatment with the new drug in relation to the costs and benefits of other treatments available both to the patient and to the health and social services. The wholesale price endorsed by the PPB serves as the basis for the basic reimbursement by the National Sickness Insurance.
In Denmark, pharmaceutical companies can now submit economic evaluations to the Danish Medicines Agency (Laegemiddelstyrelsen) when they apply for reimbursement of new products. This is in the context of a two-year agreement between the Pharmaceutical Industry Association (Laegemiddelindustriforeningen) and the Ministry of Health imposing a ceiling on pharmaceutical expenditures, and followed the rejection by both parties of a more formal arrangement. The voluntary arrangement will be evaluated over a 3-to-5 year period.
In the United Kingdom, the Department of Health has established a National Institute for Clinical Excellence (NICE). This will identify approximately 30 new health technologies per year for detailed assessment. In the case of pharmaceuticals the company will be asked to provide data. On the basis of its assessments, NICE will issue guidelines for the appropriate use of health technologies, including pharmaceuticals, within the UK National Health Service.
Finally, two countries are exploring the potential value of economic evaluation in making decisions about pharmaceuticals. In Spain, the Ministry of Health has commissioned a study to assess the interest and feasibility of introducing economic evaluation into the procedures for pricing and reimbursement of new pharmaceuticals. In France, a special expert committee has been established to review economic studies that are submitted by companies to the Transparency Commission (which decides reimbursement status) or the Price Committee (which determines price). Its first task will be to examine past decisions in order to assess the extent to which the information provided by studies could have assisted in the reimbursement or pricing decision.
Other Official Guidance About the Economic Evaluation of Health Technologies
A small number of countries are edging towards formal requirements for economic evaluation of pharmaceuticals on the Australian model. With the possible exception of the United Kingdom, European countries with large pharmaceutical markets have so far shied away from formal requirements.
There is evidence from other official statements, however, that governments and third-party payers are taking economic considerations seriously. In Italy, the National Committee of Drugs (Commissione Unica del Farmaco) lists pharmacoeconomics as one of the points to be considered in submitting approval dossiers for innovative drugs. Also, the Italian Committee for Economic Planning (Comitato Interministeriale Pianificazione Economica) mentions cost-effectiveness ratios as a criterion for price negotiations for innovative drugs.
In Spain, there are generic statements in some pieces of legislation relating to the reimbursement of drugs and health technologies. Administrative prices of drugs should officially be based on the cost of production plus a profit mark-up. However, statements refer to situations of dominance; that is, a given technology cannot be reimbursed if there are others available of the same or higher quality at a lower price.
In Germany, the Social Security Law states that “treatments should be produced economically,” otherwise these treatments cannot be reimbursed by sickness funds. However, the law does not say what is meant by economical, nor does it indicate the methods by which it is to be assessed. Nevertheless, the new Social Democrat government has indicated that economic considerations and evaluations will play an important role in formulating the planned positive list. This list will be developed by the Council of the Sickness Funds and Insurance Doctors.
In Switzerland, the Federal Social Insurance Office has issued a manual on Standardization of Clinical and Economic Evaluation of Medical Technology, which regulates the procedure for health insurance coverage. However, currently pharmaceuticals are excluded from this. In The Netherlands, the use of economic evaluation is well-established in making decisions about health insurance coverage for new health technologies .
Statements about the need for cost-effectiveness in health care can also be found in official reports in Portugal, Norway, Denmark, and the United Kingdom. Their precise impact, other than setting the general tone for discussion, however, is unclear.
