Acceptance and willingness to pay for DTaP-HBV-IPV-Hib hexavalent vaccine among parents: A cross-sectional survey in China

ABSTRACT

DTaP-HBV-IPV-Hib hexavalent vaccine has been used in high-income countries for many years to prevent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive Haemophilus influenzae type b disease. Currently, no hexavalent vaccines have been approved for use in China. Evidence of parental acceptance and interest in hexavalent vaccines can help policy makers and manufacturers make decisions about entering the vaccine market and the immunization program in China. We measured parental acceptance and willingness-to-pay (WTP) for a hexavalent vaccine to provide such evidence. We conducted a cross-sectional survey of children’s caregivers in 16 vaccination clinics in seven cities in China and obtained information on socio-demographics, knowledge of disease, confidence in vaccines, previous vaccination experience, and acceptance of and WTP for hexavalent vaccine. Multivariate logistic regression was used to determine factors influencing acceptance, and multivariate tobit regression was used to identify factors impacting WTP. Between April 28 and June 30, 2023, a total of 581 parents of children aged 0–6 years participated in the survey; 435 (74.87%, 95% CI:71.3%−78.4%) parents indicated acceptance of hexavalent vaccine. Residence location, parents’ education level, experience paying for vaccination, and disease knowledge scores were key factors affecting parents’ choices for vaccination. Mean (SD) and median (IQR) willingness to pay for full 4-dose course vaccination were 2266.66 (1177.1) CNY and 2400 (1600–2800) CNY. Children’s age (p < .001), parents’ education level (p = .024), and perceived price barriers (p < .001) were significantly associated with WTP. Parents have high acceptance and willingness to pay for hexavalent vaccine. The less money parents have to pay out of pocket, the more willing they can be to accept the vaccine. Therefore, acceptance may increase even further if the vaccine is covered by medical insurance, provided free of charge by the government, or if its price is reduced. Our results provide reference for optimizing and adjusting immunization strategies in China.

KEYWORDS:

• Hexavalent vaccine
• combination vaccine
• vaccine acceptance
• willingness to pay
• payment card method

Introduction

Vaccination is an effective way to prevent and reduce morbidity and mortality from infectious diseases that cause great harm to human beings, especially children.^1,2 Combination vaccines have been widely used in adults and children for more than half a century. The number of vaccines recommended by the World Health Organization (WHO) for essential immunization of children has increased from six vaccines in 1974, when WHO started the Expanded Program on Immunization (EPI), to 13 vaccines currently.³ Since almost all childhood vaccines are given by injection, use of pentavalent or hexavalent combination vaccines can reduce the number of injections required to provide the WHO-recommended vaccines and the vaccines available.⁴ Combination vaccines not only address parents’ concerns about multiple injections⁵ but also reduce cold-chain transportation and storage costs⁶ and improve and sustain timeliness and compliance with vaccination services.^7,8 Significant advantages of hexavalent vaccine include greatly reducing the total number of vaccine doses needed to immunize and improving coverage of childhood vaccines.⁹ Use of hexavalent vaccine can also reduce the total cost of vaccination.¹⁰ For example, a study by Mathijssen and colleagues¹¹ showed that the integration of hexavalent vaccine into the national immunization program of the United Kingdom could reduce vaccination costs by 9.07 million pounds over 10 years, and other studies have shown that hexavalent vaccine can save both direct and indirect healthcare costs for workers and parents.^6,10 Once a combination vaccine is approved as a safe and effective vaccine, there can be barriers to its use. Cost, compared to cost of the component vaccines, is one potential barrier, which is in part why we conducted our WTP analysis. China’s domestic combination vaccine research technology has not produced a hexavalent vaccine, and for a time may rely on foreign imports to meet the national demand. Thus, practical problems like vaccine approval, per-dose out-of-pocket cost, and production capacity are barriers to combination vaccine use, although they are not disadvantages of combination vaccines. Even though combination vaccines are considered highly safe, some potential AEs may be induced by the interactions among monovalent vaccines when they are administered together which may create potential difficulties in causal inference of adverse events.^12,13

