Bridging Gaps: Evaluating Strategies to Improve Vaccine Uptake and Strengthen Clinical and Translational Research Recruitment Among U.S. Adult Populations

Abstract

Background and Rationale: Despite decades of federal policy mandates and extensive public health infrastructure investment, critical gaps have persisted in the effectiveness and equity of two core activities in U.S. health research: vaccine promotion and research recruitment. Effective vaccination strategies and representative clinical and translational research enrollment have been essential to population health, yet both have continued to fail disproportionately in reaching the populations with the greatest need. Enacted in 2010, the Affordable Care Act (ACA) eliminated financial barriers to recommended vaccines, yet adult vaccination rates have remained well below Healthy People 2030 goals across populations. Simultaneously, more than 30 years after the NIH Revitalization Act mandated inclusion of underrepresented populations in federally funded research, racial and ethnic minority groups, low-income individuals, rural residents, persons with disabilities, and other structurally marginalized communities have remained systematically underrepresented in clinical and translational research samples. These twin failures have shared a common, underexamined cause: researchers have continued to design strategies for populations of convenience rather than populations of need, generating an evidence base that has reflected and reinforced existing health disparities rather than addressing them. Objectives: This dissertation pursued two parallel systematic synthesis objectives and one framework development objective. Project 1 aimed to synthesize the post-ACA peer-reviewed literature (2010-2025) on strategies designed to increase vaccine intention and improve vaccine uptake among U.S. adult populations, and to characterize the types, settings, populations served, and effectiveness of those strategies using a multiple linear regression. Project 2 aimed to synthesize and evaluate the characteristics and effectiveness of recruitment strategies used in NIH-funded clinical and translational research to engage underrepresented U.S. adult populations (1993-2025), focusing on peer-reviewed studies that evaluated strategies through comparative or controlled designs. Project 3 built upon the findings of Project 2 to develop ReFrame, a theory-informed, multi-domain framework for planning, implementing, evaluating, and reporting research recruitment strategies with an explicit health equity orientation. Methods: Both systematic reviews followed PRISMA 2020 guidelines and were registered on the Open Science Framework (Project 1: OSF 10.17605/OSF.IO/SM7YD; Project 2: OSF 10.17605/OSF.IO/BYS5G). Comprehensive multi-database searches were conducted across PubMed, Web of Science, Ovid/MEDLINE, and EBSCOhost, including CINAHL and PsycInfo, supplemented by Google Scholar gap checks and forward/backward citation chasing, with final searches completed in December 2025. Dual independent reviewers conducted screening and data extraction at each stage, with a third reviewer resolving conflicts. Study quality was assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool, and overall evidence certainty was evaluated using the GRADE framework. For Project 1, strategies were categorized according to the WHO Behavioral and Social Drivers of Vaccination (BeSD) Model, and a multiple linear regression was conducted using vaccine uptake rate as the dependent variable across 79 eligible studies. For Project 2, a multiple linear regression was conducted using enrollment rate as the dependent variable across 43 eligible studies (118 strategy arms). ReFrame was developed through the convergence of systematic review findings with established theoretical models from health behavior science, implementation science, and community-based participatory research (CBPR) principles. Results: Project 1 (Vaccine SRMA): Of the 11,219 records identified, the vaccine systematic review yielded 92 eligible studies (79 vaccine uptake, 30 vaccine intention, 17 overlapping). In the meta-regression (Adjusted R2 = 0.2285), strategies prioritized specific populations (b=0.121, p=.027), using service quality improvement approaches (b=0.226, p=.040), and recruiting through community-based partner organizations (b =0.585, p=.005) or healthcare organizations (b=0.230, p=.040) were associated with significantly higher vaccine uptake rates. Onsite vaccination was associated with significantly lower uptake rates (b=—0.185, p=.033), an effect that a sensitivity analysis confirmed was COVID-19-context-specific. Narrative synthesis identified multi-component strategies, community partnerships, and health equity-focused designs as consistently associated with more favorable outcomes across both uptake and intention domains. GRADE certainty was LOW to MODERATE across most findings. Project 2 (Recruitment SRMA): Of 5,589 records identified, 43 studies (118 strategy arms) met eligibility criteria. The median enrollment rate across all strategy arms was 32.1% (range: 0%-93%). In the meta-regression (Adjusted R2=0.385), community-based sample pool sources (b=0.331, p=.001) and EHR/registry-based sources (b=0.282, p=.003) were associated with significantly higher enrollment rates relative to other source types. Larger sample sizes were associated with significantly lower enrollment rates (b=—0.0000072, p=.026). Individual study quality was predominantly Weak by EPHPP global rating (58%), with confounders and blinding as the most frequently Weak-rated domains. Project 3 (ReFrame): ReFrame organized recruitment strategy evaluation across five interdependent domains: Strategy Planning and Design; Implementation and Adaptation; Outcome Assessment; Equity and Inclusion Analysis; and Knowledge Sharing and Reporting. The framework integrated the Health Belief Model, Social Ecological Model, CFIR, RE-AIM, CBPR principles, and Diffusion of Innovations Theory, and proposed standardized metrics, practical tools, and minimum and enhanced reporting standards applicable across diverse research contexts. Conclusions: Across both systematic reviews, a consistent pattern emerged: strategies that embedded outreach within existing relational infrastructure, whether clinical (EHR/registry-based) or community (CBPR), outperformed convenience-based approaches that relied on broad, impersonal outreach to undifferentiated audiences. For vaccination, service quality improvement and community-based recruitment pathways were robust predictors of higher uptake. For research recruitment, community-engaged and EHR/registry-based sourcing were the only statistically significant predictors of enrollment success. These findings converged on a single, equity-weighted interpretation: the participant reach and engagement have been determined primarily by where researchers have looked, and the populations most frequently overlooked were those who have borne the greatest burden of health conditions that public health and clinical research have been designed to address. ReFrame has provided an evidence-grounded framework to operationalize this insight into systematic, evaluable, and equitable recruitment practice.