Cost-effectiveness of augmenting universal hepatitis B vaccination with immunoglobulin treatment: a case study in Zhejiang Province, East China

Figures & data

Figure 1. Decision tree model. A square node represents the decision node, a circular node represents a chance node and represents a Markov model. At the end of each branch of the decision tree there is one of three types of Markov models either corresponding to ⅰ. infants under immune ⅱ. infants have got perinatal infection or ⅲ. infants are susceptible. Under each line is a probability represented by P_; HBIG, hepatitis B immunoglobulin. If the tree is cloned, it means that the tree is copied, and a corresponding number will appear under the node of the tree.

Table 1. Parameter values including ranges used in the sensitivity analyses.

Parameters	Base-case value	Range	Reference
Newborns in 2016	624,000
Vaccination-related data
Cost of implementation (CNY/per dose)	19.55	± 25%	13
Vaccine price (CNY/per dose)	3.10	± 25%	a
HBIG price (CNY/per dose)	120.0	± 25%	a
Screening
Maternal screening rate (%)	99.0	95-100	b
Cost (CNY/person)	15.0	± 25%	a
Coverage (%)
HepB3 coverage	99.0	95-100	c
HBIG injection rate	99.0	95-100	b
Efficacy (%)
HepB3 for general newborns	96.36	92.13–98.00	14-16
HepB3+ HBIG: HBsAg+	96.0	91.00–97.00	17-19
HepB3: HBsAg+	90.9	83.60–93.00	20-22
HepB3: HBsAg-	97.51	95.06–97.67	23-25
Epidemiology data (%)
HBsAg positive rate among pregnant women	8.0	5.9–13.6	Meta,26
Prenatal infection rate
HepB3 for general newborns	0.93	0.41–1.82	14,27,28
HepB3+ HBIG: HBsAg+	2.9	1.50–3.58	21,29,30
HepB3: HBsAg+	5.9	3.70–6.99	21,22,31
HBsAg+ mothers without vaccination	40.34	32.28–48.40	32,33
General newborns without vaccination	3.22	2.58–3.87
Direct medical costs (CNY)
Acute infection
Not hospitalize after symptomatic	273.00	± 25%	d
Hospitalization after symptomatic	9,661.82		d
Fulminant	49,304.40		34
Immune tolerant	1,614.94		d
HBeAg-positive CHB	16,504.05		d
Inactive carrier	1,614.94		d
HBeAg-negative CHB	13,835.49		d
CC	19,139.21		d
DC	36,428.94		d
HCC	35,225.18		d
Utility score
General Population	0.90	0.84–0.95	35
Acute infection
Asymptomatic carrier/Not fulminant	0.75	0.66–0.84	d
Fulminant	0.46	0.24–0.68	36
Immune tolerant	0.81	0.81–0.82	36,37
HBeAg-positive CHB	0.77	0.75–0.79	d
Inactive carrier	0.81	0.80–0.82	36,37
HBeAg-negative CHB	0.77	0.74–0.79	d
CC	0.66	0.60–0.73	d
DC	0.56	0.53–0.60	d
HCC	0.58	0.52–0.65	d
Duration of protection	lifelong		38
Discount rate (%)	3	0～6	39

a: procurement prices by government in 2016; b: unpublished data from the Zhejiang Provincial CDC; c: reported coverage data from the China Information Management System for Immunization Program;d: data from the field survey

Table 2. Transition probabilities for each cycle of the Markov model.

Parameters	Base-case value	Range	Reference
HBV infection rate in susceptible people by age	(b1+ b2*Exp (b3*age))* (1-P_decrease)^^(24+age)		10,40
≥ 1 year	b1 = 0.034435	0.023542–0.045328
	b2 = 0.494480	0.371654–0.617305
	b3 = −0.729443	−0.942076~-0.516809
	P_decrease = 0.02162	0.02162–0.03243
Outcome probabilities of acute infection
Symptomatic
< 15 years	0.05	0-0.5	9,41-43
≥ 15 years	0.3	0-0.5
Hospitalization after symptomatic presentation	0.3	0.1–0.5	44
Fulminant cases among symptomatic presentation
< 20 years	0.05	0-0.1	44
≥ 20 years	0.04	0-0.1
Death among fulminant patients
< 20 years	0.6	0.04–0.8	45,46
≥ 20 years	0.7	0.04–0.8
Acute infections that become immune tolerant
< 1 year	0.89	± 50%	47
≥ 1 year	e^((−0.65*^age^0.46))
From immune tolerant to:
HBsAg positive CHB
< 7 years	0.0043	± 50%	48
7-12 years	0.0067
13-18 years	0.0294
≥ 19 years	0.1423		49
HBsAg clearance
< 19 years	0.0105	± 50%	50
20-39 years	0.0155
≥ 40 years	0.043
HCC
< 30 years	0.0000288	± 50%	51,52
≥ 30 years	0.0003216
From HBsAg positive CHB to:
Inactive carrier	0.078	0.063–0.093	53
HBsAg clearance	0.013	0.002–0.028	54
CC	0.038	0.022–0.088	55
HCC
< 30 years	0.0000288	± 50%	56
≥ 30 years	0.001175
From inactive carrier to:
HBsAg clearance	0.0342	0.0171–0.0513	54,57
HBsAg negative CHB	0.0427	0.02–0.05	57
HBsAg positive CHB	0.006	0-0.011	53
CC	0.001	0.0005–0.0015	49
HCC
< 30 years	0.0000288	± 50%	56
≥ 30 years	0.0006
From HBsAg negative CHB to:
HBsAg clearance	0.02	0.0050–0.0262	58-61
CC	0.029	0.015–0.058	49
HCC
< 30 years	0.0000288	± 50%	62
≥ 30 years	0.000286
From CC to
DC	0.073	0.035–0.1	63
HCC	0.0316	0.0258–0.0374
From DC to
HCC	0.0316	0.0258–0.0374	63
Death	0.17	0.1–0.25
From HCC to death	0.34	0.22–0.45	63

Table 3. New cases of HBV-related diseases and deaths in the birth cohort.

Strategy	Acute symptomatic infection	Chronic infection	Cirrhosis	HCC	HBV-related deaths
Universal vaccination	2,154	5,352	2,338	1,587	3,634
Current PMTCT	1,972	3,137	1,466	992	2,284
Current PMTCT vs Universal vaccination	−182	−2,215	−872	−595	−1,350

Table 4. Per capital costs, QALYs, and the ICERs of two strategies.

Strategy	Costs*(CNY)			Incremental costs	QALYs	Incremental QALYs	ICER
	Program costs	Illness costs	Total
Universal vaccination	67.27	2,158.47	2,225.74	-	26.88	-	-
Current	91.44	1,341.74	1,433.18	−792.56	26.91	0.03	dominate

*Expressed as the value from 2016

Figure 2. Markov model of protection.

Figure 3. Markov model of perinatal infection and progression. A person in any state may die due to the other causes, but a person with decompensated cirrhosis or hepatocellular carcinoma may also die due to HBV infection.

Figure 4. Markov model of hepatitis B virus (HBV) infection and progression. A susceptible individual would follow the HBV infection rate by age (see Table 2 for the detail formula).

Figure 5. Tornado diagram presenting one-way sensitivity analyses. HepB3, 3-dose hepatitis B vaccination series. HBIG, hepatitis B immunoglobulin. HBsAg, hepatitis B surface antigen. QALY, quality-adjusted life year.

Figure 6. Incremental cost-effectiveness scatter plot for the current strategy compared to universal vaccination. WTP, willingness-to-pay threshold. QALY, quality-adjusted life year.

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