As of 2020, DTaP-HBV-IPV-Hib vaccine (hexavalent vaccine) has been approved by 89 countries, 46 of which have included it in their national immunization program.¹⁴ In 2020, 38 million doses were administered globally − 27.7 million doses (73%) were administered through national immunization programs, and 10.2 million (27%) were administered through private markets. The WHO regions with the highest use of hexavalent vaccine were the European, the Americas, and the African regions.¹⁴ Three acellular pertussis-containing hexavalent vaccines were licensed for use in several countries: Infanrix hexa (GSK, DTaP-HBV-IPV/Hib), first licensed in 2000 and containing three acellular pertussis components (pertussis toxoid [PT], filamentous hemagglutinin [FHA], and pertactin [PRN]); Hexaxim/Hexyon/Hexacima (Sanofi Pasteur), first licensed in 2012 and containing two acellular pertussis components (PT and FHA); and Vaxelis (MCM Vaccine B.V.), approved in Europe in 2016 and in the United States in 2018 and containing five acellular pertussis components (PT, FHA, PRN, and fimbriae types 2 and 3).⁹ At present, the most comprehensive prevalent combination vaccine in the WHO European Region (EUR) is DTaP-HBV-IPV-Hib vaccine,^15,16 which prevents diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive Haemophilus influenzae type b disease (DTaP-HBV-IPV-Hib). This WHO region has high adoption of hexavalent vaccines, and more EUR countries are shifting toward these vaccines. Among the 52 EUR countries, 28 have adopted hexavalent vaccines in their national immunization schedule. Compared with DTaP and Pentavalent vaccines, hexavalent vaccines are currently the most commonly used vaccines in EUR.

Thus far, hexavalent vaccines have not been submitted for licensure in China. A hexavalent vaccine was approved for preclinical study in China in 2023 and is still under review by the National Medical Products Administration (NMPA). But it may be introduced into the Chinese market in the near future. After the approval of a hexavalent vaccine into China, it will not immediately or necessarily be included in the national immunization program and families desiring the vaccine will need to pay for it, at least until a financing mechanism is implemented. A systematic review and meta-analysis (covering 19 different countries from 2000 to 2020 among general population) indicated that the cost was the primary influence of WTP and acceptance.¹⁷ Prior research on this topic covering China is limited. It is important to provide policy makers and vaccine manufacturers with evidence regarding parents’ acceptance and willingness to pay (WTP) for hexavalent vaccine to support decision-making regarding entering the market or the immunization program. We conducted a field survey in vaccination clinics in seven cities in China to assess parental acceptance of and willingness-to-pay for hexavalent vaccine and associated influencing factors. In the evidence-to-recommendation model for vaccine introduction, acceptance of a vaccine by the target population is important evidence for making a recommendation. The formulation of immunization program policies is evidence-based, and our study provides evidence on the association between parental acceptance and WTP. Hexavalent vaccine is classified as a non-immunization program vaccine in China. Therefore, information about WTP for the vaccines is highly valuable for vaccine manufacturers and the Chinese government in assessing the economic and practical viability of the different vaccines. We believe that the information provided by this study will help policy makers develop new immunization strategies. Our study may also provide encouraging evidence for manufacturers and for policy makers.

Methods

Study design, setting, and subject recruitment

Between April 28 and June 30, 2023, we conducted a face-to-face, cross-sectional, field survey of parents of children 0–6 years of age to determine acceptance of and WTP for hexavalent vaccine and factors associated with acceptance and willingness.

The setting was 16 vaccination clinics in community health service centers in seven cities in China’s mainland. The cities were selected to be exemplars of the three regions of China – east, central, and west. The eastern region cities were Beijing, Hangzhou, and Fuzhou; the central region cities were Zhengzhou and Wuhan; and the western region cities were Lanzhou and Chengdu. The National Bureau of Statistics of China divides China into eastern, central, and western regions by economic level.¹⁸ The cities were selected in our study represent the eastern, central, and western regions of China, which represent regions with different levels of economic development in China. The clinics were licensed vaccination clinics that are part of China’s EPI system. In the National Immunization Program of China,¹⁹ the component vaccines contained in hexavalent vaccine are targeted for use in children of 0–6 years of age, as is hexavalent vaccine. Subjects were parents of children aged 0–6 years who had brought their child to a participating clinic for routine vaccination. The surveys were conducted in urban area clinics; family residence was based on self-report and could be either urban or rural. The minimum sample size required was 385, based on the assumption that the acceptability rate was conservatively estimated to be 50% with a 5% margin of error and a confidence interval of 95%. The design, setting, analyses, and reporting within this study adhered to the STROBE guidelines for cross-sectional studies in epidemiology²⁰ (see Supplementary File 1 for the detailed checklist of STROBE criteria).

