Human Vaccines & Immunotherapeutics

ISSN: 2164-5515 (Print) 2164-554X (Online) Journal homepage: https://www.tandfonline.com/loi/khvi20

Cost-effectiveness analysis of a hepatitis B

vaccination catch-up program among children in
Shandong Province, China

Yuanxi Jia, Li Li, Fuqiang Cui, Dongliang Zhang, Guomin Zhang, Fuzhen Wang,
Xiaohong Gong, Hui Zheng, Zhenhua Wu, Ning Miao, Xiaojin Sun, Li Zhang,
Jingjing Lv & Feng Yang

To cite this article: Yuanxi Jia, Li Li, Fuqiang Cui, Dongliang Zhang, Guomin Zhang, Fuzhen
Wang, Xiaohong Gong, Hui Zheng, Zhenhua Wu, Ning Miao, Xiaojin Sun, Li Zhang, Jingjing Lv &
Feng Yang (2014) Cost-effectiveness analysis of a hepatitis B vaccination catch-up program among
children in Shandong Province, China, Human Vaccines & Immunotherapeutics, 10:10, 2983-2991,
DOI: 10.4161/hv.29944

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 RESEARCH PAPER
Human Vaccines & Immunotherapeutics 10:10, 2983--2991; October 2014; © 2014 Taylor & Francis Group, LLC

Cost-effectiveness analysis of a hepatitis B

vaccination catch-up program among children
in Shandong Province, China
Yuanxi Jia1, Li Li1,*, Fuqiang Cui1, Dongliang Zhang2, Guomin Zhang1, Fuzhen Wang1, Xiaohong Gong1, Hui Zheng1,
Zhenhua Wu1, Ning Miao1, Xiaojin Sun1, Li Zhang3, Jingjing Lv3, and Feng Yang4
1
Chinese Center for Disease Control and Prevention; Beijing, China; 2Ningbo Center for Disease Control and Prevention; Ningbo, Zhejiang, China; 3Shandong Center for Disease
Control and Prevention; Jinan, Shandong, China; 4Qingdao Center for Disease Control and Prevention; Qingdao, Shandong, China

Keywords: catch-up program, Cost-effectiveness Analysis, hepatitis B virus, ICER, QALY, vaccination
Abbreviations: HBV, Hepatitis B Virus; HBsAg, Hepatitis B Surface Antigen; GAVI, Global Alliance on Vaccines and Immuniza-
tion; HepB3, 3-dose Coverage of Hepatitis B Vaccine; MOH, Ministry of Health; NNDRS, National Notifiable Diseases Reporting
System; CHB, Chronic Hepatitis B; CC, Compensated Cirrhosis; DC, Decompensated Cirrhosis; HCC, Hepatocellular Carcinoma;
LT-1, the Year of Liver Transplantation; LT-2, Years after Liver Transplantation; QALYs, Quality-Adjusted Life Years; HRQoL,
Health-Related Quality of Life; Anti-HBs, Antibody to Hepatitis B Surface Antigen; ICER, Incremental Cost-Effectiveness Ratio;
GDP, Gross Domestic Product; BCR, Benefit-Cost Ratio

Objective: The aim of the study was to estimate long-term cost‑effectiveness of a hepatitis B vaccination catch-up
program among children born between 1994 and 2001 (when they were 8‑15 y old) in Shandong province, China, to
provide information for nationwide evaluation and future policy making.
Methods: We determined the cost-effectiveness of the catch-up program compared with the status quo (no catch-up
program). We combined a Decision Tree model and a Markov model to simulate vaccination and clinical progression
after hepatitis B virus (HBV) infection. Parameters in the models were from the literature, a field survey, program files,
and the National Notifiable Disease Reporting System (NNDRS). The incremental cost‑effectiveness ratio (ICER) was used
to compare the 2 alternative strategies. One-way sensitivity analysis, 2-way sensitivity analysis, and probability
sensitivity analysis were used to assess parameter uncertainties.
Results: The catch-up program was dominant compared with the status quo. Using a total of 5.53 million doses of
vaccines, the catch-up program could prevent 21,865 cases of symptomatic acute hepatitis B, 3,088 carrier states with
positive hepatitis B surface antigen (HBsAg), and 812 deaths due to HBV infection. The catch-up program could add
28,888 quality-adjusted life years (QALYs) and save $192.01 million in the targeted population in the future. The models
were robust, considering parameter uncertainties.
Conclusion: The catch-up program in Shandong province among children born between 1994 and 2001 was ‘very
cost-saving.’ It could save life years and reduce total future costs. Our study supported the desirability and impact of
such a catch-up program throughout China.

