The aim of this study was to quantify the value of conducting additional research and reducing uncertainty regarding the cost effectiveness of allopurinol and febuxostat for the management of gout.
We used a previously developed Markov model that evaluated the cost effectiveness of nine urate-lowering strategies: no treatment, allopurinol-only fixed dose (300 mg), allopurinol-only dose escalation (up to 800 mg), febuxostat-only fixed dose (80 mg), febuxostat-only dose escalation (up to 120 mg), allopurinol–febuxostat sequential therapy fixed dose, allopurinol–febuxostat sequential therapy dose escalation, febuxostat–allopurinol sequential therapy fixed dose, and febuxostat–allopurinol sequential therapy dose escalation. Each strategy was evaluated over the lifetime of a hypothetical gout patient. We calculated population expected value of perfect information (EVPI). We used a linear regression meta-modeling approach to calculate population expected value of partial perfect information (EVPPI), and a Gaussian approximation to calculate the population expected value of sample information for parameters (EVSI) and the expected net benefit of sampling (ENBS) for four potential study designs: (1) an allopurinol efficacy trial; (2) a febuxostat efficacy trial; (3) a prospective observational study evaluating health utilities; and (4) a comprehensive study evaluating the efficacy of allopurinol and febuxostat and health utilities. A 5-year decision time horizon was used in the base-case analysis.
EVPI varied by a decision maker’s willingness-to-pay (WTP) per quality-adjusted life-year (QALY) and was $US900 million for WTP of $US60,000 per QALY. Population EVPPI was highest across all WTP values for study design #4. For study design #4 and a WTP of $US60,000 per QALY, the optimal sample size was 735 patients per study arm.
Future studies are needed to evaluate the effectiveness of allopurinol and febuxostat dose escalation.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011;63(10):3136–41.
Khanna D, FitzGerald JD, Khanna PP, Bae S, Singh MK, Neogi T, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res. 2012;64:1431–46.
Shields GE, Beard SM. A systematic review of the economic and humanistic burden of gout. Pharmacoeconomics. 2015;33:1029–47.
Choi HK, Mount DB, Reginato AM. Pathogenesis of gout. Ann Intern Med. 2005;143:499–516.
Zhang W, Doherty M, Bardin T, Pascual E, Barskova V, Conaghan P, et al. EULAR evidence based recommendations for gout. Part II: management. Report of a task force of the EULAR standing committee for international clinical studies including therapeutics (ESCISIT). Ann Rheum Dis. 2006;65(10):1312–24.
Harrold LR, Andrade SE, Briesacher BA, Raebel MA, Fouayzi H, Yood RA, et al. Adherence with urate-lowering therapies for the treatment of gout. Arthritis Res Ther. 2009;11:R46.
Zhang W, Doherty M, Bardin T, Pascual E, Barskova V, Conaghan P, et al. EULAR evidence based recommendations for gout. Part I: diagnosis. Report of a task force of the EULAR standing committee for international clinical studies including therapeutics (ESCISIT). Ann Rheum Dis. 2006;65:1301–11.
Riedel AA, Nelson M, Joseph-Ridge N, Wallace K, MacDonald P, Becker M. Compliance with allopurinol therapy among managed care enrollees with gout: a retrospective analysis of administrative claims. J Rheumatol. 2004;31:1575–81.
Neogi T, Hunter DJ, Chaisson CE, Allensworth-Davies D, Zhang Y. Frequency and predictors of inappropriate management of recurrent gout attacks in a longitudinal study. J Rheumatol. 2006;33:104–9.
Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Eustace D, Palo WA, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005;353:2450–61.
Schumacher HR Jr, Becker MA, Wortmann RL, MacDonald PA, Hunt B, Streit J, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum. 2008;59:1540–8.
Jutkowitz E, Choi HK, Pizzi LT, Kuntz KM. Cost-effectiveness of allopurinol and febuxostat for the management of gout. Ann Intern Med. 2014;161:617.
Briggs AH, Claxton K, Sculpher MJ. Decision modelling for health economic evaluation. USA: Oxford University Press; 2006.
Tuffaha HW, Gordon LG, Scuffham PA. Value of information analysis in healthcare: a review of principles and applications. J Med Econ. 2014;17:377–83.
Claxton K, Palmer S, Longworth L, Bojke L, Griffin S, McKenna C, et al. Informing a decision framework for when NICE should recommend the use of health technologies only in the context of an appropriately designed programme of evidence development. Health Technol Assess. 2012;16(46):1–323.
Wilson ECF. A practical guide to value of information analysis. Pharmacoeconomics. 2014;33:105–21.
Keisler JM, Collier ZA, Chu E, Sinatra N, Linkov I. Value of information analysis: the state of application. Environ Syst Decis. 2014;34:3–23.
Jalal H, Goldhaber-Fiebert JD, Kuntz KM. Computing expected value of partial sample information from probabilistic sensitivity analysis using linear regression metamodeling. Med Decis Mak. 2015;35(5):584–95.
Jalal H, Alarid-Escudero F. A Gaussian approximation approach for value of information analysis. Med Decis Mak. (In Press).
Becker MA, Schumacher HR, MacDonald PA, Lloyd E, Lademacher C. Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout. J Rheumatol. 2009;36:1273–82.
Felli JC, Hazen GB. A Bayesian approach to sensitivity analysis. Health Econ. 1999;8(3):263.
Felli JC, Hazen GB. Sensitivity analysis and the expected value of perfect information. Med Decis Mak. 1998;18(1):95–109.
Meltzer DO, Hoomans T, Chung JW, Basu A. Minimal modeling approaches to value of information analysis for health research. Med Decis Mak. 2011;31(6):E1–22.
