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Design, Analysis and Presentation of Multinational Economic Studies

The Need for Guidance

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Abstract

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.

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References

  1. Drummond MF, O’Brien B, Stoddart GL, et al. Methods for the economic evaluation of health care programmes. 2nd ed. Oxford: Oxford University Press, 1997

    Google Scholar 

  2. Coyle D, Drummond M. Analysing differences in the costs of treatment across centres within economic evaluations. Int J Technol Assess Health Care 2001; 17: 155–63

    Article  PubMed  CAS  Google Scholar 

  3. Drummond MF. Economic analysis alongside controlled trials. Leeds: Department of Health, 1994

    Google Scholar 

  4. Mason J. The generalisability of pharmacoeconomic studies. Pharmacoeconomics 1997; 11: 503–14

    Article  PubMed  CAS  Google Scholar 

  5. Liedl RM. Some factors to consider when using the results of economic evaluation studies at the population level. Int J Technol Assess Health Care 1994; 10: 467–78

    Article  Google Scholar 

  6. O’Brien B. Economic evaluation of pharmaceuticals: Frankenstein’s monster or vampire of trials? Med Care 1996; 34: DS99–108

    PubMed  Google Scholar 

  7. Heyland DK, Kernerman P, Gafni A, et al. Economic evaluations in the critical care literature: do they help us improve the efficiency of our unit? Crit Care Med 1996; 24 (9): 1591–8

    Article  PubMed  CAS  Google Scholar 

  8. Bryan S, Brown J. Extrapolation of cost-effectiveness information to local settings. J Health Serv Res Policy 1998; 3: 108–12

    PubMed  CAS  Google Scholar 

  9. Coyle D. Increasing the impact of economic evaluation on health-care decision-making. York: York University, 1993, York CHE Discussion paper no. 108

    Google Scholar 

  10. Drummond M, Cooke J, Walley T. Economic evaluation under managed competition: evidence from the UK. Soc Sci Med 1997; 45 (4): 583–95

    Article  PubMed  CAS  Google Scholar 

  11. Briggs A, Sculpher M, Buxton M. Uncertainty in the economic evaluation of health care technologies: the role of sensitivity analysis. Health Econ 1994; 3: 95–104

    Article  PubMed  CAS  Google Scholar 

  12. CHE York Expert Workshops in Economic Evaluation. York, 1998

  13. Drummond MF, Blooms BS, Carrin G, et al. Issues in the crossnational assessment of health technology. Int J Technol Assess Health Care 1992; 8 (4): 671–82

    Article  PubMed  CAS  Google Scholar 

  14. Phelps C. Good technologies gone bad: how and why the cost-effectiveness of a medical intervention changes for different populations. Med Decis Making 1997; 17: 107–17

    Article  PubMed  CAS  Google Scholar 

  15. Sculpher MJ, Drummond MF, Buxton MJ. The iterative use of economic evaluation as part of the process of health technology assessment. J Health Serv Res Policy 1997; 2: 26–30

    PubMed  CAS  Google Scholar 

  16. Pang F. Multinational economic evaluations: a review of published studies, methodological issues and practice [abstract]. Value Health 1999; 2 (5): 380

    Google Scholar 

  17. Drummond MF. Comparing cost-effectiveness across countries: the model of acid-related disease. Pharmacoeconomics 1994; 5 Suppl. 3: 60–7

    Article  Google Scholar 

  18. Arikian SR, Einarson TR, Kobelt-Nguyen G, et al. A multinational pharmacoeconomic analysis of oral therapies for onychomycosis. Br J Dermatol 1994; 130 Suppl. 43: 35–44

    Article  PubMed  Google Scholar 

  19. Simpson K, Hatzaindreu EJ, Anderson F, et al. Cost effectiveness of antiviral treatment with zalcitabine plus zidovudine for AIDS patients with CD4+ counts less than 300/uL in 5 European countries. Pharmacoeconomics 1994; 6 (6): 553–62

    Article  PubMed  CAS  Google Scholar 

  20. Mark DB, Hlatky MA, Califf RM, et al. Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction. N Engl J Med 1995; 332 (21): 1418–24

    Article  PubMed  CAS  Google Scholar 

  21. Mark DB, Naylor D, Hlatky MA, et al. Use of medical resources and quality of life after acute myocardial infarction in Canada and the United States. N Engl J Med 1994; 331: 1130–5

    Article  PubMed  CAS  Google Scholar 

  22. Schulman KA, Buxton M, Glick H, et al. Results of the economic evaluation of the FIRST study: a multinational prospective economic evaluation. Int J Technol Assess Health Care 1996; 12 (4): 698–713

    Article  PubMed  CAS  Google Scholar 

  23. Jonsson B, Johannesson M, Kjekshus J, et al. Cost-effectiveness of cholesterol lowering: results from the Scandinavian Simvastatin Survival Study (4S). Eur Heart J 1996; 17: 1001–7