China has the greatest burden of hepatitis B virus (HBV) dis- (HepB3) exceeded 90% after 2003, compared with less than
ease and liver cancer in the world.1 Data from the 2006 national 60% before 1998 and 20% in 1994. These data indicated
hepatitis B sero-epidemiologic survey showed that about 7.18% that a large proportion of children born between 1994 and
(93 million people) of China’s population carried hepatitis B sur- 2001 were not vaccinated with hepatitis B vaccine and
face antigen (HBsAg).2 remained at risk of HBV infection.
China added hepatitis B vaccine into its national immuni- In order to increase HepB3 coverage among children born
zation program in 2002, allowing the vaccine to be provided between 1994 and 2001 (then aged 8‑15 years), the Ministry of
free to all newborns, nationwide. With support of the Global Health (MOH) initiated a nationwide hepatitis B vaccine catch-
Alliance on Vaccines and Immunization (GAVI), hepatitis B up program for these children that lasted from 2009 to 2011.
vaccination in China’s western region and economically During the catch-up program, approximately 68 million children
weaker areas increased rapidly.3,4 According to China’s Sur- who had not been fully vaccinated were caught up on the doses of
veillance System of Information in the National Immuniza- hepatitis B vaccine that they needed, based on their vaccination
tion Program, reported 3-dose coverage of hepatitis B vaccine history.

*Correspondence to: Li Li; Email: [email protected]

Submitted: 03/25/2014; Revised: 07/02/2014; Accepted: 07/15/2014
http://dx.doi.org/10.4161/hv.29944