US Food and Drug Administration. Orange Book: approved drug products with therapeutic equivalence. 2017. Available at: https://www.accessdata.fda.gov/scripts/cder/ob/patent_info.cfm?Product_No=001&Appl_No=021856&Appl_type=N. Accessed May 30, 2017.
Smolen LJ, Gahn JC, Mitri G, Shiozawa A. Febuxostat in the management of gout: a cost-effectiveness analysis. J Med Econ. 2015;19(3):265–76.
Wallace KL, Riedel AA, Joseph-Ridge N, Wortmann R. Increasing prevalence of gout and hyperuricemia over 10 years among older adults in a managed care population. J Rheumatol. 2004;31(8):1582–7.
Arromdee E, Michet CJ, Crowson CS, O’Fallon WM, Gabriel SE. Epidemiology of gout: is the incidence rising? J Rheumatol. 2002;29(11):2403–6.
Mikuls TR. Gout epidemiology: results from the UK general practice research database, 1990–1999. Ann Rheum Dis. 2005;64(2):267–72.
Rees F, Jenkins W, Doherty M. Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study. Ann Rheum Dis. 2013;72(6):826–30.
Ades AE, Lu G, Claxton K. Expected value of sample information calculations in medical decision modeling. Med Decis Mak. 2004;24(2):207–27.
Raiffa H, Schlaifer R. Probability and statistics for business decisions. New York: McGaw-Hill; 1959.
Johnston SC, Rootenberg JD, Katrak S, Smith WS, Elkins JS. Effect of a US National Institutes of Health programme of clinical trials on public health and costs. Lancet. 2006;367(9519):1319–27.
Emanuel EJ. The costs of conducting clinical research. J Clin Oncol. 2003;21(22):4145–50.
Romberger D. University of Nebraska Medical Center, Department of Internal Medicine Newsletter. May 2015.
Bennette CS, Veenstra DL, Basu A, Baker LH, Ramsey SD, Carlson JJ. Development and evaluation of an approach to using value of information analyses for real-time prioritization decisions within SWOG, a large cancer clinical trials cooperative group. Med Decis Mak. 2016;36(5):641–51.
Claxton K, Posnett J. An economic approach to clinical trial design and research priority-setting. Health Econ. 1996;5(6):513–24.
Sculpher M, Claxton K. Establishing the cost-effectiveness of new pharmaceuticals under conditions of uncertainty—when is there sufficient evidence? Value Health. 2010;8(4):433–46.
Philips Z, Claxton K, Palmer S, Bojke L, Sculpher M. Priority setting for research in health care: an application of value of information analysis to glycoprotein IIb/IIIa antagonists in non-ST elevation acute coronary syndrome. Int J Technol Assess Health Care. 2006;22(3):379–87.
Tuffaha HW, Gordon LG, Scuffham PA. Value of information analysis informing adoption and research decisions in a portfolio of health care interventions. MDM Policy Pract. 2016;1(1). doi:10.1177/2381468316642238.
McInnes GT, Lawson DH, Jick H. Acute adverse reactions attributed to allopurinol in hospitalized patients. Ann Rheum Dis. 1981;40(3):245–9.
Arellano F, Sacristan JA. Allopurinol hypersensitivity syndrome: a review. Ann Pharmacother. 1993;27(3):337–43.
Sarawate CA, Patel PA, Schumacher HR, Yang W, Brewer KK, Bakst AW. Serum urate levels and gout flares: analysis from managed care data. J Clin Rheumatol. 2006;12(2):61–5.
Beard SM, von Scheele BG, Nuki G, Pearson IV. Cost-effectiveness of febuxostat in chronic gout. Eur J Health Econ. 2014;15(5):453–63.
Khanna PP, Nuki G, Bardin T, Tausche A-K, Forsythe A, Goren A, et al. Tophi and frequent gout flares are associated with impairments to quality of life, productivity, and increased healthcare resource use: results from a cross-sectional survey. Health Qual Life Outcomes. 2012;10(1):117.
Sánchez J-LA, Pereperez SB, Bastida JL, Martinez MM. Cost-utility analysis applied to the treatment of burn patients in a specialized center. Arch Surg. 2007;142(1):50.
Wu EQ, Patel PA, Yu AP, Mody RR, Cahill KE, Tang J, et al. Disease-related and all-cause health care costs of elderly patients with gout. J Manag Care Pharm. 2008;14(2):164.
Sheils J. Harmonizing the Obama, Baucus and Wyden/Bennett health reform proposals: technical feasibility. Falls Church, VA: The Lewin Group; 2009. Accessed at www.lewin.com/~/media/Lewin/Site_Sections/Publications/LewinAnalysisWydenBaucusFeasibility.pdf on 5 September 2014.
2010 Red Book: Pharmacy’s Fundamental Reference, 114th Ed. Montvale, NJ: Thomson Reuters (Healthcare), 2010.
No sources of funding were used to conduct this study.
Conflict of interest
EJ reports no conflicts of interest. FAE reports no conflicts of interest. HKC has received a research grant from Astra Zeneca and served as a research consultant for Takeda, both unrelated to this manuscript. KMK reports no conflicts of interest. HJ reports no conflicts of interest.
About this article
Cite this article
Jutkowitz, E., Alarid-Escudero, F., Choi, H.K. et al. Prioritizing Future Research on Allopurinol and Febuxostat for the Management of Gout: Value of Information Analysis. PharmacoEconomics 35, 1073–1085 (2017). https://doi.org/10.1007/s40273-017-0526-0