Are pharmaceuticals cost-effective? A review of the evidence

Health Affairs

Volumn 19, Issue 2, 2000, Pages 92-109

  Neumann, Peter J ^a   Sandberg, Eileen A ^a   Bell, Chaim M ^a   Stone, Patricia W ^a   Chapman, Richard H ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

COST BENEFIT ANALYSIS; DRUG COST; DRUG INDUSTRY; ECONOMICS; EPIDEMIOLOGY; FACTUAL DATABASE; FINANCIAL MANAGEMENT; HUMAN; INSURANCE; MEDICARE; ORGANIZATION AND MANAGEMENT; PRESCRIPTION; REVIEW; STATISTICS; UNITED STATES;

BIAS (EPIDEMIOLOGY); COST-BENEFIT ANALYSIS; DATABASES, FACTUAL; DRUG COSTS; DRUG INDUSTRY; HUMANS; INSURANCE COVERAGE; MEDICARE; PRESCRIPTIONS, DRUG; PRESCRIPTIONS, NON-DRUG; RESEARCH SUPPORT; UNITED STATES;

EID: 0010178771     PISSN: 02782715     EISSN: None     Source Type: Journal    
DOI: 10.1377/hlthaff.19.2.92     Document Type: Article

References (105)

1. Pharmaceutical Research and Manufacturers of America, 1998 Industry Profile (Washington: PhRMA, 1998), 36-41; and PhRMA, 1999 Industry Profile (Washington: PhRMA, 1999), 42-47.
2. Pharmaceutical Research and Manufacturers of America, 1998 Industry Profile (Washington: PhRMA, 1998), 36-41; and PhRMA, 1999 Industry Profile (Washington: PhRMA, 1999), 42-47.
3. A.F. Holmer, "Another Prescription Plan" (Letter to the editor), Boston Globe, 11 February 1999, A26; and A.F. Holmer, "Covering Prescription Drugs under Medicare: For the Good of the Patient," Health Affairs (Jul/Aug 1999): 23-24.
4. A.F. Holmer, "Another Prescription Plan" (Letter to the editor), Boston Globe, 11 February 1999, A26; and A.F. Holmer, "Covering Prescription Drugs under Medicare: For the Good of the Patient," Health Affairs (Jul/Aug 1999): 23-24.
5. R. Pear, "Clinton Will Seek a Medicare Change on Drug Coverage," New York Times, 8 June 1999, Al; and B. Ross, "Drugs for the Elderly Can Save, Not Sink Medicare," USA Today, 11 January 1999, 15A.
6. R. Pear, "Clinton Will Seek a Medicare Change on Drug Coverage," New York Times, 8 June 1999, Al; and B. Ross, "Drugs for the Elderly Can Save, Not Sink Medicare," USA Today, 11 January 1999, 15A.
7. S.B. Soumerai and D. Ross-Degnan, "Inadequate Prescription-Drug Coverage for Medicare Enrollees - A Call to Action," New England Journal of Medicine 340, no. 9 (1999): 722-728; and S.B. Soumerai et al., "Effects of Medicaid Drug-Payment Limits on Admission to Hospitals and Nursing Homes," New England Journal of Medidne 325, no. 15 (1991): 1072-1077.
8. S.B. Soumerai and D. Ross-Degnan, "Inadequate Prescription-Drug Coverage for Medicare Enrollees - A Call to Action," New England Journal of Medicine 340, no. 9 (1999): 722-728; and S.B. Soumerai et al., "Effects of Medicaid Drug-Payment Limits on Admission to Hospitals and Nursing Homes," New England Journal of Medidne 325, no. 15 (1991): 1072-1077.
9. A. Elixhauser et al., "Health Care CBA/CEA: An Update on the Growth and Composition of the Literature," Medical Care 31, no. 7 suppl. (1993): JS1-JS138; and A. Elixhauser et al., "Health Care CBA and CEA from 1991 to 1996: An Updated Bibliography," Medical Care 36, no. 5 suppl. (1998): MS1-9, MS18-14.
10. A. Elixhauser et al., "Health Care CBA/CEA: An Update on the Growth and Composition of the Literature," Medical Care 31, no. 7 suppl. (1993): JS1-JS138; and A. Elixhauser et al., "Health Care CBA and CEA from 1991 to 1996: An Updated Bibliography," Medical Care 36, no. 5 suppl. (1998): MS1-9, MS18-14.
11. M.C. Weinstein et al. for the Panel on Cost-Effectiveness in Health and Medicine, "Recommendations of the Panel on Cost-Effectiveness in Health and Medicine," Journal of the American Medical Association 276, no. 15 (1996): 1253-1258; and M.F. Drummond et al., Methods for the Economic Evaluation of Health Care Programmes (Oxford: Oxford University Press, 1997). Other analytic approaches are cost-consequence analysis (which involves estimating and listing separately the net costs and health consequences of competing interventions) and cost-benefit analysis (in which all costs and benefits are measured and compared in dollar terms). An appeal of CEA is that unlike cost-benefit analysis, it avoids the requirement for the monetary valuation of health benefits, which raises measurement difficulties and often political objections.
12. M.C. Weinstein et al. for the Panel on Cost-Effectiveness in Health and Medicine, "Recommendations of the Panel on Cost-Effectiveness in Health and Medicine," Journal of the American Medical Association 276, no. 15 (1996): 1253-1258; and M.F. Drummond et al., Methods for the Economic Evaluation of Health Care Programmes (Oxford: Oxford University Press, 1997). Other analytic approaches are cost-consequence analysis (which involves estimating and listing separately the net costs and health consequences of competing interventions) and cost-benefit analysis (in which all costs and benefits are measured and compared in dollar terms). An appeal of CEA is that unlike cost-benefit analysis, it avoids the requirement for the monetary valuation of health benefits, which raises measurement difficulties and often political objections.