To ensure data quality, trained interviewers administered the survey in-person. When the parents completed the questionnaire, the interviewers checked the questionnaire to ensure that it was filled out accurately and that there were no omissions.

Questionnaire design

Our questionnaire was self-designed with reference to previous relevant studies.^20–22 The instrument was pilot tested at the Sanlitun Community Health Service Center in Beijing in April 2023 to assess comprehensibility, acceptability, and validity of the instrument. The questionnaire was further improved and modified through expert consultation to determine the final questions and formats used for this study. The questionnaire had five parts: (1) socio-demographic characteristics, (2) knowledge of the diseases covered by hexavalent vaccine, (3) confidence in vaccination in general, (4) previous experience paying out-of-pocket for vaccination, and (5) acceptance and WTP for hexavalent vaccine. The third and fourth parts of the questionnaire, which are independent of the specific vaccine being evaluated, were based on studies evaluating WTP for vaccines against cervical cancer and dengue.^21–23 The other parts were based on the population and purpose of this study and were designed by ourselves. The National Immunization Program of China does not include hexavalent vaccine, and parents will need to pay for the vaccine at their own expense once it is licensed if they desire the vaccine. Given the difference between vaccine acceptance and WTP, respondents can logically only have willingness to pay if they indicate acceptance of hexavalent vaccine. We included acceptance and WTP in the same part of the questionnaire in consideration of the close relationship between these concepts. Sections 3 and 4 used 5-point Likert scales. Open-ended and other WTP question formats were pilot tested at the Sanlitun Community Health Service Center in Beijing in April 2023, and we found that parents had difficulty answering the open-ended question format, as well as understanding the double-bounded alternative choice method. Therefore, based on comprehensibility and acceptability, we chose the payment card method to elicit WTP. Respondents were asked, “if hexavalent vaccine was approved for use in childhood vaccination in China, would you choose this vaccine?” Those answering yes were considered to be accepting of a hexavalent vaccine. If they said “yes,” they were asked, “what is the maximum amount you are willing to pay for a full 4-dose course of the hexavalent vaccine?” Payment amount options were 800, 1200, 1600, 2000, 2400, 2800, 3200, 3600, 4000, and 4400 CNY. This price range covers the market prices of all non-EPI vaccines in China.²⁴ If parents said they would not pay out of pocket, they were asked if they would be willing to accept the vaccine if it was paid for by medical insurance. If parents said they would not accept hexavalent vaccine even if paid for by insurance, they were further asked if they would be willing to accept the vaccine if the government provided it at no charge.

Study variables

Knowledge of the diseases prevented by hexavalent vaccine was investigated with 12 questions, two questions for each of the six diseases, with answer options of “yes,” “no,” and “don’t know.” A correct answer was scored as 1 point, and an incorrect or “don’t know” answer was assigned 0 points; scores ranged from 0 to 12 points.²¹ Our study samples are from the provincial capital cities in China, respondents were relatively well educated, so they have relatively good knowledge of the disease. To better distinguish between good and poor disease cognition, we set the cutoff value to 40% instead of 50%, which has been used in previous studies.^21,22 Parents were asked three questions to assess confidence and were considered confident only if they indicated confidence in all three questions.²⁵ Parents’ prior vaccination experiences were addressed with five questions. Likert scale questions were ordinal variables, and non-Likert scale questions were based on predefined categories. In our study, gender, occupation, number of children, monthly income, education level, and disease cognition score were treated as categorical variables, whereas child’s age, age, as well as WTP were treated as continuous variables. Supplementary File 2 Table S1 provides additional detail on the explanatory variables in our model.

