A United Kingdom-based economic evaluation of ranibizumab for patients with retinal vein occlusion (RVO)

Figures & data

Figure 1. Model structure. Although different scales (e.g., logMAR, Snellen) exist to measure the severity of a patient’s visual impairment, the Early Treatment of Diabetic Retinopathy Study letter scale was chosen for this model because it is commonly used in clinical trials and is the scale used in the BRAVO and CRUISE clinical studies.

Table 1. Model inputs for effectiveness data (and adverse event rates for ranibizumab only).

	BRVO		CRVO
	Ranibizumab	Grid laser photocoagulation	Ranibizumab	Observation
Month 1	BRAVO	BRAVO	CRUISE	CRUISE
Months 2–6	BRAVO	BRAVO	CRUISE	CRUISE
Months 7–12	BRAVO	Same as ranibizumab	CRUISE	Same as months 2–6
Year 2	HORIZON (Cohort 2)	Same as ranibizumab	HORIZON (Cohort 2)	Natural history
Year 3+	Natural history	Natural history	Natural history	Natural history

BRVO, branch retinal vein occlusion; CRVO, central retinal vein occlusion.

Table 2. Adverse event rates in years 1 and 2.

	Year 1		Year 2
	Ranibizumab	Grid laser photocoagulation/observation	Ranibizumab	Grid laser photocoagulation/observation
Cataract	6.60%	0.00%	5.42%	0.00%
Increased IOP (treated with drug)	10.00%	0.00%	5.42%	0.00%
Increased IOP (treated with surgery)	0.00%	0.00%	0.49%	0.00%
Iris neovascularization	2.35%	0.00%	0.98%	0.00%
Endophthalmitis	0.40%	0.00%	0.40%	0.00%

IOP, intraocular pressure.

Table 3. Utility scores by health state.

Health state	Utility score26	Utility score, assuming 0.30 overall gain
BCVA letter score 86–100	0.87	0.92
BCVA letter score 76–85	0.76	0.88
BCVA letter score 66–75	0.65	0.83
BCVA letter score 56–65	0.61	0.79
BCVA letter score 46–55	0.54	0.75
BCVA letter score 36–45	0.46	0.71
BCVA letter score 26–35	0.39	0.66
BCVA letter score <25	0.35	0.62
Death	0.00	0.00
Adverse events	Disutility	Duration
Cataract	−0.14	6 months
Increased IOP (treated with drug)	−0.01	1 day
Increased IOP (treated with surgery)	−0.01	6 months
Iris neovascularization	0.00	N/A
Endophthalmitis	−0.30	3 months

BCVA, best-corrected visual acuity; IOP, intraocular pressure; N/A, not applicable.

Table 4. Frequency and cost of treatment and follow-up.

	BRVO		CRVO
	Ranibizumab	Grid laser photocoagulation	Ranibizumab	Observation
Year 1
Treatment visits	8.015	1.5^a	9.016	0.0^b
Follow-up visits	4.0^c	2.5^d	3.0^c	6.0^e
Year 2
Treatment visits	1.917	1.0^a	3.017	0.0^b
Follow-up visits	4.1^e	3.0^d	7.0^f	4.0^d
Year 3+
Treatment visits	0.0^b	0.0^b	0.0^b	0.0^b
Follow-up visits	4.0^d	4.0^d	4.0^d	4.0^d
Cost per treatment	£742.1733	£0^g	£742.1733	£0
Cost of administration	£192.00^h	£192.00^h	£192.00^h	£0
Adverse events
Cataract		£800.002
Increased IOP (treated with drug)		£31.6724
Increased IOP (treated with surgery)		£872.6324
Stroke		£10,28134
Iris neovascularization		£576 Three sessions of pan-retinal photocoagulation27
Endophthalmitis		£207027

^aAssumption6.

^bAssumption.

^cAssumption (based on a total of 12 visits of any type per year).

^dAssumption (based on a total of four visits of any type per year).

^eAssumption (based on a total of six visits of any type per year).

^fAssumption (based on a total of 10 visits of any type per year).

^gNo marginal depreciation cost was assumed for each time the equipment was used—only an administration cost was applied.

^hAccumulated cost of optical coherence tomography (ultrasound scan less than 20 min)27 and cost of injection visit (BZ23Z: outpatient procedures [office based])29.

BRVO, branch retinal vein occlusion; CRVO, central retinal vein occlusion; IOP, intraocular pressure.

Table 5. Parameter values for probabilistic sensitivity analyses.