13. M.R. Gold et al., Cost-Effectiveness in Health and Medicine (Oxford: Oxford University Press, 1996).
14. Note that many cost-effectiveness analysts have expressed health benefits in terms of intermediate outcomes specific to the treatment and disease under investigation or in terms of life-years gained. See T.O. Tengs et al., "Five-Hundred life-Saving Interventions and Their Cost-Effectiveness," Risk Analysis 15, no. 3 (1995): 369-390. For example, a researcher studying alternative strategies to prevent cancer might evaluate and compare each strategy according to the costs incurred per cancer case prevented. The approach is advantageous in that it focuses narrowly on the clinical problem and is familiar to the clinicians who treat the disease, but it does not permit comparisons of treatments for cancer with interventions for other conditions.
15. Drummond et al., Methods for the Economic Evaluation, 139-204.
16. P.J. Neumann et al., "A Formal Audit of 228 Published Cost-Utility Analyses" (Working paper, Harvard School of Public Health, 1999).
17. Elixhauser et al., "Health Care CBA/CEA"; and Elixhauser et al., "Health Care CBA and CEA from 1991 to 1996."
18. Elixhauser et al., "Health Care CBA/CEA"; and Elixhauser et al., "Health Care CBA and CEA from 1991 to 1996."
19. R.H. Chapman et al., "A Comprehensive League Table of Cost-Utility Ratios and a Sub-Table of 'Panel-Worthy' Ratios," Medical Decision Making 19, no. 4 (1999): 521 (abstract).
20. J. Kassirer and M. Angell, "The Journal's Policy on Cost-Effective Analyses," New England Journal of Medicine 331, no. 10 (1994): 669-670; R. Evans, "Manufacturing Consensus, Marketing Truth: Guidelines for Economic Evaluation," Annals of Internal Medicine 123, no. 1 (1995): 59-60; and M. Friedberg et al., "Evaluation of Conflict of Interest in Economic Analyses of New Drugs Used in Oncology," Journal of the American Medical Association 282, no. 15 (1999): 1453-1457.
21. J. Kassirer and M. Angell, "The Journal's Policy on Cost-Effective Analyses," New England Journal of Medicine 331, no. 10 (1994): 669-670; R. Evans, "Manufacturing Consensus, Marketing Truth: Guidelines for Economic Evaluation," Annals of Internal Medicine 123, no. 1 (1995): 59-60; and M. Friedberg et al., "Evaluation of Conflict of Interest in Economic Analyses of New Drugs Used in Oncology," Journal of the American Medical Association 282, no. 15 (1999): 1453-1457.
22. J. Kassirer and M. Angell, "The Journal's Policy on Cost-Effective Analyses," New England Journal of Medicine 331, no. 10 (1994): 669-670; R. Evans, "Manufacturing Consensus, Marketing Truth: Guidelines for Economic Evaluation," Annals of Internal Medicine 123, no. 1 (1995): 59-60; and M. Friedberg et al., "Evaluation of Conflict of Interest in Economic Analyses of New Drugs Used in Oncology," Journal of the American Medical Association 282, no. 15 (1999): 1453-1457.
23. The calculation of medians includes cost-saving interventions that also produce gains in QALYs.
24. J.E. Paul, J.A. Mauskopf, and L. Bell, "Cost-Consequence Models for Varicella-Zoster Virus Infections" (Part 2), Pharmacotherapy 15, no. 5 (1995): 49S-58S; J. Tsevat, D. Duke, and L. Goldman, "Cost-Effectiveness of Captopril Therapy after Myocardial Infarction," Journal of the American College of Cardiology 26, no. 4 (1995): 914-919; and A.S. Zbrozek, S.B. Cantor, and M.P. Cardenas, "Pharmacoeconomic Analysis of Ondansetron versus Metoclopramide for Cisplatin-Induced Nausea and Vomiting," American Journal of Hospital Pharmacy 51, no. 12 (1994): 1555-1563.
25. J.E. Paul, J.A. Mauskopf, and L. Bell, "Cost-Consequence Models for Varicella-Zoster Virus Infections" (Part 2), Pharmacotherapy 15, no. 5 (1995): 49S-58S; J. Tsevat, D. Duke, and L. Goldman, "Cost-Effectiveness of Captopril Therapy after Myocardial Infarction," Journal of the American College of Cardiology 26, no. 4 (1995): 914-919; and A.S. Zbrozek, S.B. Cantor, and M.P. Cardenas, "Pharmacoeconomic Analysis of Ondansetron versus Metoclopramide for Cisplatin-Induced Nausea and Vomiting," American Journal of Hospital Pharmacy 51, no. 12 (1994): 1555-1563.
26. J.E. Paul, J.A. Mauskopf, and L. Bell, "Cost-Consequence Models for Varicella-Zoster Virus Infections" (Part 2), Pharmacotherapy 15, no. 5 (1995): 49S-58S; J. Tsevat, D. Duke, and L. Goldman, "Cost-Effectiveness of Captopril Therapy after Myocardial Infarction," Journal of the American College of Cardiology 26, no. 4 (1995): 914-919; and A.S. Zbrozek, S.B. Cantor, and M.P. Cardenas, "Pharmacoeconomic Analysis of Ondansetron versus Metoclopramide for Cisplatin-Induced Nausea and Vomiting," American Journal of Hospital Pharmacy 51, no. 12 (1994): 1555-1563.
