Supplemental Appendix
Jutkowitz E, Alarid-Escudero F, Choi HK, Kuntz KM, Jalal H. Prioritizing Future Research on Allopurinol and Febuxostat for the Management of Gout: Value of Information Analysis
eTable 1 Research study designs, parameters informed, and cost of data collection
Research Study / Parameters Informed / Study Design / Fixed Cost / Cost Per PatientStudy Design 1
Allopurinol dose-escalation vs. placebo / · Efficacy allopurinol dose-escalation
· Probability of hypersensitivity syndrome
· Probability of death due to hypersensitivity syndrome
· Probability of non-hypersensitivity adverse event
· Probability of discontinuing treatment due to therapeutic failure
· Probability of discontinuing treatment due to adverse event
· Probability of flares (uncontrolled on treatment, uncontrolled off treatment, controlled)
· Max time remain uncontrolled on treatment before stopping treatment or becoming long-term uncontrolled / RCT / $8,740,000 / $8,440
Study Design 2
Febuxostat dose-escalation vs. placebo / · Efficacy febuxostat dose-escalation
· Probability of adverse event
· Probability of discontinuing treatment due to therapeutic failure
· Probability of discontinuing treatment due to adverse event
· Probability of discontinuing treatment due to adverse event
· Probability of flares (uncontrolled on treatment, uncontrolled off treatment, controlled)
· Max time remain uncontrolled on treatment before stopping treatment or becoming long-term uncontrolled / RCT / $8,740,000 / $8,440
Study Design 3
Evaluation of health utilizes / · Difference in utility between controlled and uncontrolled on medication
· Difference in utility between uncontrolled on medication and uncontrolled off medication
· Flare disutility
· Adverse event disutility
· Hypersensitivity disutility / Obs / $50,000 / $500
Study Design 4
Allopurinol dose-escalation vs. febuxostat dose-escalation / · Parameters evaluated in study design 1 + study design 2 + study design 3 / RCT / $8,740,000 / $8,440
RCT = Randomized controlled trial, Obs = Prospective observational study
eTable 2 Cost-Effectiveness of Gout Treatment Strategies
Strategy / Lifetime Costs / Incremental Costs / QALYs / Incremental QALYs / ICERAllopurinol only dose-escalation / $9,968 / 11.92 / Reference
Allopurinol only fixed-dose / $10,059 / - / 11.84 / - / Dominated
No treatment / $10,374 / - / 11.73 / - / Dominated
Allopurinol-febuxostat sequential therapy dose-escalation / $11,766 / $1,798 / 11.95 / 0.03 / $59,900
Allopurinol-febuxostat sequential therapy fixed-dose / $12,572 / - / 11.91 / - / Dominated
Febuxostat-allopurinol sequential therapy fixed-dose / $14,348 / - / 11.94 / - / Dominated
Febuxostat only fixed-dose / $15,285 / - / 11.94 / - / Dominated
Febuxostat-allopurinol sequential therapy dose-esclation / $15,089 / $3,323 / 11.96 / 0.01 / $332,300
Febuxostat only dose-escalation / $16,173 / - / 11.94 / - / Dominated
ICER = incremental cost-effectiveness ratio; QALY = quality-adjusted life-year.
eFigure 1. Model Schematic
Figure Legend. Model states are represented by circles, and the probability of moving between states is represented by arrows. Hypothetical gout patients can remain in same state and from any state a patient can die. Transitions to second-line treatment are only available for patients in a sequential treatment strategy.
eFigure 2. Cost-effectiveness Acceptability Curve All Strategies
Figure Legend. QALY = quality-adjusted life-years
eFigure 3. Individual Expected Value of Perfect Information
Figure Legend. EVPI = expected value of perfect information. QALY = quality-adjusted life-years.
eFigure 4. Individual Expected Value of Partial Perfect Information
Figure Legend. EVPPI = expected value of partial perfect information. QALY = quality-adjusted life-years. Hypothetical study designs are presented in increasing value. Study design #1: randomized controlled trial evaluating the efficacy of allopurinol dose-escalation. Study design #2: randomized controlled trial evaluating the efficacy of febuxostat dose-escalation. Study design #3: a prospective observational study evaluating the health utility of gout patients. Study design #4: a comprehensive randomized controlled trial evaluating the efficacy of allopurinol dose-escalation, febuxostat dose-escalation, ancillary outcomes, and the health utilities of gout patients.
eFigure 5 Population Expected Value of Sample Information and Expected Net Benefit of Sampling to Collect Data on Allopurinol Dose-Escalation (study design #1)
Figure Legend. popEVSI = Population Expected Value of Sample Information, ENBS = Expected Net Benefit of Sampling, n* = optimal sample size per arm of a two arm trial given the Population EVSI and the ENBS.
eFigure 6 Population Expected Value of Sample Information and Expected Net Benefit of Sampling to Collect Data on Febuxostat Dose-Escalation (study design #2)
Figure Legend. popEVSI = Population Expected Value of Sample Information, ENBS = Expected Net Benefit of Sampling, n* = optimal sample size per arm of a two arm trial given the Population EVSI and the ENBS.
eFigure 7 Population Expected Value of Sample Information and Expected Net Benefit of Sampling to Collect Data on Health Utilities (study design #3)
Figure Legend. popEVSI = Population Expected Value of Sample Information, ENBS = Expected Net Benefit of Sampling, n* = optimal sample size per arm of a two arm trial given the Population EVSI and the ENBS.