Cost-effectiveness of ranibizumab and aflibercept to treat diabetic macular edema from a US perspective: analysis of 2-year Protocol T data

Figures & data

Figure 1. Model schematic: eight VA health states with the five most common 1-year transitions in Protocol T for the (a) study eye (solid arrows) and (b) untreated fellow eye (dashed arrows). Abbreviation. VA, visual acuity.

Table 1. Cost and health utility model parameters.

Parameter	Base case estimate	Range^a	References
Treatment-related costs
Ranibizumab product (0.3 mg)^b	$1,170/vial	$936–1,404	• Administration and laser costs based on Medicare reimbursement; product costs based on WAC
Aflibercept product (2.0 mg)^c	$1,850/vial	$1,480–2,220
Intravitreal administration (CPT 67028)	$103	—
Laser treatment (CPT 67210)	$525	$420–630
AE probabilities (2 years) and 1-time costs
Ranibizumab-related AEs			• Probabilities of AEs based on rates of pre-specified AEs in a recently published study^11 • Medical resources used to treat/manage AEs based on clinical expert opinion • Resource costs based on Medicare reimbursement
Traction retinal detachment	<1%/$2,093	—
Vitreous hemorrhage	5%/$3,377	—
Increased intraocular pressure	16%/$1,130	—
Cataract	0%/$3,125	—
Ocular inflammation	2%/$63	—
Non-fatal myocardial infarction	3%/$57,213 (year 1); $20,873 (year 2)	—
Non-fatal stroke	5%/$47,972 (year 1); $24,411 (year 2)	—
Vascular death	4%/$5,825	—
Total expected ranibizumab AE costs	$1,986 (year 1); $3,246 (year 2)	$1,589–2,383 (year 1); $2,597–3,895 (year 2)
Aflibercept-related AEs
Traction retinal detachment	1%/$2,093	—
Vitreous hemorrhage	7%/$3,377	—
Increased intraocular pressure	17%/$1,130	—
Cataract	1%/$3,125	—
Ocular inflammation	3%/$63	—
Non-fatal myocardial infarction	3%/$57,213 (year 1); $20,873 (year 2)	—
Non-fatal stroke	<1%/$47,972 (year 1); $24,411 (year 2)	—
Vascular death	1%/$5,825	—
Total expected aflibercept AE costs	$1,326 (year 1); $1,784 (year 2)	$1,061–1,591 (year 1); $1,427–2,141 (year 2)
Annual incremental expected medical costs relative to normal vision
Depression			• Estimates from published literature^13^,^14 were inflated to 2016 USD using the Medical Care component of the Consumer Price Index^15
Health states 1–3 (20/40 or better)	$0	—
Health states 4–6 (>20/40–20/80)	$864	$681–1,037
Health state 7 (>20/80–20/200)	$1,204	$963–1,445
Health state 8 (worse than 20/200)	$1,366	$1,093–1,639
Fractures
Health states 1–3 (20/40 or better)	$0	—
Health states 4–6 (>20/40–20/80)	$921	$737–1,105
Health state 7 (>20/80–20/200)	$1,022	$818–1,226
Health state 8 (worse than 20/200)	$1,253	$1,002–1,504
Skilled nursing facility
Health states 1–3 (20/40 or better)	$0	—
Health states 4–6 (>20/40–20/80)	$824	$659–989
Health state 7 (>20/80–20/200)	$1,074	$859–1,289
Health state 8 (20/200 or worse)	$1,552	$1,242–1,862
Nursing home
Health states 1–3 (20/40 or better)	$0	—
Health states 4–6 (>20/40–20/80)	$6,121	$4,897–7,345
Health state 7 (>20/80–20/200)	$7,472	$5,978–8,966
Health state 8 (worse than 20/200)	$11,061	$8,849–13,273
Annual expected caregiver costs associated with VA
Health states 1–2 (better than 20/32)	$372	$298–446	• Caregiver time estimates from published literature^18 were monetized in 2016 USD using hourly wage data^19
Health states 3–4 (20/32 to >20/50)	$2,241	$1,793–2,689
Health states 5–6 (20/50 to >20/80)	$5,882	$4,706–7,058
Health state 7 (20/80 to >20/200)	$23,325	$18,660–27,990
Health state 8 (20/200 or worse)	$77,370	$61,896–92,844
VA health state utilities
Health state 1 (20/25 or better)	0.799	0.719–0.879	• Czoski-Murray et al.^16
Health state 2 (>20/25–20/32)	0.744	0.670–0.818
Health state 3 (>20/32–20/40)	0.707	0.636–0.778
Health state 4 (>20/40–20/50)	0.670	0.603–0.737
Health state 5 (>20/50–20/63)	0.633	0.570–0.696
Health state 6 (>20/63–20/80)	0.597	0.537–0.657
Health state 7 (>20/80–20/200)	0.505	0.455–0.556
Health state 8 (worse than 20/200)	0.321	0.289–0.353

Costs are expressed in 2016 USD.

^a Minimum and maximum of range used in one-way sensitivity analyses.

^b Lucentis, Genentech, Inc., South San Francisco, CA.

^c Eylea, Regeneron Pharmaceuticals, Inc., Tarrytown, NY.

Abbreviations. AE, adverse event; CPT, Current Procedural Terminology; USD, US dollars; VA, visual acuity; WAC, wholesale acquisition costs.

Table 2. Base case and extrapolated 10-year cost, QALY, and ICER results.

