Understanding caregivers' decision to vaccinate childhood cancer survivors against COVID‐19

Abstract Background Vaccination against COVID‐19 is recommended for childhood cancer survivors (CCS). This study aimed to identify antecedents contributing to caregivers' decisions to vaccinate CCS aged 5–17 years against COVID‐19 by applying the Theory of Planned Behavior. Methods Participants in this cross‐sectional study completed an online survey assessing caregiver attitudes, subjective norms, perceived behavioral control, intention to vaccinate CCS, CCS vaccination status, COVID‐19 health literacy, and frequency of COVID‐19 information‐seeking. Surveys were completed between May and June 2022 following approval for the emergency use of COVID‐19 vaccines among children aged ≥5 years in the U.S. Data were analyzed using unadjusted linear regressions and structural equation modeling. Results Participants were caregivers (n = 160, 87.5% biological mothers, 75.6% white/non‐Hispanic) of CCS (n = 160, 44.4% female, mean (M) = 12.5 years old, M = 8.0 years off treatment). 70.0% (n = 112) of caregivers and 53.8% (n = 86) of CCS received a COVID‐19 vaccine. Over one‐third (37.5%) of caregivers reported disagreement or indecision about future COVID‐19 vaccination for the CCS. Caregivers' intention (β = 0.962; standard error [S.E.] = 0.028; p < 0.001) was highly related to CCS vaccination status. Attitudes (β = 0.568; S.E. = 0.078; p < 0.001) and subjective norms (β = 0.322; S.E. = 0.062; p < 0.001) were associated with intention. Higher frequency of COVID‐19 information‐seeking (β = 0.313; S.E. = 0.063; p < 0.001) and COVID‐19 health literacy (β = 0.234; S.E. = 0.059; p < 0.001) had a positive indirect effect on intention through attitudes and subjective norms. Conclusions Caregivers' vaccination intentions for minor CCS are highly related to vaccination behavior and shaped by attitudes, subjective norms, COVID‐19 health literacy, and frequency of COVID‐19 information‐seeking. Promoting tailored communication with caregivers of CCS and encouraging them to review reputable sources of information can address their vaccine hesitancy.


| INTRODUCTION
Childhood cancer survivors (CCS) may be at higher risk of contracting coronavirus disease 2019 (COVID-19), 1 while CCS experiencing specific late effects of treatment face increased chances of a severe course of COVID-19. 2These include chronic conditions such as gastrointestinal 3 and endocrine problems 4,5 that might be risk factors for severe COVID-19 in children. 6Furthermore, while a cancer history may be a risk factor for long-lasting symptoms following COVID-19 in adults, 7 its long-term impact on young CCS remains unknown.Given these risks, the ongoing prevalence of COVID-19, and the continuing emergence of new variants, 8 the Children's Oncology Group (COG) recommends that all eligible CCS receive a COVID-19 vaccine. 9When survivors are minors, their caregivers decide if they receive the COVID-19 vaccine; thus, understanding caregiver COVID-19 vaccine decision-making is essential to long-term health outcomes for CCS.
Previous research indicates that parents of CCS were more likely to accept COVID-19 vaccines for their CCS when they were confident in the governmental response to COVID-19, received information on COVID-19 from cancer care professionals, trusted in science, medicine, and vaccination, including COVID-19 vaccinations, and believed that CCS are at greater risk of complications due to COVID-19. 10Characteristics deterring their decision included concerns about the rapidness of vaccine development and its safety for children and CCS. 10 A study addressing COVID-19 vaccine hesitancy in parents of children with cancer and CCS found greater hesitancy was associated with both parents' factors (younger age, male sex, lower income) and children's factors (younger age at diagnosis and being on treatment). 11Caregiver health literacy remains understudied in pediatric oncology 12 and may contribute to COVID-19 vaccine uptake among young CCS.Health literacy refers to people's capability to acquire and interpret health information to maintain and further improve health. 13,14The relationship between health literacy and vaccination acceptance is unclear, with different studies showing contrasting results. 15Recent studies addressing the relationship between health literacy and COVID-19 vaccination found lower health literacy is associated with lower vaccine uptake [16][17][18][19] and results in higher vaccination hesitancy by mediating the effect of distrust 20 or with the moderating role of stress. 21Data on caregivers' decision to vaccinate young CCS against COVID-19 is scarce, and the current study seeks to fill this knowledge gap.Caregivers of CCS often have more experience with medical information acquisition and decision-making, which may increase their overall health literacy and ultimately affect their information behavior, critical thinking, and health decision-making.
According to the Theory of Reasoned Action (TRA) 22 and the Theory of Planned Behavior (TPB), 23 the intention to perform behaviors best predicts actual behavioral performance (Figure 1).The TRA suggests that intention is formed by attitudes (i.e., subjective evaluation of a specific behavior) and subjective norms (i.e., perception of the social support regarding a specific behavior), which result from behavioral and normative beliefs, respectively. 22The TPB extends the TRA 24 by adding the concept of perceived behavioral control (i.e., perception of the ease or difficulty of performing a specific behavior), which is formed by control beliefs. 23,25 according to original and more recent formulations of the TPB, perceived behavioral control mediates attitudes and subjective norms. 26That is, the direction and degree to which attitudes and subjective norms contribute to the intention to perform a behavior are determined by perceived behavioral control.Furthermore, background variables (e.g., sociodemographic characteristics) only indirectly influence intention through attitudes, subjective norms, and perceived behavioral control.0][31][32] We aimed to use the TPB to identify antecedents contributing to caregivers' decision to vaccinate young CCS against COVID-19, including health literacy related to COVID-19 aspects (referred to as "COVID-19 health literacy" hereafter) and frequency of COVID-19 information-seeking.
For all significant antecedents of intention (H1-H4b), we further expected that higher caregiver COVID-19 health literacy (H6) and frequency of COVID-19 information-seeking (H7) are indirectly related to higher intention.

