Enablers and barriers to participation in vaccine trials: a narrative synthesis

To synthesise evidence on barriers and enablers to participation in vaccine clinical trials (2010-2024), with a focus on underserved populations, to support the design of more inclusive vaccine trials.

A rapid narrative review was conducted using PubMed, identifying 145 peer-reviewed studies published between 2010 and 2024. Data extraction captured study design, participant population, and factors influencing trial enrolment. Findings were thematically analysed, with subgroup synthesis for underserved populations, including pregnant individuals, parents, ethnic minority groups, and LGBTQ+ communities.

Analysis of the 145 included studies identified five themes for enablers and four themes for barriers. Safety concerns were the most frequent deterrent, particularly for proxy decision-makers such as parents and pregnant participants. Institutional mistrust and misinformation were consistent barriers, with the COVID-19 pandemic heightening distrust of governments and pharmaceutical companies and amplifying misinformation through social media. Additional barriers included sociocultural expectations and logistical burdens, particularly in low-resource settings. Enrolment was enabled by altruistic motivations, perceived personal or community benefit, transparent safety communication, logistical ease, and community engagement. Community-led engagement, culturally concordant staff, and proportionate incentives were consistently associated with improved enrolment.

Vaccine trial participation is shaped by a dynamic risk-benefit calculus that manifests differently across populations. Addressing inequities requires sustained community partnerships, culturally competent trial design, proportionate material support, and proactive communication strategies to counter misinformation. These findings provide actionable guidance for designing more inclusive vaccine trials.