A latanoprost cationic emulsion (STN1013001) vs. other latanoprost formulations (Latanoprost) in open angle glaucoma/ocular hypertension and ocular surface disease: an Italian cost-utility analysis

Figures & data

Figure 1. Markov model. Abbreviations: OAG/OHT, open angle glaucoma/ocular hypertension.

Table 1. Base case analysis – Methods – Unit cost for healthcare resources, utility and disutility values (Costs in €2020).

Model main items	Point estimate (95% CI)^a,b		Source
OAG/OHT stages 0–5
Drugs
Medications^c,d
STN1013001	€0.30		Santen GmbH, 2020
Latanoprost	€0.21		[41,42]
Add-on therapies^d,e
Acetazolamide	€0.17		[41,42]
Brimonidine	€0.18		[41,42]
Brinzolamide + brimonidine	€0.41		[41,42]
Dorzolamide	€0.16		[41,42]
Timolol	€0.18		[41,42]
Timolol + brimonidine	€0.19		[41,42]
Timolol + dorzolamide	€0.22		[41,42]
Healthcare procedures
Breakup time test	€44.20 (€35.54;€52.86)		[44] (Code: 09.19)
Diurnal curve of intraocular pressure measurement	€13.94 (€11.21;€16.67)		[43] (Code: 89.11)
Gonioscopy	€7.75 (€6.23;€9.27)		[43] (Code: 95.26)
Optical coherence tomography retinal nerve fiber layer	€35.30 (€28.38;€42.22)		[43] (Code: 95.03.3)
Pachimetry	€38.73 (€31.14;€46.32)		[43] (Code: 95.13.1)
Retinal nerve fiber thickness assessment	€15.49 (€12.45;€18.53)		[43] (Code: 95.14)
Slit lamp examination	€30.99 (€24.92;€37.06)		[43] (Code: 95.13.2)
Tonometry	€13.94 (€11.21;€16.67)		[43] (Code: 89.11)
Visual field test	€16.78 (€13.49;€20.07)		[43] (Code: 95.05)
Specialist visits
Ophthalmologist	€20.66 (€16.61;€24.71)		[43] (Code: 89.7)
Optometrist	€20.66 (€16.61;€24.71)		[43] (Elaborated on Code: 89.7)
Utility and disutility values^f	STN1013001^g	Latanoprost^h
OAG/OHT stage 0	0.900 (0.857;0.936)	0.900 (0.855;0.938)	[38]
OAG/OHT stage 1	0.892 (0.851;0.927)	0.877 (0.832;0.915)	Experts opinion
OAG/OHT stage 2	0.879 (0.841;0.913)	0.846 (0.804;0.884)	Experts opinion
OAG/OHT stage 3	0.876 (0.839;0.908)	0.836 (0.795;0.873)	Experts opinion
OAG/OHT stage 4	0.832 (0.792;0.869)	0.800 (0.756;0.840)	Experts opinion
OAG/OHT stage 5	0.790 (0.737;0.838)	0.790 (0.739;0.837)	[38]
OSD-related disutility	−0.120 (−0.231;-0.045)	−0.120 (−0.231;-0.045)	[39]
Death	0.000 (-)	0.000 (-)	[19,20]

Abbreviations: CI, confidence interval; IOP, intraocular pressure; OAG/OHT, open angle glaucoma/ocular hypertension; OSD, ocular surface disease.

^a95% CI was calculated assuming a Normal probability distribution [22,23].

^b95% CI was not calculated for the unit cost of drugs since they are exogenous variables [22].

^cMedications refer to STN1013001 and Latanoprost only.

^dCost per diem calculated on ex-factory price.

^eAdd-on therapies prescribed in addition to STN1013001 or Latanoprost due to poor IOP control.

^f95% CI for utility and disutility values was calculated assuming a Beta and a Gamma probability distribution, respectively [22,23].

^gAnnual number of expected patients on STN1013001 or Latanoprost stratified by OAG/OHT stage according to experts opinion (female %): 0 = 222 (43.56%); 1 = 253 (44.19%); 2 = 313 (44.55%); 3 = 348 (44.83%); 4 = 358 (39.51%); 5 = 248 (40.30%).