www.landesbioscience.com Human Vaccines & Immunotherapeutics 2983

 Traditionally, catch-up vaccination for unvaccinated children Tree model was constructed using data from the program files,
has not been included in the global strategy to control hepatitis while the Markov model was based on published literature.1,7-9
B. Therefore, very few studies are available on such a catch-up The Markov model consisted of 10 infectious conditions:
strategy, especially studies on a national scale using data from immune, susceptible, carriers, chronic hepatitis B (CHB), com-
completed campaigns.5 There was a study of this catch-up strat- pensated cirrhosis (CC), decompensated cirrhosis (DC), hepato-
egy based on a hypothesized situation, and this study supported cellular carcinoma (HCC), the year of liver transplantation
such a strategy for China.6 Considering the rapidly changing and (LT-1), years after liver transplantation (LT-2), and death. We
complicated economic situation and society in China, including distinguished between carriers and CHB patients using standards
the downward trend of HBsAg prevalence, more precise evalua- from the Chinese Medical Association.10 Since we measured
tions and analyses are needed for future decision-making. In our health and economic outcomes for all children over their life-
study we focused on the economic benefits of a completed catch- times, the Markov model cycled in yearly increments for 100 y.
up program using original data collection. We selected Shandong The construction of models was accomplished in TreeAge Pro
province for the study because it has a vigorous economy and a 2012.
good research infrastructure. Cost‑effectiveness information on The Markov model was based on several assumptions11,12: (1)
the catch-up program in Shandong province will provide infor- the targeted population would be protected from HBV infection
mation for more comprehensive evaluations nationwide. if the serum anti-HBs was positive after administration of HBV
vaccine; (2) the population with no response or a low response to
HBV vaccine incurred costs, but were assumed to have no protec-
Methods tion from HBV infection; and (3) since the vaccine was known to
be safe, costs and loss of quality-adjusted life years (QALYs) due
In our cost-effective analysis,7 we used the Shandong catch-up to adverse reaction were neglected.
program and the status quo (i.e., no catch-up program) as 2 alter-
native strategies for comparison. All children born between 1994 Parameters
and 2002 without full hepatitis B immunization took part in the The parameters used in the model were categorized into 4
catch-up program. Children with local residency and without groups: (1) transition probabilities for disease progression; (2)
previous vaccination, children with one previous dose, and chil- costs of the catch-up program and of treatment of patients
dren with 2 previous doses would receive 3 doses, 2 doses and with HBV infection; (3) health-related quality of life
one dose of hepatitis B vaccine, respectively. We categorized the (HRQoL) of patients with HBV infection; (4) other parame-
children into 8 cohorts based on their birth year, and each cohort ters (Table 1).
consisted of 3 groups. Immunization histories were confirmed by Transition Probabilities of Disease Progression: Susceptible
vaccination certificates, without serological tests. Decision Tree persons were at risk of HBV infection. The probability of becom-
and Markov models were used in the analysis. ing a carrier after infection varied with age at infection. DC and
HCC were the major causes of death for patients with HBV;
Data and resources however, some patients could recuperate following liver trans-
Data in our study were from a field survey, program files, the plantation.11,12 Parameters for this group were primarily
National Notifiable Diseases Reporting System (NNDRS), and obtained from the published literature (Table 1).
published literature. After completion of the catch-up program, Cost Parameters: We used the societal perspective to calculate
the government of Shandong province summarized the program costs. Costs of the catch-up program consisted of the implemen-
in several files. These files included descriptions of the age cohorts tation costs of the program and of the treatment costs for patients
and population vaccinated, program costs, and program achieve- with HBV infection. Costs of the status quo strategy group
ments. In order to improve the accuracy and reliability of the included only the treatment costs.
model parameters, we gave priority preference to the field survey, Costs of the catch-up program were subdivided into 10 parts
the program files, and to NNDRS. If data were not available (Table 1). Parameters from the program files were prioritized to
from these sources, we performed a literature review of studies in be used in the model, including costs of vaccines and single-use
both Chinese and English. Studies set in Shandong province or syringes, staff remuneration, training, supervision, and adminis-
with a similar population in China, or neighboring districts with tration. The costs of vaccines and single-use syringes were
a relatively large sample size were preferred. If we found that obtained from the central government; others were obtained
there was limited published literature, we chose the most appro- from provincial, municipal, and county governments. If no data
priate study to be the point estimation for each parameter, and were available in files, we used data from a study13 of the costs of
other studies were used to form confidence intervals for sensitiv- a national immunization program in regions of China, including
ity analysis. Shandong province.
Treatment costs of patients with HBV infection were primar-
Model construction ily obtained from published literature. Both outpatient and inpa-
A Decision Tree model and a Markov model were combined tient costs were included in the study in which only direct and
to simulate the catch-up strategy and the clinical consequences in indirect medical costs were used, whereas other costs such as loss
the target population of HBV infection (Fig. 1). The Decision in productivity and intangible costs were embodied in HRQoL.7

2984 Human Vaccines & Immunotherapeutics Volume 10 Issue 10

 Figure 1. The Markov Model.

All costs were adjusted with respect to the cost of US dollar in August, 2013.16 We first confirmed the applicability of EQ-5D-
2013 according to the consumer price index and the exchange 5L in the targeted population. HRQoL of 5 HBV infectious con-
rate.14,15 ditions, including carriers, CHB, CC, DC, and HCC, were
Effectiveness Parameters: Effectiveness was quantified by obtained from a field survey. HRQoL of patients with liver trans-
QALY in the form of HRQoL. We performed a field survey plantation were obtained from the published literature. Since dif-
using EQ-5D-5L, the 5-level version of EQ-5D to determine the ferent general instruments using the same population may result
HRQoL of the targeted population in Shandong province in in different outcomes and lead to opposite conclusions,17 only

www.landesbioscience.com Human Vaccines & Immunotherapeutics 2985

Table 1. Point and Interval Estimation of Parameters in the Markov Model

Parameters Point Estimation (%) Interval Estimation (%) Ref.