Methodological Guidelines for Economic Evaluation
Methodological guidelines exist in a number of European countries. Sometimes they are linked to an official requirement for economic evaluation as in The Netherlands. Sometimes they arise from a more general concern about the maintenance of methodological standards. In Table 1, existing guidelines are classified by their source (government or academia) and their purpose. In some cases, such as in Belgium and Germany, the groups developing guidelines had broad membership from government, industry, and academia. In such cases, the classification has been made according to the main actor driving the discussion and publishing the guidelines, i.e., the Belgian Society for Pharmacoepidemiology in Belgium, and the University of Hannover in Germany.
|Source||Pricing or Reimbursement||Maintenance of Methodological Standards|
|Government or Payers||Sickness Fund Council (NL)||Department of Health (with the ABPI) (UK)|
|Academia||Alban et al (on behalf of the Ministry of Health) (DK)||British Medical Journal (UK)|
|Alban et al (on behalf of the Ministry of Health) (DK)|
|College of Economists (F)|
|Hannover Consensus (D)|
|Garattini et al (I)|
|Rovira et al (E)|
Detailed examination of the various guidelines indicates that there are some minor differences in the methodological advice given, but there are many similarities, for example in guidance on the perspective to be adopted, the choice of comparator regimen and the discount rate to be used. In addition to the published guidelines listed in Table 1, discussions have taken place in Norway, Sweden, Italy, and the United Kingdom on this general topic. However, none of these discussions has yet resulted in published guidelines. Guidelines are promised by the PPB in Finland in support of the formal requirement for economic evaluation, although these have not appeared to date.
Current Practice of Economic Evaluation of Pharmaceuticals in Europe
A number of economic evaluations have been conducted in all of the 13 countries studied here. The landmark studies identified by the study coordinators are listed in the Appendix. These cover a wide range of health care conditions and pharmaceutical products.
In addition, a fuller picture of trends in pharmacoeconomics in Europe can be obtained from the Health Economic Evaluation Database (HEED) . This lists more than 10,000 items, comprising empirical studies (economic evaluations and quality of life studies), methodology papers, costing studies, and reviews and editorials. Table 2 shows the empirical studies of pharmaceuticals (classified by form of economic evaluation) for the 13 countries considered here, for the three years 1995, 1996, and 1997. It should be noted that the coverage of the database is much more comprehensive for the English-language literature than others. Therefore it does not fully reflect pharmacoeconomic activity in some countries but does give a general flavor of the research being undertaken.
|Type of Economic Evaluation||Number of Studies (N = 541)*|
|Cost of illness||59|
Table 3 shows the disease areas covered in pharmacoeconomic studies for all 13 countries. In every one the major funder of studies to date has been the pharmaceutical industry, although in Denmark, Germany, The Netherlands, Sweden, Switzerland, and the United Kingdom, a minority of studies have been funded by the government or third-party payers.
|Disease Area||Number of Studies (N = 541)*|
|Alimentary tract and metabolism||50|
|Blood and blood forming organs||46|
|Genito-urinary system and sex hormones||15|
|Systematic hormonal preparations excluding sex hormones||28|
|General antiinfectives for systematic use||130|
|Antineoplastic and immunomodulating agents||71|
|Antiparasitic products, insecticides and repellents||4|
|No code assigned||35|
A wide range of individuals and groups actually conduct the studies, including academic centers, private consultancies, clinicians, and pharmaceutical companies. Both trial-based and modeling studies are conducted, although the latter are in the majority in most countries. Often this is because there is a need to adapt, through a model, data from elsewhere to the country concerned.
Many studies are published in all countries, although the motivations of the various parties may differ. For example, in settings in which studies are used in negotiations about price or reimbursement, there may be no perceived additional benefit on the part of the individual pharmaceutical company from making the study more widely available. When studies are undertaken for marketing purposes, however, publication in a good quality journal is often seen as a major asset. Also, academic centers may expect or require publication of the study as part of their agreement to participate, whereas company authors or those from private consultancies may regard wider publication as desirable but not essential.
Uses of Economic Evaluations
There are a number of potential uses for economic evaluations, both at the national and local level. These are discussed below. However, it should be recognized that the nature of the decision-making process, and the confidentiality that often surrounds it, sometimes makes it difficult to identify the precise contribution made by a particular study.
Also, it should be recognized that the various decision-making functions such as pricing and reimbursement may be handled by different committees, whereas economics would implicitly link them. That is, in an economic model of decision-making, whether or not a particular drug is purchased or reimbursed, depends on its value for money and hence price. This potential link sometimes blurs the precise contribution made by a given economic study.