^hAnnual number of expected patients on STN1013001 or Latanoprost stratified by OAG/OHT stage according to experts opinion (female %): 0 = 200 (43.25%); 1 = 240 (44.58%); 2 = 310 (45.48%); 3 = 345 (44.93%); 4 = 350 (40.57%); 5 = 265 (41.89%).

Table 2. Base case analysis – Results – Markov trace – Hypothetical cohorts of patients on STN1013001 and on Latanoprost (Costs in €2020).

STN1013001
Year	Markov states								Cumulative results
	Dead	OAG/OHT stage 0^a	OAG/OHT stage 1	OAG/OHT stage 2	OAG/OHT stage 3	OAG/OHT stage 4	OAG/OHT stage 5	Total	Cost	LYS	QALYs
0	0	1000	0	0	0	0	0	1000	0	0	0
1	121	614	141	68	30	16	11	1000	€704.61	0.940	0.625
2	198	419	173	99	53	33	25	1000	€1060.58	1.756	1.088
3	284	285	167	108	68	47	41	1000	€1377.04	2.472	1.493
4	374	192	144	104	73	55	58	1000	€1648.63	3.086	1.815
5	464	129	116	92	70	58	71	1000	€1878.89	3.603	2.080
Mean number (SD) of OAG/OHT notional patients in each Markov state during a 5-year time horizon [%]
	240 (170) [23.99%]	440 (324) [43.98%]	123 (64) [12.34%]	79 (41) [43.98%]	49 (29) [4.88%]	35 (23) [3.49%]	34 (28) [3.44%]	1000 (-) [100.00%]
Latanoprost
Year	Markov states								Cumulative results
	Dead	OAG/OHTstage 0^a	OAG/OHT stage 1	OAG/OHT stage 2	OAG/OHT stage 3	OAG/OHT stage 4	OAG/OHT stage 5	Total	Cost	LYS	QALYs
0	0	1000	0	0	0	0	0	1000	0	0	0
1	121	601	150	71	29	18	11	1000	€671.76	0.940	0.598
2	199	404	179	102	53	37	26	1000	€1017.49	1.755	1.043
3	285	270	169	111	68	53	45	1000	€1326,38	2.470	1.430
4	376	179	142	105	72	63	63	1000	€1593.77	3.082	1.738
5	467	118	111	91	69	65	79	1000	€1821.29	3.596	1.991
Mean number (SD) of OAG/OHT notional patients in each Markov state during a 5-year time horizon [%]
	241 (171) [24.14%]	429 (329) [42.86%]	125 (66) [12.53%]	80 (42) [7.98%]	48 (29) [4.84%]	39 (26) [3.93%]	37 (31) [3.72%]	1000 (-) [100.00%]

Abbreviations: LYS, life-year saved; OAG/OHT, open-angle glaucoma/ocular hypertension; QALYs, quality-adjusted life years; SD, standard deviation.

^aNotional patients are assumed to enter the Markov model at OAG/OHT stage 0.

Table 3. Base case analysis – Results – Costs per patient and cost-utility analysis (€2020).

Items	STN1013001 (%)	Latanoprost (%)	Difference (%) [95% CI]^a,b
INHS viewpoint
Cost
Diagnosis	€289.13 (15.39)	€274.29 (15.06)	€14.84 (25.76) [-€39.93;€70.09]
Medications^c	€287.86 (15.32)	€198.60 (10.90)	€89.27 (154.98) [€82.43;€99.00]
Add-on therapies and follow-up	€949.12 (50.52)	€953.16 (52.33)	-€4.04 (−7.01) [-€109.30;€113.62]
OSD management	€352.78 (18.78)	€395.25 (21.70)	-€42.47 (−173.73) [-€87.84;-€1.72]
Overall	€1878.89 (100.00)	€1821.29 (100.00)	€57.60 (100.00) [-€67.26;€188.60]
LYS and QALYs
LYS	3.603	3.596	0.006 [−0.066;0.087]
QALYs	2.080	1.991	0.089 [−0.028;0.207]
Cost-utility analysis
Incremental costs (ΔC)	€57.60
Incremental QALYs (ΔQALYs)	0.089
ICUR (ΔC/ΔQALYs)	€647.65 (NE sector of the cost-effectiveness plane)

Abbreviations: CI, confidence interval; INHS, Italian national health service; ICUR, incremental cost-utility ratio; LYS, life-year saved; NE, north- east; OAG/OHT, open angle glaucoma/ocular hypertension; OSD = ocular surface disease; QALYs = quality-adjusted life years.

