Effectiveness of Pay It Forward Intervention Compared to Free and User-Paid Vaccinations on Seasonal Influenza Vaccination Among Older Adults across Seven Cities in China: Study Protocol of A Three-Arm Cluster Randomized Controlled Trial

Effectiveness of Pay It Forward Intervention Compared to Free and User-Paid Vaccinations on Seasonal Influenza Vaccination Among Older Adults across Seven Cities in China: Study Protocol of A Three-Arm Cluster Randomized Controlled Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol Effectiveness of Pay It Forward Intervention Compared to Free and User-Paid Vaccinations on Seasonal Influenza Vaccination Among Older Adults across Seven Cities in China: Study Protocol of A Three-Arm Cluster Randomized Controlled Trial Qing-Qing Li, Zizhen Huang, Jiangyun Chen, Junjie Wang, Duqiao Li, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4751218/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Jul, 2025 Read the published version in BMC Public Health → Version 1 posted 4 You are reading this latest preprint version Abstract Background Seasonal influenza poses an enormous burden worldwide, with older adults facing preventable morbidity and mortality. However, seasonal influenza vaccination coverage is poor among older populations in China. Pay-it-forward (giving a person a free vaccine and an opportunity to donate to support others) and financial incentives ( e.g. free vaccination) could be effective in improving influenza vaccine uptake, but there are no prospective comparisons of these two strategies among older adults. The proposed study aims to compare the effectiveness of the pay-it-forward strategy in increasing influenza vaccination against free vaccination and user-paid vaccination among older adults in China. Methods This study is a three-arm cluster randomized controlled trial, which will be conducted in 21 community health centers across seven cities in China. A total of 1113 eligible older adults aged ≥ 60 years will be recruited. Three clusters in each city (total of 21 clusters in 7 cities) will be randomized into three arms in a 1:1:1 ratio, including (1) pay-it-forward arm: free vaccination and participants donate any amount of money to help other people; (2) free vaccination arm; and (3) standard-of-care arm (user-paid vaccination). The primary outcomes are influenza vaccination verified by administrative records, and cost-effectiveness calculated as incremental cost-effectiveness ratio. Secondary outcomes include willingness to be vaccinated, willingness to donate, and amount of donation. The primary outcome will be calculated for each arm and compared using one-way variance analysis. Discussion This study will examine the effectiveness of pay-it-forward strategy in comparison to the free vaccination and user-paid vaccination in improving influenza vaccination among older adults. Our findings will provide insights into better strategies for enhancing influenza vaccination, and support evidence-based policy decisions for promoting influenza vaccination. Trial registration: Chinese Clinical Trial Registry (No.ChiCTR2400086840). Registered on 11 July 2024. Older adults Influenza vaccine Pay it forward Free vaccination Cluster randomized controlled trial (RCT) Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Seasonal influenza is one of the most prevalent infectious diseases. Annual epidemics cause substantial morbidity and mortality worldwide as well as in China, particularly among older adults aged 60 years and above. The World Health Organization (WHO) has reported that around one billion cases of seasonal influenza occur annually worldwide, with estimates indicating about 3 to 5 million cases of severe illness [ 1 ] . In terms of mortality, influenza has been estimated to cause approximately 33 to 74 influenza-related deaths every hour globally (annual deaths of 290,000-650,000) [ 1 , 2 ] . In China, an average of 10 influenza-related deaths per hour has been estimated, equating to an annual average of 88,100 deaths [ 3 , 4 ] . Older adults are especially vulnerable to seasonal influenza, with approximately 84–95% of influenza-associated deaths occurring in this population [ 5 ] . China is one of the fastest aging countries in the world, and has the largest elderly population globally [ 6 , 7 ] . As indicated by the Chinese seventh national population census, the population aged ≥ 60 years has surged to 264 million (18.70%) in 2020, with projections indicating a rise beyond 20% by 2025 [ 6 ] . Given that, some actions should be taken to mitigate the potential overwhelming burden caused by influenza among the older population in the future. Low vaccination coverage has also become a global challenge in the fight against influenza. WHO has emphasized that vaccination is the best way to prevent influenza, particularly crucial for individuals at high risk of influenza complications and their caregivers [ 1 ] . Previous studies also suggested that influenza vaccination is the most cost-effective preventive measure, which can significantly reduce the risk of influenza and serious complications for the vaccinated [ 5 ] . However, influenza vaccination coverage is low in many countries, such as in the United States (14.2%-40.2%), Qatar (41%-70%), France (30%-70%) [ 8 ] , and Asian countries (with a median of 14.3%, ranging from 0.8–45%) [ 9 ] , which is substantially below the WHO target of 75% [ 10 ] . In China, the overall influenza vaccine coverage among general population has only increased from 0.92–2.94% over the years 2014–2021 [ 11 ] . And the influenza vaccine uptake among older adults remains lower in China than in the United States (4.0% vs. 64.9%) [ 5 ] . Low influenza vaccine coverage is associated with poor influenza vaccination knowledge, public mistrust in vaccination delivery, and economic development [ 11 , 12 ] . Efforts to increase vaccine coverage among at-risk population are needed. In light of this need, some governments in China have implemented an encouraging policy to fully subsidize influenza vaccination for older adults. Research evidence previously reported that a free vaccine policy could improve influenza vaccination in comparison to routine care (user-paid vaccination) [ 13 , 14 ] . This policy was estimated to have yielded a 98% probability of being cost-effective [ 15 ] . For instance, a nationwide survey across all 31 provinces in China found that the average vaccination coverage among the general population was only 1.5 ~ 2.2% from 2004 to 2014, while the uptake rate reached 20% among priority populations such as old adults and children who benefited from the free national vaccination program [ 14 ] . However, only a few economically developed cites in China provide free vaccination to the older adults aged ≥ 60 years. Most of cities in China do not offer free vaccination against influenza because of the limited financial budgets. To our knowledge, pay it forward is another brilliant strategy that could not only encourage people to passionately participate in public health, but also help fill the financial budget [ 3 , 16 – 18 ] . Pay it forward (PIF) is a behavioral intervention to promote health service and delivery. With PIF, people have an opportunity to receive a free health service and donate money to support other individuals accessing the same service [ 19 ] . Upstream reciprocity and warm glow (positive emotions felt upon donating) could explain the potential mechanisms for the PIF strategy [ 16 ] . Previous studies have demonstrated that the PIF intervention could enhance public health services such as hepatitis virus testing [ 20 ] , chlamydia and gonorrhea testing [ 17 , 21 – 23 ] , human papilloma virus vaccination [ 18 ] , and influenza vaccination [ 3 ] . However, the relevant evidence on the effectiveness of a PIF intervention in increasing influenza vaccination remains limited. To date, only one quasi-experimental trial has explored the PIF intervention’s effectiveness in increasing influenza vaccination, and the findings indicated that the vaccine uptake rates among older adults aged ≥ 60 years in the PIF group were three times higher than those in the user-paid group (60% vs. 20%) [ 3 ] . Another quasi-experimental study suggests that direct full economic subsidies seem to be more effective in promoting influenza vaccination among older adults (≥ 60 yeas). The vaccine uptake rates of older adults with and without a free vaccination policy were 68.4% (95%CI: 64.7–72.1%) and 8.1% (95%CI: 5.9–10.3%), respectively [ 13 ] . While the aforementioned findings provide valuable contributions to the field of health services, further research is warranted to address remaining research gaps. The current evidence on the effectiveness of PIF intervention in improving influenza vaccine uptake across various settings and demographic groups remains limited. Furthermore, the cost-effectiveness of the PIF strategy relative to the free policy is not yet clear. This article describes a study protocol of a three-arm cluster randomized controlled trial in detail, aiming to assess the effectiveness (and cost-effectiveness) of a PIF intervention compared with free vaccination and user-paid (standard-of-care) policies in improving influenza vaccination uptake among older adults aged ≥ 60 years across 21 sites in seven different cities in China, including Guangzhou, Zhanjiang, Liuyang, Shaoyang, Chengdu, Hohhot, and Yining. We hypothesized that both a pay-it-forward intervention and free vaccination against user-paid vaccination could significantly increase influenza vaccine uptake among older adults, and that the effectiveness (or the cost-effectiveness) between those two strategies would be similar. Our study will provide scientific evidence on the policy decision regarding influenza vaccination and health promotion for the older population. Methods/Design Objectives and design overview We aimed to assess the effectiveness of the pay-it-forward strategy in increasing influenza vaccination compared to free vaccination and user-paid vaccination among older adults in China, and determine their cost-effectiveness. Figure 1 shows the overall design of the study. This study will be a three-arm cluster randomized controlled trial (RCT) among older adults aged ≥ 60 years at twenty-one study sites across seven cities. Eligible older adults will be randomly selected from the resident information registration in administrative systems of community health centers and invited to participate in this trial by a telephone call. Participants will be assigned to the pay-it-forward arm, the free vaccination arm, or the standard-of-care arm (user-paid vaccination) using a cluster randomization approach. The study protocol has been approved by the Ethics Committee of Southern Medical University (SMU Ethics Approval [2024] No.23, Additional file1) and registered on the Chinese Clinical Trial Registry website (No.ChiCTR2400086840). We report this study protocol according to the SPIRIT guidelines ( https://spirit-statement.org/publications-downloads/ , Additional file 2). Study setting and recruitment strategy We will employ a convenience sampling approach to select study settings. We plan to perform this study based on the settings established in our previous trials ( eg. , “Brief verbal intervention to promote seasonal influenza vaccination using a randomized controlled trial”) in the following Chinese cities: (1) Eastern cities: Guangzhou and Zhanjiang, (2) Central cities: Liuyang and Shaoyang, and (3) Western cities: Chengdu, Hohhot, and Yining ( Shown as Fig. 2 ). We chose these cities because they have a higher burden of influenza and represent different levels of economic development in China. The findings from these cities would be potentially relevant to many other urban areas. Of these cites, Guangzhou, Chengdu, Hohhot, and Liuyang are larger