27. Of the subset of studies dealing with pharmaceutical interventions, the median cost-utility ratios were $5,900 for industry-sponsored analyses and $12,000 for non-industry-sponsored analyses (p = .11)
28. P. Doubilet, M.C. Weinstein, and B.J. McNeil, "Use and Misuse of the Term 'Cost-Effectiveness' in Medicine," New England Journal of Medicine 314, no. 4 (1986): 253-256.
29. B.F. Gage, A.B. Cardinalli, and G.W. Albers, "Cost-Effectiveness of Warfarin and Aspirin for Prophylaxis of Stroke in Patients with Non Valvular Atrial Fibrillation," Journal of the American Medical Association 274, no. 23 (1995): 1839-1845; T. Schneider, F. Fagnani, and J.L Lanoe, "Economic Analysis of an Immunosuppressive Strategy in Renal Transplantation," Health Policy 9, no. 1 (1988): 75-89; and M.S. Kamlet, N. Paul, and J. Greenhouse, "Cost Utility Analysis of Maintenance Treatment for Recurrent Depression," Controlled Clinical Trials 16, no. 1 (1995): 17-40.
30. B.F. Gage, A.B. Cardinalli, and G.W. Albers, "Cost-Effectiveness of Warfarin and Aspirin for Prophylaxis of Stroke in Patients with Non Valvular Atrial Fibrillation," Journal of the American Medical Association 274, no. 23 (1995): 1839-1845; T. Schneider, F. Fagnani, and J.L Lanoe, "Economic Analysis of an Immunosuppressive Strategy in Renal Transplantation," Health Policy 9, no. 1 (1988): 75-89; and M.S. Kamlet, N. Paul, and J. Greenhouse, "Cost Utility Analysis of Maintenance Treatment for Recurrent Depression," Controlled Clinical Trials 16, no. 1 (1995): 17-40.
31. B.F. Gage, A.B. Cardinalli, and G.W. Albers, "Cost-Effectiveness of Warfarin and Aspirin for Prophylaxis of Stroke in Patients with Non Valvular Atrial Fibrillation," Journal of the American Medical Association 274, no. 23 (1995): 1839-1845; T. Schneider, F. Fagnani, and J.L Lanoe, "Economic Analysis of an Immunosuppressive Strategy in Renal Transplantation," Health Policy 9, no. 1 (1988): 75-89; and M.S. Kamlet, N. Paul, and J. Greenhouse, "Cost Utility Analysis of Maintenance Treatment for Recurrent Depression," Controlled Clinical Trials 16, no. 1 (1995): 17-40.
32. In our database, for example, seventy-eight (34 percent) of the 228 articles mention an explicit dollar threshold for this value, with a median amount of $50,000. Note, though, that this threshold has no solid analytic foundation. So-called value-of-life studies in the United States have estimated revealed preferences on the order of $100,000 to $500,000 per life year saved, with no quality adjustment. See K.P. Viscusi, Fatal Trade-offs (New York: Oxford University Press, 1992).
33. Doubilet et al., "Use and Misuse of the Term 'Cost-Effectiveness' in Medicine."
34. Cost-effective might also include situations in which a strategy is less costly and less effective, as long as society is willing to trade off the loss in health outcomes for dollar savings.
35. L Goldman et al., "Cost-Effectiveness of HMG-CoA Reductase Inhibition for Primary and Secondary Prevention of Coronary Heart Disease," Journal of the American Medical Association 265, no. 9 (1991): 1145-1151.
36. Soumerai et al., "Effects of Medicaid Drug-Payment Limits."
37. Statement of Dan L. Crippen, director, Congressional Budget Office, on the president's proposal for Medicare reform, before the Senate Committee on Finance, 22 July 1999. In estimating the cost of the Clinton proposal, the CBO noted that projections for the rate of growth in drug use and prices is highly uncertain. On the one hand, new breakthrough drugs would tend to increase both the use and the average price of prescription drugs in the future. On the other hand, a number of heavily used brand-name drugs are about to lose their patent protection, which would allow entry of generic substitutes and drive prices down somewhat. The CBO also emphasizes that another area of uncertainty is the extent to which the new coverage would actually increase enrollees' use of drugs, given the fact that half of them already have drug coverage and that the proposed benefit has a cap.
38. P.J. Neumann and M.C. Weinstein, "Diffusion of New Technology: Costs and Benefits to Health Care," in The Changing Economics of Technological Innovation in Medicine, ed. A.C. Gelijns and E.A. Halm (Washington: National Academy Press, 1991), 21-34.
39. J.A. Poisal et al., "Prescription Drug Coverage and Spending for Medicare Beneficiaries," Health Care Financing Review (Spring 1999): 18-28.
40. Milton Weinstein, professor of health policy and management, Harvard School of Public Health, personal communication, September 1999.
41. P.J. Neumann, "Paying the Piper for Pharmacoeconomic Studies," Medical Decision Making (Supplement 1998): S23-S26.
42. Kassirer and Angell, "The Journal's Policy on Cost-Effective Analyses"; and R. Evans, "Manufacturing Consensus, Marketing Truth."
43. Kassirer and Angell, "The Journal's Policy on Cost-Effective Analyses"; and R. Evans, "Manufacturing Consensus, Marketing Truth."
44. Kassirer and Angell, "The Journal's Policy on Cost-Effective Analyses." Note that the policy stipulates that the journal will publish industry-funded CEAs if the research is in the form of a grant to a not-for-profit entity.
45. M.F. Drummond et al, "Guidelines for Authors and Peer Reviewers of Economic Submissions to BMJ," British Medical Journal 313, 7052 (1996): 275-283; A. Elstein, "MDM Policy Regarding Financial Support of Authors," Medical Decision Making 17, no. 4 (1997): 497-498; and Neumann, "Paying the Piper."