| Participants
This cross-sectional study is part of a larger clinical trial of Cancer SurvivorLink™ (www.cance rsurv ivorl ink.org; NCT03543852), which includes CCS who are at least 2 years off therapy, English-or Spanish-speaking, without any terminal diagnosis, and engaged in survivor care at one of 12 COG clinics across the Midwest (n = 4), Northeast (n = 4), West (n = 3), and South (n = 1) regions of the U.S. 33 Eligible participants were caregivers of CCS who were aged 5-17 years at survey completion and engaged in long-term follow-up care in a cancer survivor clinic.Caregivers who were not fluent in either English or Spanish were excluded.

| Procedure
Eligible caregivers enrolled in the clinical trial were invited to complete an ancillary online survey on COVID-19, with up to three email reminders.Data were collected and managed using secure, web-based REDCap (Research Electronic Data Capture) tools hosted at Emory University. 34,35Participants provided online consent before completing the survey and received a $20 gift card.Data collection was conducted between May and June 2022.At the time of data collection, the U.S. Food and Drug Administration (FDA) emergency approval of the Pfizer-BioNTech COVID-19 vaccine against COVID-19 among children five through 11 years of age had been in place for 6 months. 36Considering that COVID-19 vaccines were previously available for older age groups, 37,38 at the time of data collection, all CCS have been eligible for a COVID-19 vaccine for at least 6 months.The study received ethical approvals from the Western Institutional Review Board (20200913) and Emory Institutional Review Board (00101506).