Transition Probabilities in Disease Progress

Proportion of Symptomatic Acute Hepatitis B in total Acute Hepatitis B 30.00 — 11
Proportion of Fulminant Hepatitis B in Symptomatic Acute Hepatitis B Age<20 0.10 0.10–0.60 8, 35
Age
20 0.50 0.10–0.60
Mortality of Fulminant Hepatitis B Age<15 63.00 — 8, 35
Age<45 80.00
Age
45 92.00
Proportion of Fulminant Hepatitis B becaming Carriers 6.25 — 22
eð ¡ 0:65 £ age Þ
0:46
Proportion of Acute Hepatitis B became Carriers — 23
Natural Clearance of HBV Carriers 1.80 1.47–1.80 24, 25
Probability of HBV Carriers became CHB 0.38 0.38–3.00 24, 25
Probability of HBV Carriers became CC 0.25 — 26
Probability of HBV Carriers became HCC 0.36 — 27
Mortality of HBV Carriers due to HBV Infection 0.73 — 25
Natural Clearance of CHB 1.20 — 28
Probability of CHB became CC 1.16 0.84–3.25 29
Probability of CHB became HCC 0.68 0.45–0.68 30, 31
Mortality of CHB due to HBV Infection 0.77 0.77–1.58 32, 33
Probability of CC became DC 3.56 2.51–4.98 33
Probability of CC became HCC 0.28 0.06–3.25 32, 33
Mortality of CC due to HBV Infection 3.52 2.43–4.87 32, 33
Probability of DC became HCC 0.82 0.34–3.25 32, 33
Mortality of DC due to HBV Infection 15.96 15.96–39.32 32, 34
Probability of DC receiving Liver Transplantation 0.15 0.00–0.40 35
Mortality of HCC Due to HBV Infection 80.35 48.52–80.35 34, 36
Probability of HCC Receiving Liver Transplantation 0.08 0.08–0.10 35
Mortality of LT-1 22.42 22.42–28.32 37
Mortality of LT-2 13.78 13.78–13.92 37
Costs of Treatments After HBV Infection (Per Year Per Person)
HBV Carriers 110.23 — 38
Symptomatic Acute HBV Infection 2632.15 2632.15–5285.22 38–40
Fulminant Hepatitis B 11163.49 — 39
CHB 3051.69 730.52–3051.69 38–40
CC 4699.74 2224.89–4699.74 38, 39
DC 7176.04 4528.10–7176.04 38, 39
HCC 10568.54 6493.13–10568.54 38–40
LT-1 38659.00 — 41
LT-2 3381.46 — 41
Costs of the Catch-up Program (Per Dose)*
Vaccines and Single-Use Syringe 0.34 — Program files
Surveillance 0.29 — 12
Staff Remuneration, Training, Supervision, Administration 0.18 Program files
Transportation 0.23 — 12
Publicity 0.12 — 12
Cold Chain 0.09 — 12
Other Equipment 0.13 — 12
HRQoL of the Targeted Population
General Population 0.848 17
HBV Carriers 0.813 — 15
Symptomatic Acute Hepatitis B 0.739 — 19
CHB 0.789 — 15
Liver Transplantation 0.766 — 42
CC 0.763 — 15
HCC 0.699 — 15
DC 0.661 — 15
Other Parameters
Prevalence Proportion with Previous Vaccination 4.30 2.69–5.91 20
Prevalence Proportion without Previous Vaccination 4.95 1.27–8.63 20
Natural Immunization Proportion 36.75 31.26–43.24 20
Anti-HBs Positive Conversion Rate with 1 Dose 14.50 — 43

(continued on next page)

