Development of a health economic model to evaluate the cost-effectiveness of roxadustat in treating anemia associated with non-dialysis-dependent chronic kidney disease

Figures & data

Table 1. Roxadustat clinical trials in populations with NDD CKD stages 3–5.

Study	ALPS^21^,^22	ANDES ^23^,^24	OLYMPUS ^25^,^26	DOLOMITES ^28^,^29
Comparator	Placebo	Placebo	Placebo	ESA
N (R/comparator)	594 (391/203)	922 (616/306)	2,781 (1,393/1,388)	616 (323/293)
Treatment duration (weeks)	52–104	52–156	≤208	≤104

Abbreviations. CKD, Chronic kidney disease; ESA, Erythropoiesis-stimulating agent; NDD, Non-dialysis-dependent; R, Roxadustat.

Figure 1. Model overview. Abbreviations. ESA, Erythropoiesis-stimulating agent; Hb, Hemoglobin; IV, Intravenous; QALY, Quality-adjusted life-year; TRAE, Treatment-related adverse event.

Table 2. Summary of model settings included in the base case and scenario analysis.

Parameter	Setting in base case	Alternative explored in
Trials informing base case analysis	All NDD trials	n/a
Time horizon	Lifetime	n/a
Discount rate (costs)	3.5%	n/a
Discount rate (benefits)	3.5%	n/a
Cost-effectiveness threshold	£20,000 per QALY gained	£30,000 per QALY gained
Treatment effect included within all-cause mortality calculations (i.e. additional survival benefit assumed with roxadustat)?	No	Scenario analysis (Yes)
All-cause mortality parametric distribution	Exponential	Scenario analysis (Weibull)
Time to dialysis parametric distribution	Log-logistic	Scenario analysis (Exponential)
Source of TRAE rates	Clinical trial data	Scenario analysis (Literature values)
Include a method of drug administration utility value?	No	Scenario analysis (Yes)
Proportion of patients needing a nurse home visit to administer ESA	20%	n/a

Abbreviations. ESA, Erythropoiesis-stimulating agent; n/a, Not applicable; NDD, Non-dialysis-dependent; QALY, Quality-adjusted life-year; TRAE, Treatment-related adverse event.

Table 3. Summary of unit costs in the economic model.

Treatment costs	Unit	Unit cost	Source
Roxadustat	Per mg	£0.25	BNF^61
Epoetin alfa	Per unit of μg ESA	£0.66	BNF^50
Darbepoetin alfa	Per unit of μg ESA	£1.47	BNF^51
Epoetin beta	Per unit of μg ESA	£0.85	BNF^52
Epoetin zeta	Per unit of μg ESA	£0.58	BNF^53
Methoxy polyethylene glycol-epoetin beta	Per unit of μg ESA	£1.47	BNF^54
ESA administration	Per administration	£21	PSSRU 2019^62
Home dialysis visit	Per 15-minute band 6 home nurse visit	£28.25	PSSRU 2019^62
Monitoring cost	Per 15-minute consultant visit	£29.75	PSSRU 2020^63
Blood transfusion cost	Per transfusion	£516	National cost collection 2018/19^58
Dialysis
Hemodialysis	Weekly (3 sessions per week)	£461	National cost collection 2018/19^58
Peritoneal dialysis	Weekly (7 sessions per week)	£495	National cost collection 2018/19^58
Iron
Oral iron cost	Per mg of ferrous iron	£0.001	BNF and PCA^59^,^64–66
IV iron cost	Per mg	£0.17	BNF and PCA^59^,^67–69
IV iron administration	Per IV iron dose	£275	National cost collection 2018/19^58
Adverse events
Cost of stroke	Per event	£8,625	National cost collection 2018/19 and Xu et al.^a^58^,^70
Cost of MI	Per event	£3,057	National cost collection 2018/19 and TA317^a^58^,^71
Cost of VAT	Per event	£3,601	National cost collection 2018/19^58

^a Costs inflated to 2020 costs using Hospital and Community Health Services and NHS Cost Inflation Index pay and prices inflation indices from the PSSRU.

Abbreviations. BNF, British National Formulary; ESA, Erythropoiesis-stimulating agent; IV, Intravenous; MI, Myocardial infarction; PCA, Prescription cost analysis; PSSRU, Personal social services research unit; VAT, Vascular associated thrombosis.