    Article  PubMed  CAS  Google Scholar 

  24. Menzin J, Oster G, Davies L, et al. A multinational economic evaluation of rhDNase in the treatment of cystic fibrosis. Int J Technol Assess Health Care 1996; 12: 52–61

    Article  PubMed  CAS  Google Scholar 

  25. Jonsson B, Weinstein MC. Economic evaluation alongside multinational clinical trials: study considerations for GUSTO IIb. Int J Technol Assess Health Care 1997; 13 (1): 49–58

    Article  PubMed  CAS  Google Scholar 

  26. Janssen B, Capri S, Nuijten MJC, et al. Economic evaluation of meloxicam (7.5 mg) versus sustained release diclofenac (100mg) treatment for osteoarthritis: a cross-national assessment for France, Italy and the UK. Br J Med Econ 1997; 11: 9–22

    Google Scholar 

  27. Glick H, Willke R, Polsky D, et al. Economic analysis of tirilazad mesylate for aneurysmal subarachnoid hemorrhage. Int J Technol Assess Health Care 1998; 14 (1): 145–60

    Article  PubMed  CAS  Google Scholar 

  28. Glick H, Polsky D, Willke R, et al. Comparison of the use of medical resources and outcomes in the treatment of aneurismal subarachnoid hemorrhage between Canada and the United States. Stroke 1998; 29: 351–8

    Article  PubMed  CAS  Google Scholar 

  29. Rutten-van Molken M, Van Doorslaer EKA, Till MD. Cost-effectiveness analysis of formoterol versus salmeterol in patients with asthma. Pharmacoeconomics 1998; 14 (6): 671–84

    Article  PubMed  CAS  Google Scholar 

  30. Caro JJ, Huybrechts KF, Duchesne I. Management patterns and costs of acute ischemic stroke: an international study. Stroke 2000; 31: 582–90

    Article  PubMed  CAS  Google Scholar 

  31. Coyle D, Lee KM. The problem of protocol driven costs in pharmacoeconomic analysis. Pharmacoeconomics 1998; 14 (4): 357–63

    Article  PubMed  CAS  Google Scholar 

  32. Rice N, Jones A. Multilevel models and health economics. Health Econ 1997; 6: 561–75

    Article  PubMed  CAS  Google Scholar 

  33. Pang F. The application of multilevel modelling and cluster analysis to multinational economic data [abstract]. Value Health 1999; 2 (3): 219

    Article  Google Scholar 

  34. Van de Werf F, Topol EJ, Lee KL, et al. Variations in patient management and outcomes for acute myocardial infarction in the United States and other countries: results from the GUSTO trial. JAMA 1995; 273: 1586–91

    Article  PubMed  Google Scholar 

  35. Willke RJ, Glick HA, Polsky D, et al. Estimating country-specific cost-effectiveness from multinational clinical trials. Health Econ 1998; 7: 481–93

    Article  PubMed  CAS  Google Scholar 

  36. Ellwein LB, Drummond MF. Economic analysis alongside clinical trials: bias in the assessment of economic outcomes. Int J Technol Assess Health Care 1996; 12: 691–7

    Article  PubMed  CAS  Google Scholar 

  37. Johnston K, Gerard K, Brown J. Generalising costs from the breast screening frequency and age trials. Uxbridge: Brunel University; 1997. Health Economics Research Group Discussion paper no. 19

    Google Scholar 

  38. Cook J, Drummond MF, Glick H, et al. Analyzing economic data from multinational clinical trials. Issues and recommendations. Paper presented at the Health Economists Study group meeting; York, 9–11 Jul 1997, York

    Google Scholar 

  39. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 334: 1383–9

    Google Scholar 

  40. Schulman KA, Glick H, Buxton M, et al. The economic evaluation of the FIRST study: design of a prospective analysis alongside a mutinational phase III clinical trial. Control Clin Trials 1996; 17: 304–15

    Article  PubMed  CAS  Google Scholar 

  41. Raikou M, Briggs A, Gray A, et al. Centre-specific or average unit costs in multi-centre studies? Some theory and simulation. Health Econ 2000; 9: 191–8

    Article  PubMed  CAS  Google Scholar 

  42. Schulman K, Burke J, Drummond M, et al. Resource costing for multinational neurological clinical trials: methods and results. Health Econ 1998; 7: 629–38

    Article  PubMed  CAS  Google Scholar 

  43. Organisation for Economic Cooperation and Development. Purchasing Power Parities. Paris: OECD, 1993

    Google Scholar 

  44. Donaldson C, Birch S, Gafni A. The ‘distribution problem’ in economic evaluation: income considerations in the valuation of costs and consequences of health care programmes. CHEPA Working Paper no. 98-10. Hamilton (ON): Centre for Health Economics and Policy Analysis, 1998