As mentioned above, it is often difficult to disentangle pricing and reimbursement decisions even though they are often made by different committees. Indeed, in Sweden and Finland, pricing and reimbursement decisions are made by the same committee.
When a formal role is prescribed for economic evaluation, it is usually in the context of reimbursement, because in those countries where there is price regulation, this decision is usually made before the price negotiation. Also, the reimbursement decision often includes a recommendation about whether a given product should attract a premium price. Thus, the economic evaluation seeks to establish that there are additional economic benefits from the new drug, over and above existing treatment alternatives, that would justify a premium.
In France, 72 health economic studies have been submitted to the Transparency Commission over the past 6 years. However, the majority are either cost of illness studies (26) or cost identification studies (20). Only 16 are economic evaluations, comparing both costs and consequences. The impact of studies has so far been limited, although there are a few examples of situations in which the study has affected the ranking of the new drug on the scale used to establish a hierarchy among innovations. For example, Le Pen  cites one case in which a drug (sparfloxacine) was not classed as a major innovation but was reimbursed at a premium price, possibly partly as a result of an economic study that was submitted.
In Spain, the only known example of an economic evaluation being formally considered is a study of centoxin . The drug was only reimbursed for the more restrictive indication of septic shock, whereas in many European countries it was reimbursed for the broader indication of sepsis. The economic evaluation may have influenced this decision, although overall budgetary impact was probably a more important factor.
Due to the voluntary arrangement in Denmark, it has been possible since March 1997 to include information from economic evaluations as part of the decision-making process on the reimbursement of new products. This requires that the pharmaceutical companies submit an economic evaluation together with the ordinary application for reimbursement.
In Belgium, economic evaluation has played a role in setting the criteria for the reimbursement of vaccination (e.g., for hepatitis B) within Belgian regional care programs.
Although formal economic evaluation requirements are being introduced in Finland, The Netherlands, and Portugal, the key issue in most countries is still assessment of the clinical equivalence of the drug or otherwise with existing alternatives. Therefore, an innovative drug with no obvious comparators always has a higher probability of attracting a premium price. As mentioned above, a potential role for economic evaluation is to explore the range within which that premium might fall.
In general, the use of economic evaluation in price negotiations is limited and there are no formal requirements. In Switzerland and France, manufacturers have presented economic data to pricing committees without knowing the likely impact. Indeed, in France the Price Committee states that the pricing process is multifactorial and will not depend on the results of an economic study. In Sweden, studies are accepted by the National Social Insurance Board as a basis for consultation on price. In Norway, the pharmacoeconomics unit of the Medicines Control Authority (Statens Legemiddel-Kontroll) produces a number of reports but these are not in the public domain. Finally, in Italy the recent equal drugs–equal prices rule, introduced by CUF in 1997, may have increased the use of pharmacoeconomic studies to justify premium prices.
To the extent that pharmacoeconomics studies help differentiate new products from existing ones, they may justify premium prices. Nevertheless, as Drummond et al.  argue, the final price for a drug will always be subject to negotiation. This negotiation establishes the proportion of any economic gain to be returned to the company, rather than given to society more generally. The most a pharmacoeconomic study can contribute is to delineate a range of prices within which a new drug is potentially good value for money.
Local Formulary Discussions.
In most of the countries studied, formularies exist at the hospital level. In a minority of countries they also exist at the level of the physician group practice (as in the United Kingdom) or at the level of the local authority such as the Regional Formulary Committees in The Netherlands, and the County Councils in Denmark and Sweden.
Evidence of the use of economic evaluation in formulary discussions is difficult to show, given the large number of local decision-making groups that would be difficult to survey systematically. However, the study coordinators from The Netherlands, the United Kingdom, Denmark, and Germany provided evidence of the use of economic studies in formulary decision-making. In Sweden, the drug formulary committees of the county councils are required by law to take economic aspects into account when selecting a drug. It is also likely that economic criteria are applied informally in a much wider range of local settings.
Developing Clinical Practice Guidelines.