46. M.F. Drummond et al, "Guidelines for Authors and Peer Reviewers of Economic Submissions to BMJ," British Medical Journal 313, 7052 (1996): 275-283; A. Elstein, "MDM Policy Regarding Financial Support of Authors," Medical Decision Making 17, no. 4 (1997): 497-498; and Neumann, "Paying the Piper."
47. M.F. Drummond et al, "Guidelines for Authors and Peer Reviewers of Economic Submissions to BMJ," British Medical Journal 313, 7052 (1996): 275-283; A. Elstein, "MDM Policy Regarding Financial Support of Authors," Medical Decision Making 17, no. 4 (1997): 497-498; and Neumann, "Paying the Piper."
48. ,0,0,0Note that the difference in the means of the cost-effectiveness ratios funded by industry and nonindustry sources also is statistically significant and is heavily influenced by a few non-industry-funded studies with extremely high cost- effectiveness ratios (for example, exceeding $50 million per QALY).
49. R. King, "Bitter Pill: How a Drug Company Paid for University Study, Then Undermined It," Wall Street Journal, 25 April 1996, 1; and D. Rennie, "Thyroid Storm" (Editorial), Journal of the American Medical Association 277, no. 15 (1997): 1238-1243.
50. R. King, "Bitter Pill: How a Drug Company Paid for University Study, Then Undermined It," Wall Street Journal, 25 April 1996, 1; and D. Rennie, "Thyroid Storm" (Editorial), Journal of the American Medical Association 277, no. 15 (1997): 1238-1243.
51. M.L. Brown and L. Fintor, "Cost-Effectiveness of Breast Cancer Screening: Preliminary Results of a Systematic Review of the Literature," Breast Cancer Research and Treatment 25, no. 2 (1993): 113-118.
52. C.B. Begg, "Publication Bias," in The Handbook of Research Synthesis, ed. H. Cooper and L.V. Hedges (New York: Russell Sage Foundation, 1994); and N. Freemantle and J. Mason, "Publication Bias in Clinical Trials and Economic Analyses," Pharmacoeconomics 12, no. 1 (1997): 10-16.
53. C.B. Begg, "Publication Bias," in The Handbook of Research Synthesis, ed. H. Cooper and L.V. Hedges (New York: Russell Sage Foundation, 1994); and N. Freemantle and J. Mason, "Publication Bias in Clinical Trials and Economic Analyses," Pharmacoeconomics 12, no. 1 (1997): 10-16.
54. D. Blumenthal et al., "University-Industry Research Relationships in Biotechnology: Implications for the University" Science 232, no. 4756 (1986): 1361-1366; R.P. Schwarz, "Maintaining Integrity and Credibility in Industry-Sponsored Research," Controlled Clinical Trials 12, no. 6 (1991): 753-760; D.F. Thompson, "Understanding Financial Conflicts of Interest," New England Journal of Medicine 329, no. 8 (1993): 573-576; T. Lemmens and P.A. Singer, "Bioethics for Clinicians: 17. Conflict of Interest in Research, Education, and Patient Care," Canadian Medical Association Journal 159, no. 8 (1998): 960-965; and S. Krimsky and L.S. Rothenberg, "Financial Interest and Its Disclosure in Scientific Publications," Journal of the American Medical Association 280, no. 3 (1998): 225-226.
55. D. Blumenthal et al., "University-Industry Research Relationships in Biotechnology: Implications for the University" Science 232, no. 4756 (1986): 1361-1366; R.P. Schwarz, "Maintaining Integrity and Credibility in Industry-Sponsored Research," Controlled Clinical Trials 12, no. 6 (1991): 753-760; D.F. Thompson, "Understanding Financial Conflicts of Interest," New England Journal of Medicine 329, no. 8 (1993): 573-576; T. Lemmens and P.A. Singer, "Bioethics for Clinicians: 17. Conflict of Interest in Research, Education, and Patient Care," Canadian Medical Association Journal 159, no. 8 (1998): 960-965; and S. Krimsky and L.S. Rothenberg, "Financial Interest and Its Disclosure in Scientific Publications," Journal of the American Medical Association 280, no. 3 (1998): 225-226.
56. D. Blumenthal et al., "University-Industry Research Relationships in Biotechnology: Implications for the University" Science 232, no. 4756 (1986): 1361-1366; R.P. Schwarz, "Maintaining Integrity and Credibility in Industry-Sponsored Research," Controlled Clinical Trials 12, no. 6 (1991): 753-760; D.F. Thompson, "Understanding Financial Conflicts of Interest," New England Journal of Medicine 329, no. 8 (1993): 573-576; T. Lemmens and P.A. Singer, "Bioethics for Clinicians: 17. Conflict of Interest in Research, Education, and Patient Care," Canadian Medical Association Journal 159, no. 8 (1998): 960-965; and S. Krimsky and L.S. Rothenberg, "Financial Interest and Its Disclosure in Scientific Publications," Journal of the American Medical Association 280, no. 3 (1998): 225-226.
57. D. Blumenthal et al., "University-Industry Research Relationships in Biotechnology: Implications for the University" Science 232, no. 4756 (1986): 1361-1366; R.P. Schwarz, "Maintaining Integrity and Credibility in Industry-Sponsored Research," Controlled Clinical Trials 12, no. 6 (1991): 753-760; D.F. Thompson, "Understanding Financial Conflicts of Interest," New England Journal of Medicine 329, no. 8 (1993): 573-576; T. Lemmens and P.A. Singer, "Bioethics for Clinicians: 17. Conflict of Interest in Research, Education, and Patient Care," Canadian Medical Association Journal 159, no. 8 (1998): 960-965; and S. Krimsky and L.S. Rothenberg, "Financial Interest and Its Disclosure in Scientific Publications," Journal of the American Medical Association 280, no. 3 (1998): 225-226.