2986 Human Vaccines & Immunotherapeutics Volume 10 Issue 10

Table 1. Point and Interval Estimation of Parameters in the Markov Model (Continued)
Parameters Point Estimation (%) Interval Estimation (%) Ref.
Anti-HBs Positive Conversion Rate with 2 Doses 81.00 79.5–82.9 43, 44
Anti-HBs Positive Conversion Rate with 3 Doses 98.10 — 45
Proportion of HBV Susceptible Persons with 0 Previous Dose 58.30 31.51–67.47 —
Proportion of HBV Susceptible Persons with 1 Previous Doses 50.40 43.48–56.47 —
Proportion of HBV Susceptible Persons with 2 Previous Doses 11.20 9.66-12.55 —
Proportion of HBV Susceptible Persons with 3 Previous Doses 1.12 9.66–12.55 —
All-Cause Mortality — — 46
Discount Rate 0.03 0–0.07 6
The proportion of HBV Susceptible Persons Becoming HBV Infectious Each Year 0.000756 0.00020–0.00500 NNDRS

CC: Compensated cirrhosis; CHB: Chronic hepatitis B; DC: Decompensated cirrhosis; HBs: Hepatitis B surface; HBV: Hepatitis B virus; HCC: Hepatocellular carci-
noma; HRQoL: Health-Related Quality of Life; LT-1: The year of liver transplantation; LT-2: Years after liver transplantation; NNDRS: National Notifiable Disease
Reporting System.

studies using EQ-5D as the survey instrument were included in The proportion of HBV susceptible persons becoming
our model. infected each year was estimated using data from NNDRS.
Since there was no study of HRQoL of acute hepatitis B NNDRS data showed that the incidence of acute hepatitis B in
patients using EQ-5D, we estimated this parameter by compar- Shandong province was 3.58/100,000 in 2008. We assumed that
ing 2 instruments. According to a model used in Japan, the value 30% of the patients with acute hepatitis B would have clinical
by EQ-5D ranged from ¡0.106 to 0.848,18 while for SF-6D, symptoms; 31.51% of the total population was susceptible for
the value ranged from 0.30 to 1.00.19 Therefore, HRQoL for HBV infection; and that 50% of patients were hospitalized for
acute hepatitis B patients was estimated as 0.766.20 treatment after onset of symptoms. We therefore assumed that
Other Parameters: Information on the targeted cohorts was the proportion of HBV susceptible persons becoming infected
extracted from program files, including the number of children each year could be estimated as 75.6/100,000. Since the estimate
in each cohort and the number of doses received previously in of this proportion has varied considerably in studies,7,9 we used a
each group (Table 2). wide interval from 20/100,000 to 500/100,000 in the sensitivity
Since there were no serological tests available, and since it was analysis.
not possible to trace targeted children by the information col-
lected during the program, the proportion of HBV susceptible Model analysis
persons in each cohort was estimated based on a sero-epidemio- We used the Incremental Cost-Effectiveness Ratio (ICER) to
logic survey by age groups,21 using a formula given below: compare the 2 alternative strategies. The ICER was determined by
calculating the difference in costs of the 2 strategies divided by the
Ps D .1 ¡ P1 ¡ P2 / £ .1 ¡ P3 / difference in health effects. According to WHO, an intervention
can be considered ’very cost-effective’ if the ICER is lower than
the annual per capita Gross Domestic Product (GDP) or 3 times
Ps represents the proportion of HBV susceptible persons in each the annual per capita GDP.47 These values were $5,414 and
group and P1 and P2 represent the HBV prevalence proportion $16,242,14,15 respectively. We used one-way sensitivity, 2-way sen-
and natural immunization proportion in each group, respec- sitivity, and probabilistic sensitivity analysis based on Monte-Carlo
tively. P3 represents the antibody to hepatitis B surface antigen simulation with 10,000 iterations to evaluate the impact of param-
(Anti-HBs) positive conversion rate after different doses of eter uncertainty on the ICER. Since the distributions of parameters
vaccination. were unclear due to limited literature-based estimates, all parame-
ters were assigned triangular distributions.7
Table 2. Information on the Targeted Cohorts