metropolitan with an older population comprising over 18% of residents, and represent the highly developed city. While, Yining, Shaoyang, and Zhanjiang are considered the less developed city in China. Twenty-one community health centers (three sites per city) will be selected using a purposive sampling approach. All sites can offer influenza vaccination services and delivery to the eligible older adults who have already registered on the administrative systems of community health centers. Our staff at each site will be responsible for recruitment, intervention, survey, and outcome measures. All sites will be required to adhere to the same study procedures. Study population and eligibility criteria The study population of this trial will be the older adults, they will be randomly selected from the resident information registration in administrative systems of public community health centers. The inclusion criteria for selecting eligible participants will be as follows: (1) aged 60 years and older; (2) living in the communities served by the selected community health centers; (3) not having received influenza vaccination within one year; (4) no acute moderate or severe illness, severe chronic illness or acute exacerbation of chronic illness, and fever; (5) no history of allergies to influenza vaccines and related components; (6) no any other conditions that the public physician diagnoses unsuitable for influenza vaccination. Sample size calculation The calculation of sample size in this study was completed based on previous research reports. Fan J et al. conducted a national cross-sectional survey of 74,484 individuals aged 40 years or older in China [ 24 ] . Their study results showed that the overall influenza vaccination rate was 3.8% (95% CI 1.6–5.9) for the groups aged ≥ 60 years. In addition, Dan W et al. [ 3 ] and Jiang X et al. [ 13 ] detected the influenza vaccination rate among older adults assigned to the pay-it-forward arm (60% vs. 20%) and the free vaccination arm (68.4% vs. 8.1%) compared to the standard-of-care arm in quasi-experimental trials. Therefore, we assumed that when the seasonal influenza vaccine coverage rate among the older adults aged ≥ 60 years in three arms are approximately 43.8% (pay-it-forward arm), 23.8% (free vaccination arm), and 3.8% (standard-of-care arm), their differences in the effectiveness could be statistically significant. We applied the Bonferroni correction method, and assumed a significance level of 0.0167 (0.05/3) for a two-side test with a power of 0.8. A 10% loss to follow-up rate was also considered. PASS15 software was used to calculate a sample size of 371 people for each group, totaling 1113 participants. Randomization and allocation Figure 3 shows the process of randomization and allocation in this three-arm cluster RCT trial. We will define each community health center as one cluster to control potential contamination resulting from the close communication among older adults within the same community. Subsequently, three clusters in each city (totaling 21 cluster across 7 cities) will be randomized into three arms at a ratio of 1:1:1 using a cluster-randomization approach to mitigate the potential biases arising from individual preferences. We will recruit and screen eligible older adults until the trial meets a total sample size of 1113 participant. Blinding and concealment The interventions we implemented in our trial are a class of behavioral interventions, which are impossible to conduct in a blind trial. Nevertheless, we will try our best to apply several blinding approaches during the study procedure to reduce potential biases according to a previously reported protocol [ 25 ] . Firstly, the process to generate the sequence of random digits for selecting and allocating participants will be kept confidential from all on-site research assistants who recruit and allocate participants. Secondly, all interventions will be concealed from study participants until they are in the trial, as our interventions will not pose a risk to human health. Thirdly, the on-site research assistants in charge of interventions for each arm will be trained separately to ensure that they will not be aware of the intervention content of the other arms. Lastly, all interventions will be blinded to the public physicians who provide influenza vaccine service and delivery. Interventions and participation consent When randomization and allocation are completed, the trained staff charged of each arm will call the eligible older adults and invite them to participate in this trial. Participation in the trial will be voluntary and anonymous, and participants can withdraw at any time without providing any explanations. After obtaining informed consent (Additional file 3), trained staff will provide a brief introduction to influenza and influenza vaccination (Additional file 4). Then, all participants will be required to complete a survey (Additional file 5) regarding their vaccination willingness and donation willingness (only for pay-it-forward arm), their demographic information will be collected from the administrative systems of community health centers. The specific interventions for each arm are listed as follows ( shown in Fig. 4 ): Pay-it-forward arm The older adults assigned to this arm will receive an educational introduction on influenza and influenza vaccination. All participants will be told that the normal price to receive influenza vaccination is 150 RMB ( $ 20.65 in US dollars) but they have the opportunity to receive free vaccination because previous participants donated this vaccination to them. Additionally, they will be asked whether they are willing to donate any amount of money to help other people receive vaccination, and will be informed that donation willingness does not affect their eligibility for free vaccination. Their vaccination uptake will be recorded by the administrative systems of community health centers within one week after interventions. Participants who wish to donate money will be required to scan the QR code for payment, and their donation amount will be ascertained by electronic payment systems ( e.g. , Wechat and Alipay). Free vaccination arm : The participant allocated to the free vaccination arm will receive the following interventions: (1) obtaining an educational introduction about influenza and influenza vaccination; (2) being informed that the normal price to receive influenza vaccination (150 RMB, $ 20.65 in US dollars); (3) then being asked whether they are willing to received free vaccination or not. The vaccination uptake will be recorded within one week by the administrative systems of community health centers. Standard-of-care arm (user-paid vaccination) The older adults allocated to the standard-of-care arm will receive the same educational introduction about influenza and influenza vaccination, but no other details about specific interventions will be provided. After that, those participants who are willing to receive influenza vaccination will be asked to pay out of pocket at the standard market price ( $ 20.65 in US dollars). Influenza vaccine uptake in this arm will be recorded by the administrative systems of community health centers within one week after the interventions. Outcome measures Primary outcome The primary outcome of this RCT will be influenza vaccine uptake in each arm, which will be recorded by the administrative systems of community health centers within one week after interventions. Another primary outcome is the cost-effectiveness, which will be calculated as the incremental cost-effectiveness ratio (ICER). ICER refers to the incremental cost that needs to be paid for each 1% increase in the influenza vaccines uptake rate of the intervention groups compared to the control groups (standard-care-of arm). To calculate ICERs, we will adopt the perspective of the healthcare sector for cost assessment. Since administration costs are uniform across all three arms, the study will only focus on the wholesale cost of acquiring the vaccine, offset by funds received either as fees in the user-paid arm (standard-of-care arm) or donations in the pay-it-forward arm. The following mock table outlines our approach to calculating ICERs (Table 1 ). Net costs (C1) for the standard-of-care arm will be estimated as wholesale vaccine cost minus fee paid. Net Cost (C2) for free vaccination arm will be wholesale vaccine cost. Net Cost (C3) for pay-it-forward arm will be the wholesale vaccine cost minus total of all donations received. Uncertainty analysis for confidence intervals between the ICERs will be estimated by bootstrapping from the sample distributions of V1, V2, V3, C1, C2, and C3. Table 1 Calculation of incremental cost-effectiveness ratio for cost-effectiveness analysis. Study arms Vaccine Uptake (%) ΔV Cost ( $ ) ΔC ICER Standard-of-care arm V1 / C1 / / Free vaccination arm V2 V2-V1 C2 C2-C1 (C2-C1)/ (V2-V1) Pay-if-forward arm V3 V3-V1 C3 C3-C1 (C3-C1)/(V3-V1) Secondary outcomes : The secondary outcomes will include vaccination willingness, donation willingness, and donation amount. We will measure vaccination willingness using self-designed questionnaires in the REDCap system (Research Electronic Data Capture, https://www.wcrcnet.cn/redcap/ ) for each study arm. Donation willingness toward pay-it-forward arm will be surveyed via the same approach. Participants allocated to this arm who would like to donate money will be required to scan the QR code to pay, and their donation amount will be ascertained by electronic payment systems ( e.g. , Wechat and Alipay). Statistical analysis Primary analysis SAS software (version 9.4, SAS Institute Inc., Cary, NC, USA) and R language software (version 3.5.0, the R Foundation for Statistical Computing) will be applied to data analysis, p value small than 0.05 with two-tailed tests will be considered as statistically significant. When describing the demographic characteristics of older adults in each arm, continuous variables will be presented as the mean ± standard deviation (or median with interquartile range), and categorical variables as n (%). To further compare the demographic characteristics of different groups, we will conduct Wilcoxon rank sum test for continuous variables and a chi-square test for categorical variables. To determine the effectiveness of the PIF strategy in promoting influenza vaccination among the Chinese elderly population compared to user-paid and free vaccination policies, we will conduct an analysis to identify the differences in seasonal influenza vaccination uptake rates and incremental cost-effectiveness ratio (primary outcomes) among the older population in the three arms through one-way variance analysis. Secondary analysis The inter-group differences in secondary outcomes, including vaccination willingness, donation willingness, and donation amount, will be also analyzed by one-way variance analysis. Additionally, we would like to use the TOPSIS model (Technique for Order Preference by Similarity to an Ideal Solution) to evaluate the comprehensive effectiveness of PIF intervention in comparison to the user-paid and free vaccination policies in improving influenza vaccination among older adults, which will take all primary and secondary outcomes into account. Sensitivity analysis Several sensitivity analyses will be performed to evaluate the robustness of the main results. In the sensitivity analyses, we will apply generalized linear regression model to access the correlation between interventions and vaccination uptake rates (and incremental cost-effectiveness ratio), and control for some potential confounders such as age, gender, education level, family income, and setting sites. Correspondingly, β value and 95% confidence intervals (CIs) will be estimated. We will further estimate the odds ratios (ORs) and 95% CIs [OR = exp (β)]. If the OR