    Google Scholar 

  45. National Institute for Clinical Excellence. Revised guidelines for manufacturers and sponsors of technologies making submissions to the institute [online]. Available from URL: http://www.nice.org.uk/ [Accessed 2001 Sep]

    Google Scholar 

  46. Kassell NF, Haley C, Apperson-Hansen C, et al. Randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in Europe, Australia, and New Zealand. J Neurosurg 1996; 84: 221–8

    Article  PubMed  CAS  Google Scholar 

  47. Briggs AH, Hoch JS, Willan AR. Something old, something new, something borrowed, something BLUE: a framework for the marriage of health econometrics and cost-effectiveness analysis. Paper presented at the Health Economists Study Group meeting; Oxford, 3–5 Jan 2001

    Google Scholar 

  48. Ikeda S, Ikegami N, Oliver AJ, et al. A case for the adoption of pharmacoeconomic guidelines in Japan. Pharmacoeconomics 1996; 10: 546–51

    Article  PubMed  CAS  Google Scholar 

  49. Drummond M, Dubois D, Garattini L, et al. Current trends in the use of pharmacoeconomics and outcomes research in Europe. Value Health 1999; 2 (5): 323–32

    Article  PubMed  CAS  Google Scholar 

  50. Genduso LA, Kotsanos JG. Review of health economic guidelines in the form of regulations, principles, policies and positions. Drug Inf J 1996; 30: 1003–16

    Article  Google Scholar 

  51. Cochrane Economics Methods Group. Paper presented at the Health Economists Study Group meeting, 1999. Aberdeen, 14–16 Jul

    Google Scholar 

  52. Murray CJL, Evans DB, Acharya A, et al. Development of WHO guidelines on generalized cost-effectiveness analysis. Health Econ 2000; 9: 235–51

    Article  PubMed  CAS  Google Scholar 

  53. NHS R&D Health Technology Assessment Programme. The stability of cost-effectiveness analysis. Call for proposal. Southampton: NHS R&D Health Technology Assessment, 1999 Apr. SGHT no.98/22

    Google Scholar 

  54. Krahn M, Gafni A. Discounting in the economic evaluation of health care interventions. Med Care 1993; 31 (5): 403–18

    Article  PubMed  CAS  Google Scholar 

  55. Commonwealth Department of Health, Housing and Community Services. Guidelines for the pharmaceutical industry on preparation of submissions to the pharmaceutical benefits advisory committee: including major submissions involving economic analysis. Canberra: Australian Government Publishing Service of Australia, 1995

    Google Scholar 

  56. Canadian Co-ordinating Office for Health Technology Assessment (CCOHTA). Guidelines for economic evaluation of pharmaceuticals 2nd ed. Ottawa (ON): CCOHTA, 1997

    Google Scholar 

  57. Ziekenfondsraad — National Insurance Council. Pharmacoeconomic research guideline. The Netherlands: Ziekenfondsraad, 1999

  58. Danish Ministry of Health. Guidelines for the drawing up of economic analyses of medicines in Denmark. Copenhagen: Ministry of Health, 1998

    Google Scholar 

  59. Levy E, on behalf of Expert Committee of the College des Economistes de la Sante. La letter du collage. Guidelines and recommendations for French pharmaco-economic studies. Paris: College des Economistes de la Sante, 1996

    Google Scholar 

  60. Pharmaceutical Research and Manufacturers of America (PhRMA). Methodological and conduct principles for pharmacoeconomic research. Washington, D.C.: PhRMA, 1995

    Google Scholar 

  61. Task Force on Principles for Economic Analysis of Health Care Technology. Economic analysis of health care technology. Ann Intern Med 1995; 123: 61–70

    Google Scholar 

  62. Division of Drug Marketing, Advertising and Communications, Food and Drug Adminstration. Principles for the review of pharmacoeconomic promotion. Washington, D.C.: Food and Drug Administration, 1995

    Google Scholar 

  63. Consensus Conference on Guidelines on Economic Modelling in Health Technology Assessment: consensus statement and background papers. Pharmacoeconomics 2000; 17 (5): 443–51

    Google Scholar 

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Acknowledgements

The author is grateful for comments received on an earlier draft from two anonymous referees and for research direction from M Drummond, K Claxton, T Hitiris, L Davies, K Tolley, S Duttagupta and N Wells. An earlier version of this paper was presented at the 2nd ISPOR European Meeting, Edinburgh 1999. The author was previously a recipient of an educational fellowship grant from Pfizer for research into multinational economic evaluations.

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Pang, F. Design, Analysis and Presentation of Multinational Economic Studies. Pharmacoeconomics 20, 75–90 (2002). https://doi.org/10.2165/00019053-200220020-00001

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