Digestive Diseases and Sciences

, Volume 41, Supplement 12, pp 56S–62S | Cite as

Modeling therapeutic benefit in the midst of uncertainty

Therapy for hepatitis C
  • William G. Bennett
  • Stephen G. Pauker
  • Gary L. Davis
  • John B. Wong


Randomized, double-blind, controlled clinical trials are the gold standard for medical therapy. When a disease is rare or slowly progressive over many years, such a trial may not be feasible. Decision analysis provides a bridge between current studies with short-term surrogate markers and a large, longitudinal clinical trial. With decision analysis, results of current studies can be summarized and the outcome of a long-term study projected under explicit assumptions. Chronic hepatitis C is a disease that is slowly progressive, and the requirements of a longitudinal clinical study could be prohibitive. Therefore, we review the basic steps of decision analysis, apply these steps to two recent decision analyses evaluating the use of interferon-α2b (IFN) in the treatment of chronic hepatitis C, and discuss possible implications of decision modeling for this disease. The estimated marginal cost per year of life gained from IFN therapy ranged from approximately $3000 to $55,000 in these two studies. The wide range is based on different estimates of treatment costs and disease progression. This analysis has identified gaps in the current knowledge regarding the natural progression of hepatitis C and has established criteria to evaluate new developments and their impact on chronic hepatitis C.

Key words

cost-effectiveness analysis decision analysis hepatitis C interferon decision making 


