Table 1.

Model inputs of the analysis. In the probabilistic sensitivity analysis, the parameter inputs were simultaneously varied within the lower and upper estimates according to the distribution shown. In the deterministic sensitivity analysis, the parameter inputs were varied one-by-one between lower and upper inputs, while the “scenario” column shows inputs based on other plausible assumptions or sources

Variable	Base case	Lower	Upper	Distribution	Scenario	Reference (base case/scenario)
Demography
Cohort size						Statistics Netherlands [29]
50 years	253,491
60 years	222,845
70 years	217,058
80 years	93,547
Background mortality	Age-specific					Statistics Netherlands [28]
HZ epidemiology
HZ incidence per 100,000 person-years						NIVEL [30]/incidence adjusted for immunocompetent population using Schroder [4]
50–59 years	591	575	607	Beta	461
60–69 years	857	835	878	Beta	669
70–79 years	1190	1157	1222	Beta	929
≥ 80 years	1481	1435	1527	Beta	1156
False positive HZ diagnoses (%)	10.0	7.9	12.4	Beta	0	Van Hoek [31]/assuming no false positives
HZ hospitalization incidence per 100,000 person-years						Dutch Hospital Data [32]/incidence adjusted for the immunocompetent population using Hobbelen [49]
50–59 years	2.5	2.1	2.9	Beta	2.2
60–69 years	4.9	4.3	5.5	Beta	4.3
70–79 years	9.5	8.4	10.6	Beta	8.3
≥ 80 years	18.4	16.4	20.4	Beta	16.1
HZ 1-day hospital admission incidence per 100,000 person-years						Dutch Hospital Data [32]/incidence adjusted for the immunocompetent population using Hobbelen [49]
50–59 years	3.6	3.1	4.0	Beta	3.1
60–69 years	9.6	8.8	10.5	Beta	8.4
70–79 years	21.8	20.1	23.4	Beta	19.1
≥ 80 years	28.2	25.8	30.7	Beta	24.8
HZ mortality incidence per million person-years						Statistics Netherlands [34]/incidence adjusted for the immunocompetent population using Hobbelen [49]
50–59 years	0.1	–	0.3	Beta	0.1
60–69 years	0.4	0.05	0.7	Beta	0.3
70–79 years	1.8	0.9	2.8	Beta	1.6
80–89 years	16.5	12.6	20.5	Beta	14.3
≥ 90 years	108.9	84.6	133.2	Beta	94.5
Misclassification HZ as underlying cause of death (%)	47.5	32.0	63.0	Beta	0	Mahamud [35]/assuming no misclassification
QALY loss
QALY loss per HZ episode						Van Wijck [6]/utilities Van Hoek/QALY loss per HZ episode Van Hoek [31]
50–59 years	0.040	0.025	0.063	a	0.034/0.067
≥ 60 years	0.057	0.039	0.093	a	0.053/0.200
QALY loss per HZ death	Age-specific					Statistics Netherlands [28], Szende [36]
QALY loss grade 3 adverse event per dose						Excluded/QALY loss for grade 3 adverse events (see Additional file 1)
HZ/su	0				0.000329
ZVL	0				0.000022
Costs (€, 2017)
Health care costs
GP visit, medication, specialist visit						Based on multiple sources (see Additional file 1)
50–59 years	158	130	186	a
≥ 60 years	198	163	233	a
Hospital admission
50–59 years	2856	2490	3222	a
60–69 years	3632	3166	4097	a
70–79 years	3671	3325	4016	a
≥ 80 years	4504	4093	4915	a
One-day hospital admission	282					Hakkaart-van Roijen [38]
Healthcare costs in gained life years per averted HZ death	Age-specific				0	Statistics Netherlands [28], Van Baal [40]/excluding costs in gained life years
Vaccine administration	11.36					SNPG [41]
Patient costs
OTC medication per HZ episode						Based on multiple sources (see Additional file 1)
50–59 years	10.42	8.85	12.00	a
≥ 60 years	12.65	10.75	14.56	a
Travel costs GP visit, medication, specialist care per HZ episode						Based on multiple sources (see Additional file 1)
50–59 years	3.33	2.61	4.06	a
≥ 60 years	4.07	3.19	4.95	a
Travel costs hospital per HZ hospital visit/hospitalization	5.79
Travel costs per vaccination	0.43
Productivity losses
HZ episode						Based on multiple sources (see Additional file 1)
50–59 years	398	230	744	a
60–69 years	136	78	262	a
≥ 70 years	0
HZ death						Friction period of 84 working days [27]
50–59 years	14,937
60–69 years	5074
≥ 70 years	–
Vaccine characteristics
Vaccine uptake (%)	50					Assumption based on Eilers [42]
Adherence to the second dose of HZ/su (%)	100				90, 70, 50	Assumption
Efficacy HZ/su over time (linear function)						Function fitted using data from Cunningham [20], Lal [19] and Curran [47]
Intercept
50–69 years	0.981	0.904	1.057c	Normal
≥ 70 years	0.992	0.956	1.028c	Normal
Slopeb	− 0.041	0.018	0.065	Beta
Efficacy ZVL over time (one-minus-exponential function)d					Additional efficacy against PHN /post-licensure effectiveness against HZ	Function fitted using data from Oxman [11], Schmader [46] and Morrison [12]/see Additional file 1
Intercept	− 0.893	− 1.04	− 0.75	Normal
Slope	0.0807	0.058	0.104	Beta
Risk ratio of efficacy by age						Estimated using Rohan [45] and Schmader [44]/see Additional file 1
50–59 years	1.282
60–64 years	1.274
65–69 years	1.219
70–74 years	0.852
75–79 years	0.711
80–84 years	0.391
≥ 85 years	0.152

HZ herpes zoster, HZ/su HZ subunit vaccine, PHN post-herpetic neuralgia, QALY quality-adjusted life year, SNPG Stichting Nationaal Programma Grieppreventie, ZVL zoster vaccine live

^aAggregated costs from multiple cost items which were varied individually in the probabilistic sensitivity analysis (see Additional file 1)

^bThe slope of 0.009 was only used for 50- to 69-year-olds over the first 4 years covered by the trial. After 4 years, the slope of ≥ 70-year-olds was used

^cThe efficacy was rounded to 1 during the period that the efficacy function was above 1

^dThe efficacy of ZVL over time (in years) was modelled using a one-minus-exponential function 1 − exp(β₁ + β₂ × years), in which β₁ is the intercept and β₂ the slope. Risk ratios by age were used to modify the intercept. For instance, the efficacy of 60–64 years at time point zero was 1 − exp(1.274 × − 0.893 + 0 × 0.0807) = 67.9%. In our model, we used the VE of the age group 60–64 for vaccination of 60-year-olds, 70–74 for 70-year-olds, 80–84 for 80-year-olds and ≥ 85 years for the booster for 90-year-olds