Vaccination Histories Results

Birth Year 1 Dose Needed 2 Doses Needed 3 Doses Needed Total
Base case: The catch-up program could not only increase the
1994 70,219 58,426 172,279 300,924 QALYs of the targeted population, but could also save costs
1995 72,944 61,006 193,212 327,162
related to hepatitis B. This indicated that the status quo was dom-
1996 76,791 62,866 188,935 328,592
1997 81,622 61,994 185,395 329,011 inated (inferior), and the catch-up program was ‘cost-saving.’
1998 80,154 64,795 172,589 317,538 According to our estimate, the cost to provide a single dose was
1999 77,230 56,143 155,918 289,291 $1.42. A total of 5.53 million doses of vaccines were used in the
2000 75,041 51,651 138,871 265,563 catch-up program, so the implementation costs of the program
2001 68,219 45,955 127,286 241,460
in Shandong province totaled to $7.89 million. The costs of the
Total 602,220 462,836 1,334,485 2,399,541
status quo was only the treatment costs ($208.26 million), while

www.landesbioscience.com Human Vaccines & Immunotherapeutics 2987

Table 3. Costs and Effectiveness Outcomes by Age Cohort

Cost ($) (Per Person)* Effectiveness

Birth Catch-up Status Incremental Catch-up Status Incremental Whether Cost-effective

Year Vaccination Quo Cost Vaccination Quo Effectiveness or Not

1994 6.58 78.89 ¡72.30 22.24 22.23 0.01 Very Cost-saving

1995 6.71 82.17 ¡75.47 22.36 22.35 0.01 Very Cost-saving
1996 6.73 83.93 ¡77.21 22.46 22.45 0.01 Very Cost-saving
1997 6.75 85.57 ¡78.83 22.57 22.56 0.01 Very Cost-saving
1998 6.79 88.18 ¡81.39 22.67 22.66 0.01 Very Cost-saving
1999 6.84 90.23 ¡83.39 22.77 22.75 0.02 Very Cost-saving
2000 6.88 92.38 ¡85.50 22.86 22.85 0.01 Very Cost-saving
2001 6.99 96.36 ¡89.37 22.96 22.94 0.02 Very Cost-saving
Total 6.78 86.79 ¡80.02 22.59 22.58 0.01 Very Cost-saving

*All costs were adjusted with respect to the cost of dollar in 2013.

the costs of the catch-up strategy were composed of the imple- probabilistic sensitivity analysis. All the points are in the fourth
mentation costs ($7.89 million) and the reduced treatment costs quadrant, indicating that all the samples derived supported our
($8.38 million). The saved treatment costs of $199.88 million conclusion that the catch-up program was always dominant with
were greater than the implementation costs of the vaccination reduced costs and increased QALYs. Taking all parameter uncer-
program ($7.89 million). tainties into account, the model remained robust and reliable.
The catch-up program dominated in all the cohorts，indicat-
ing that the program was not sensitive to the age parameter of
the targeted population (Table 3). By using a total of 5.53 million Discussion
doses of vaccines, the catch-up program could prevent 21,865
cases with symptomatic acute hepatitis B, 3,088 carriers with pos- In recent years, China has made great efforts to control and
itive HBsAg, and 812 deaths due to HBV infection compared prevent HBV infection. But before the extensive use of vaccines,
with the status quo (Table 4). The catch-up program could many newborns were not vaccinated and remained susceptible to
increase 28,888 QALYs and reduce $192.01 million in the HBV infection. According to WHO, implementation of catch-
future. up immunization in such populations will produce broad immu-
Sensitivity analysis: According to the one-way sensitivity anal- nity to HBV infection and eventually prevent transmission
ysis (Table 5), none of the single parameters could change the among all age groups.10
conclusion that the program was ’cost-saving.’ The model was A review showed that in regions with intermediate or high lev-
robust to the uncertainty of any single parameter. Parameters els of HBV epidemic, universal vaccination of newborns would
that showed the greatest impact on the ICER were the probabil- be cost-effective,5 and this conclusion extends to Taiwan,8 Gam-
ity of HBV carriers becoming CHB, the proportion of HBV sus- bia,9 and India.48 Many studies using cost‑effectiveness analysis
ceptible persons becoming HBV infectious each year, and the or cost-benefit analysis in small populations showed that vaccina-
discount rate. We conducted 2-way sensitivity analyses using tion of newborns,49-52 and of some specific group (soldiers,53,54
these parameters, and no combination could change the conclu- workers,55 or middle school students,56 or children under 15 y of
sion of being ‘cost-saving.’ Figure 2 shows the results of the age57) in mainland China, can also be economically acceptable.