In a number of European countries the development of evidence-based clinical practice guidelines is becoming increasingly popular. The vast majority of these consider clinical evidence alone and indeed the inclusion of economic data may cause tension . Nevertheless, the study coordinators did identify examples of guidelines incorporating cost-effectiveness evidence in a number of countries.
In Sweden, economic studies in the fields of hypertension and hyperlipidemia have been cited in the development of practice guidelines. In The Netherlands, it was recommended in a guideline from the Dutch hemato-oncology group, that GM-CSF should not be used in patients with therapy-induced neutropenic fever as a result of an economic evaluation. Also, the economic evaluations of statins in primary and secondary prevention of hyperlipidemia were influential in determining which risk groups should receive therapy. It was decided that only those groups for which the incremental cost-effectiveness ratio was less than or equal to 40,000 NLG (Netherlands Guilders) per life-year gained should receive treatment.
In Germany, the sponsor of an economic evaluation of the cost-effectiveness of combination therapy for asthma is seeking to have this included in treatment guidelines being developed by the German Association of Pneumologists. In Denmark, an economic study of a screening and treatment program for children with urinary tract infections was carried out at the request of the National Board of Health (Sundhedsstyrelsen) and was taken into account when developing the model health care program for this condition . Finally, in the United Kingdom, as part of the Evidence Based Outreach (EBOR) project funded by the Department of Health, economic considerations have been taken into account in developing prescribing guidelines in the areas of ACE inhibitors for symptomatic heart failure, NSAIDs in arthritis, drugs for treatment of depression, and antiplatelet therapy . The experience gained in developing these guidelines has also thrown some light on the broader issues involved with incorporating economic evaluation into practice guidelines .
Communications to Prescribers.
The pharmaceutical industry has traditionally viewed communications to prescribers as one of its most powerful marketing tools. The same view has been taken by some governments, which now invest a considerable amount of resources in informing prescribers about the relative merits and demerits of particular drugs.
Communications to prescribers tend to concentrate on efficacy and safety of medicines, but some do include economic data. For example, in the United Kingdom the publications from the Drug and Therapeutics Bulletin and the Medicines Resource Centre (MeReC) usually mention the comparative costs of medicines, although they rarely discuss formal economic evaluations. The same approach is used by Infarmed and the Regional Health Authorities in Portugal. In Sweden, the Medical Products Agency conducts workshops and communicates the results through publications. In The Netherlands, considerable effort goes into disseminating consensus guidelines, some of which contain pharmacoeconomic information to general practitioners and medical specialists. For example, the cholesterol guidelines are now being communicated to GPs and cardiologists.
Finally, in Norway the Medicines Control Authority used a study to discourage doctors from prescribing an osteoporosis drug (alendronate) on the basis of cost considerations. However, the scientific content of the study was disputed by the drug's manufacturer in the courts.
In general, very little is known about the impact of communicating pharmacoeconomic data to prescribers and this is clearly an area for further research. One would suspect, however, that a critical question is whether the prescriber perceives him or herself as responsible for a defined drugs budget, as budgetary initiatives in the United Kingdom and Germany have previously shown.
The overall position regarding the use of economic evaluation of pharmaceuticals is extremely varied. This position is summarized in Table 4. An asterisk indicates that there is some evidence of the use of economic evaluation in the particular function or activity in the country concerned. However, it is important to remember that, since most of the discussions in pricing, reimbursement, and formulary committees are not made public, it is difficult to produce clear examples. Nevertheless, our impression is that value for money criteria are applied informally in many such discussions.
|Reimbursement decisions||Price negotiations||Local formulary discussions||Developing clinical practice guidelines||Communications to prescribers|
The situation with regard to the practice and potential for pharmacoeconomics and outcomes research varies among the 13 European countries studied. Different countries have different approaches to making pricing and reimbursement decisions and the formal evidence for use of pharmacoeconomic studies is unclear.
However, more European countries are introducing formal requirements for economic evaluation of new medicines, particularly in the case of innovative products, or in situations in which the manufacturer is seeking a premium price.