Statistical analysis

We analyzed demographic characteristics of frequencies and odds ratios for categorical variables and means and standard deviations for continuous variables. Bivariate analyses were performed to test study hypotheses. Chi-square test (for larger samples such as relationship [mother or father]) and fisher exact tests (for smaller samples such as residence [urban or rural]) were used to test the null hypothesis that [Chi-squared test: Parents’ vaccine acceptance (accept = 1 vs. accept = 0) is independent of their relationship of children; Fisher’s exact test: Parents’ vaccine acceptance (accept = 1 vs. accept = 0) is independent of their residence]; and Kruskal–Wallis test was used to test the null hypothesis that the location parameters of the distribution of parents’ vaccine acceptance (values of acceptance [1 or 0] whose distributions were compared across levels) are equal across levels of ordered categorical variables (such as the four level categorical variable of education level). Details of the Kruskal-Wallis test are provided in Supplementary File 2. We used multivariate stepwise logistic regression to determine influencing factors for acceptance of hexavalent vaccine. Multicollinearity was assessed using variance inflation factor (VIF) analysis. A VIF value lower than 10 and a tolerance value (1/VIF) greater than 0.1 were used indicate no significant multicollinearity.²⁶ Tobit regression was used to study the willingness to pay for vaccines as the WTP determined by the payment card method consists of intervals data and censoring observations.²⁷ The results of model fitting and multicollinearity testing are provided in the Supplementary File 2 (Table S2-S4). We used multivariate tobit regression to identify factors impacting WTP and estimate marginal effects of each factor. To quantify the effect of each level change in the variable on willingness to pay, we also calculated the average marginal effect (AME) for each variable. AME refers to the change of the expected value of the response variable when the value of the explanatory variable changes by one unit.²⁸

$\mathit{AME}=\frac{1}{N}\sum _{\mathit{i}=1}^N\mathit{\beta }\cdot \text{empty}\left(\frac{x_i\mathit{\beta }}{\mathit{\sigma }}\right)$

where N is the total number of observations, x_i is the explanatory variable of the i observation, β is the coefficient of the model, ϕ is the probability density function of the standard normal distribution, and σ is the standard deviation of the model.

In the tobit model, we included only parents who indicated that they accept the vaccine for the out-of-pocket WTP. Regarding payment by medical insurance or government provided, we conducted only descriptive analyses.

We determined 95% confidence intervals of proportions were determined as CI = p± z*√(p(1-p)/n), where p is the proportion, z = 1.96 for a 95% CI, and n is the sample size. Statistical tests were two-sided, and we considered p values of 0.05 or less to be statistically significant without correction for multiple testing. Because of the small sample size, we did not perform sensitivity analyses. STATA 17.0 was used for all analyses.

Ethical review

The study protocol and informed consent form were approved by the Medical Ethics Committee of the Chinese Center for Disease Control and Prevention (approval 202,312). Written informed consent was obtained from participants prior to study procedures.

Results

Respondent characteristics

A total of 581 parents of children aged 0–6 years participated in the survey. The mean (SD) age of the parents was 33.28 (4.28) years, and the mean (SD) age of their children was 1.99 (2.17) years. Most of the respondents were mothers (443, 76.25%). Most of the parents had one child (369, 63.51%), had a bachelor’s degree or above (416, 71.6%), and had an average monthly income of more than 6000 CNY (442, 76.08%). Approximately one quarter (23.75%) of respondents were medical practitioners. The characteristics of the respondents and the results of the comparison of different levels of acceptance within each variable are shown in Table 1.

Table 1. Bivariate analysis and logistic regression of hexavalent vaccine acceptance among parents.

