Skip to main content
SpringerLink
Log in

Prioritizing Future Research on Allopurinol and Febuxostat for the Management of Gout: Value of Information Analysis

  • Original Research Article
  • Published:
PharmacoEconomics Aims and scope Submit manuscript

Abstract

Objectives

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.

Methods

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.

Results

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.

Conclusions

Future studies are needed to evaluate the effectiveness of allopurinol and febuxostat dose escalation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. 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.

    Article  PubMed  Google Scholar 

  2. 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.

    Article  CAS  Google Scholar 

  3. Shields GE, Beard SM. A systematic review of the economic and humanistic burden of gout. Pharmacoeconomics. 2015;33:1029–47.

    Article  PubMed  Google Scholar 

  4. Choi HK, Mount DB, Reginato AM. Pathogenesis of gout. Ann Intern Med. 2005;143:499–516.

    Article  CAS  PubMed  Google Scholar 

  5. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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.

    PubMed  Google Scholar 

  9. 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.

    PubMed  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Article  CAS  PubMed  Google Scholar 

  12. 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.

    Article  PubMed  Google Scholar 

  13. Briggs AH, Claxton K, Sculpher MJ. Decision modelling for health economic evaluation. USA: Oxford University Press; 2006.

    Google Scholar 

  14. 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.

    Article  PubMed  Google Scholar 

  15. 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.

    Article  CAS  PubMed  Google Scholar 

  16. Wilson ECF. A practical guide to value of information analysis. Pharmacoeconomics. 2014;33:105–21.

    Article  Google Scholar 

  17. 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.

    Article  Google Scholar 

  18. 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.

    Article  Google Scholar 

  19. Jalal H, Alarid-Escudero F. A Gaussian approximation approach for value of information analysis. Med Decis Mak. (In Press).

  20. 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.

    Article  CAS  PubMed  Google Scholar 

  21. Felli JC, Hazen GB. A Bayesian approach to sensitivity analysis. Health Econ. 1999;8(3):263.

    Article  CAS  PubMed  Google Scholar 

  22. Felli JC, Hazen GB. Sensitivity analysis and the expected value of perfect information. Med Decis Mak. 1998;18(1):95–109.

    Article  CAS  Google Scholar 

  23. 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.

    Article  Google Scholar 

  24. 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.

  25. 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.

    Article  PubMed  Google Scholar 

  26. 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.

    PubMed  Google Scholar 

  27. 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.

    PubMed  Google Scholar 

  28. Mikuls TR. Gout epidemiology: results from the UK general practice research database, 1990–1999. Ann Rheum Dis. 2005;64(2):267–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. 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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  31. Raiffa H, Schlaifer R. Probability and statistics for business decisions. New York: McGaw-Hill; 1959.

    Google Scholar 

  32. 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.

    Article  PubMed  Google Scholar 

  33. Emanuel EJ. The costs of conducting clinical research. J Clin Oncol. 2003;21(22):4145–50.

    Article  PubMed  Google Scholar 

  34. Romberger D. University of Nebraska Medical Center, Department of Internal Medicine Newsletter. May 2015.

  35. 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.

    Article  Google Scholar 

  36. Claxton K, Posnett J. An economic approach to clinical trial design and research priority-setting. Health Econ. 1996;5(6):513–24.

    Article  CAS  PubMed  Google Scholar 

  37. 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.

    Article  Google Scholar 

  38. 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.

    Article  PubMed  Google Scholar 

  39. 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.

  40. McInnes GT, Lawson DH, Jick H. Acute adverse reactions attributed to allopurinol in hospitalized patients. Ann Rheum Dis. 1981;40(3):245–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Arellano F, Sacristan JA. Allopurinol hypersensitivity syndrome: a review. Ann Pharmacother. 1993;27(3):337–43.

    Article  CAS  PubMed  Google Scholar 

  42. 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.

    Article  PubMed  Google Scholar 

  43. 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.

    PubMed  Google Scholar 

  44. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  45. 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.

    Article  PubMed  Google Scholar 

  46. 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.

    PubMed  Google Scholar 

  47. 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.

  48. 2010 Red Book: Pharmacy’s Fundamental Reference, 114th Ed. Montvale, NJ: Thomson Reuters (Healthcare), 2010.

Download references

Author information

Authors and Affiliations

  1. Department of Health Services, Policy and Practice, Brown University School of Public Health, 121 S. Main Street, 6th Floor, Box G-S121-6, Providence, RI, 02912, USA

    Eric Jutkowitz

  2. Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN, USA

    Fernando Alarid-Escudero & Karen M. Kuntz

  3. Division of Rheumatology, Allergy and Immunology, Department of Medicine, Gout and Crystal Arthropathy Center, Clinical Epidemiology and Health Outcomes, Massachusetts General Hospital, Boston, MA, USA

    Hyon K. Choi

  4. Division of Health Policy and Management, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    Hawre Jalal

Authors
  1. Eric Jutkowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fernando Alarid-Escudero
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hyon K. Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karen M. Kuntz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hawre Jalal
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

EJ, FAE, HJ: study design and analysis. All authors participated in the interpretation of data, drafting of manuscript, critical revision of manuscript, and approval of final manuscript.

Corresponding author

Correspondence to Eric Jutkowitz.

Ethics declarations

Funding

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.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 2722 kb)

Supplementary material 2 (XLS 9936 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40273-017-0526-0

Search

Navigation