value is greater than 1, it indicates that the interventions (pay-it-forward or free vaccination) are more effective in improving the seasonal influenza vaccination rate of the elderly compared to the control group (standard-of-care arm). The analysis of correlation between interventions and secondary outcomes will be also conducted. Discussion Seasonal influenza causes a substantial global burden, particularly in China. Older adults are vulnerable to influenza and experiencing excessive morbidity and mortality, but have low vaccine uptake [ 5 ] . Innovative strategies to improve vaccine coverage for the older population are urgently needed. Pay-it-forward (PIF) is one such strategy, previous studies have evaluated PIF intervention’s effectiveness in public health services [ 3 , 17 , 18 , 21 – 23 ] . However, evidence on the effectiveness of PIF intervention in improving influenza vaccine uptake remains limited. And the cost-effectiveness of PIF strategy and free policy is not yet clear. Furthermore, it’s unclear whether the PIF strategy is more effective than the free policy. We plan to conduct a programmatic three-arm cluster randomized controlled trial (RCT) among older adults aged ≥ 60 years across 21 sites in Guangzhou, Zhanjiang, Liuyang, Shaoyang, Chengdu, Hohhot, and Yining, China. We aim to evaluate the effectiveness of the PIF strategy, free vaccination, and user-paid (standard-of-care) vaccination policies, and compare their effectiveness in improving influenza vaccination. Referring to findings from previous researches [ 3 , 13 ] , we hypothesized that both pay-it-forward intervention and free vaccination compared to user-paid vaccination could significantly increase influenza vaccine uptake among older adults. Also, we hypothesized that the effectiveness (or the cost-effectiveness) between those two strategies is similar. This study will attempt to generate scientific evidence to comprehensively understand the effectiveness of different strategies and promote evidence-based policy development for increasing influenza vaccination. Our findings will have significant implications for further research, evidence-based practice, and policy development to improve the public health service and delivery in influenza vaccination program. To our knowledge, only one quasi-experimental trial has explored the PIF intervention’s effectiveness in increasing influenza vaccination among old adults [ 3 ] , and another quasi-experimental study has suggested that the free policy seems to be more effective [ 13 ] . Since relevant evidence is scarce, our trial will contribute to filling this gap and provide valuable insights for further study. Our study will also inform evidence-based practice for implementing vaccine programs with a more effective strategy in real-world settings in the future. In China, influenza vaccination is various in different cities. The routine for influenza vaccination in most of Chinese cities requires people to pay out of pocket. In some cities, the government provides free influenza vaccination to older adults and scientific research suggests that this policy is effective in increasing vaccination coverage rate approximately from 5–40% after offering free vaccination [ 26 ] . However, only a few economically developed cites are able to offer free vaccination to the elderly aged ≥ 60 years, most cities in China do not offer free vaccination against influenza. Local governments have limited finances for public health service and delivery, and are unable to afford free vaccination for all vulnerable groups, such as children and pregnant women. The Pay-it-forward (PIF) strategy might be developed as another cost-effective strategy, where individuals receiving PIF interventions are encouraged to make donations to help others [ 3 , 16 – 18 , 20 ] . This could potentially reduce the economic burden on governments. In summary, this national study across seven cities in China is dedicated to exploring the effectiveness of different strategies (pay-it-forward, free vaccination, and user-paid vaccination) in improving influenza vaccination among older adults through a multiple-center, three-arm, cluster RCT. We hope to inform the development of evidence-based policy and contribute to promoting influenza vaccine coverage in a more effective manner. Study status This proposed study has undergone independent peer-review from the China Postdoctoral Science Foundation and has been approved (grant number: 2023M741549). At the time of submission, this proposed study has not yet begun participant recruitment. The study protocol was developed and reported in accordance with the SPIRIT guidelines ( https://spirit-statement.org/publications-downloads/ ). Ethics approval has been obtained from the Ethics Committee of Southern Medical University (SMU Ethics Approval [2024] No.23), and the trial has been registered on the Chinese Clinical Trial Registry website (No.ChiCTR2400086840). A pilot study will be conducted firstly, and relevant data will be analyzed for protocol modifications. Abbreviations Pay it forward (PIF) Randomized Controlled Trial (RCT) Incremental cost-effectiveness ratio (ICER) Research Electronic Data Capture (REDCap) Standard Protocol Items: Recommendation for Interventional Trials (SPIRIT) Declarations Ethics approval and consent to participate The study protocol has been approved by the Ethics Committee of Southern Medical University (SMU Ethics Approval [2024] No.23) and registered on the Chinese Clinical Trial Registry website (No.ChiCTR2400086840). All procedures will be carried out in accordance with the principles of Helsinki Declaration. Participants will be informed of the purpose, potential risks, and benefits of this trial and their informed consents will be obtained at the time of enrollment. Participation in the trial will be voluntary and subjects can withdraw at any time without obligation. All personal information will be kept confidential. Consent for publication Not applicable. Availability of data and materials Not applicable. Competing interests The authors declare that they have no competing interests. Funding This study was supported by the China Postdoctoral Science Foundation under Grant Number 2023M741549 (Additional file 6), and the Swiss Agency for Development and Cooperation under Grant Number 81067392 (Additional file 7). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. Authors’ contributions Qing-Qing Li and Zizhen Huang conceived and designed the study. Xiaoshan Chen, Qing Zhao, Siyuan Liu, Wenjun He, Huanyuan Luo, Yuting Wan, and Guangyu Tong provided statistical expertise for sample size calculation and suggestions for study design. Junjie Wang and Duqiao Li assisted in preparing supplementary materials. Dong (Roman) Xu, Jiangyun Chen, Yiyuan Cai, and Huijuan Liang contributed to developing the study settings. Qing-Qing Li wrote the initial drafts of the paper and revised it with inputs from Dexin Zhang, Dan Wu, David Bishai, and Dong (Roman) Xu. Roman also provided overall concept for the study design and exposition. All authors read and authorized the final version. Acknowledgments The authors thank all people who contributed to this study. References World Health Origanization. Influenza (Seasonal) , https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal) ; 2023 [accessed 25 April 2024]. Iuliano AD, et al. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet. 2018;391(10127):1285–300. Wu D, et al. Effectiveness of a pay-it-forward intervention compared with user-paid vaccination to improve influenza vaccine uptake and community engagement among children and older adults in China: a quasi-experimental pragmatic trial. Lancet Infect Dis. 2022;22(10):1484–92. Li L, et al. Influenza-associated excess respiratory mortality in China, 2010-15: a population-based study. Lancet Public Health. 2019;4(9):e473–81. Li P et al. Impact of video-led educational intervention on the uptake of influenza vaccine among adults aged 60 years and above in China: a study protocol for a randomized controlled trial. BMC Public Health, 2021. 21(1). National Bureau of Statistics of China. The Seventh National Population Census. https://www.gov.cn/guoqing/2021-05/13/content_5606149.htm . 2030 [accessed 2nd May 2024]. 2021. The Word Bank. Population ages 65 and above (% of total population). https://data.worldbank.org/indicator/SP.POP.65 UP.TO.ZS?view=map. 2022 [accessed 2nd May 2024]. Kini A, et al. Differences and disparities in seasonal influenza vaccine, acceptance, adverse reactions, and coverage by age, sex, gender, and race. Vaccine. 2022;40(11):1643–54. Sheldenkar A, et al. Acceptance and uptake of influenza vaccines in Asia: A systematic review. Vaccine. 2019;37(35):4896–905. Young BE, Chen M. Influenza in temperate and tropical Asia: a review of epidemiology and vaccinology. Hum Vaccin Immunother. 2020;16(7):1659–67. Zundong L. Analysis of estimated reported coverage of influenza vaccine in China in flu season 2014–2021. Chin J Viral Dis. 2023;13(3):226–32. Welch VL et al. Understanding the Barriers and Attitudes toward Influenza Vaccine Uptake in the Adult General Population: A Rapid Review. Vaccines (Basel), 2023. 11(1). Jiang X, et al. Impacts of free vaccination policy and associated factors on influenza vaccination behavior of the elderly in China: A quasi-experimental study. Vaccine. 2021;39(5):846–52. Yang J, et al. Seasonal influenza vaccination in China: Landscape of diverse regional reimbursement policy, and budget impact analysis. Vaccine. 2016;34(47):5724–35. Yang J, et al. Cost-effectiveness of introducing national seasonal influenza vaccination for adults aged 60 years and above in mainland China: a modelling analysis. BMC Med. 2020;18(1):90. Byrne M, et al. Mechanisms explaining a pay-it-forward approach: A qualitative analysis among men who have sex with men in China. Volume 5. SSM - Qualitative Research in Health; 2024. Katherine T, Li WT, Wu D, Huang W, Wu F, Lee A, Feng H, Pan SW, Han L, Mak V, Yang L. Tucker Pay-it-forward dual gonorrhea/chlamydia test uptake among men who have sex with men in China: A pragmatic, quasi-experimental study . Lancet Infect Dis. 2019;19(1):76–82. Qin C, et al. Pay-it-forward to increase uptake among 15-18-year-old adolescent girls compared with user-paid vaccination: The pilot results of a two-arm randomized controlled trial in China. Res Sq; 2023. Marley G, et al. Pay-it-forward gonorrhea and chlamydia testing among men who have sex with men and male STD patients in China: the PIONEER pragmatic, cluster randomized controlled trial protocol. BMC Public Health. 2023;23(1):1182. Zhang Y, et al. Pay-it-forward incentives for hepatitis virus testing in men who have sex with men: a cluster randomized trial. Nat Med. 2023;29(9):2241–7. Yang F, et al. Pay-it-forward gonorrhoea and chlamydia testing among men who have sex with men in China: a randomised controlled trial. Lancet Infect Dis. 2020;20(8):976–82. Li KT, et al. A Secondary Mixed Methods Analysis of a Pay-it-Forward Gonorrhea/Chlamydia Testing Program Among Men Who Have Sex With Men in China. Sex Transm Dis. 2020;47(6):395–401. Tang W, Xie Y, Xiong M, Wu D, Ong JJ, Wi TE, Yang B, Tucker JD, Wang C. A Pay-It-Forward Approach to Improve Chlamydia and Gonorrhea Testing Uptake among Female Sex Workers in China: Results from a Venue-based Superiority Cluster Randomized Controlled Trial. MIR public health surveillance. 2023;9:e43772–805. Fan J, et al. Influenza vaccination rate and its association with chronic diseases in China: Results of a national cross-sectional study. Vaccine. 2020;38(11):2503–11. Li Y, et al. The effectiveness of pay-it-forward in addressing HPV vaccine delay and increasing uptake among 15-18-year-old adolescent girls compared to user-paid vaccination: a study protocol for a two-arm randomized controlled trial in China. BMC Public Health. 