Variables	Frequency (%)	Accept (%)	Bivariate analysis	Multivariable logistic regression
			p-value	OR (mean [95%CI])	p-value
Region^b
Eastern region	277 (47.68)	217 (78.34)	.015
Central region	150 (25.82)	116 (77.33)
Western region	154 (26.51)	102 (66.23)
Child’s gender^a
Male	294 (50.60)	222 (75.55)	.719
Female	287 (49.40)	213 (74.22)
Child’s age^b
<1	227 (39.07)	168 (74.01)	.782
1–3	211 (36.32)	104 (73.76)
4–6	143 (24.61)	213 (76.53)
Relationship^a
Mother	443 (76.25)	335 (75.62)	.455
Father	138 (23.75)	100 (72.46)
Age (years)^b
≤29	104 (17.90)	73 (70.19)	.310
30–39	424 (72.98)	319 (75.24)
≥40	53 (9.12)	43 (81.13)
Ethnicity^c
Han	556 (95.70)	415 (74.64)	.644
Others	25 (4.30)	20 (80)
Number of children^b
1	369 (63.51)	277 (75.07)	.047
2	191 (32.87)	147 (76.96)
≥3	21 (3.61)	11 (52.38)
Current residence^c
Urban	534 (91.91)	410 (76.78)	< .001	Ref
Rural	47 (8.09)	25 (53.19)		0.47(0.24–0.94)	.028
Monthly income (CNY)^b
≤5999	139 (23.92)	90 (64.75)	< .001
6000–9999	156 (26.85)	111 (71.15)
10000–14999	151 (25.99)	117 (77.48)
≥15000	135 (23.24)	117 (86.67)
Education level^b
High school and below	48 (8.26)	20 (41.67)	< .001	Ref
Junior college	117 (20.14)	82 (70.09)		2.82(1.35–5.90)	.006
Bachelor’s degree	329 (56.63)	259 (78.72)		3.41(1.74–6.71)	< .001
Master’s degree and above	87 (14.97)	74 (85.06)		5.32(2.24–12.68)	< .001
Occupation^a
Medical practitioners	138 (23.75)	114 (82.61)	.016
Non-medical practitioners	443 (76.25)	321 (72.46)
Previously paid for vaccination^a
Yes	63 (89.16)	27 (42.86)	< .001	Ref
No	518 (10.84)	408 (78.76)		4.00(2.25–7.11)	< .001
Medical insurance type^a
Medical insurance for urban workers	471 (81.07)	367 (77.92)	< .001
Medical insurance for urban and rural residents	78 (13.43)	47 (60.23)
Free medical care	11 (1.89)	10 (90.91)
Other	21 (3.61)	11 (52.38)
Disease cognition score^c
≤8	353 (60.73)	242 (68.56)	< .001	Ref
>8	228 (39.24)	193 (84.65)		1.91(1.22–2.99)	.005
Confidence in vaccines generally^c
Poor	543 (93.46)	418 (76.98)	< .001
Good	38 (6.54)	17 (44.74)

^aχ2 test ; ^bKruskal-Wallis test ; ^cFisher exact test. OR, odds ratio; CI, confidence interval. P-values represent difference from reference values.

Acceptance for a hexavalent vaccine and associated factors

Among all respondents, 435 (74.87%, 95% CI: 71.3%−78.4%) indicated acceptance of hexavalent vaccine. Residential location, parental education, history of paying for non-program vaccines, and disease cognition score were factors most associated with parents’ choice of vaccination. Families living in rural areas less likely to choose hexavalent vaccine than urban residents (OR [mean] = 0.47, 95%CI: 0.24–0.94); parents with a master’s degree or above more likely to accept hexavalent vaccine than parents with a high-school education or below (OR = 5.32, 95%CI: 2.24–12.68); Parents with a history of paying for non-program vaccines were more likely to choose hexavalent vaccine (OR = 4.00, 95%CI: 2.25–7.11), and parents with good knowledge of the diseases were more likely to choose hexavalent vaccine than those with low knowledge (OR = 1.91; 95%CI:1.22–2.99) (Table 1).

WTP for a full course of hexavalent vaccination

Forty-six (7.92%) parents indicated that they would not consider hexavalent vaccine even if the government provided it for free, expressing in free-text comments concern about safety and lack of knowledge about hexavalent vaccine; 73 (12.56%) said that they would accept hexavalent vaccine if medical insurance covered it, and if government purchase, the percent of parental acceptance will continue to increase by 4.65% (Figure 1). Among parents willing to pay for hexavalent vaccine, acceptance decreased with increasing vaccine price. At 1600 CNY, 2400 CNY, and 3600 CNY per full-course vaccination, respectively, 75.40%, 51.72%, and 11.26%, of parents were willing to pay for hexavalent vaccine (Figure 1). The mean (SD) price parents were willing to pay was 2266.66 (1177.14) CNY, and the median (IQR) was 2400 (1600–2800) CNY.