Table 4. Numbers of Infections and Deaths Prevented by the Catch-up Vaccination

Symptomatic Acute Infections HBsAg Carriers Deaths

Birth Status Catch-up Infections Status Catch-up Carriers Status Catch-up Deaths
Year Quo Vaccination Prevented Quo Vaccination Prevented Quo Vaccination Prevented

1994 2728 66 2,662 327 9 318 86 2 84

1995 3044 72 2,972 380 10 370 100 3 97
1996 3068 74 2,994 403 11 392 106 3 103
1997 3071 74 2,997 422 11 411 111 3 108
1998 2987 72 2,915 433 12 421 114 3 111
1999 2721 66 2,655 414 11 403 109 3 106
2000 2491 62 2,429 403 11 392 106 3 103
2001 2298 57 2,241 391 10 381 103 3 100
Total 22408 543 21,865 3173 85 3088 835 23 812

2988 Human Vaccines & Immunotherapeutics Volume 10 Issue 10

Table 5. Results of One-way Sensitivity Analysis

ICER Vaccination vs. Status quo

Parameters Minimum Value Maximum Value

Proportion of Fulminant Hepatitis B in Symptomatic Acute Hepatitis B Age< 20 Cost-saving Cost-saving

Age
20 Cost-saving Cost-saving
Natural Clearance of HBV Carriers Cost-saving Cost-saving
Probability of HBV Carriers became CHB Cost-saving Cost-saving
Probability of CHB became CC Cost-saving Cost-saving
Probability of CHB became HCC Cost-saving Cost-saving
Mortality of CHB due to HBV Infection Cost-saving Cost-saving
Probability of CC became DC Cost-saving Cost-saving
Probability of CC became HCC Cost-saving Cost-saving
Mortality of CC due to HBV Infection Cost-saving Cost-saving
Probability of DC became HCC Cost-saving Cost-saving
Mortality of DC due to HBV Infection Cost-saving Cost-saving
Probability of DC receiving Liver Transplantation Cost-saving Cost-saving
Mortality of HCC Due to HBV Infection Cost-saving Cost-saving
Probability of HCC Receiving Liver Transplantation Cost-saving Cost-saving
Mortality of LT-1 Cost-saving Cost-saving
Mortality of LT-2 Cost-saving Cost-saving
Symptomatic Acute HBV Infection Cost-saving Cost-saving
Costs of Treatment of CHB Cost-saving Cost-saving
Costs of Treatment of CC Cost-saving Cost-saving
Costs of Treatment of DC Cost-saving Cost-saving
Costs of Treatment of HCC Cost-saving Cost-saving
Prevalence Proportion with Previous Vaccination Cost-saving Cost-saving
Prevalence Proportion without Previous Vaccination Cost-saving Cost-saving
Natural Immunization Proportion Cost-saving Cost-saving
Anti-HBs Positive Conversion Rate with 2 Doses Cost-saving Cost-saving
Proportion of HBV Susceptible Persons with 0 Previous Dose Cost-saving Cost-saving
Proportion of HBV Susceptible Persons with 1 Previous Doses Cost-saving Cost-saving
Proportion of HBV Susceptible Persons with 2 Previous Doses Cost-saving Cost-saving
Proportion of HBV Susceptible Persons with 3 Previous Doses Cost-saving Cost-saving
Discount Rate Cost-saving Cost-saving
The proportion of HBV Susceptible Persons Becoming HBV Infectious Each Year Cost-saving Cost-saving