2023;23(1):48. Zhang X, et al. Evaluating the effectiveness and cost-effectiveness of free influenza vaccination policy for older adults in Yinzhou, China: Study protocol of a real-world analyses. Vaccine. 2023;41(34):5045–52. Additional Declarations No competing interests reported. Supplementary Files Additionalfile1EthicsapprovalEnglishversion.pdf Additional file 1: Ethics approval (English version). Additionalfile2SPIRITChecklist.pdf Additional file 2: SPIRIT Checklist. This is the SPIRIT Checklist for our protocol report. Additionalfile3InformedconsentformEnglishversion.pdf Additional file 3: Informed consent form (English version). This is the English version of the informed consent form for our study. Additionalfile4Introductiontoinfluenzavaccination.pdf Additional file 4: Introduction to influenza and influenza vaccination (English version). This is the English version of the pamphlet used to introduce influenza and influenza vaccination to eligible older adults. Additionalfile5Selfdesignedquestionnaires.pdf Additional file 5: Self-designed questionnaires (English version). This is the English version of the survey for our study. Additionalfile6FundingapprovalofCPSF.pdf Additional file 6: Funding approval of the China Postdoctoral Science Foundation(CPSF). Additionalfile7FundingapprovalofSDC.pdf Additional file 7: Funding approval of Swiss Agency for Development and Cooperation(SDC) GA.png Graphical abstract Cite Share Download PDF Status: Published Journal Publication published 03 Jul, 2025 Read the published version in BMC Public Health → Version 1 posted Editorial decision: Revision requested 29 Apr, 2025 Editor assigned by journal 18 Jul, 2024 Submission checks completed at journal 18 Jul, 2024 First submitted to journal 16 Jul, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4751218","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Study protocol","associatedPublications":[],"authors":[{"id":332042446,"identity":"9ce88226-c057-4fad-ad7b-0ec7f03493f4","order_by":0,"name":"Qing-Qing Li","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qing-Qing","middleName":"","lastName":"Li","suffix":""},{"id":332042447,"identity":"0c093417-67a9-4880-bcb8-fdc6c4854966","order_by":1,"name":"Zizhen Huang","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zizhen","middleName":"","lastName":"Huang","suffix":""},{"id":332042450,"identity":"ff770f15-fbaa-45f6-b5c4-158850b07b11","order_by":2,"name":"Jiangyun Chen","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jiangyun","middleName":"","lastName":"Chen","suffix":""},{"id":332042458,"identity":"cac31129-3777-4420-b899-02d35a53ac23","order_by":3,"name":"Junjie Wang","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Junjie","middleName":"","lastName":"Wang","suffix":""},{"id":332042459,"identity":"58f02a2c-6b3d-44de-94ba-75c1ce8a1dfd","order_by":4,"name":"Duqiao Li","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Duqiao","middleName":"","lastName":"Li","suffix":""},{"id":332042460,"identity":"935abece-b9d5-4c02-b1c3-cef881de7ced","order_by":5,"name":"Xiaoshan Chen","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoshan","middleName":"","lastName":"Chen","suffix":""},{"id":332042461,"identity":"1c4da7e7-057a-489f-b0c0-734e226eb668","order_by":6,"name":"Qing Zhao","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qing","middleName":"","lastName":"Zhao","suffix":""},{"id":332042462,"identity":"1bca58a9-66a7-48d0-a945-43fbe5c61f00","order_by":7,"name":"Siyuan Liu","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Siyuan","middleName":"","lastName":"Liu","suffix":""},{"id":332042463,"identity":"f70b8e62-e88f-477a-aaf1-ec8d42f934c8","order_by":8,"name":"Wenjun He","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wenjun","middleName":"","lastName":"He","suffix":""},{"id":332042464,"identity":"1b8e5242-6300-4104-9832-8ad0a7204f1a","order_by":9,"name":"Huanyuan Luo","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Huanyuan","middleName":"","lastName":"Luo","suffix":""},{"id":332042465,"identity":"9a435356-45c3-4ea6-8c58-fe7d7e5c4175","order_by":10,"name":"Yuting Wan","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yuting","middleName":"","lastName":"Wan","suffix":""},{"id":332042466,"identity":"bdf3988b-9650-4f74-b60d-9117942b69c4","order_by":11,"name":"Guangyu Tong","email":"","orcid":"","institution":"Yale School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Guangyu","middleName":"","lastName":"Tong","suffix":""},{"id":332042467,"identity":"70e75d0f-9465-4ebe-abd3-df209aa77bed","order_by":12,"name":"Dexing Zhang","email":"","orcid":"","institution":"The Chinese University of Hong Kong","correspondingAuthor":false,"prefix":"","firstName":"Dexing","middleName":"","lastName":"Zhang","suffix":""},{"id":332042468,"identity":"b8e50647-7587-4bb2-8497-c62159462266","order_by":13,"name":"Yiyuan Cai","email":"","orcid":"","institution":"Guizhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yiyuan","middleName":"","lastName":"Cai","suffix":""},{"id":332042469,"identity":"64aa7d27-0ba7-4deb-9a91-d88a3a185389","order_by":14,"name":"Huijuan Liang","email":"","orcid":"","institution":"Inner Mongolia Medical University","correspondingAuthor":false,"prefix":"","firstName":"Huijuan","middleName":"","lastName":"Liang","suffix":""},{"id":332042470,"identity":"df6871f3-1ed5-4375-ab7b-1a99831d73e1","order_by":15,"name":"Dan Wu","email":"","orcid":"","institution":"Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Dan","middleName":"","lastName":"Wu","suffix":""},{"id":332042471,"identity":"e867113e-0787-467b-98d9-39e43f08eb51","order_by":16,"name":"David Bishai","email":"","orcid":"","institution":"The University of Hong Kong","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Bishai","suffix":""},{"id":332042472,"identity":"624bdca2-47c1-45e7-97f4-aaca10f87b45","order_by":17,"name":"Dong (Roman) Xu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyElEQVRIiWNgGAWjYBADOTYog7GBWC3GpGtJhKkkrMW8vTvxc2Hb4fQ+Bvanm3kYbGQ3HGB+9gCfFpkzZzdLzzhzOLeNgcfsNg9DmvGGA2zmBvi0SEjkbpDmqQBrYQNqOZy44QAPmwQBLZt/8xgcTmdjYH8G1PKfKC3bQLYkAEMM5LADRGjhObvNmudMumEbM4/ZzTkGycYzD7OZ4dfC3rv5Nm+btbx8e/uzG28q7GT7jjc/w6sFAZhBhAGMMQpGwSgYBaOAIgAAd91APY+oEewAAAAASUVORK5CYII=","orcid":"","institution":"Southern Medical University","correspondingAuthor":true,"prefix":"","firstName":"Dong","middleName":"(Roman)","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2024-07-16 16:36:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4751218/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4751218/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12889-025-23301-2","type":"published","date":"2025-07-03T15:58:31+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":62657331,"identity":"ff2eb84b-75dd-4fc7-9176-68c424801141","added_by":"auto","created_at":"2024-08-17 02:10:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":106007,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe overall design of this study\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote: This flow diagram was developed according to the SPIRIT guidelines.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4751218/v1/4de251ce71100514440c151c.png"},{"id":62657334,"identity":"7afcfe46-0b66-4a59-9cee-112249a637b4","added_by":"auto","created_at":"2024-08-17 02:10:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":213910,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe study settings of this trail across seven cities in China\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote: GDP per capita (GDPP) refers to the gross domestic product (GDP) of a city divided by its population. Aging rate refers to the population aged ≥60 years divided by the total population of a city. UMIE: Upper-middle-income economy. HIE: High-income economy. Population data were sourced from the Chinese seventh national population census (https://www.gov.cn/guoqing/2021-05/13/content_5606149.htm). GDP data sourced from Statistical Bulletin on National Economic and Social Development in 2023 were collected from the government websites. Economic status cutoff levels were determined according to 2022 World Bank Economic Status (https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4751218/v1/193be092767e0feb064d723c.png"},{"id":62657336,"identity":"9f6bf494-2b85-457e-944e-fa800eff09e7","added_by":"auto","created_at":"2024-08-17 02:10:04","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":108162,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ethe flowchart of randomization and allocation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote: As mentioned before, the standard-of-care-arm in this trial is user-paid vaccination arm. The proposed trial will include seven cities in China: Guangzhou, Zhanjiang, Liuyang, Shaoyang, Chengdu, Hohhot, and Yining, totaling twenty-one community health centers (three sites per city).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4751218/v1/584e55531f369ab99f1b1465.png"},{"id":62658579,"identity":"44ac4834-8a7c-45a8-9042-5edb87a7014d","added_by":"auto","created_at":"2024-08-17 02:18:04","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":190848,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ethe flowchart of interventions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote: As mentioned before, the standard-of-care-arm in this trial is user-paid vaccination arm.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4751218/v1/fb94247bea0d54f84122bfc0.png"},{"id":86179216,"identity":"3dd729ea-5ac7-425b-bc3e-e1a26de2e54f","added_by":"auto","created_at":"2025-07-07 16:17:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1469941,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4751218/v1/091d3068-9ca0-4865-a574-30967a4334e9.pdf"},{"id":62657333,"identity":"ed948fb2-8b67-43fd-9410-58a78184c26f","added_by":"auto","created_at":"2024-08-17 02:10:03","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":708420,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 1: Ethics approval (English version).\u003c/p\u003e","description":"","filename":"Additionalfile1EthicsapprovalEnglishversion.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4751218/v1/1a91f4c0f1ffeefee106b335.pdf"},{"id":62657332,"identity":"35a7fcde-b3a3-41fa-b4cf-5d100bde4451","added_by":"auto","created_at":"2024-08-17 02:10:03","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":112416,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 2: SPIRIT Checklist. This is the SPIRIT Checklist for our protocol report.\u003c/p\u003e","description":"","filename":"Additionalfile2SPIRITChecklist.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4751218/v1/416d0e828508eda8b992dd70.pdf"},{"id":62657338,"identity":"2ef2b673-0593-45b6-b996-7a19a8d0cc67","added_by":"auto","created_at":"2024-08-17 02:10:04","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":122375,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 3: Informed consent form (English version). This is the English version of the informed consent form for our study.\u003c/p\u003e","description":"","filename":"Additionalfile3InformedconsentformEnglishversion.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4751218/v1/cc133b7d06f10d25e903e69c.pdf"},{"id":62657342,"identity":"2a6d7f69-ba3f-4408-8262-4af1a21ce322","added_by":"auto","created_at":"2024-08-17 02:10:04","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":671900,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 4: Introduction to influenza and influenza vaccination (English version). This is the English version of the pamphlet used to introduce influenza and influenza vaccination to eligible older adults.\u003c/p\u003e","description":"","filename":"Additionalfile4Introductiontoinfluenzavaccination.