Figure 1. A. Parents’ willingness to pay for a full course of hexavalent vaccination; B. Acceptance of different payment schemes.

Tobit model regression results showed that children’s age (β [mean] =-98.55, 95%CI: −157.08 to −40.02, p < .001), parents’ education level (β = 168.44, 95%CI: 4.73–332.14, p = .024), and perceived price barriers (β=-164.43, 95%CI: −249.58 to −79.27, p < .001) were significantly associated with willingness to pay for hexavalent vaccine (Table 2). The older the children were, the lower the parents’ willingness to pay for a full course of hexavalent vaccination. For each 1-year increase in child age, WTP decreased by 83.97CNY (95%CI: −133.50 to −34.44). WTP increased with increasing parental education, with the willingness to pay increased 143.52 CNY (95%CI: 4.57–282.46) for each level of education attainment. Perceived price barriers had a negative impact on parents’ willingness to pay, and the willingness to pay decreased by 140.10 CNY (95%CI: −211.69 to −68.21) for each level of perceived price barrier.

Table 2. Influencing factors of willingness to pay from the tobit regression.

Variable	Coefficients				AME
	Mean	SE	95% CI	p-value	Mean	SE	95%CI	p-value
Region	−79.11	74.03	−224.63 to 66.41	.286	−67.41	63.07	−191.01 to 56.20	.285
Child’s age	−98.55	29.78	−157.08 to −40.02	.001	−83.97	25.27	−133.50 to −34.44	.001
Child’s gender	167.13	111.97	−52.96 to 387.23	.136	142.41	95.29	−44.36 to 329.17	.135
Age	19.95	15.86	−11.23 to 51.13	.209	17.00	13.51	−9.47 to 43.47	.208
Relationship	−9.76	139.25	−283.48 to 263.96	.944	−8.32	118.65	−240.86 to 224.23	.944
Ethnic	−69.87	275.95	−612.30 to 472.57	.800	−59.53	235.12	−520.36 to 401.30	.800
Number of children	−116.38	115.46	−343.34 to 110.58	.314	−99.16	98.33	−291.89 to 93.57	.313
Current residence	−409.80	252.73	−906.59 to 86.98	.106	−349.17	215.09	−770.74 to 72.39	.105
Monthly income	71.90	44.31	−15.20 to 159.00	.105	61.26	37.70	−12.63 to 135.12	.104
Education level	168.44	83.28	4.73 to 332.14	.044	143.52	70.89	4.57 to 282.46	.043
Occupation	179.37	141.70	−99.16 to 457.91	.206	152.84	120.60	−83.53 to 389.20	.205
Have paid for vaccination	−235.43	239.49	−706.19 to 235.34	.326	−200.59	203.97	−600.36 to 199.17	.325
Medical insurance type	87.09	122.97	−154.63 to 328.80	.479	74.20	104.74	−131.09 to 279.50	.479
Disease cognition score	−14.89	18.18	−50.62 to 20.84	.413	−12.69	15.49	−43.04 to 17.66	.413
Confidence in general vaccines	−205.945	297.072	−789.90 to 378.01	.489	−175.48	253.08	−671.50 to 320.55	.488
Access to vaccination services	34.21	161.80	−283.85 to 352.26	.833	29.15	137.85	−241.04 to 299.33	.833
Convenience of transportation	122.37	106.02	−86.03 to 330.78	.249	104.27	90.35	−72.81 to 281.35	.248
Time spent on vaccination	−67.64	43.59	−153.32 to 18.04	.121	−57.63	37.09	−130.33 to 15.07	.120
Price barriers	−164.43	43.32	−249.58 to −79.27	.000	−140.10	36.68	−211.99 to −68.21	.000
Trust in vaccination physicians	−56.42	102.18	−257.28 to 144.44	.581	−48.07	87.05	−218.69 to 122.55	.581

OR, odds ratio; CI, confidence interval; AME, average marginal effect.