Figure 2. Probabilistic results. Probabilistic sensitivity results are shown for incremental costs and benefits on the cost-effectiveness plane (a). individual points represent separate simulations, and the dashed line corresponds to the willingness-to-pay threshold of £20,000. Points below the dashed line would be considered cost-effective, while points to the right of the y-axis (positive change in QALY) and below the x-axis (decreased costs) are considered dominant. In the cost-effectiveness acceptability curve (B), the percentage of simulations is shown as a function of varying the willingness-to-pay threshold. Abbreviations. ICER, Incremental cost-effectiveness ratio; QALY, Quality-adjusted life-year.

Table 4. Probabilistic results at WTP thresholds £20,000 and £30,000 per QALY gained.

	Average (lower, upper 95% CrI)
	Roxadustat	ESAs	Difference
WTP threshold £20,000 per QALY gained
Cost per patient	£145,574 (£98,108, £178,755)	£145,605 (£97,765, £178,866)	-£32 (-£1,138, £871)
QALYs per patient	4.12 (3.12, 4.97)	4.11 (3.11, 4.96)	0.01 (0.001, 0.04)
ICER (cost per QALY gained)			Dominant (-£62,173, £252,784)
NMB (£20,000 per QALY gained)			£312 (-£745, £1,822)
Probability of cost-effectiveness at WTP threshold £20,000 per QALY gained	67.3%
WTP threshold £30,000 per QALY gained
Cost per patient	£143,856 (£94,114, £180,288)	£143,877 (£94,001, £180,463)	-£21 (-£976, £891)
QALYs per patient	4.08 (3.09, 5.02)	4.07 (3.08, 5.01)	0.01 (0.002, 0.03)
ICER (cost per QALY gained)			Dominant (-£58,741, £177,314)
NMB (£30,000 per QALY gained)			£429 (-£725, £1,897)
Probability of cost-effectiveness at WTP threshold £30,000 per QALY gained	75.4%

Interventions that produce an increase in QALYs while also being cost-saving are considered dominant.

Abbreviations. ESA, Erythropoiesis-stimulating agent; CrI, Credible interval; ICER, Incremental cost-effectiveness ratio; NMB, Net monetary benefit; QALYs, Quality-adjusted life-years; WTP, Willingness-to-pay.

Table 5. Summary of scenario results at WTP thresholds £20,000 and £30,000 per QALY gained.

Scenario	ΔCosts	ΔQALYs	ICER	WTP threshold £20,000 per QALY gained
				NMB	NHB
Base case	£93	0.01	£8,048	£138	0.01
Alternative mortality distribution (Weibull)	£86	0.01	£7,950	£131	0.01
Alternative time to dialysis distribution (exponential)	£83	0.01	£7,144	£149	0.01
Hb level fixed at 5 years	£205	0.01	£17,994	£23	0.00
Hb level fixed at 10 years	£112	0.01	£9,587	£121	0.01
Hb level fixed at 15 years	£96	0.01	£8,251	£136	0.01
Include treatment effect on mortality	£1,054	0.03	£34,603	-£445	−0.02
Include method of treatment administration utility increment	£93	0.29	£320	£5,719	0.29
Alternative TRAE rate source (literature)	−£79	0.01	Dominant	£324	0.02
Scenario	Δcosts	ΔQALYs	ICER	WTP threshold £30,000 per QALY gained
				NMB	NHB
Base case	£93	0.01	£8,048	£254	0.01

Interventions that produce an increase in QALYs while also being cost-saving are considered dominant.

Abbreviations. ESA, Erythropoiesis-stimulating agent; Hb, Hemoglobin; ICER, Incremental cost-effectiveness ratio; NHB, Net health benefit; NMB, Net monetary benefit; QALY, Quality-adjusted life-year; TRAE, Treatment-related adverse event.

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Data availability statement

The datasets analyzed during the current study were sourced from the original trial publications, the results of which have been fully referenced and are publicly available.

Researchers may request access to anonymized participant-level data, trial-level data and protocols from Astellas-sponsored clinical trials at www.clinicalstudydatarequest.com. For the Astellas criteria on data sharing see: https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Astellas.aspx.