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



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.

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Author information




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.

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Correspondence to Eric Jutkowitz.

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No sources of funding were used to conduct this study.

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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.

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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).

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