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4751218/v1/26badbe5e749031aa2d87d4a.pdf"},{"id":62657335,"identity":"af5f4cfa-04e9-47a1-8fda-fc4159d663f6","added_by":"auto","created_at":"2024-08-17 02:10:04","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":140630,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 5: Self-designed questionnaires (English version). This is the English version of the survey for our study.\u003c/p\u003e","description":"","filename":"Additionalfile5Selfdesignedquestionnaires.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4751218/v1/99d3e1408be318b43714f640.pdf"},{"id":62657341,"identity":"86521c51-f29e-4842-ba07-335100475f12","added_by":"auto","created_at":"2024-08-17 02:10:04","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":226885,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 6: Funding approval of the China Postdoctoral Science Foundation(CPSF).\u003c/p\u003e","description":"","filename":"Additionalfile6FundingapprovalofCPSF.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4751218/v1/72592bf2a3fe73db73332596.pdf"},{"id":62657340,"identity":"f7ca0a21-0654-4ea1-9dcc-0b7dd1440ae5","added_by":"auto","created_at":"2024-08-17 02:10:04","extension":"pdf","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":1405391,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 7: Funding approval of Swiss Agency for Development and Cooperation(SDC)\u003c/p\u003e","description":"","filename":"Additionalfile7FundingapprovalofSDC.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4751218/v1/7c889fb88dff81dd6d75ee4e.pdf"},{"id":62657339,"identity":"538a6438-38f5-43db-a9e6-ac5293e15c29","added_by":"auto","created_at":"2024-08-17 02:10:04","extension":"png","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":66406,"visible":true,"origin":"","legend":"\u003cp\u003eGraphical abstract\u003c/p\u003e","description":"","filename":"GA.png","url":"https://assets-eu.researchsquare.com/files/rs-4751218/v1/f4ffbba1de29f0f828e1d14a.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effectiveness of Pay It Forward Intervention Compared to Free and User-Paid Vaccinations on Seasonal Influenza Vaccination Among Older Adults across Seven Cities in China: Study Protocol of A Three-Arm Cluster Randomized Controlled Trial","fulltext":[{"header":"Background","content":"\u003cp\u003eSeasonal influenza is one of the most prevalent infectious diseases. Annual epidemics cause substantial morbidity and mortality worldwide as well as in China, particularly among older adults aged 60 years and above. The World Health Organization (WHO) has reported that around one billion cases of seasonal influenza occur annually worldwide, with estimates indicating about 3 to 5\u0026nbsp;million cases of severe illness\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. In terms of mortality, influenza has been estimated to cause approximately 33 to 74 influenza-related deaths every hour globally (annual deaths of 290,000-650,000)\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. In China, an average of 10 influenza-related deaths per hour has been estimated, equating to an annual average of 88,100 deaths \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Older adults are especially vulnerable to seasonal influenza, with approximately 84\u0026ndash;95% of influenza-associated deaths occurring in this population\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. China is one of the fastest aging countries in the world, and has the largest elderly population globally \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. As indicated by the Chinese seventh national population census, the population aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years has surged to 264\u0026nbsp;million (18.70%) in 2020, with projections indicating a rise beyond 20% by 2025\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Given that, some actions should be taken to mitigate the potential overwhelming burden caused by influenza among the older population in the future.\u003c/p\u003e \u003cp\u003eLow vaccination coverage has also become a global challenge in the fight against influenza. WHO has emphasized that vaccination is the best way to prevent influenza, particularly crucial for individuals at high risk of influenza complications and their caregivers \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Previous studies also suggested that influenza vaccination is the most cost-effective preventive measure, which can significantly reduce the risk of influenza and serious complications for the vaccinated\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. However, influenza vaccination coverage is low in many countries, such as in the United States (14.2%-40.2%), Qatar (41%-70%), France (30%-70%)\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e, and Asian countries (with a median of 14.3%, ranging from 0.8\u0026ndash;45%)\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e, which is substantially below the WHO target of 75%\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. In China, the overall influenza vaccine coverage among general population has only increased from 0.92\u0026ndash;2.94% over the years 2014\u0026ndash;2021\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. And the influenza vaccine uptake among older adults remains lower in China than in the United States (4.0% \u003cem\u003evs.\u003c/em\u003e 64.9%)\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Low influenza vaccine coverage is associated with poor influenza vaccination knowledge, public mistrust in vaccination delivery, and economic development\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Efforts to increase vaccine coverage among at-risk population are needed.\u003c/p\u003e \u003cp\u003eIn light of this need, some governments in China have implemented an encouraging policy to fully subsidize influenza vaccination for older adults. Research evidence previously reported that a free vaccine policy could improve influenza vaccination in comparison to routine care (user-paid vaccination)\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. This policy was estimated to have yielded a 98% probability of being cost-effective\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. For instance, a nationwide survey across all 31 provinces in China found that the average vaccination coverage among the general population was only 1.5\u0026thinsp;~\u0026thinsp;2.2% from 2004 to 2014, while the uptake rate reached 20% among priority populations such as old adults and children who benefited from the free national vaccination program\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. However, only a few economically developed cites in China provide free vaccination to the older adults aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years. Most of cities in China do not offer free vaccination against influenza because of the limited financial budgets. To our knowledge, pay it forward is another brilliant strategy that could not only encourage people to passionately participate in public health, but also help fill the financial budget \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePay it forward (PIF) is a behavioral intervention to promote health service and delivery. With PIF, people have an opportunity to receive a free health service and donate money to support other individuals accessing the same service \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Upstream reciprocity and warm glow (positive emotions felt upon donating) could explain the potential mechanisms for the PIF strategy\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Previous studies have demonstrated that the PIF intervention could enhance public health services such as hepatitis virus testing\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e, chlamydia and gonorrhea testing\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e, human papilloma virus vaccination\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e, and influenza vaccination\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. However, the relevant evidence on the effectiveness of a PIF intervention in increasing influenza vaccination remains limited. To date, only one quasi-experimental trial has explored the PIF intervention\u0026rsquo;s effectiveness in increasing influenza vaccination, and the findings indicated that the vaccine uptake rates among older adults aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years in the PIF group were three times higher than those in the user-paid group (60% \u003cem\u003evs.\u003c/em\u003e 20%)\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Another quasi-experimental study suggests that direct full economic subsidies seem to be more effective in promoting influenza vaccination among older adults (\u0026ge;\u0026thinsp;60 yeas). The vaccine uptake rates of older adults with and without a free vaccination policy were 68.4% (95%CI: 64.7\u0026ndash;72.1%) and 8.1% (95%CI: 5.9\u0026ndash;10.3%), respectively\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. While the aforementioned findings provide valuable contributions to the field of health services, further research is warranted to address remaining research gaps. The current evidence on the effectiveness of PIF intervention in improving influenza vaccine uptake across various settings and demographic groups remains limited. Furthermore, the cost-effectiveness of the PIF strategy relative to the free policy is not yet clear.\u003c/p\u003e \u003cp\u003e This article describes a study protocol of a three-arm cluster randomized controlled trial in detail, aiming to assess the effectiveness (and cost-effectiveness) of a PIF intervention compared with free vaccination and user-paid (standard-of-care) policies in improving influenza vaccination uptake among older adults aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years across 21 sites in seven different cities in China, including Guangzhou, Zhanjiang, Liuyang, Shaoyang, Chengdu, Hohhot, and Yining. We hypothesized that both a pay-it-forward intervention and free vaccination against user-paid vaccination could significantly increase influenza vaccine uptake among older adults, and that the effectiveness (or the cost-effectiveness) between those two strategies would be similar. Our study will provide scientific evidence on the policy decision regarding influenza vaccination and health promotion for the older population.\u003c/p\u003e"},{"header":"Methods/Design","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eObjectives and design overview\u003c/h2\u003e\n \u003cp\u003eWe aimed to assess the effectiveness of the pay-it-forward strategy in increasing influenza vaccination compared to free vaccination and user-paid vaccination among older adults in China, and determine their cost-effectiveness. Figure \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e shows the overall design of the study. This study will be a three-arm cluster randomized controlled trial (RCT) among older adults aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years at twenty-one study sites across seven cities. Eligible older adults will be randomly selected from the resident information registration in administrative systems of community health centers and invited to participate in this trial by a telephone call. Participants will be assigned to the pay-it-forward arm, the free vaccination arm, or the standard-of-care arm (user-paid vaccination) using a cluster randomization approach. The study protocol has been approved by the Ethics Committee of Southern Medical University (SMU Ethics Approval [2024] No.23, Additional file1) and registered on the Chinese Clinical Trial Registry website (No.ChiCTR2400086840). We report this study protocol according to the SPIRIT guidelines (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://spirit-statement.org/publications-downloads/\u003c/span\u003e\u003c/span\u003e, Additional file 2).