| Measurements
Item wording and descriptive statistics of all Likert-type questions are available in Appendix S1.Attitudes (3 items, e.g., "I believe vaccines can help control the spread of COVID-19."),subjective norms (2 items, e.g., "Now that the COVID-19 vaccine is available in my community, my decision of whether or not to get my child vaccinated would depend on: Recommendation from my family doctor"), and perceived behavioral control (1 item, i.e., "Now that the COVID-19 vaccine is available in my community, my decision of whether or not to get my child vaccinated would depend on: How easy it is to get the vaccine (e.g., available out-of-hours or in pharmacies)") were measured on 7-point Likert-type scales.All items were extracted from the survey tool and guidance developed by the World Health Organization (WHO). 39When necessary, question-wording was adapted to better fit the context of the current study.Composite scores measuring attitudes (range: 3-21) and subjective norms (range: 2-14) were generated, with higher scores indicating higher (or more positive) levels of the respective constructs.Perceived behavioral control was used in further analyses as a single item (range: 1-7).Internal consistency of the composite scores of attitudes (Cronbach's alpha (α) = 0.750) and subjective norms (α = 0.908) was good to very good.Intention (measured on a 5-point Likert-type scale) and behavior (yes/no) were assessed using one item each.To facilitate the analysis, we generated a binary variable of intention with labels "no or undecided" (strongly disagree, disagree, or undecided) and "yes" (agree or strongly agree).
COVID-19 health literacy (9 items) and frequency of COVID-19 information-seeking (1 item) were assessed as recommended in the survey tool and guidance of the WHO. 39Answer options were given on 5-point (COVID-19 health literacy) and 7-point (frequency of COVID-19 information-seeking) Likert-type scales.We generated a composite variable for COVID-19 health literacy by summing individual item scores (range: 9-45, α = 0.910).
Information on COVID-19 included caregivers' vaccination status (yes/no), their perceptions about the risk for severe COVID-19 symptoms if the CCS gets infected (yes/ no), having received a personal recommendation from a healthcare professional (HCP) to have the CCS vaccinated (yes/no), and information about the COVID-19 history of the CCS (no diagnosis, suspected diagnosis, or confirmed diagnosis).
The baseline survey of the larger trial assessed additional sociodemographic data about the caregiver (relationship to the child, race/ethnicity, marital status, education, household income, and employment in healthcare within the household) and CCS (sex, age, original cancer diagnosis, time since diagnosis, and time since end of treatment).

| Analysis
Descriptive statistics, including means (M), standard deviations (S.D.), skewnesses, kurtoses, and frequencies, were computed for all dependent and independent variables.Unadjusted linear regressions were used to identify significant background variables associated with attitudes, subjective norms, and perceived behavioral control.When the categories of the independent variables were very small (<20 observations), we combined them to form larger categories to reduce the risk of over-fitting the model.The results of unadjusted linear regressions are available in Appendix S2.Stata (version 17) 40 was used to run descriptive statistics and unadjusted linear regressions.
Structural equation modeling was conducted in Mplus 8.8. 41Model building was sequential based on the hypotheses from regression models to the full path model.Four models were estimated to test our hypotheses.Model 1 examined the direct relationship between caregivers' vaccination intentions and attitudes, subjective norms, and perceived behavioral control.Model 2 tested the indirect relationships between attitudes and intention, and subjective norms and intention, through the moderation of perceived behavioral control.Model 3 tested the full TPB model.Model 4 tested all the previously identified significant paths and incorporated relevant background variables.All models used full information maximum likelihood assuming data missing at random.Due to the inclusion of noncontinuous endogenous variables, the weighted least squares mean and variance adjusted (WLSMV) estimator was used. 41Model fit was assessed using Root Mean Square Error of Approximation (RMSEA), Comparative Fit Index (CFI), Tucker-Lewis Index (TLI), Standardized Root Mean Square Residual (SRMR), and chi-square. 42tatistical significance for all analyses was set at p < 0.05, using a two-sided test.The data analyzed for this study are available upon request.

| Sample characteristics
Of the 237 caregivers invited to participate, 160 caregivers (87.5% biological mothers) of 160 CCS completed the survey and were included in the analyses (67.5% response rate).Caregiver and CCS demographics are outlined in Tables 1 and 2, respectively.No demographic differences were found between caregivers who participated in this survey and those who did not respond to the invitation (all p-values > 0.20).CCS (44.4% female) were, on average, 12.5 years old at study (S.D. = 2.9; range: 6-17).70.0% (n = 112) of caregivers and 53.8% (n = 86) of CCS had received at least one vaccine against COVID-19.Caregivers reported that most CCS had not received a COVID-19 diagnosis (n = 73; 45.6%), while 30.0%(n = 48) were confirmed with COVID-19, and 18.8% (n = 30) were suspected to have had COVID-19.