AME: refers to the change of the expected value of the WTP when the value of the explanatory variable changes by one unit.

Discussion

Our questionnaire-based survey of parents in China found that 75% would be willing to have their children receive a four-dose series of DTaP-HBV-IPV-Hib hexavalent vaccine, once such a vaccine is approved. More than 70% of parents were willing to pay at least 800 CNY for a full series; half were willing to pay 2400 CNY or more, which is similar to the current price of a pentavalent vaccine series in China (hexavalent without HBV), reflecting the strong demand for hexavalent vaccination. The high acceptance of hexavalent vaccine demonstrated price elasticity, with lower acceptance at higher prices, which can be offset by government purchase or medical insurance coverage.

Some studies about the acceptance and WTP of non-immunization vaccines have been conducted in China. These studies concern individual vaccines such as HPV vaccine,^21,29 pneumococcal vaccine,³⁰ COVID-19 vaccines, influenza vaccines.^29,31,32 To our knowledge, this is the first time that parental WTP for hexavalent vaccine has been investigated in China’s mainland. However, few studies^33,34 have investigated the vaccination intention and WTP for combination vaccines. Similar to previous studies,³⁵ our results suggest that urban vs rural residence, education level, and disease knowledge are key factors influencing parents’ choice. It is worth noting that parents who had previously paid for vaccines for their children were four times more likely to accept hexavalent vaccine. A systematic review and meta-analysis (covering 19 different countries from 2000 to 2020 among general population) indicated that cost is the primary reason influencing WTP and acceptance.¹⁷ To our knowledge, no previous study has shown such a high acceptance of non-NIP vaccines by parents who had previously paid for vaccines for their children. Large combination vaccines in China are all non-program vaccines, and parents who previously paid for vaccines out of pocket appear to have a higher acceptance of new combination vaccines that may be introduced into China.

Parents were willing to pay significantly more for hexavalent vaccine than for other non-program vaccines, which range in price from 15 CNY to 638 CNY.²⁴ Few studies^32,36 have examined the association between parents’ WTP and children’s age. Regression analyses showed that children’s age affects WTP for hexavalent vaccine, with the younger the age group, the greater the willingness to pay (infancy, 1–3 years, 4–6 years). Parents are known to have concerns that children receive too many vaccinations in their first 6 months of life,⁵ which may increase their WTP for combination vaccines that reduce the number of vaccination injections, consistent with other studies.^37,38 Parental education level was the most influential factor for both hexavalent vaccine acceptance and WTP, with willingness increasing 140 CNY for each level increase in education. Tarekegn and colleagues³⁹ showed that educational attainment positively correlated with preference for and utilization of various health services. Out-of-pocket costs remain a key deterrent for parents to have their children vaccinated with non-program (parent-pay) vaccines. The average WTP of the full-course hexavalent vaccination in our study was 2267 CNY, which is approximately 11% of the per capita disposable income of Chinese residents.⁴⁰ Other non-program vaccines that require parents to pay include pneumococcal vaccines and rotavirus vaccines. The high cost of vaccination brings heavy economic burden to families. Governments, vaccine manufacturers, and health insurers can improve access to vaccines by reducing the cost of vaccination.

Although more than 70% of parents were willing to pay for full coverage of the hexavalent vaccine for their children, some parents wanted to pay for hexavalent vaccine through their personal medical insurance account or have the government provide the vaccine at no charge. With medical insurance, 87% of parents would accept hexavalent vaccine, and if the government provided the vaccine at no cost, 92% would accept hexavalent vaccine. The high cost of vaccination, whether explicit or implicit, creates obstacles for vaccination and reduces vaccine coverage,⁴¹ especially for people in lower economic strata. Therefore, a program implication is that lowering or eliminating out-of-pocket hexavalent vaccination costs will yield greater acceptance and higher coverage while reducing injections and vaccination visits.

There are several methods that are commonly used to elicit WTP – bidding game method,⁴² open-ended method,⁴³ double-bounded dichotomous choice method,⁴⁴ and payment card method – each with advantages and disadvantages.⁴⁵ The bidding game method has starting point bias, and open-ended (OE) questions can be difficult to interpret; the dichotomy method needs a large number of observations; the payment card method is easily affected by its scope set, but easy to implement.^31,45 We ultimately selected the payment card method as the most suitable method for our study based on feasibility.