Parameter	Mean	Variation	Type	α	β	Notes
General
Starting age, years	66.8	5	Normal	N/A	N/A	BRAVO and CRUISE
Treatment in the BSE at baseline, %	10	N/A	β	52	470	BRAVO and CRUISE
Treatment in the BSE at 12 months, %	21.5	N/A	β	112	410	BRAVO and CRUISE
Effectiveness multipliers
Treatment effectiveness probabilities: month 1	1	0.1	Log-normal	N/A	N/A	Multiplier/assumption
Treatment effectiveness probabilities: months 2–6	1	0.1	Log-normal	N/A	N/A	Multiplier/assumption
Treatment effectiveness probabilities: months 7–12	1	0.1	Log-normal	N/A	N/A	Multiplier/assumption
Comparator effectiveness probabilities: month 1	1	0.1	Log-normal	N/A	N/A	Multiplier/assumption
Comparator effectiveness probabilities: months 2–6	1	0.1	Log-normal	N/A	N/A	Multiplier/assumption
Comparator effectiveness probabilities: months 7–12	1	0.1	Log-normal	N/A	N/A	Multiplier/assumption
Natural deterioration per monthly cycle	0.031%	N/A	β	3.1	9996.9	Assumes n = 10,000
Mortality RR (BCVA 36–55 letters in the BSE, <36 letters in the WSE)	1.23	0.1	Log-normal	N/A	N/A	Assumption
Mortality RR (BCVA <36 letters in the BSE)	1.54	0.1	Log-normal	N/A	N/A	Assumption
Quality-of-life
Utility multiplier (all)	1	0.05	Normal	N/A	N/A	Assumption
Disutility for cataract	−0.14	0.0284	Normal	N/A	N/A	Assumption (±20%)
Disutility for increased IOP (treated with drug)	−0.01	0.0026	Normal	N/A	N/A	Assumption (±20%)
Disutility for increased IOP (treated with surgery)	−0.01	0.002	Normal	N/A	N/A	Assumption (±20%)
Disutility for stroke	−0.27	0.052	Normal	N/A	N/A	Assumption (±20%)
Costs
Administration costs (multiplier)	1.000	0.200	γ	25	0.04	Assumption (±20%)
Follow-up costs (all treatments) (multiplier)	1.000	0.200	γ	25	0.04	Assumption (±20%)
Treatment visits year 1 (ranibizumab) BRVO	8.0	0.8	γ	100	0.08	Assumption (±10%)
Treatment visits year 2 (ranibizumab) BRVO	1.9	0.19	γ	100	0.025	Assumption (±10%)
Treatment visits year 1 (laser)	1.5	0.15	γ	100	0.02	Assumption (±10%)
Treatment visits year 2 (laser)	1.0	0.1	γ	100	0.01	Assumption (±10%)
Treatment visits year 1 (ranibizumab) CRVO	9.0	0.9	γ	100	0.09	Assumption (±10%)
Treatment visits year 2 (ranibizumab) CRVO	3.0	0.30	γ	100	0.038	Assumption (±10%)
Cost of cataract	£800.00	160	γ	25	32	Assumption (±20%)
Cost of increased IOP (treated with drug)	£31.67	6.33	γ	25	1.267	Assumption (±20%)
Cost of increased IOP (treated with surgery)	£872.63	174.5	γ	25	34.905	Assumption (±20%)
Cost of blindness	£6067.93	1213.59	γ	25	0.04	Assumption (±20%)
Adverse event rates
Cataracts (ranibizumab; year 1/year 2)	6.60%/5.42%	N/A	β	34	488	BRAVO and CRUISE
Iris neovascularization (ranibizumab; year 1/year 2)	2.35%/0.98%	N/A	β	52	470	BRAVO and CRUISE

BSE, best-seeing eye; BRVO, branch retinal vein occlusion; CRVO, central retinal vein occlusion; IOP, intraocular pressure; N/A, not applicable; RR, risk ratio.

Table 6. Base case cost-effectiveness results.

	Ranibizumab	Observation	Grid laser photocoagulation	Incremental
BRVO
Total costs	£17,908	£9767		£8141
QALYs	8.516	7.998		0.518
Months without blindness	194	181		12
Incremental cost per QALY				£15,710
Incremental cost per month free of blindness				£658
CRVO
Total costs	£20,646		£11,430	£9216
QALYs	7.383		6.844	0.539
Months without blindness	171		150	22
Incremental cost per QALY				£17,103
Incremental cost per month free from blindness				£423

BRVO, branch retinal vein occlusion; CRVO, central retinal vein occlusion; QALY, quality-adjusted life-year.

Figure 2. Sensitivity analysis tornado diagrams for (a) BRVO and (b) CRVO.

Figure 3. Probabilistic scatter planes and cost-effectiveness acceptability curves for (a) BRVO and (b) CRVO.

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