| Structural equation modeling
A graphic representation of the four estimated models is available in Appendix S3, and all model fit data are available in Table 3.In Model 1, attitudes (standardized beta coefficient (β) = 0.508; standard error (S.E.) = 0.082; p-value (p) < 0.001) and subjective norms (β = 0.320; S.E.= 0.065; p < 0.001) were both positively associated with intention, supporting H1 and H2.We did not find any direct (p = 0.560) association between perceived behavioral control and intention, rejecting H3.In Model 2, both moderations of attitudes (p = 0.551) and subjective norms (p = 0.582) were not associated with intention, rejecting H4a and H4b.Model 3 showed that caregivers' intention (β = 0.864; S.E.= 0.054; p < 0.001) was related to the CCS Note: Total percentages might not add up exactly to 100 because of rounding issues.

| DISCUSSION
Improving COVID-19 vaccination rates among CCS may help reduce their risk for a severe disease course and other complications later in life.Despite national recommendations and the widespread availability of vaccines against COVID-19, only half of the CCS in our sample had received According to a nationally representative study conducted in October-November 2021, 54.0% of parents of children aged 5-11 years old and 69.7% of parents of children aged 12-17 years old indicated a likelihood of vaccinating or having already vaccinated their child against COVID-19. 43The current study suggests that acceptance rates among parents of CCS might be slightly lower, even though CCS may be at higher risk for COVID-19 infection, a severe course of the disease, long-lasting symptoms, and further complications.Compared to previous research conducted among caregivers of minor CCS in the U.S., 10,11 our study identified more unfavorable and less neutral intentions toward COVID-19 vaccines for CCS.Further, our results showed that most caregivers were either strongly favorable or unfavorable in their intentions toward COVID-19 vaccines for their CCS, with very few participants reporting moderate views or indecision.Previous research on CCS caregivers' COVID-19 vaccine acceptancy was conducted in early 2021, 10,11 when the Pfizer-BioNTech COVID-19 vaccine was authorized for emergency use in individuals aged 16 and older, and no vaccines were available for younger children. 44As vaccines became available for children worldwide, online information promoting mistrust in the vaccine and misinformation may have raised concerns among caregivers. 45dditionally, the increasing polarization toward COVID-19 vaccines associated with political beliefs may have also contributed to observed differences in intentions. 46ur results showed that attitudes and perceived support were associated with caregivers' vaccine intentions.Perceived behavioral control was not directly associated with intention or moderate the relationships between attitudes or subjective norms and intention.The TRA applies to straightforward behaviors over which individuals have reasonable control. 24Given that COVID-19 vaccination is relatively easy, accessible, and under people's control, perceived behavioral control may have less influence in explaining intention.Previous studies that used the TPB to examine parents' COVID-19 vaccination intentions for their children have produced contrasting results in the general population.Two studies were conducted in China 30 and Hong Kong 32 before vaccines were authorized for children and at the time the first vaccines were becoming available for children, respectively.Both studies found all constructs, attitudes, subjective norms, and perceived behavioral control to be related to intention.Conversely, a study conducted in China after the authorization for COVID-19 vaccines among children showed similar results to ours and did not find perceived behavioral control to be indicative of parents' intentions. 31Based on our findings and the previous research, we can conclude that perceived behavioral control is important for caregivers when vaccines are not accessible for their child.However, when vaccines become accessible, attitudes and perceived support from HCP may be more critical in shaping vaccine intentions and behavior.
Misconceptions and safety concerns regarding COVID-19 vaccines may contribute to vaccine hesitancy, 47 especially among individuals with lower health literacy or those who are underinformed and more vulnerable to misinformation.Our study found that more frequent COVID-19 information-seeking and higher COVID-19 health literacy were indirectly associated with positive intentions for vaccination.These findings are consistent with previous research on COVID-19 vaccination [16][17][18][19] and highlight the importance of caregivers' health literacy in understanding the risks and benefits of vaccination and making informed decisions for their children.Given the extensive media coverage and conflicting information surrounding COVID-19 vaccines, individuals with lower COVID-19 health literacy may have difficulty distinguishing accurate information from myths or misinformation, leading to lower vaccination intentions.Conversely, actively seeking and evaluating reliable sources of information may increase positive beliefs toward vaccination and intention to vaccinate. 48Thus, promoting clear communication about COVID-19 vaccines, especially tailored to the childhood cancer context, encouraging caregivers to review reputable sources of accurate information, and monitoring and counteracting disinformation around vaccines, especially in the pediatric setting, may help address vaccine hesitancy and increase positive beliefs about COVID-19 vaccination among caregivers of CCS.