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy setting and recruitment strategy\u003c/h2\u003e\n \u003cp\u003eWe will employ a convenience sampling approach to select study settings. We plan to perform this study based on the settings established in our previous trials (\u003cem\u003eeg.\u003c/em\u003e, \u0026ldquo;Brief verbal intervention to promote seasonal influenza vaccination using a randomized controlled trial\u0026rdquo;) in the following Chinese cities: (1) Eastern cities: Guangzhou and Zhanjiang, (2) Central cities: Liuyang and Shaoyang, and (3) Western cities: Chengdu, Hohhot, and Yining (\u003cstrong\u003eShown as\u003c/strong\u003e Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). We chose these cities because they have a higher burden of influenza and represent different levels of economic development in China. The findings from these cities would be potentially relevant to many other urban areas. Of these cites, Guangzhou, Chengdu, Hohhot, and Liuyang are larger metropolitan with an older population comprising over 18% of residents, and represent the highly developed city. While, Yining, Shaoyang, and Zhanjiang are considered the less developed city in China.\u003c/p\u003e\n \u003cp\u003eTwenty-one community health centers (three sites per city) will be selected using a purposive sampling approach. All sites can offer influenza vaccination services and delivery to the eligible older adults who have already registered on the administrative systems of community health centers. Our staff at each site will be responsible for recruitment, intervention, survey, and outcome measures. All sites will be required to adhere to the same study procedures.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy population and eligibility criteria\u003c/h2\u003e\n \u003cp\u003eThe study population of this trial will be the older adults, they will be randomly selected from the resident information registration in administrative systems of public community health centers. The inclusion criteria for selecting eligible participants will be as follows: (1) aged 60 years and older; (2) living in the communities served by the selected community health centers; (3) not having received influenza vaccination within one year; (4) no acute moderate or severe illness, severe chronic illness or acute exacerbation of chronic illness, and fever; (5) no history of allergies to influenza vaccines and related components; (6) no any other conditions that the public physician diagnoses unsuitable for influenza vaccination.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003eSample size calculation\u003c/h2\u003e\n \u003cp\u003eThe calculation of sample size in this study was completed based on previous research reports. Fan J et al. conducted a national cross-sectional survey of 74,484 individuals aged 40 years or older in China\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. Their study results showed that the overall influenza vaccination rate was 3.8% (95% CI 1.6\u0026ndash;5.9) for the groups aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years. In addition, Dan W et al.\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e and Jiang X et al. \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003edetected the influenza vaccination rate among older adults assigned to the pay-it-forward arm (60% \u003cem\u003evs.\u003c/em\u003e 20%) and the free vaccination arm (68.4% \u003cem\u003evs.\u003c/em\u003e 8.1%) compared to the standard-of-care arm in quasi-experimental trials. Therefore, we assumed that when the seasonal influenza vaccine coverage rate among the older adults aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years in three arms are approximately 43.8% (pay-it-forward arm), 23.8% (free vaccination arm), and 3.8% (standard-of-care arm), their differences in the effectiveness could be statistically significant. We applied the Bonferroni correction method, and assumed a significance level of 0.0167 (0.05/3) for a two-side test with a power of 0.8. A 10% loss to follow-up rate was also considered. PASS15 software was used to calculate a sample size of 371 people for each group, totaling 1113 participants.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003eRandomization and allocation\u003c/h2\u003e\n \u003cp\u003eFigure \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e shows the process of randomization and allocation in this three-arm cluster RCT trial. We will define each community health center as one cluster to control potential contamination resulting from the close communication among older adults within the same community. Subsequently, three clusters in each city (totaling 21 cluster across 7 cities) will be randomized into three arms at a ratio of 1:1:1 using a cluster-randomization approach to mitigate the potential biases arising from individual preferences. We will recruit and screen eligible older adults until the trial meets a total sample size of 1113 participant.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eBlinding and concealment\u003c/h2\u003e\n \u003cp\u003eThe interventions we implemented in our trial are a class of behavioral interventions, which are impossible to conduct in a blind trial. Nevertheless, we will try our best to apply several blinding approaches during the study procedure to reduce potential biases according to a previously reported protocol \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. Firstly, the process to generate the sequence of random digits for selecting and allocating participants will be kept confidential from all on-site research assistants who recruit and allocate participants. Secondly, all interventions will be concealed from study participants until they are in the trial, as our interventions will not pose a risk to human health. Thirdly, the on-site research assistants in charge of interventions for each arm will be trained separately to ensure that they will not be aware of the intervention content of the other arms. Lastly, all interventions will be blinded to the public physicians who provide influenza vaccine service and delivery.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003eInterventions and participation consent\u003c/h2\u003e\n \u003cp\u003eWhen randomization and allocation are completed, the trained staff charged of each arm will call the eligible older adults and invite them to participate in this trial. Participation in the trial will be voluntary and anonymous, and participants can withdraw at any time without providing any explanations. After obtaining informed consent (Additional file 3), trained staff will provide a brief introduction to influenza and influenza vaccination (Additional file 4). Then, all participants will be required to complete a survey (Additional file 5) regarding their vaccination willingness and donation willingness (only for pay-it-forward arm), their demographic information will be collected from the administrative systems of community health centers. The specific interventions for each arm are listed as follows (\u003cstrong\u003eshown in\u003c/strong\u003e Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e):\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePay-it-forward arm\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe older adults assigned to this arm will receive an educational introduction on influenza and influenza vaccination. All participants will be told that the normal price to receive influenza vaccination is 150 RMB (\u003cspan\u003e$\u003c/span\u003e20.65 in US dollars) but they have the opportunity to receive free vaccination because previous participants donated this vaccination to them. Additionally, they will be asked whether they are willing to donate any amount of money to help other people receive vaccination, and will be informed that donation willingness does not affect their eligibility for free vaccination. Their vaccination uptake will be recorded by the administrative systems of community health centers within one week after interventions. Participants who wish to donate money will be required to scan the QR code for payment, and their donation amount will be ascertained by electronic payment systems (\u003cem\u003ee.g.\u003c/em\u003e, Wechat and Alipay).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFree vaccination arm\u003c/strong\u003e: The participant allocated to the free vaccination arm will receive the following interventions: (1) obtaining an educational introduction about influenza and influenza vaccination; (2) being informed that the normal price to receive influenza vaccination (150 RMB, \u003cspan\u003e$\u003c/span\u003e20.65 in US dollars); (3) then being asked whether they are willing to received free vaccination or not. The vaccination uptake will be recorded within one week by the administrative systems of community health centers.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eStandard-of-care arm (user-paid vaccination)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe older adults allocated to the standard-of-care arm will receive the same educational introduction about influenza and influenza vaccination, but no other details about specific interventions will be provided. After that, those participants who are willing to receive influenza vaccination will be asked to pay out of pocket at the standard market price (\u003cspan\u003e$\u003c/span\u003e20.65 in US dollars). Influenza vaccine uptake in this arm will be recorded by the administrative systems of community health centers within one week after the interventions.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003eOutcome measures\u003c/h2\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary outcome\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe primary outcome of this RCT will be influenza vaccine uptake in each arm, which will be recorded by the administrative systems of community health centers within one week after interventions. Another primary outcome is the cost-effectiveness, which will be calculated as the incremental cost-effectiveness ratio (ICER). ICER refers to the incremental cost that needs to be paid for each 1% increase in the influenza vaccines uptake rate of the intervention groups compared to the control groups (standard-care-of arm). To calculate ICERs, we will adopt the perspective of the healthcare sector for cost assessment. Since administration costs are uniform across all three arms, the study will only focus on the wholesale cost of acquiring the vaccine, offset by funds received either as fees in the user-paid arm (standard-of-care arm) or donations in the pay-it-forward arm. The following mock table outlines our approach to calculating ICERs (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Net costs (C1) for the standard-of-care arm will be estimated as wholesale vaccine cost minus fee paid. Net Cost (C2) for free vaccination arm will be wholesale vaccine cost. Net Cost (C3) for pay-it-forward arm will be the wholesale vaccine cost minus total of all donations received. Uncertainty analysis for confidence intervals between the ICERs will be estimated by bootstrapping from the sample distributions of V1, V2, V3, C1, C2, and C3.\u0026nbsp;\u003c/p\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCalculation of incremental cost-effectiveness ratio for cost-effectiveness analysis.