58. D. Blumenthal et al., "University-Industry Research Relationships in Biotechnology: Implications for the University" Science 232, no. 4756 (1986): 1361-1366; R.P. Schwarz, "Maintaining Integrity and Credibility in Industry-Sponsored Research," Controlled Clinical Trials 12, no. 6 (1991): 753-760; D.F. Thompson, "Understanding Financial Conflicts of Interest," New England Journal of Medicine 329, no. 8 (1993): 573-576; T. Lemmens and P.A. Singer, "Bioethics for Clinicians: 17. Conflict of Interest in Research, Education, and Patient Care," Canadian Medical Association Journal 159, no. 8 (1998): 960-965; and S. Krimsky and L.S. Rothenberg, "Financial Interest and Its Disclosure in Scientific Publications," Journal of the American Medical Association 280, no. 3 (1998): 225-226.
59. P.A. Rochon et al., "A Study of Manufacturer-Supported Trials of Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Arthritis," Archives of Internal Medicine 154, no. 2 (1994): 157-163; R. Koepp and S.H. Miles, "Meta-Analysis of Tacrine for Alzheimer Disease: The Influence of Industry Sponsors," Journal of the American Medical Association 281, no. 24 (1999): 2287-2288; and H.T. Stelfox et al., "Conflict of Interest in the Debate over Calcium-Channel Antagonists," New England Journal of Medicine 338, no. 2 (1998): 101-106.
60. P.A. Rochon et al., "A Study of Manufacturer-Supported Trials of Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Arthritis," Archives of Internal Medicine 154, no. 2 (1994): 157-163; R. Koepp and S.H. Miles, "Meta-Analysis of Tacrine for Alzheimer Disease: The Influence of Industry Sponsors," Journal of the American Medical Association 281, no. 24 (1999): 2287-2288; and H.T. Stelfox et al., "Conflict of Interest in the Debate over Calcium-Channel Antagonists," New England Journal of Medicine 338, no. 2 (1998): 101-106.
61. P.A. Rochon et al., "A Study of Manufacturer-Supported Trials of Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Arthritis," Archives of Internal Medicine 154, no. 2 (1994): 157-163; R. Koepp and S.H. Miles, "Meta-Analysis of Tacrine for Alzheimer Disease: The Influence of Industry Sponsors," Journal of the American Medical Association 281, no. 24 (1999): 2287-2288; and H.T. Stelfox et al., "Conflict of Interest in the Debate over Calcium-Channel Antagonists," New England Journal of Medicine 338, no. 2 (1998): 101-106.
62. Friedberg et al., "Evaluation of Conflict of Interest."
63. Only 23 percent of the ratios in our database were above $50,000 per QALY, for example, and only 13 percent were over $100,000 per QALY. But of the seventy-six ratios above $100,000, only 4 percent were industry sponsored.
64. A follow-up investigation of the articles that did not disclose the funding source revealed that few of these were funded by the pharmaceutical industry. Of the seventy-eight articles, twenty-four (31 percent) were self-financed, twelve (15 percent) were government funded, seven (9 percent) were funded by a foundation, and only three (4 percent) were funded by a pharmaceutical company. In thirty-six cases (46 percent), the authors did not respond to our inquiry. (Note that some articles have more than one source of funding.)
65. See, for example, J. Lax and E. Moench, "Phaimacoeconomics and Managed Care: Understanding the Issues, Concerns, and the Environment"; W. Zellmer, "Comments of the American Society of Health-System Pharmacists" (Presentations at the Food and Drug Administration hearing, "Pharmaceutical Marketing and Information Exchange in Managed Care Environments," Silver Spring, Maryland, 19 October 1995); and F.A. Sloan, K. Whetten-Goldstein, and A. Wilson, "Hospital Pharmacy Decisions, Cost-Containment, and the Use of Cost-Effectiveness Analysis," Social Science and Medicine 45, no. 4 (1997): 525-533.
66. See, for example, J. Lax and E. Moench, "Phaimacoeconomics and Managed Care: Understanding the Issues, Concerns, and the Environment"; W. Zellmer, "Comments of the American Society of Health-System Pharmacists" (Presentations at the Food and Drug Administration hearing, "Pharmaceutical Marketing and Information Exchange in Managed Care Environments," Silver Spring, Maryland, 19 October 1995); and F.A. Sloan, K. Whetten-Goldstein, and A. Wilson, "Hospital Pharmacy Decisions, Cost-Containment, and the Use of Cost-Effectiveness Analysis," Social Science and Medicine 45, no. 4 (1997): 525-533.
67. See, for example, J. Lax and E. Moench, "Phaimacoeconomics and Managed Care: Understanding the Issues, Concerns, and the Environment"; W. Zellmer, "Comments of the American Society of Health-System Pharmacists" (Presentations at the Food and Drug Administration hearing, "Pharmaceutical Marketing and Information Exchange in Managed Care Environments," Silver Spring, Maryland, 19 October 1995); and F.A. Sloan, K. Whetten-Goldstein, and A. Wilson, "Hospital Pharmacy Decisions, Cost-Containment, and the Use of Cost-Effectiveness Analysis," Social Science and Medicine 45, no. 4 (1997): 525-533.
68. Neumann, "Paying the Piper."
69. Ibid.
70. G. Crosbie, The Health Economic Evaluations Database: Trends in Economic Evaluation, No. 36 (London: OHE-IFPMA Database Ltd., April 1998).
71. Ibid. See also Elixhauser et al., "Health Care CBA/CEA"; and Elixhauser et al., "Health Care CBA and CEA from 1991 to 1996."
72. Ibid. See also Elixhauser et al., "Health Care CBA/CEA"; and Elixhauser et al., "Health Care CBA and CEA from 1991 to 1996."
