Vaccine hesitancy is widely recognized as one of the most significant public health problems of the 21^st Century. The World Health Organization (WHO) identifies vaccine hesitancy as a top ten threat to global health, reflecting persistent gaps between scientific innovation and public acceptance and confidence.

Despite extraordinary advances in vaccine science, the diffusion of new vaccines into routine medical practice typically proceeds unevenly and slowly. This disconnect is not primarily a scientific problem; a central challenge is the low level of public trust requiring more effective education and engagement strategies and practices.

Research conducted by the Tufts Center for the Study of Drug Development (Tufts CSDD) provides valuable insight into how vaccine developers can address this challenge. By examining vaccines that achieved unusually rapid uptake, our study highlights an important paradox: the most effective patient-engagement practices were not intentionally designed.

Instead, they were implemented through ad hoc decisions, local experimentation, and individual initiative. Yet these practices—transparency, community engagement, representative clinical trials, and targeted communication—were executed relatively well and consistently supported faster vaccine adoption.

The central strategic implication is clear. Vaccine developers must transition from episodic and reactive engagement to deliberate, enterprise-level patient-engagement strategies embedded within development and commercialization planning and implementation.

Doing so can transform vaccine hesitancy from a persistent structural barrier into a manageable operational challenge.

Assessing the Drivers of Vaccine Hesitancy

Vaccine hesitancy is shaped by a complex ecosystem of influences. The SAGE Working Group on Vaccine Hesitancy organizes these influences into three broad domains: contextual influences, individual and group influences, and vaccine-specific concerns.

Contextual influences include historical, cultural, and institutional factors that shape public perceptions about clinical care and clinical research. Longstanding mistrust in medical institutions—especially among historically marginalized populations—creates a structural barrier to vaccine acceptance.

Individual and group influences arise from personal beliefs, risk perceptions, social networks, and trust in health and clinical research professionals. Vaccine-specific concerns, in turn, reflect characteristics of the vaccine itself, including perceived safety, development speed, duration of protection, and fear of adverse effects.

Although these factors are widely recognized, the speed of vaccine uptake varies dramatically across products within the same therapeutic area. Some vaccines diffuse relatively quickly, while others receive marginal or no meaningful uptake.

This variation suggests that adoption outcomes are not predetermined by the nature of the disease or the science of immunology. Instead, adoption reflects executional excellence centered around the principles of patient education and engagement.

Studying Vaccines That Achieved Rapid Uptake

To understand what drives successful adoption, Tufts CSDD conducted a mixed-methods analysis examining vaccines that did not follow a seasonal pattern, approved between 2006 and 2024, that targeted infectious diseases affecting broad populations. Using data from the FDA, Tufts CSDD identified five vaccine categories: COVID-19, respiratory syncytial virus (RSV), hepatitis B, human papillomavirus (HPV), and H1N1 influenza.

Within each category, we identified the vaccine demonstrating the fastest uptake relative to its peers. These included Comirnaty, Heplisav-B, Gardasil 9, the 2009 H1N1 Monovalent Vaccine, and Arexvy.

Based on this quantitative diffusion mapping, Tufts CSDD next conducted qualitative interviews among healthcare providers, vaccine experts, and medical affairs professionals directly involved in each vaccine’s development. The interviews yielded an unexpected finding: there was little evidence that sponsors systematically implemented structured patient-engagement strategies.

Instead, interviewees described improvised activities—community partnerships, transparent communication, tailored education materials, and inclusive clinical trials—that were well executed and, as a result, inadvertently fostered trust and facilitated vaccine adoption.

Interviewees identified three primary barriers that undermine vaccine confidence:

• Lack of transparency in clinical evidence and access to information.
• Historical mistrust of clinical trial results.
• Insufficient diversity in clinical trials.

These barriers correspond directly to the three domains of vaccine hesitancy identified earlier:

• Limited transparency affects contextual trust.
• Historical injustices influence community perceptions of healthcare institutions.
• Narrow clinical trial populations create vaccine-specific uncertainty about safety and effectiveness across diverse patient groups.

These barriers highlight a deeper strategic opportunity: Vaccine developers traditionally focus on regulatory approval as the primary milestone in product development. Yet regulatory approval alone does not guarantee market adoption.

Trust must be earned long before regulatory review and maintained long after commercialization. The companies associated with the fastest-adopted vaccines appeared to recognize this implicitly—even if their actions were not formally structured.

Transparency and Access as Strategic Assets

Transparency in clinical research was one of the most powerful drivers of vaccine confidence. Interviewees emphasized that open communication about both positive and negative findings strengthens credibility with clinicians and the public.

In practice, however, many vaccine developers treat unfavorable findings as reputational liabilities rather than opportunities for trust-building. When data are inaccessible or communicated in highly technical language, the public may interpret this opacity as evidence of concealment.

Conversely, transparent disclosure signals institutional integrity. When companies publish protocol designs, safety data, and unsuccessful trial outcomes, they demonstrate accountability to patients and healthcare providers.

Such transparency may temporarily reduce short-term acceptance but ultimately increase long-term trust. From a strategic perspective, transparency should therefore be viewed as a reputational investment rather than a regulatory obligation.

The long-term return on that investment is greater credibility across clinical and patient communities. Rapid vaccine uptake was also associated with efforts to improve access and education.

