The scientific literature and guidance from major public-health bodies show persistent gaps in trial participation that reduce generalizability and trust. The World Health Organization Katherine O'Brien World Health Organization and the Centers for Disease Control and Prevention emphasize that trial populations often do not reflect those who will ultimately receive vaccines. Patterns vary by disease and trial phase, but several groups are repeatedly underrepresented.
Populations most underrepresented
Pregnant and lactating people are frequently excluded from early-phase vaccine trials despite pregnancy altering immune responses and disease risk. Older adults with multiple comorbidities are also underrepresented, particularly in initial efficacy studies where strict eligibility criteria favor healthier participants. Racial and ethnic minorities including Black, Hispanic and Indigenous communities often have lower enrollment relative to their disease burden, a disparity noted by the Centers for Disease Control and Prevention. People living in low- and middle-income countries are underrepresented in trials run primarily in high-income settings, limiting understanding of vaccine performance across different epidemiological and nutritional contexts. Other omitted groups include people with disabilities, people who are immunocompromised, incarcerated individuals, and gender-diverse populations. Children and infants are treated case-by-case; ethical and safety concerns lead to staggered inclusion across age groups.
Causes, relevance, and consequences
Multiple causes drive underrepresentation. Historical exclusion stems from ethical caution, regulatory uncertainty, and liability concerns that lead sponsors to narrow eligibility. Structural barriers include limited trial sites in rural or low-resource territories, language and accessibility hurdles, and community mistrust rooted in past abuses and ongoing inequities. The National Institutes of Health Office of Research on Women's Health National Institutes of Health has promoted inclusion policies, but implementation remains uneven.
Consequences are practical and ethical. Without diverse participants, safety signals and effectiveness estimates may not generalize, leaving clinicians uncertain about dosing, risk profiles, and benefit–harm balances for excluded groups. Public health responses can be less equitable when data gaps slow vaccine access or fuel hesitancy among communities whose experience is not reflected in trials. Cultural and territorial nuances matter: Indigenous sovereignty, local health priorities, and differing disease exposures in low-resource settings influence both trial participation and the acceptability of vaccination programs.
Addressing these gaps requires deliberate trial design, community partnership, and regulatory frameworks that enable safe inclusion. Strengthening representation improves scientific validity and supports fair distribution of the benefits and burdens of vaccine research.