	Base case			Extrapolated 10-year costs
	AFL 2.0 mg	RBZ 0.3 mg	Difference (AFL – RBZ)	AFL 2.0 mg	RBZ 0.3 mg	Difference (AFL – RBZ)
Full cohort
Treatment costs	$43,693	$33,645	$10,049	$95,458	$74,675	$20,784
Product	$38,069	$25,661	$12,407	$67,275	$44,132	$23,143
Administration	$2,120	$2,259	–$140	$3,746	$3,885	–$140
Laser procedure	$394	$493	–$98	$541	$640	–$98
AEs	$3,111	$5,232	–$2,121	$23,897^b	$26,018^b	–$2,121^b
Visual impairment/blindness costs^a	$730	$885	–$155	$908	$1,084	–$176
Total costs	$44,423	$34,529	$9,894	$96,367	$75,759	$20,608
Total QALYs	1.476	1.466	0.010	5.978	5.949	0.029
ICER ($/QALY gained)	$986,159/QALY gained for AFL vs RBZ			$711,301/QALY gained for AFL vs RBZ
VA sub-group 1 (20/40 or better at baseline)
Treatment costs	$40,519	$31,577	$8,942	$92,284	$72,607	$19,678
Product	$35,062	$23,761	$11,301	$64,268	$42,232	$22,036
Administration	$1,952	$2,092	–$140	$3,578	$3,718	–$140
Laser procedure	$394	$493	–$98	$541	$640	–$98
AEs	$3,111	$5,232	–$2,121	$23,897^b	$26,018^b	–$2,121^b
Visual impairment/blindness costs^a	$335	$320	$15	$426	$383	$43
Total costs	$40,854	$31,897	$8,957	$92,710	$72,989	$19,721
Total QALYs	1.517	1.519	–0.002	6.131	6.164	–0.032
ICER ($/QALY gained)	RBZ dominates AFL			RBZ dominates AFL
VA sub-group 2 (20/50 or worse at baseline)
Treatment costs	$47,064	$35,779	$11,285	$98,829	$76,809	$22,020
Product	$41,262	$27,623	$13,639	$70,468	$46,094	$24,374
Administration	$2,297	$2,432	–$134	$3,923	$4,058	–$134
Laser procedure	$394	$493	–$98	$541	$640	–$98
AEs	$3,111	$5,232	–$2,121	$23,897^b	$26,018^b	–$2,121^b
Visual impairment/blindness costs^a	$1,150	$1,467	–$318	$1,420	$1,807	–$387
Total costs	$48,214	$37,246	$10,967	$100,249	$78,616	$21,633
Total QALYs	1.433	1.412	0.021	5.816	5.728	0.088
ICER ($/QALY gained)	$523,377/QALY gained for AFL vs RBZ			$246,978/QALY gained for AFL vs RBZ

^a Depression, fractures, skilled nursing facility.

^b Two-year AEs and 10-year myocardial infarction/stroke.

Abbreviations. AE, adverse event; AFL, aflibercept; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year; RBZ, ranibizumab; VA, visual acuity.

Figure 2. One-way sensitivity analysis results for the full cohort^a. ^aExcept where otherwise noted, parameters varied by ±20%. ^bIncrease in parameter estimate to 75th percentile value; decrease in parameter estimate to 25th percentile value. ^cThe base case analysis excluded nursing home and caregiver costs; therefore, these costs were added in the sensitivity analysis. ^dBase case injection frequency assumptions for patients treated in the fellow eye (a) from baseline through 1 year or more (2× median number of injections) or (b) any time before 2 years but not at baseline (1.5×) were reduced to 1.5× and 1.25×, respectively. Abbreviations. ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year; VA, visual acuity.

Table 3. Multi-way sensitivity analysis of the better-seeing eye:worse-seeing eye weighting function.

Analysis	AFL 2.0 mg total costs	RBZ 0.3 mg total costs	AFL 2.0 mg QALYs	RBZ 0.3 mg QALYs	ICER ($/QALY gained)
Full cohort
Base case results, 75%:25% (better:worse)	$44,423	$34,529	1.476	1.466	$986,159
100%:0% (better:worse)	$44,078	$34,112	1.509	1.507	$3,565,898
50%:50% (better:worse)	$44,769	$34,947	1.443	1.426	$568,689
25%:75% (better:worse)	$45,115	$35,365	1.409	1.385	$397,794
0%:100% (better:worse)	$45,460	$35,783	1.376	1.344	$304,824
0%:100% (better:worse) with NH and CG costs	$63,358	$59,110	1.376	1.344	$133,814
VA sub-group 1 (20/40 or better at baseline)
Base case results, 75%:25% (better:worse)	$40,854	$31,897	1.517	1.519	RBZ dominates AFL
100%:0% (better:worse)	$40,609	$31,664	1.543	1.547	RBZ dominates AFL
50%:50% (better:worse)	$41,098	$32,130	1.490	1.490	RBZ dominates AFL
25%:75% (better:worse)	$43,343	$32,363	1.464	1.462	$5,049,321
0%:100% (better:worse)	$41,587	$32,596	1.437	1.434	$2,543,876
0%:100% (better:worse) with NH and CG costs	$52,170	$44,464	1.437	1.434	$2,180,333
VA sub-group 2 (20/50 or worse at baseline)
Base case results, 75%:25% (better:worse)	$48,214	$37,246	1.433	1.412	$523,377
100%:0% (better:worse)	$47,761	$36,638	1.473	1.465	$1,345,712
50%:50% (better:worse)	$48,667	$37,855	1.392	1.359	$321,353
25%:75% (better:worse)	$49,120	$38,463	1.352	1.305	$229,986
0%:100% (better:worse)	$49,573	$39,072	1.311	1.252	$177,905
0%:100% (better:worse) with NH and CG costs	$75,238	$74,224	1.311	1.252	$17,187

Abbreviations. AFL, aflibercept; CG, caregiver; ICER, incremental cost-effectiveness ratio; NH, nursing home; QALY, quality-adjusted life-year; RBZ, ranibizumab; VA, visual acuity.

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