^a(STN1013001 – Latanoprost).

^b95% CI was calculated via the percentile method [22].

^cMedications refer to STN1013001 and Latanoprost only.

Figure 2. One-way sensitivity analysis - Results concerning the first 10 parameters of the Markov model that causes the widest variation in base case ICUR STN1013001 (€647.65; NE sector of the cost-effectiveness plane) (€2020).^a Abbreviations: ICUR, incremental cost-utility ratio; LL 95% CI, lower limit 95% confidenceinterval; NE, north-east; OAG/OHT, open angle glaucoma/ocular hypertension; UL 95% CI, upper limit 95% confidence interval. ^aY and X-axes intersect at the baseline ICUR.

Figure 3. Probabilistic sensitivity analysis- I - Cost-effectiveness plane (10,000 out of 10,000 Monte Carlo iterationsreported) (€2020).^a,b Abbreviations: ΔC, incrementalcost; ΔQALYs,incremental quality-adjusted life years; ICUR, incremental cost-utility ratio; NE, north-east; NW, north-west; SE, south-east; SW, south-west. ^aBase caseICUR STN1013001: €647.65; NE sector of the cost-effectiveness plane. ^bNumber of Monte Carlo iterations (%) for each sector of the cost-effectiveness plane: NE=7721 (77.21%); NW=498 (4.98%); SW=146 (1.46%); SE=1635 (16.35%).

Figure 4. Probabilistic sensitivity analysis - II - Cost-effectiveness acceptability curve and frontier (1000 out of 1000 threshold values reported) (€2020).^a,b,c Abbreviations: CEAC,cost-effectiveness acceptability curve; CEAF,cost-effectiveness acceptability frontier; ICUR, incremental cost-utility ratio; NE, north-east; NMB, net monetary benefit; WTP, willingness-to-pay. ^aBase case ICUR STN1013001: €647.65; NE sector of the cost-effectiveness plane. ^bThe dotted line represents the CEAF. ^cCEAF shows that Latanoprost has the highest expected NMB up to a WTP <€800.80 and a decreasing probabilityof being optimal; STN1013001 has the highest expected NMB from a WTP ≥€800.80 and an increasing probability of being optimal.

Table 4. Scenario sensitivity analyses – I – Results (€2020).

Items	ICUR (ΔC/ΔQALYs) STN1013001	Δ vs. baseline CUA (%)	Sector of the cost- effectiveness plane
INHS viewpoint
Cost-utility analysis – Base case	€647.65	0.00%	NE
Cost-utility analysis – Scenario sensitivity analysis – Markov model time horizon
Markov model time horizon = 1 year	€1256.30	+93.98%	NE
Markov model time horizon = 2 years	€958.81	+48.04%	NE
Markov model time horizon = 3 years	€799.06	+23.38%	NE
Markov model time horizon = 4 years	€711.73	+9.89%	NE
Markov model time horizon = 5 years^a	€647.65	0.00%	NE
Markov model time horizon = 6 years	€391.38	−39.57%	NE
Markov model time horizon = 7 years	€211.16	−67.40%	NE
Markov model time horizon = 8 years	€86.43	−86.65%	NE
Markov model time horizon = 9 years	€2.43	−99.62%	NE
Markov model time horizon = 10–19 years^b	STN1013001 is strongly dominant (ΔC<0;ΔQALYs>0)	-	SE

Abbreviations: CUA, cost-utility analysis; ΔC, incremental cost; ΔQALYs, incremental quality-adjusted life years; ICUR, incremental cost-utility ratio; INHS, Italian national health service; NE, North-East; SE, South-East.

^aBase case ICUR.