In China, vaccines are categorized as Expanded Programme on Immunization (EPI) vaccines, which are provided free of charge by government, and non-EPI vaccines, which are considered optional and may be selected and paid for by parents or guardians.⁴⁶ Hexavalent vaccine is neither in China’s market nor in the EPI system. Our study provides information relevant to policy makers and vaccine manufacturers about parental acceptance and WTP for a hexavalent vaccine. This includes a study assessing the willingness to pay for future leptospirosis vaccines among urban residents in Manila, the Philippines, the results of which serve as a policy guide for public health authorities and vaccine manufacturers in developing appropriate strategies for leptospirosis vaccine delivery.⁴⁷ This is evidence of value for the Chinese government and vaccine manufacturers when considering the economic and practical feasibility of hexavalent vaccine introduction to the market and the program and for future adjustment and optimization of the vaccination schedule. This is because in the evidence-to-recommendation model for vaccine introduction, acceptance and WTP of a vaccine by the target population are important evidence for making a recommendation.

Our study has limitations. First, the sample size is not large, and the setting was limited to seven provincial capitals, limiting generalizability of the findings and potentially affecting the goodness-of-fit of the model. We also did not perform sensitivity analyses, which may have resulted in less robust results. Because we did not conduct multiple-test correction, it may lead to false-positive errors in our results.⁴⁸ Second, we used the payment card method to assess WTP, and the payment price range may affect respondents’ decisions, resulting in range bias.³¹ Our questionnaire is self-designed and has not calculated the value of Cronbach’s alpha that may affect the internal and external validity of the results, so the results should be interpreted with caution. Third, the surveys were conducted in provincial capital cities, and the study had fewer subjects residing in rural areas, reducing precision in the evaluation of differences in vaccination intention and WTP between urban and rural areas. Fourth, social desirability bias was inevitable in which participants might tend to give perceived favorable answers about acceptance and WTP. Finally, questions of interest other than those relating to WTP, such as real-world acceptance of a hexavalent, were not addressed in the study but will be important to address once a hexavalent vaccine is approved for use in China.

Conclusions

Parents indicated that they are highly accepting of the currently unapproved hexavalent vaccine. Residence, education level, and disease knowledge are key factors affecting parents’ acceptance of hexavalent vaccine. Payment by medical insurance or government purchase of hexavalent vaccination can greatly increase parents’ willingness to have their children vaccinated with DTaP-HBV-IPV-Hib combination vaccine. Stakeholders should consider incorporating hexavalent vaccination into medical insurance reimbursement to improve vaccine accessibility and coverage. Parents were willing to pay 2400 CNY for a full series of hexavalent vaccine. Children’s age, parents’ education level, and perceived price barriers influence parents’ WTP, with price being the most important factor hindering parents from selecting hexavalent vaccine for their children.

Author’s contributions

FW conceived the study. AH, LT, LH, XZ, QZ, FW designed the study protocol and the questionnaire. AH performed the statistical analysis under the supervision of LT, LF, JL1 FW. AH wrote the original manuscript. FW, LT, LH, QZ, XW, QL, SL and ZY contributed in reviewing the protocol, questionnaire and manuscript. AH, LH, JL1, XZ, JL2, YZ, BZ, LW, XX, ZZ, YW were responsible for data collection. All authors reviewed and approved the final report.

Ethical approval

The study protocol and informed consent form were approved by the Medical Ethics Committee of the Chinese Center for Disease Control and Prevention (approval 202,312). Written informed consent was obtained from participants prior to study procedures.

Date availability statement

Data would be available on reasonable request by contacting the corresponding author.

Acknowledgments

We thank the participants for their contribution to this study and thank Lance Rodewald of China CDC for English language editing of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2024.2333098

Additional information

Funding

This work was supported by the Operation of Public Health Emergency Response Mechanism of the Chinese Center for Disease Control and Prevention [131031001000150001]; the National Natural Science Foundation of China [11971137] and Chinese Foundation for Hepatitis Prevention and Control [2022SR043].