| Strengths and limitations
When interpreting our results, it is important to consider the limitations related to our sample.Firstly, only caregivers of CCS who were engaged in long-term follow-up care at a cancer survivor clinic were eligible for participation, which might limit the generalizability of our findings.Because these caregivers were engaged in long-term follow-up care, they may have more concerns about the health of the CCS and, therefore, more favorable and willing to have them vaccinated against COVID-19.Secondly, while we could recruit sufficient participants, we acknowledge that our sample size was still relatively limited for SEM analyses.To address this limitation, we reduced the complexity of our model, which nevertheless successfully explained COVID-19 vaccination intentions for CCS among caregivers.Thirdly, our sample was predominantly composed of white/non-Hispanic biological mothers and showed higher educational attainment and income than the U.S. population, which may limit the generalizability of our findings to other subpopulations of CCS.We recommend that future research includes more male caregivers and specifically seeks to understand vaccine intentions among Black and Hispanic families of CCS, as well as among families with lower socioeconomic status, given observed racial/ethnic 49 and socioeconomic 50 disparities in rates of COVID-19 infection and vaccine uptake.Lastly, our study was cross-sectional, and we could not assess vaccination intention and behavior at different times.However, we expect that current vaccination status and future vaccination behavior are related, given that caregivers had sufficient time to decide whether to vaccinate the CCS.
Several strengths suggest that this study's results are reliable and informative for understanding COVID-19 vaccination intentions for CCS among caregivers.Firstly, the data were collected from families recruited from 12 clinics across the U.S., increasing the geographic reach and generalizability of the findings.Secondly, the analysis showed an outstanding model fit to the data, demonstrating the statistical methods' robustness.Furthermore, the study was theory-driven.We used well-established health behavior theories to guide measurement and interpret our findings.This theoretical foundation enhances the rigor and coherence of the study and supports the validity of our results.

| Conclusion
Attitudes, perceived support, frequency of COVID-19 information-seeking, and COVID-19 health literacy shape caregivers' COVID-19 vaccination intentions and behavior for their minor CCS.Our results may have several important implications for future research and practice in pediatric vaccinations, such as MMR or HPV vaccines, and vaccines against future pandemics, where similar attitudes, norms, and control perceptions may apply.Further research is needed to explore the relationship between these psychological factors and understand how they influence vaccine acceptance and uptake in other scenarios.The TRA was a valuable and comprehensive framework for studying CCS caregivers' COVID-19 vaccine intentions, overperforming the more complex TPB.Furthermore, our results suggest that communication persuading caregivers to vaccinate their CCS should not focus on the easiness of receiving a vaccine once it is widely accessible.Frequency of COVID-19 information-seeking and COVID-19 health literacy were important indicators for explaining caregivers' intention toward COVID-19 vaccination.These are modifiable variables to which public health efforts should be dedicated to increase vaccination intentions and ultimately improve vaccine uptake among young CCS.
While attitudes and subjective norms are direct predictors of intention, The Theory of Reasoned Action and the Theory of Planned Behavior.
Characteristics of caregivers.Characteristics of childhood cancer survivors (CCS).
T A B L E 1Note: Total percentages might not add up exactly to 100 because of rounding issues.TA B L E 2 Models fit data.COVID-19 vaccine.Applying the TPB, we found that the COVID-19 vaccination status of CCS was strongly associated with caregivers' vaccine intentions, with intentions being shaped by caregivers' attitudes, subjective norms (i.e., perceived support), COVID-19 health literacy, and frequency of COVID-19 information-seeking.
T A B L E 3 a