Identifying the Barriers and Facilitators to Complete Revaccination in Adult Hematopoietic Stem Cell Transplant Survivors in the United States

Abstract

Background: Comprehensive hematopoietic stem cell transplant (HSCT) survivorship care includes revaccination after transplant to restore immunity to vaccine-preventable diseases (VPDs). Revaccination after HSCT to restore VPD immunity is a complex undertaking for HSCT survivors, and current revaccination uptake is sub-optimal. As HSCT survivors are at higher risk for morbidity and mortality from infectious causes, efforts to reduce infectious risk in this population, such as improving the rate of fully revaccinated survivors, are imperative. No existing published studies have reported comprehensive barriers and facilitators to complete revaccination among adult HSCT survivors in the US. Purpose: The overall objective of this dissertation is to advance understanding of the factors influencing revaccination uptake among adult HSCT survivors living in the US. This dissertation had three specific aims: 1a) Determine the prevalence of adult HSCT survivors who are completely, partially, or not revaccinated 2-8 years after HSCT using a well-characterized and geographically diverse sample, 1b) Examine associations between demographic variables, social determinants of health, clinical variables, past vaccine behaviors, vaccine hesitancy (Vaccine Confidence Scale), and revaccination status in adult HSCT survivors, 2) Explore vaccine hesitancy in the context of revaccination among adult HSCT survivors by describing the level of agreement between quantitative results of vaccine hesitancy (Vaccination Confidence Scale) and qualitative results (open-ended survey items regarding vaccine confidence), and 3) Identify barriers and facilitators to complete revaccination using fixed and open-ended responses and describe the extent to which these factors explain the three revaccination status categories (completely, partially, or not revaccinated) among adult HSCT survivors. Methods: This dissertation comprised one quantitative analysis and two convergent mixed methods analyses of a cross-sectional revaccination survey of adult HSCT survivors between 2-8 years after transplant and living in the US. The survey was sent to eligible survivors in the Fred Hutchinson Cancer Center (FHCC) Long-term Follow-up (LTFU) research cohort. The first analysis (quantitative, n=338) determined the point prevalence of revaccination outcomes with descriptive statistics and examined associations between revaccination outcomes and predictors using logistic regression. The second analysis (quantitative, n=332 and qualitative, n=189) determined the point prevalence of vaccine confidence, examined relationships between vaccine confidence levels and revaccination outcomes and intent to complete revaccination using the Fisher’s exact test, and associations between vaccine confidence levels and predictors using logistic regression. Additionally, open-ended responses related to benefits, trust, and harms (the constructs of the Vaccine Confidence Scale) were analyzed using inductive thematic analysis. Lastly, a merged analysis to compare quantitative and qualitative findings was completed. The third analysis (quantitative and qualitative=194) determined the prevalence of barriers and facilitators using descriptive statistics, examined the association between the number of barriers and facilitators and revaccination outcome using logistic regression, and tested relationships between the most frequent specific barriers and facilitators and revaccination using the Fisher’s exact test. Additionally, open-ended responses were analyzed using deductive content analysis using the WHO behavioural and social drivers of vaccination framework. Finally, a merged analysis was conducted to compare quantitative and qualitative findings. Results: In the first analysis, the point prevalence of revaccination outcomes was 62% completely revaccinated, 33% partially revaccinated, and 4% not revaccinated. Factors associated with incomplete revaccination were shorter time from transplant, inadequate immune reconstitution, and not having received all childhood vaccines as a child. In the second analysis, the point prevalence of vaccine confidence was 69% high confidence, 20% medium confidence, and 11% low confidence. Revaccination outcomes and intent to revaccinate were significantly different across vaccine confidence levels. Factors associated with high vaccine confidence included: living in a zip code that voted for the Democratic presidential candidate in 2020, having means to pay out-of-pocket or health insurance coverage for vaccines, receiving all pre-HSCT adult vaccines, and receiving all the recommended COVID-19 vaccines. Themes were categorized as 1) Physical and mental benefits and beliefs about benefits (Benefits); 2) Existing factors for trust, prerequisites for trust, and impeding factors to trust (Trust); 3) Vaccine quantity, vaccine side effects, vaccines and harm, and not all vaccines are the same (Harms); and 4) Uniqueness of HSCT vaccinees and revaccination motivation and behavior (Other). The merged analysis showed congruence between Vaccine Confidence Scale scores and overall vaccine confidence coding from open-ended responses. Finally, the merged analysis created a narrative about the relative importance of the constructs when approaching revaccination by vaccine confidence level: the low confidence group relayed (dis)trust>harm>benefits, the medium confidence group relayed trust>benefits~harm, and the high confidence group relayed benefits>trust>harm. In the third analysis, the most frequent barriers were the inability to receive live vaccines because of continued immunosuppression, finding a place in the community that would give childhood vaccines to adults, and delayed immune system recovery. The most frequent facilitators were having healthcare insurance covering vaccines and having a clear calendar of what vaccines to receive and when. Further, with each additional reported barrier, the odds of being completely revaccinated were lower, OR=0.58 (95% CI 0.459-0.722), and with each additional reported facilitator, the odds of being completely revaccinated were higher, OR=1.31 (95% CI 1.05-1.63), p <0.001. Two of the five most reported barriers were significantly associated with no or partial revaccination: taking immunosuppressive therapy so not eligible for live vaccines (p= 0.001) and immune system not recovered enough for vaccines (p <0.001). Three of the five most reported facilitators were significantly associated with being fully revaccinated: having a clear calendar of what vaccines to get when (p= 0.032), being able to contact LTFU for vaccine questions (p= 0.018), and getting vaccines at FHCC (p= 0.041). Content analysis suggested that most barriers were in the “practical issues” construct, especially service quality and availability. A surprising, but important theme was the transplant center as vaccination site, with 15% of all respondents commenting in free text that they believed that is where revaccination should be offered. The merged analysis mostly indicated convergence. Overall, the barriers seemed to outweigh the facilitators as influencing factors in the no and partial revaccination groups. Conversely, the facilitators seemed to outweigh the barriers as influencing factors in the complete revaccination group. Discussion: As few factors were associated with revaccination outcomes, interventions to increase revaccination uptake do not need to be targeted to certain survivors. Since many survivors cannot be revaccinated promptly due to delayed immune recovery, clinicians must extend the period to evaluate for revaccination readiness and ensure eventual revaccination. We can no longer ignore that HSCT survivors experience vaccine hesitancy and that vaccine hesitant HSCT survivors are less likely to complete revaccination. We must develop population-specific interventions to help vaccine-hesitant survivors choose to revaccinate. Reducing barriers and enhancing facilitators associated with poor revaccination outcomes is required. Clinicians can assess patients for barriers and facilitators and formulate individual plans towards complete revaccination. Novel programs for reducing system barriers, such as a vaccine clinic co-located within the HSCT survivorship clinic, should be designed and tested. Conclusions: In these studies, revaccination outcomes were associated with few factors, only 69% of survivors had high vaccine confidence which significantly affected revaccination intent and outcome, and practical barriers and facilitators played a consequential role in revaccination uptake. Taken together, these findings significantly expand our knowledge of the factors influencing revaccination uptake among US HSCT survivors. Future research that builds on these findings should focus on prospective methods and intervention testing.