73. Ibid. See also Elixhauser et al., "Health Care CBA/CEA"; and Elixhauser et al., "Health Care CBA and CEA from 1991 to 1996."
74. S.C. Fagan et al., "Cost-Effectiveness of Tissue Plasminogen Activator for Acute Ischemic Stroke," Neurology 50, no. 4 (1998): 883-890; R.F. Legg et al., "Cost-Effectiveness of Sumatriptan in a Managed Care Population" American Journal of Managed Care 3, no. 1 (1997): 117-122; and R. Rosenheck et al., "A Comparison of Clozapine and Haloperidol in Hospitalized Patients with Refractory Schizophrenia," New England Journal of Medicine 337, no. 12 (1997): 809-815.
75. S.C. Fagan et al., "Cost-Effectiveness of Tissue Plasminogen Activator for Acute Ischemic Stroke," Neurology 50, no. 4 (1998): 883-890; R.F. Legg et al., "Cost-Effectiveness of Sumatriptan in a Managed Care Population" American Journal of Managed Care 3, no. 1 (1997): 117-122; and R. Rosenheck et al., "A Comparison of Clozapine and Haloperidol in Hospitalized Patients with Refractory Schizophrenia," New England Journal of Medicine 337, no. 12 (1997): 809-815.
76. S.C. Fagan et al., "Cost-Effectiveness of Tissue Plasminogen Activator for Acute Ischemic Stroke," Neurology 50, no. 4 (1998): 883-890; R.F. Legg et al., "Cost-Effectiveness of Sumatriptan in a Managed Care Population" American Journal of Managed Care 3, no. 1 (1997): 117-122; and R. Rosenheck et al., "A Comparison of Clozapine and Haloperidol in Hospitalized Patients with Refractory Schizophrenia," New England Journal of Medicine 337, no. 12 (1997): 809-815.
77. A. Mehrez and A. Gafni, "Quality Adjusted Life Years, Utility Theory, and Healthy-Years Equivalents," Medical Decision Making 9, no. 2 (1989): 142-149; A. Mehrez and A. Gafni, "Healthy-Years Equivalents versus Quality-Adjusted Life Years: In Pursuit of Progress," Medical Decision Making 13, no. 4 (1993): 287-292; E. Nord, "The Person Trade-Off Approach to Valuing Health Care Programs," Medical Decision Making 15, no. 3 (1995): 201-208; D. Cox et al., "Quality-of-Life Assessment: Can We Keep It Simple?" Journal of the Royal Statistical Society, Series A, 155, no. 3 (1992): 353-393; P.A. Ubel et al., "Individual Utilities Are Inconsistent with Rationing Choices: A Partial List of Why Oregon's Cost-Effectiveness List Failed," Medical Decision Making 16, no. 2 (1996): 108-116; and P.C. Langley, "Meeting the Information Needs of Drug Purchasers: The Evolution of Formulary Submission Guidelines," Clinical Therapeutics 21, no. 4 (1999): 768-787.
78. A. Mehrez and A. Gafni, "Quality Adjusted Life Years, Utility Theory, and Healthy-Years Equivalents," Medical Decision Making 9, no. 2 (1989): 142-149; A. Mehrez and A. Gafni, "Healthy-Years Equivalents versus Quality-Adjusted Life Years: In Pursuit of Progress," Medical Decision Making 13, no. 4 (1993): 287-292; E. Nord, "The Person Trade-Off Approach to Valuing Health Care Programs," Medical Decision Making 15, no. 3 (1995): 201-208; D. Cox et al., "Quality-of-Life Assessment: Can We Keep It Simple?" Journal of the Royal Statistical Society, Series A, 155, no. 3 (1992): 353-393; P.A. Ubel et al., "Individual Utilities Are Inconsistent with Rationing Choices: A Partial List of Why Oregon's Cost-Effectiveness List Failed," Medical Decision Making 16, no. 2 (1996): 108-116; and P.C. Langley, "Meeting the Information Needs of Drug Purchasers: The Evolution of Formulary Submission Guidelines," Clinical Therapeutics 21, no. 4 (1999): 768-787.
79. A. Mehrez and A. Gafni, "Quality Adjusted Life Years, Utility Theory, and Healthy-Years Equivalents," Medical Decision Making 9, no. 2 (1989): 142-149; A. Mehrez and A. Gafni, "Healthy-Years Equivalents versus Quality-Adjusted Life Years: In Pursuit of Progress," Medical Decision Making 13, no. 4 (1993): 287-292; E. Nord, "The Person Trade-Off Approach to Valuing Health Care Programs," Medical Decision Making 15, no. 3 (1995): 201-208; D. Cox et al., "Quality-of-Life Assessment: Can We Keep It Simple?" Journal of the Royal Statistical Society, Series A, 155, no. 3 (1992): 353-393; P.A. Ubel et al., "Individual Utilities Are Inconsistent with Rationing Choices: A Partial List of Why Oregon's Cost-Effectiveness List Failed," Medical Decision Making 16, no. 2 (1996): 108-116; and P.C. Langley, "Meeting the Information Needs of Drug Purchasers: The Evolution of Formulary Submission Guidelines," Clinical Therapeutics 21, no. 4 (1999): 768-787.