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStudy arms\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVaccine Uptake (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026Delta;V\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCost (\u003cspan\u003e$\u003c/span\u003e)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026Delta;C\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eICER\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStandard-of-care arm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eV1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFree vaccination arm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eV2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eV2-V1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC2-C1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(C2-C1)/ (V2-V1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePay-if-forward arm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eV3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eV3-V1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC3-C1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(C3-C1)/(V3-V1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSecondary outcomes\u003c/strong\u003e: The secondary outcomes will include vaccination willingness, donation willingness, and donation amount. We will measure vaccination willingness using self-designed questionnaires in the REDCap system (Research Electronic Data Capture, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.wcrcnet.cn/redcap/\u003c/span\u003e\u003c/span\u003e) for each study arm. Donation willingness toward pay-it-forward arm will be surveyed via the same approach. Participants allocated to this arm who would like to donate money will be required to scan the QR code to pay, and their donation amount will be ascertained by electronic payment systems (\u003cem\u003ee.g.\u003c/em\u003e, Wechat and Alipay).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eStatistical analysis\u003c/h2\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary analysis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eSAS software (version 9.4, SAS Institute Inc., Cary, NC, USA) and R language software (version 3.5.0, the R Foundation for Statistical Computing) will be applied to data analysis, \u003cem\u003ep\u003c/em\u003e value small than 0.05 with two-tailed tests will be considered as statistically significant. When describing the demographic characteristics of older adults in each arm, continuous variables will be presented as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (or median with interquartile range), and categorical variables as n (%). To further compare the demographic characteristics of different groups, we will conduct Wilcoxon rank sum test for continuous variables and a chi-square test for categorical variables. To determine the effectiveness of the PIF strategy in promoting influenza vaccination among the Chinese elderly population compared to user-paid and free vaccination policies, we will conduct an analysis to identify the differences in seasonal influenza vaccination uptake rates and incremental cost-effectiveness ratio (primary outcomes) among the older population in the three arms through one-way variance analysis.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSecondary analysis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe inter-group differences in secondary outcomes, including vaccination willingness, donation willingness, and donation amount, will be also analyzed by one-way variance analysis. Additionally, we would like to use the TOPSIS model (Technique for Order Preference by Similarity to an Ideal Solution) to evaluate the comprehensive effectiveness of PIF intervention in comparison to the user-paid and free vaccination policies in improving influenza vaccination among older adults, which will take all primary and secondary outcomes into account.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSensitivity analysis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eSeveral sensitivity analyses will be performed to evaluate the robustness of the main results. In the sensitivity analyses, we will apply generalized linear regression model to access the correlation between interventions and vaccination uptake rates (and incremental cost-effectiveness ratio), and control for some potential confounders such as age, gender, education level, family income, and setting sites. Correspondingly, \u0026beta; value and 95% confidence intervals (CIs) will be estimated. We will further estimate the odds ratios (ORs) and 95% CIs [OR\u0026thinsp;=\u0026thinsp;exp (\u0026beta;)]. If the OR value is greater than 1, it indicates that the interventions (pay-it-forward or free vaccination) are more effective in improving the seasonal influenza vaccination rate of the elderly compared to the control group (standard-of-care arm). The analysis of correlation between interventions and secondary outcomes will be also conducted.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eSeasonal influenza causes a substantial global burden, particularly in China. Older adults are vulnerable to influenza and experiencing excessive morbidity and mortality, but have low vaccine uptake\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Innovative strategies to improve vaccine coverage for the older population are urgently needed. Pay-it-forward (PIF) is one such strategy, previous studies have evaluated PIF intervention\u0026rsquo;s effectiveness in public health services\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. However, evidence on the effectiveness of PIF intervention in improving influenza vaccine uptake remains limited. And the cost-effectiveness of PIF strategy and free policy is not yet clear. Furthermore, it\u0026rsquo;s unclear whether the PIF strategy is more effective than the free policy.\u003c/p\u003e \u003cp\u003eWe plan to conduct a programmatic three-arm cluster randomized controlled trial (RCT) among older adults aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years across 21 sites in Guangzhou, Zhanjiang, Liuyang, Shaoyang, Chengdu, Hohhot, and Yining, China. We aim to evaluate the effectiveness of the PIF strategy, free vaccination, and user-paid (standard-of-care) vaccination policies, and compare their effectiveness in improving influenza vaccination. Referring to findings from previous researches \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e, we hypothesized that both pay-it-forward intervention and free vaccination compared to user-paid vaccination could significantly increase influenza vaccine uptake among older adults. Also, we hypothesized that the effectiveness (or the cost-effectiveness) between those two strategies is similar. This study will attempt to generate scientific evidence to comprehensively understand the effectiveness of different strategies and promote evidence-based policy development for increasing influenza vaccination.\u003c/p\u003e \u003cp\u003eOur findings will have significant implications for further research, evidence-based practice, and policy development to improve the public health service and delivery in influenza vaccination program. To our knowledge, only one quasi-experimental trial has explored the PIF intervention\u0026rsquo;s effectiveness in increasing influenza vaccination among old adults\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e, and another quasi-experimental study has suggested that the free policy seems to be more effective\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Since relevant evidence is scarce, our trial will contribute to filling this gap and provide valuable insights for further study. Our study will also inform evidence-based practice for implementing vaccine programs with a more effective strategy in real-world settings in the future. In China, influenza vaccination is various in different cities. The routine for influenza vaccination in most of Chinese cities requires people to pay out of pocket. In some cities, the government provides free influenza vaccination to older adults and scientific research suggests that this policy is effective in increasing vaccination coverage rate approximately from 5\u0026ndash;40% after offering free vaccination\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. However, only a few economically developed cites are able to offer free vaccination to the elderly aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years, most cities in China do not offer free vaccination against influenza. Local governments have limited finances for public health service and delivery, and are unable to afford free vaccination for all vulnerable groups, such as children and pregnant women. The Pay-it-forward (PIF) strategy might be developed as another cost-effective strategy, where individuals receiving PIF interventions are encouraged to make donations to help others \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. This could potentially reduce the economic burden on governments.\u003c/p\u003e \u003cp\u003eIn summary, this national study across seven cities in China is dedicated to exploring the effectiveness of different strategies (pay-it-forward, free vaccination, and user-paid vaccination) in improving influenza vaccination among older adults through a multiple-center, three-arm, cluster RCT. We hope to inform the development of evidence-based policy and contribute to promoting influenza vaccine coverage in a more effective manner.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eStudy status\u003c/h2\u003e \u003cp\u003e This proposed study has undergone independent peer-review from the China Postdoctoral Science Foundation and has been approved (grant number: 2023M741549). At the time of submission, this proposed study has not yet begun participant recruitment. The study protocol was developed and reported in accordance with the SPIRIT guidelines (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://spirit-statement.org/publications-downloads/\u003c/span\u003e\u003cspan address=\"https://spirit-statement.org/publications-downloads/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). Ethics approval has been obtained from the Ethics Committee of Southern Medical University (SMU Ethics Approval [2024] No.23), and the trial has been registered on the Chinese Clinical Trial Registry website (No.ChiCTR2400086840). A pilot study will be conducted firstly, and relevant data will be analyzed for protocol modifications.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePay it forward (PIF)\u003c/p\u003e \u003cp\u003eRandomized Controlled Trial (RCT)\u003c/p\u003e \u003cp\u003eIncremental cost-effectiveness ratio (ICER)\u003c/p\u003e \u003cp\u003eResearch Electronic Data Capture (REDCap)\u003c/p\u003e \u003cp\u003eStandard Protocol Items: Recommendation for Interventional Trials (SPIRIT)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol has been approved by the Ethics Committee of Southern Medical University (SMU Ethics Approval [2024] No.23) and registered on the Chinese Clinical Trial Registry website (No.ChiCTR2400086840). All procedures will be carried out in accordance with the principles of Helsinki Declaration. Participants will be informed of the purpose, potential risks, and benefits of this trial and their informed consents will be obtained at the time of enrollment. Participation in the trial will be voluntary and subjects can withdraw at any time without obligation. All personal information will be kept confidential.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the China Postdoctoral Science Foundation under Grant Number 2023M741549 (Additional file 6), and the Swiss Agency for Development and Cooperation under Grant Number 81067392 (Additional file 7). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthors\u0026rsquo; contributions\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQing-Qing Li and Zizhen Huang conceived and designed the study. Xiaoshan Chen, Qing Zhao, Siyuan Liu, Wenjun He, Huanyuan Luo, Yuting Wan, and Guangyu Tong provided statistical expertise for sample size calculation and suggestions for study design. Junjie Wang and Duqiao Li assisted in preparing supplementary materials. Dong (Roman) Xu, Jiangyun Chen, Yiyuan Cai, and Huijuan Liang contributed to developing the study settings. Qing-Qing Li wrote the initial drafts of the paper and revised it with inputs from Dexin Zhang, Dan Wu, David Bishai, and Dong (Roman) Xu. Roman also provided overall concept for the study design and exposition. All authors read and authorized the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgments\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank all people who contributed to this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e\u003cem\u003eWorld Health Origanization. Influenza (Seasonal)\u003c/em\u003e, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal)\u003c/span\u003e\u003cspan address=\"https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal)\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e; 2023 \u003cem\u003e[accessed 25 April 2024].\u003c/em\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIuliano AD, et al. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet. 2018;391(10127):1285\u0026ndash;300.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu D, et al. Effectiveness of a pay-it-forward intervention compared with user-paid vaccination to improve influenza vaccine uptake and community engagement among children and older adults in China: a quasi-experimental pragmatic trial. Lancet Infect Dis. 2022;22(10):1484\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi L, et al. Influenza-associated excess respiratory mortality in China, 2010-15: a population-based study. Lancet Public Health. 2019;4(9):e473\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi P et al. Impact of video-led educational intervention on the uptake of influenza vaccine among adults aged 60 years and above in China: a study protocol for a randomized controlled trial. BMC Public Health, 2021. 21(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u003cem\u003eNational Bureau of Statistics of China. The Seventh National Population Census.\u003c/em\u003e \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.gov.cn/guoqing/2021-05/13/content_5606149.htm\u003c/span\u003e\u003cspan address=\"https://www.gov.cn/guoqing/2021-05/13/content_5606149.htm\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 2030 \u003cem\u003e[accessed 2nd May 2024].\u003c/em\u003e 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u003cem\u003eThe Word Bank. Population ages 65 and above (% of total population).\u003c/em\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://data.worldbank.org/indicator/SP.POP.65\u003c/span\u003e\u003cspan address=\"https://data.worldbank.org/indicator/SP.POP.65\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cem\u003eUP.TO.ZS?view=map. 2022 [accessed 2nd May 2024].\u003c/em\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKini A, et al. Differences and disparities in seasonal influenza vaccine, acceptance, adverse reactions, and coverage by age, sex, gender, and race. Vaccine. 2022;40(11):1643\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSheldenkar A, et al. Acceptance and uptake of influenza vaccines in Asia: A systematic review. Vaccine. 2019;37(35):4896\u0026ndash;905.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoung BE, Chen M. Influenza in temperate and tropical Asia: a review of epidemiology and vaccinology. Hum Vaccin Immunother. 2020;16(7):1659\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZundong L. Analysis of estimated reported coverage of influenza vaccine in China in flu season 2014\u0026ndash;2021. Chin J Viral Dis. 2023;13(3):226\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWelch VL et al. Understanding the Barriers and Attitudes toward Influenza Vaccine Uptake in the Adult General Population: A Rapid Review. Vaccines (Basel), 2023. 11(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJiang X, et al. Impacts of free vaccination policy and associated factors on influenza vaccination behavior of the elderly in China: A quasi-experimental study. Vaccine. 2021;39(5):846\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang J, et al. Seasonal influenza vaccination in China: Landscape of diverse regional reimbursement policy, and budget impact analysis. Vaccine. 2016;34(47):5724\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang J, et al. Cost-effectiveness of introducing national seasonal influenza vaccination for adults aged 60 years and above in mainland China: a modelling analysis. BMC Med. 2020;18(1):90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eByrne M, et al. Mechanisms explaining a pay-it-forward approach: A qualitative analysis among men who have sex with men in China. Volume 5. SSM - Qualitative Research in Health; 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatherine T, Li WT, Wu D, Huang W, Wu F, Lee A, Feng H, Pan SW, Han L, Mak V, Yang L. Tucker \u003cem\u003ePay-it-forward dual gonorrhea/chlamydia test uptake among men who have sex with men in China: A pragmatic, quasi-experimental study\u003c/em\u003e. Lancet Infect Dis. 2019;19(1):76\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQin C, et al. Pay-it-forward to increase uptake among 15-18-year-old adolescent girls compared with user-paid vaccination: The pilot results of a two-arm randomized controlled trial in China. Res Sq; 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarley G, et al. Pay-it-forward gonorrhea and chlamydia testing among men who have sex with men and male STD patients in China: the PIONEER pragmatic, cluster randomized controlled trial protocol. BMC Public Health. 2023;23(1):1182.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Y, et al. Pay-it-forward incentives for hepatitis virus testing in men who have sex with men: a cluster randomized trial. Nat Med. 2023;29(9):2241\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang F, et al. Pay-it-forward gonorrhoea and chlamydia testing among men who have sex with men in China: a randomised controlled trial. Lancet Infect Dis. 2020;20(8):976\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi KT, et al. A Secondary Mixed Methods Analysis of a Pay-it-Forward Gonorrhea/Chlamydia Testing Program Among Men Who Have Sex With Men in China. Sex Transm Dis. 2020;47(6):395\u0026ndash;401.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTang W, Xie Y, Xiong M, Wu D, Ong JJ, Wi TE, Yang B, Tucker JD, Wang C. A Pay-It-Forward Approach to Improve Chlamydia and Gonorrhea Testing Uptake among Female Sex Workers in China: Results from a Venue-based Superiority Cluster Randomized Controlled Trial. MIR public health surveillance. 2023;9:e43772\u0026ndash;805.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFan J, et al. Influenza vaccination rate and its association with chronic diseases in China: Results of a national cross-sectional study. Vaccine. 2020;38(11):2503\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, et al. The effectiveness of pay-it-forward in addressing HPV vaccine delay and increasing uptake among 15-18-year-old adolescent girls compared to user-paid vaccination: a study protocol for a two-arm randomized controlled trial in China. BMC Public Health. 2023;23(1):48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang X, et al. Evaluating the effectiveness and cost-effectiveness of free influenza vaccination policy for older adults in Yinzhou, China: Study protocol of a real-world analyses. Vaccine. 2023;41(34):5045\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-public-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pubh","sideBox":"Learn more about [BMC Public Health](http://bmcpublichealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pubh/default.aspx","title":"BMC Public Health","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Older adults, Influenza vaccine, Pay it forward, Free vaccination, Cluster randomized controlled trial (RCT)","lastPublishedDoi":"10.21203/rs.3.rs-4751218/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4751218/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSeasonal influenza poses an enormous burden worldwide, with older adults facing preventable morbidity and mortality. However, seasonal influenza vaccination coverage is poor among older populations in China. Pay-it-forward (giving a person a free vaccine and an opportunity to donate to support others) and financial incentives (\u003cem\u003ee.g.\u003c/em\u003e free vaccination) could be effective in improving influenza vaccine uptake, but there are no prospective comparisons of these two strategies among older adults. The proposed study aims to compare the effectiveness of the pay-it-forward strategy in increasing influenza vaccination against free vaccination and user-paid vaccination among older adults in China.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a three-arm cluster randomized controlled trial, which will be conducted in 21 community health centers across seven cities in China. A total of 1113 eligible older adults aged ≥ 60 years will be recruited. Three clusters in each city (total of 21 clusters in 7 cities) will be randomized into three arms in a 1:1:1 ratio, including (1) pay-it-forward arm: free vaccination and participants donate any amount of money to help other people; (2) free vaccination arm; and (3) standard-of-care arm (user-paid vaccination). The primary outcomes are influenza vaccination verified by administrative records, and cost-effectiveness calculated as incremental cost-effectiveness ratio. Secondary outcomes include willingness to be vaccinated, willingness to donate, and amount of donation. The primary outcome will be calculated for each arm and compared using one-way variance analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study will examine the effectiveness of pay-it-forward strategy in comparison to the free vaccination and user-paid vaccination in improving influenza vaccination among older adults. Our findings will provide insights into better strategies for enhancing influenza vaccination, and support evidence-based policy decisions for promoting influenza vaccination.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChinese Clinical Trial Registry (No.ChiCTR2400086840). Registered on 11 July 2024.\u003c/p\u003e","manuscriptTitle":"Effectiveness of Pay It Forward Intervention Compared to Free and User-Paid Vaccinations on Seasonal Influenza Vaccination Among Older Adults across Seven Cities in China: Study Protocol of A Three-Arm Cluster Randomized Controlled Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-17 02:09:58","doi":"10.21203/rs.3.rs-4751218/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-30T03:09:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-18T06:55:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-18T06:51:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Public Health","date":"2024-07-16T16:33:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-public-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pubh","sideBox":"Learn more about [BMC Public Health](http://bmcpublichealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pubh/default.aspx","title":"BMC Public Health","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0d5d3537-9157-42f6-8603-f41fbddfd6ba","owner":[],"postedDate":"August 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-07T16:08:07+00:00","versionOfRecord":{"articleIdentity":"rs-4751218","link":"https://doi.org/10.1186/s12889-025-23301-2","journal":{"identity":"bmc-public-health","isVorOnly":false,"title":"BMC Public Health"},"publishedOn":"2025-07-03 15:58:31","publishedOnDateReadable":"July 3rd, 2025"},"versionCreatedAt":"2024-08-17 02:09:58","video":"","vorDoi":"10.1186/s12889-025-23301-2","vorDoiUrl":"https://doi.org/10.1186/s12889-025-23301-2","workflowStages":[]},"version":"v1","identity":"rs-4751218","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4751218","identity":"rs-4751218","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}