In our study, we examined a nationwide catch-up program using capita GDP has increased as well. It can be inferred that in
original data collection to improve the accuracy and reliability of coming years such catch-up programs may be necessary and
parameters and obtain credible results. Although there were dif- affordable.
ferences in benefit-cost ratio (BCR) and ICER between studies, In previous research on this catch-up strategy, the annual inci-
the conclusion always remained that universal vaccination of dence of acute HBV infection was the only parameter could
newborns and catch-up programs for specific groups was a cost- reverse the conclusion.6 Additionally, the discount rate and the
saving strategy. transition rate from carrier to CHB were among the critical
Our study showed that the catch-up program not only parameters35 that we found in our study. According to different
increased the QALYs of the targeted population, but also populations and vaccination strategies, there are differences in
reduced total costs substantially. Although the incremental the contribution of parameter uncertainties. Since there were not
cost and incremental effectiveness varied in different cohorts, sufficient data on the distribution of parameters, we applied tri-
the program was always ‘cost-saving’ for all the age groups. angular distributions in our models,7 while previous studies used
Since most parameters from the literature had uncertainties other parameter distributions.8,50 Compared with prior work6
of their true values, these uncertainties might influence model arriving at the same conclusion, the accuracy and reliability of
results. We used sensitivity analysis to explore the direction parameters have been improved by our study. It was the first
and degree of effects from each and all parameters. The time in mainland China that EQ-5D-5L was used as the instru-
results showed that even within a wide range, no single ment of HRQoL, and that data from program files was used
parameter could reverse the conclusion of program of being directly as a resource in a cost‑effectiveness analysis. We received
‘cost-saving.’ The models were always robust, considering the data and support from NNDRS managed by Chinese Center for
combination of all uncertainties from parameters. Our study Disease Control and Prevention to form parameters in the Mar-
provided evidence to support the economic benefits of the kov model.
catch-up program in Shandong province. Recently, China has We conducted our study in Shandong province, while the
experienced rapid economic progress, and its annual per program was implemented nationally. We believe that the

www.landesbioscience.com Human Vaccines & Immunotherapeutics 2989

 a long time, treatment improve-
ment in future might reduce treat-
ment costs and change the natural
disease progression. Such
evolution would be against the
efficacy and feasibility of a
catch-up program. Progression
and symptoms of hepatitis B are
complicated, and in our model, we
used simplified assumptions to fit
the model and make the analysis
clearer and more practical. How-
ever, this may results in biased
estimate.
In conclusion, the catch-up
program in Shandong province
among children born between
1994 and 2001 was ’cost-saving.’
The catch-up program could save
life years and reduce total future
costs. Our study supports the feasi-
bility and efficacy of such a catch-
up program on hepatitis B, and
therefore provides information for
a more comprehensive evaluation
Figure 2. Results of Probabilistic Sensitivity Analysis nationwide and evidence for pol-
icy-makers to consider.
results of a nationwide cost‑effectiveness study would not differ
greatly from our study because: (1) the cost, effectiveness, and Disclosure of Potential Conflicts
transition parameters were obtained primarily from national of Interest
literature rather than being restricted in Shandong province
No potential conflicts of interest were disclosed.
and, (2) our sensitivity analysis showed that the influence of
parameter uncertainty was rather limited. In addition, data
from NNDRS showed that the acute incidence of hepatitis B
Acknowledgments
in Shandong province was only 3.5753/100,000, compared
with 6.8295/100,000 nationwide. Since the incidence had a We would like to express the special thanks to Dr. Lance
positive correlation with cost-effective, it could be inferred that Rodewald, who provided comments and suggestions on the
if we conducted a cost‑effectiveness analysis across the country, manuscript.
the conclusion would be even more cost-saving than in
Shandong province.
Our study had some limitations. Although we tried to Funding
improve the accuracy of the parameters, limited availability of lit- This study was sponsored by National Health and Family
erature about the target population still existed. Our estimate was Planning Commission and Minister of Science and Technology
based on current treatments and costs, and since CHB could last (No.2012ZX10002001).
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