80. A. Mehrez and A. Gafni, "Quality Adjusted Life Years, Utility Theory, and Healthy-Years Equivalents," Medical Decision Making 9, no. 2 (1989): 142-149; A. Mehrez and A. Gafni, "Healthy-Years Equivalents versus Quality-Adjusted Life Years: In Pursuit of Progress," Medical Decision Making 13, no. 4 (1993): 287-292; E. Nord, "The Person Trade-Off Approach to Valuing Health Care Programs," Medical Decision Making 15, no. 3 (1995): 201-208; D. Cox et al., "Quality-of-Life Assessment: Can We Keep It Simple?" Journal of the Royal Statistical Society, Series A, 155, no. 3 (1992): 353-393; P.A. Ubel et al., "Individual Utilities Are Inconsistent with Rationing Choices: A Partial List of Why Oregon's Cost-Effectiveness List Failed," Medical Decision Making 16, no. 2 (1996): 108-116; and P.C. Langley, "Meeting the Information Needs of Drug Purchasers: The Evolution of Formulary Submission Guidelines," Clinical Therapeutics 21, no. 4 (1999): 768-787.
81. A. Mehrez and A. Gafni, "Quality Adjusted Life Years, Utility Theory, and Healthy-Years Equivalents," Medical Decision Making 9, no. 2 (1989): 142-149; A. Mehrez and A. Gafni, "Healthy-Years Equivalents versus Quality-Adjusted Life Years: In Pursuit of Progress," Medical Decision Making 13, no. 4 (1993): 287-292; E. Nord, "The Person Trade-Off Approach to Valuing Health Care Programs," Medical Decision Making 15, no. 3 (1995): 201-208; D. Cox et al., "Quality-of-Life Assessment: Can We Keep It Simple?" Journal of the Royal Statistical Society, Series A, 155, no. 3 (1992): 353-393; P.A. Ubel et al., "Individual Utilities Are Inconsistent with Rationing Choices: A Partial List of Why Oregon's Cost-Effectiveness List Failed," Medical Decision Making 16, no. 2 (1996): 108-116; and P.C. Langley, "Meeting the Information Needs of Drug Purchasers: The Evolution of Formulary Submission Guidelines," Clinical Therapeutics 21, no. 4 (1999): 768-787.
82. A. Mehrez and A. Gafni, "Quality Adjusted Life Years, Utility Theory, and Healthy-Years Equivalents," Medical Decision Making 9, no. 2 (1989): 142-149; A. Mehrez and A. Gafni, "Healthy-Years Equivalents versus Quality-Adjusted Life Years: In Pursuit of Progress," Medical Decision Making 13, no. 4 (1993): 287-292; E. Nord, "The Person Trade-Off Approach to Valuing Health Care Programs," Medical Decision Making 15, no. 3 (1995): 201-208; D. Cox et al., "Quality-of-Life Assessment: Can We Keep It Simple?" Journal of the Royal Statistical Society, Series A, 155, no. 3 (1992): 353-393; P.A. Ubel et al., "Individual Utilities Are Inconsistent with Rationing Choices: A Partial List of Why Oregon's Cost-Effectiveness List Failed," Medical Decision Making 16, no. 2 (1996): 108-116; and P.C. Langley, "Meeting the Information Needs of Drug Purchasers: The Evolution of Formulary Submission Guidelines," Clinical Therapeutics 21, no. 4 (1999): 768-787.
83. Langley, "Meeting the Information Needs of Drug Purchasers."
84. Weinstein et al., "Recommendations of the Panel on Cost-Effectiveness"; and Drummond et al., Methods for the Economic Evaluation.
85. Weinstein et al., "Recommendations of the Panel on Cost-Effectiveness"; and Drummond et al., Methods for the Economic Evaluation.
86. D. Menon, F. Schubert, and G.W. Torrance, "Canada's New Guidelines for the Economic Evaluation of Pharmaceuticals," Medical Care 34, no. 12 suppl. (1996): DS77-DS86; and A. Mitchell, "Update and Evaluation of Australian Guidelines," Medical Care 34, no. 12 suppl. (1996): DS216-DS225.
87. D. Menon, F. Schubert, and G.W. Torrance, "Canada's New Guidelines for the Economic Evaluation of Pharmaceuticals," Medical Care 34, no. 12 suppl. (1996): DS77-DS86; and A. Mitchell, "Update and Evaluation of Australian Guidelines," Medical Care 34, no. 12 suppl. (1996): DS216-DS225.
88. M. Drummond et al., "Current Trends in the Use of Pharmacoeconomics and Outcomes Research in Europe," Value in Health 2, no. 5 (1999): 323-332.
89. Menon et al., "Canada's New Guidelines"; and Mitchell, "Update and Evaluation of Australian Guidelines."
90. Menon et al., "Canada's New Guidelines"; and Mitchell, "Update and Evaluation of Australian Guidelines."
91. P. Gorham, "Cost-Effectiveness Guidelines: The Experience of Australian Manufacturers," Pharmacoeconomics 8, no. 5 (1995): 369-373.
92. P.J. Neumann, "Government Uses of Cost-Effectiveness Information on Drugs," in Policy Issues in Pharmaceutical Cost-Effectiveness Research (Presentation at the American Enterprise Institute, Washington, D.C., November 1996).
93. Ibid; and T.O. Tengs et al., "Oregon's Medicaid Rankings and Cost-Effectiveness: Is There Any Relationship?" Medical Decision Making 16, no. 2 (1996): 99-107.
94. Ibid; and T.O. Tengs et al., "Oregon's Medicaid Rankings and Cost-Effectiveness: Is There Any Relationship?" Medical Decision Making 16, no. 2 (1996): 99-107.
95. H.H. Schauffler, "Disease Prevention Policy under Medicare: A Historical and Political Analysis," American Journal of Preventive Medicine 9, no. 2 (1993): 71-77; Centers for Disease Control and Prevention, "Final Results: Medicare Influenza Vaccine Demonstration - Selected States, 1988-92," Morbidity and Mortality Weekly Report 42, no. 31 (1993): 601-604; U.S. Office of Technology Assessment, Effectiveness and Cost of Osteoporosis Screening and Hormone Replacement Therapy, Vol 1: Cost-Effectivaiess Analysis, Pub. no. OTA-BP-H-160 (Washington: OTA, August 1995, available online at www.ota.nap.edu); and J.L Wagner, "Cost-Effectiveness of Screening for Common Cancers," Cancer Metastasis Review 16, no. 3-4 (1997): 281-294.