  1. 1.
    The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986, 1993Google Scholar
  2. 2.
    Davis GL, Lau JYN, Lim HL: Therapy for chronic hepatitis C. Gastroenterol Clin North Am 23:603–613, 1994Google Scholar
  3. 3.
    Kiyosawa K, Sodeyama T, Tanaka E, Gibo Y, Yoshizawa K, Nakano Y, Furuta S, Akahane Y, Nishioka K, Purcell RH, Alter HJ: Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology 12:671–675, 1990Google Scholar
  4. 4.
    Seeff LB, Buskell-Bales Z, Wright EC, Durako SJ, Alter HJ, Iber FL, Hollinger FB, Gitnick G, Knodell RG, Perrillo RP, Stevens CE, Hollingsworth CG, and the National Heart, Lung, and Blood Institute Study Group: Long-term mortality after transfusion-associated non-A, non-B hepatitis. N Engl J Med 327:1906–1911, 1992Google Scholar
  5. 5.
    Dusheiko GM, Roberts GA: Treatment of chronic type B and C hepatitis with alpha interferon: An economic appraisal. Hepatology 22:1863–1873, 1995Google Scholar
  6. 6.
    Shiell A, Briggs A, Farrell GC: The cost effectiveness of alpha interferon in the treatment of chronic active hepatitis C. Med J Aust 160:268–272, 1994Google Scholar
  7. 7.
    Davis GL, Balart LA, Schiff ER, Lindsay K, Bodenheimer HC, Perrillo RP, Carey W, Jacobson IM, Payne J, Dienstag JL, Van Thiel DH, Tamburro C, Lefkowitch J, Albrecht J, Meschievitz C, Ortego TJ, Gibas A, and the Hepatitis Interventional Therapy Group: Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. N Engl J Med 321:1501–1506, 1989Google Scholar
  8. 8.
    Kleter GEM, Brouwer JT, Heijtink RA, Schalm SW, Quint WGV: Detection of hepatitis C virus RNA in patients with chronic hepatitis C virus infections during and after therapy with alpha interferon. Antimicrob Agents Chemother 37:595–597, 1993Google Scholar
  9. 9.
    Nishiguchi S, Kuroki T, Nakatani S, Morimoto H, Takeda T, Nakajima S, Shiomi S, Seki S, Kobayashi K, Otani S: Randomised trial of effects of interferon-α on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet 346:1051–1055, 1995Google Scholar
  10. 10.
    Saracco G, Rosina F, Torrani Cerenzia MR, Lattore V, Chiandussi L, Gallo V, Petrino R, De Micheli AG, Donegani E, Solinas A, Deplano A, Tocco A, Cossu P, Pintus C, David E, Mazzucco G, Verme G, Rizzetto M: A randomized controlled trial of interferon alfa-2b as therapy for chronic non-A, non-B hepatitis. J Hepatol 11(suppl 1):S43-S49, 1990Google Scholar
  11. 11.
    Takahashi M, Yamada G, Miyamoto R, Doi T, Endo H, Tsuji T: Natural course of chronic hepatitis C. Am J Gastroenterol 88:240–243, 1993Google Scholar
  12. 12.
    Tremolada F, Casarin C, Alberti A, Drago C, Tagger A, Ribero ML, Realdi G: Long-term follow-up of non-A, non-B (type C) posttransfusion hepatitis. J Hepatol 16:273–281, 1992Google Scholar
  13. 13.
    Mattsson L: Chronic non-A, non-B hepatitis with special reference to the transfusion-associated form. Scand J Infect Dis 59(suppl):1–55, 1989Google Scholar
  14. 14.
    Fattovich G: Risk factors for hepatic decompensation and hepatocellular carcinoma in patients with HbsAg-positive compensated cirrhosis.In: European Study Group on Viral Hepatitis (Eurohep), Report of the Seventh Eurohep Workshop; February 12–13, 1993, Paris, The Wellcome Foundation, 1993Google Scholar
  15. 15.
    Columbo M, De Franchis R, Del Minno E, Sangiovanni A, De Fazio C, Tommasini M, Donato MF, Piva A, Di Carlo V, Dioguardi N: Hepatocellular carcinoma in Italian patients with cirrhosis. N Engl J Med 325:675–680, 1991Google Scholar
  16. 16.
    Beck JR, Kassirer JP, Pauker SG: A convenient approximation of life expectancy (the “DEALE”). I. Validation of the method. Am J Med 73:883–888, 1982Google Scholar
  17. 17.
    Beck JR, Pauker SG, Gottlieb JE, Klein K, Kassirer JP: A convenient approximation of life expectancy (“the DEALE”). II. Use in medical decision-making. Am J Med 73:889–897, 1982Google Scholar
  18. 18.
    Beck JR, Pauker SG: The Markov process in medical prognosis. Med Decis Making 3:419–458, 1983Google Scholar
  19. 19.
    Sonnenberg FA, Beck JR: Markov models in medical decision making: A practical guide. Med Decis Making 13:322–338, 1993Google Scholar
  20. 20.
    Finkler SA: The distinction between cost and charges. Ann Intern Med 96:102–109, 1982Google Scholar
  21. 21.
    Wong JB, Koff RS, Tinè F, Pauker SG: Cost-effectiveness of interferon α-2b treatment for hepatitis B antigen-positive chronic hepatitis B. Ann Intern Med 122:664–675, 1995Google Scholar
  22. 22.
    Goldman L, Gordon DJ, Rifkind BM, Hulley SB, Detsky AS, Goodman DS, Kinosian B, Weinstein MC: Cost and health implications of cholesterol lowering. Circulation 85:1960–1968, 1992Google Scholar
  23. 23.
    Wong JB, Sonnenberg FA, Salem DN, Pauker SG: Myocardial revascularization for chronic stable angina. Analysis of the role of percutaneous transluminal coronary angioplasty based on data available in 1989. Ann Intern Med 113:852–871, 1990Google Scholar
  24. 24.
    Sisk JE, Riegelman RK: Cost effectiveness of vaccination against pneumococcal pneumonia: An update. Ann Intern Med 104:79–86, 1986Google Scholar
  25. 25.
    Wagner JL, Herdman RC, Wadhwa S: Cost effectiveness of colorectal cancer screening in the elderly. Ann Intern Med 115:807–817, 1991Google Scholar
  26. 26.
    Eisenstaedt RS, Getzen TE: Screening blood donors for human immunodeficiency virus antibody: cost-benefit analysis. Am J Public Health 78:450–454, 1988Google Scholar
  27. 27.
    Eddy DM: Screening for breast cancer. Ann Intern Med 111:389–399, 1989Google Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • William G. Bennett
    • 1
    • 2
  • Stephen G. Pauker
    • 1
    • 2
  • Gary L. Davis
    • 1
    • 2
  • John B. Wong
    • 1
    • 2
  1. 1.From the Division of Clinical Decision Making, New England Medical CenterTufts University School of MedicineBostonUSA
  2. 2.Section of Hepatobiliary DiseasesUniversity of Florida College of MedicineGainesvilleUSA

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