There are a number of guidelines for economic evaluation in Europe, some linked to the formal requirements for studies and some having the more general objective of maintaining or improving methodological standards. In general, the similarities among the guidelines outweigh the differences. Overall, methodologies employed in studies and current methodological debates are similar to those that are ongoing in North America.
Beyond the formal requirements for studies, different countries employ a range of mechanisms for encouraging the cost-effective use of medicines, including reference-based pricing and education of physicians in economics. If any trend is emerging, it seems that in a growing number of countries major innovative products are likely to be subjected to formal economic evaluation, whereas cost-effectiveness in the use of the vast majority of medicines will be achieved through other means.
Although it is difficult to obtain clear evidence of the use of pharmacoeconomic studies in different settings due to the lack of transparency in decision-making procedures, the trend is toward more use rather than less. It is also likely that the informal application of value for money principles extends beyond the use of studies. In general, the use of pharmacoeconomic and outcomes research is expanding in Europe, although the pace of change differs from one country to another. Perhaps the greater use of economic evaluation, and the development of formal guidelines or requirements, may lead to greater transparency in the decision-making procedures themselves.
An earlier version of this paper was presented at the Inaugural ISPOR European Conference, Köln, 11 December 1998. The authors are grateful to the Steering Group of the EUROMET Project for permission to use data collected as part of that study. No additional funding was sought for the study beyond the support offered by our own organizations. Finally, we are grateful to Julie Glanville for the literature review, Vanessa Windass for manuscript preparation, and anonymous referees for suggestions made.
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Appendix: Landmark Studies from Different European Countries
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De Backer G. Cost effectiveness analysis of the use of lipid lowering agents. (In Dutch: Kosteneffectiviteitsanalyse van het gebruik van vetverlagende medicamenten.) Tijdschr. Voor Geneeskunde 1998; 54:236–42.
Annemans L, De Backer G, De Backer, D, De Bacquer D, De Henauw S. Economic evaluation of atorvastatin versus other statins in the prevention of coronary heart disease. 5th National BESPE Symposium on Pharmacoepidemiology, 1998. Abstract Book; p25.
Defever M, Kesteloot K, Coucke K, Steeman E, Gruwez T. Socio-economic evaluation of incontinence in adults. (Report). Faculty of Medicine, School of Public Health, Centre for Health Services and Nursing Research, 1997.
Ankjaer-Jensen A, Johnell O. Prevention of osteoporosis: cost-effectiveness of different pharmaceutical treatments. Osteoporosis Int 1996;6:265–75.
Heiberg I, Søgaard J. Evaluation of pharmacoeconomic analyses of Risperidon (Risperdal®) used in the treatment of chronic schizophrenia. CHS Working Paper 1996:5. Centre for Health and Social Policy, Odense University, 1996. [In Norwegian: Evaluering av farmako-økonomiske analyser av Risperidon (Risperdal®) brukt i behandling av kronisk schizofrene pasienter.]
Langkilde LK. Cost analysis of the use of Interferon a2-b in the treatment for Hepatitis C. CHS Working Paper 1995: 4. Centre for Health and Social Policy, Odense University, 1995. [In Danish: Omkostningsanalyse for anvendelse af rekombinant alfa interferon 2-b i behandlingen af hepatitis C.]
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Franzosi MG, Maggioni AP, Santoro E, Tognoni G, Cavalieri E. Cost effectiveness analysis of early lisinopril use in patients with acute myocardial infarction. Pharmacoeconomics 1998;3:337–45.
Garattini L, Brunetti M, Salvioni F, Barosi M. Economic evaluation of ACE inhibitor treatment of nephropathy inpatients with insulin dependent diabetes mellitus in Italy. Pharmacoeconomics 1997;1:7–74.
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Liberato NL, Quaglini S, Barosi G. Cost-effectiveness of interferon alfa in chronic myelogenous leukemia. J Clin Oncol 1997;15:2673–82.
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Al MJ, Michel BC, Rutten FFH. The cost effectiveness of diclofenac plus misoprostol compared with diclofenac monotherapy in patients with rheumatoid arthritis. Pharmacoeconomics 1996;10:141–51.
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