96. H.H. Schauffler, "Disease Prevention Policy under Medicare: A Historical and Political Analysis," American Journal of Preventive Medicine 9, no. 2 (1993): 71-77; Centers for Disease Control and Prevention, "Final Results: Medicare Influenza Vaccine Demonstration - Selected States, 1988-92," Morbidity and Mortality Weekly Report 42, no. 31 (1993): 601-604; U.S. Office of Technology Assessment, Effectiveness and Cost of Osteoporosis Screening and Hormone Replacement Therapy, Vol 1: Cost-Effectivaiess Analysis, Pub. no. OTA-BP-H-160 (Washington: OTA, August 1995, available online at www.ota.nap.edu); and J.L Wagner, "Cost-Effectiveness of Screening for Common Cancers," Cancer Metastasis Review 16, no. 3-4 (1997): 281-294.
97. H.H. Schauffler, "Disease Prevention Policy under Medicare: A Historical and Political Analysis," American Journal of Preventive Medicine 9, no. 2 (1993): 71-77; Centers for Disease Control and Prevention, "Final Results: Medicare Influenza Vaccine Demonstration - Selected States, 1988-92," Morbidity and Mortality Weekly Report 42, no. 31 (1993): 601-604; U.S. Office of Technology Assessment, Effectiveness and Cost of Osteoporosis Screening and Hormone Replacement Therapy, Vol 1: Cost-Effectivaiess Analysis, Pub. no. OTA-BP-H-160 (Washington: OTA, August 1995, available online at www.ota.nap.edu); and J.L Wagner, "Cost-Effectiveness of Screening for Common Cancers," Cancer Metastasis Review 16, no. 3-4 (1997): 281-294.
98. H.H. Schauffler, "Disease Prevention Policy under Medicare: A Historical and Political Analysis," American Journal of Preventive Medicine 9, no. 2 (1993): 71-77; Centers for Disease Control and Prevention, "Final Results: Medicare Influenza Vaccine Demonstration - Selected States, 1988-92," Morbidity and Mortality Weekly Report 42, no. 31 (1993): 601-604; U.S. Office of Technology Assessment, Effectiveness and Cost of Osteoporosis Screening and Hormone Replacement Therapy, Vol 1: Cost-Effectivaiess Analysis, Pub. no. OTA-BP-H-160 (Washington: OTA, August 1995, available online at www.ota.nap.edu); and J.L Wagner, "Cost-Effectiveness of Screening for Common Cancers," Cancer Metastasis Review 16, no. 3-4 (1997): 281-294.
99. Regence Washington Health Pharmacy Service, "Guidelines for Submission of Clinical and Economic Data Supporting Formulary Considerations" (Seattle: Regence Washington Health, University of Washington, 1997); and Blue Cross Blue Shield of Colorado and Blue Cross Blue Shield of Nevada, "Guidelines for Formulary Submissions for Pharmaceutical Product Evaluation" (Denver: Blue Cross Blue Shield of Colorado, October 1998).
100. Regence Washington Health Pharmacy Service, "Guidelines for Submission of Clinical and Economic Data Supporting Formulary Considerations" (Seattle: Regence Washington Health, University of Washington, 1997); and Blue Cross Blue Shield of Colorado and Blue Cross Blue Shield of Nevada, "Guidelines for Formulary Submissions for Pharmaceutical Product Evaluation" (Denver: Blue Cross Blue Shield of Colorado, October 1998).
101. Neumann et al., "A Formal Audit of 228 Published Cost-Utility Analyses."
102. M.C. Weinstein, C.M. Coley, and J.M. Richter, "Medical Management of Gallstones: A Cost-Effectiveness Analysis," Journal of General Internal Medicine 5, no. 4 (1990): 277-284.
103. I.S. Udvarhelyi et al., "Cost-Effectiveness and Cost-Benefit Analyses in the Medical Literature: Are the Methods Being Used Correctly?" Annals of Internal Medicine 116, no. 3 (1992): 238-244; Neumann et al., "A Formal Audit of 228 Published Cost-Utility Analyses"; and K. Gerard, I. Smoker, and J. Seymour, "Raising the Quality of Cost-Utility Analyses: Lessons Learnt and Still to Learn," Health Policy 46, no. 3 (1999): 217-238.
104. I.S. Udvarhelyi et al., "Cost-Effectiveness and Cost-Benefit Analyses in the Medical Literature: Are the Methods Being Used Correctly?" Annals of Internal Medicine 116, no. 3 (1992): 238-244; Neumann et al., "A Formal Audit of 228 Published Cost-Utility Analyses"; and K. Gerard, I. Smoker, and J. Seymour, "Raising the Quality of Cost-Utility Analyses: Lessons Learnt and Still to Learn," Health Policy 46, no. 3 (1999): 217-238.
105. I.S. Udvarhelyi et al., "Cost-Effectiveness and Cost-Benefit Analyses in the Medical Literature: Are the Methods Being Used Correctly?" Annals of Internal Medicine 116, no. 3 (1992): 238-244; Neumann et al., "A Formal Audit of 228 Published Cost-Utility Analyses"; and K. Gerard, I. Smoker, and J. Seymour, "Raising the Quality of Cost-Utility Analyses: Lessons Learnt and Still to Learn," Health Policy 46, no. 3 (1999): 217-238.