^bFrom year 20 onwards, no notional patient on STN1013001 or Latanoprost is expected to be still alive.

Table 5. Scenario sensitivity analyses – II – Results (€2020).

Items
INHS viewpoint	Cost difference for STN1013001
Cost-utility analysis – Base case analysis	Diagnosis	Medications	Add-on therapies and follow-up	OSD management	ΔC^a	ΔQALYs	ICUR STN1013001 (ΔC/ΔQALYs)	Sector of the cost- effectiveness plane
	€14.84	€89.27	-€4.04	-€42.47	€57.60	0.089	€647.65	NE
Cost-utility analysis – Scenario sensitivity analysis – Annual probability of concomitant OSD and OSD-related disutility
Deterministic
No concomitant OSD for both monotherapies	€14.84	€89.27	-€4.04	€0.00	€100.07	0.069	€1450.11	NE
Δ vs. baseline CUA (%)	0.00%	0.00%	0.00%	−100.00%	+73.73%	−22.47%	+123.90%
Annual probability of concomitant OSD Latanoprost for both monotherapies	€14.84	€89.27	-€4.04	-€7.67	€92.40	0.065	€1416.39	NE
Δ vs. baseline CUA (%)	0.00%	0.00%	0.00%	+453.72%	+60.42%	−26.97%	+118.70%
Annual probability of concomitant OSD STN1013001 for both monotherapies	€14.84	€89.27	-€4.04	-€6.98	€93.08	0.066	€1419.57	NE
Δ vs. baseline CUA (%)	0.00%	0.00%	0.00%	+508.45%	+62.85%	−25.84%	+119.19%
Reverse annual probabilities of concomitant OSD between STN1013001 and Latanoprost	€14.84	€89.27	-€4.04	€27.68	€127.75	0.042	€3044.38	NE
Δ vs. baseline CUA (%)	0.00%	0.00%	0.00%	−165.17%	+121.79%	−52.81%	+370.07%
No concomitant OSD-related disutility for both monotherapies	€14.84	€89.27	-€4.04	-€42.47	€57.60	0.069	€834.68	NE
Δ vs. baseline CUA (%)	0.00%	0.00%	0.00%	0.00%	0.00%	−22.47%	+28.88%
Probabilistic^b
Probability that STN1013001 is cost-effective				Probability that STN1013001 is optimal
Threshold value per ΔQALY gained	€25,000		€40,000	from €1001.00 onwards		from €1601.60 onwards		from €3203.20 onwards
No concomitant OSD for both monotherapies	85.83%		86.40%	-		53.71%		-
Annual probability of concomitant OSD Latanoprost for both monotherapies	85.91%		86.35%	-		53.86%		-
Annual probability of concomitant OSD STN1013001 for both monotherapies	86.13%		86.68%	-		53.99%		-
Reverse annual probabilities of concomitant OSD between STN1013001and Latanoprost	73.36%		74.37%	-		-		50.69%
No concomitant OSD-related disutility for both monotherapies	86.91%		87.24%	55.26%		-		-

Abbreviations: CUA, cost-utility analysis; ΔC, incremental cost; ICUR, incremental cost-utility ratio; ΔQALYs, incremental quality-adjusted life years; INHS, Italian national health service; NE, North-East; OSD, ocular surface disease; PSA, probabilistic sensitivity analysis.

^aΔC = (Diagnosis + Medications + Add-on therapies and follow-up + OSD management).

^bPSA was calculated via 10,000 Monte Carlo iterations.

Figure 5. Value of information analysis - Expected value of perfect information and expectedvalueof parameter perfect information scaled up to a population of 94,342 patients (i.e., 100,000 in total over 5 years discounted at 3%) (€2020).^a,b Abbreviations: AE, adverse events; EVPI, expected value of perfect information; EVPPI, expected value of parameter perfect information; FU, follow-up; OAG/OHT, open angle glaucoma/ocular hypertension; OSD, ocular surface disease. ^aEVPI: 10,000 out of 10,000 Monte Carlo iterations reported. ^bEVPPI: 100 and 200 Monte Carlo iterations reported for the inner and outer loop, respectively.

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