Vaccination programs that reduced logistical barriers—such as requiring appointments, identification, or insurance—expanded participation among underserved populations. Conveniently located community-based vaccination clinics (e.g., at local schools, municipal buildings and community centers, grocery stores and pharmacies) provided accessible venues where individuals could receive vaccines without bureaucratic obstacles.

These programs were particularly effective in reaching individuals lacking regular access to a healthcare provider. Education initiatives complemented these access improvements.

Tailored communication materials explained disease risks, vaccine benefits, and potential adverse effects in culturally relevant ways. By addressing misinformation directly, these materials helped counteract narratives circulating within social networks and online platforms.

Building Awareness and Trust through Community Collaboration

Another major driver of vaccine adoption involves rebuilding trust through targeted community engagement. Historical experiences with healthcare institutions—such as unethical research practices or unequal treatment—have left many communities skeptical of medical recommendations. Overcoming this skepticism requires collaborating with trusted intermediaries based within the community.

Interviewees highlighted the role of community leaders and influencers, religious organizations, and local advocacy groups in bridging the gap between vaccine developers and the public. Collaboration with African American churches, for example, helped facilitate recruitment for HPV vaccine trials. Community leaders validated public concerns while also communicating evidence-based information about vaccine safety and benefits.

These partnerships produced measurable operational benefits. Clinical trials achieved more representative enrollment and stronger participant retention.

More importantly, the clinical trial results appeared more credible to the communities that the vaccines were intended to serve. This experience underscores a fundamental principle: trust cannot be outsourced to public health agencies alone.

Vaccine manufacturers must actively participate in community engagement and collaboration efforts. Patient advocacy groups were also particularly effective partners in community engagement efforts.

These organizations often possess deeper relationships with patient communities and can articulate real-world concerns that may otherwise be overlooked in clinical development planning. Advocacy groups contributed to disease awareness campaigns, advocated for inclusion of special populations in clinical trials, and helped ensure ethical safeguards for participants.

Their involvement improved communication effectiveness. Moreover, advocacy groups’ input into educational materials helped to better tailor those communications to patient needs, cultural contexts, and language preferences.

In several initiatives, educational resources—including videos, fact sheets, and myth-busting documents—were translated into multiple languages and tested with community members to ensure clarity and relevance. Healthcare providers represent another critical community collaboration partner.

Physicians and pharmacists serve as trusted advisors whose recommendations strongly influence patient decisions. Interviewees emphasized the importance of sustained relationships between sponsor companies and healthcare providers.

Medical affairs teams that maintain ongoing dialogue with clinicians are better positioned to understand their concerns, address data gaps, and tailor educational resources. One physician described having greater confidence in vaccines from companies that maintained long-term professional relationships and provided transparent updates regarding new data.

Even when evidence was incomplete, candid communication and collaboration reinforced trust.

Representation in Clinical Trials as a Trust-Building Mechanism

Another consistent theme across interviews involved the importance of diversity in clinical trials. When study populations fail to reflect the demographics of patients who will actually receive and benefit by the vaccine, clinicians and patients alike question whether the results apply to them.

This concern is particularly acute for populations with complex medical conditions, such as immunocompromised patients. If clinical trials exclude these groups, physicians must extrapolate safety and efficacy data, increasing uncertainty and reducing confidence in vaccine recommendations.

These insights suggest that inclusive clinical trials not only improve the scientific robustness of evidence but also signal respect for the communities that the vaccines aim to protect. Participant diversity in clinical trials is not only a scientific necessity but also a trust-building mechanism.

Moving from Ad Hoc Inadvertent Practices to Intentional Sustainable Practices

The most important insight emerging from this research is not the specific practices themselves, but their lack of institutionalization. Vaccine developers repeatedly demonstrated effective engagement approaches, yet these efforts remained isolated and episodic.

Despite the clear and widely recognized importance of patient education and engagement practices, the interviews revealed that these activities were rarely systematically operationalized. Instead, project teams often rediscovered the same lessons across different vaccine programs.

Addressing this critical gap requires that sponsor companies embrace new, standardized processes and procedures. Sponsors should establish internal repositories documenting engagement strategies, community partnerships, and measurable outcomes.

Routine and periodic cross-functional forums can facilitate knowledge sharing across clinical, regulatory, and commercial teams. Regularly gathered and shared performance metrics can evaluate the impact of engagement initiatives on clinical trial enrollment, community trust, and vaccine adoption.

Vaccine hesitancy represents a multifaceted challenge rooted in historical mistrust, informational gaps, and concerns about safety and relevance. Insights from this Tufts CSDD study suggest that these barriers are addressable.

They can be mitigated through transparent and accessible communication, inclusive clinical trials, community engagement and collaboration with advocacy groups and healthcare providers. The most striking lesson from the Tufts CSDD analysis is that these practices were inadvertent and unintentional.

Yet when they were implemented well, they consistently supported faster vaccine adoption. By embedding and standardizing these practices, sponsor companies can convert ad hoc patient education and engagement practices into scalable strategic capabilities that ultimately prevent vaccine hesitancy.

Acknowledgement:Tufts CSDD appreciates and acknowledges that this study was supported in part by a research grant from The Investigator-Initiated Studies Program of Merck Sharp and Dohme Corp.

About the Authors

Hana Do, MPH; Madison Ford, MPH; Abigail Dirks, MS; Kenneth Getz, MBA, Tufts Center for the Study of Drug Development, Tufts University School of Medicine.