Bridging ethics and efficacy in IRB review of vaccine trials

As vaccine clinical development faces scrutiny, understanding the origins and the rigorous review that takes place prior to the approval and implementation of a new vaccine is essential.

Institutional Review Boards (IRBs) play a key role in evaluating scientific integrity and participant safety, strengthening the credibility of vaccine development as impartial ethical reviewers (Desai et al., 2024). Increased transparency about IRB oversight activities can close knowledge gaps and rebuild trust in public health vaccination efforts. In this article, we explore how IRB oversight is essential to and embedded within vaccine research and development.

A foundation of modern trials

The inseparability of vaccine research and ethical oversight becomes clearer when viewed through the lens of the 1954 poliomyelitis vaccine trial. More than a landmark scientific achievement, this trial arguably established the foundation of modern American clinical trials (Mitchell & Steingrub, 1988; Salk, 1956).

Employing rigorous methodology and evidence-based design, this research drew on animal data and operated on an unprecedented scale (n=1,829,916) to address a major public health issue. Although formal IRBs had not yet been established, this study incorporated ethical principles that continue to guide IRBs and ethics committees today.

Indeed, today's IRB reflects the underpinnings of the poliomyelitis vaccine trial, objectively reviewing human research, while promoting ethical and scientifically sound practices. They assess scientific validity, ensure methodological reliability, and monitor research to minimise risks and balance benefits. IRBs also require clear communication of study aims, procedures, risks, benefits, and participant rights through informed consent (21 CFR §56.111, 45 CFR §46.111) throughout the life-cycle development of the vaccines. It is perhaps more important than ever to highlight this role.

Public trust in vaccination programmes

Growing levels of vaccine hesitancy underscore the need for transparent, independent oversight in vaccine research. The NFID 2025 National Survey on Respiratory Diseases indicated that nearly half of adults in the United States report uncertainty or reluctance toward receiving routine respiratory virus vaccinations, citing concerns around overall side effects, safety, and conflicting information (NFID, 2025). This hesitancy is further fuelled by a complex mix of social, psychological, and environmental influences, including the spread of misinformation, and heightened sensitivity to perceived vaccine risks (

These factors spill into other domains, undermining public trust in vaccination programmes, negatively impacting vaccine uptake, and ultimately contributing to an influx of vaccine-preventable diseases. As public confidence continues to fluctuate, the IRB’s role as an independent, regulatory-anchored review body becomes even more essential. More to the point, while the IRB’s job description remains largely unchanged, there is an urgent need to communicate the work of the IRB and the protections offered by this independent oversight committee to the public.

Ethical guardrails and regulatory requirements

IRBs operate as independent bodies that comply with federal, state, international, and institutional regulations, including FDA, OHRP, and ICH GCP standards. They protect participant privacy and data confidentiality, evaluate investigator qualifications, and manage conflicts of interest — whether involving researchers or IRB members — to uphold research integrity (21 CFR 312.53(a); 21 CFR 812.43(a)). Regulations require IRB members to disclose conflicts of interest and recuse themselves from related reviews [21 CFR 56.107(e), 45 CFR 46.107(e), ICH E6(R2) Sections 3.2.1 and 3.2.4], ensuring that ethical principles and participant protection guide decision-making.

Research under IRB oversight must report unanticipated problems involving risks to participants or others and serious noncompliance. Annual review is mandatory to assess ongoing safety and progress, highlighting the IRB’s constant vigilance over research integrity (21 CFR 56.108-9(f)). IRBs monitor study safety, review protocol changes, deviations, adverse events, and new data affecting participant welfare or risk-benefit analysis. IRBs provide essential safeguards for ethical standards and scientific rigour, with their influence extending beyond procedures.

The spread of IRB-reviewed vaccine protocols in the past decade shows the IRBs’ support for vaccine development. While most vaccine studies target infectious diseases, others include direct oncology vaccines and post-market surveillance for safety and efficacy. All studies in humans, from Phase I tests for safety to large Phase III proof-of-effectiveness studies, must pass and maintain this high level of oversight throughout their life cycles. This underscores the importance of IRB oversight and its public health impact across populations. IRB activities directly support trust in vaccination programmes.

How regulatory requirements become visible protections

Let’s consider what this looks like in practice. In any vaccine study, IRB review begins by testing the logic of the risk-benefit balance: are pre-specified safety thresholds and pause criteria adequate? Is the consent form written so a layperson can understand what participation involves? Oversight continues throughout the life of the study.

The IRB evaluates protocol changes, reviews deviations and adverse events, and requires prompt reporting of unanticipated problems, maintaining authority to demand modifications or suspend enrolment if participant rights or welfare are at risk. When new safety information emerges, it is submitted to the IRB for consideration, and the Board determines whether the proposed response is sufficient or whether further action is required.

This ongoing ethical and regulatory oversight shapes the development of every vaccine as it moves from bench to bedside. Communicating these checkpoints into plain language – what the IRB examined, how conflicts are managed, what contested issues were discussed – transforms “independent oversight” from an abstract assurance into a visible safeguard. In other words, in the wake of increased vaccine hesitancy, IRBs have an opportunity to support the restoration of trust in public health by making the independent ethical deliberation and accountability that underpin every vaccine brought to market visible.

The IRB’s enduring role in vaccine research, rooted in principles that trace back to the foundational poliomyelitis trials, remains essential across every stage of research, from early-phase studies with the highest uncertainty to participant risk and scientific uncertainty through later phase, large-scale trials conducted prior to market release. IRB oversight ensures ethical conduct, scientific rigour, appropriate risk mitigation, and ongoing safety monitoring, bridging regulatory requirements and their real-world application.

In the current environment of heightened vaccine hesitancy, rigorous review alone is insufficient; the protections IRBs offer must also be understandable to the communities they affect. Making oversight processes more transparent through clear communication, public-facing explanations of key ethical review points, and consistent engagement all help to translate regulatory obligations into visible participant protections.

Sustained independence, accountability, and transparency will remain central to rebuilding and maintaining public confidence in vaccine research and the ethical conduct of clinical trials.

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About the authors

Currien MacDonald, MD, CIP, is medical chair director at WCG. Dr MacDonald contributes to biosafety reviews for WCG’s institutional biosafety committee. Prior to joining WCG, Dr MacDonald served for four years as the medical director for Aspire IRB and vice-chair of Canadian REB. After graduating top of his class from the University of Minnesota Medical School US, he completed a rigorous family medicine residency programme as chief resident. He then delivered primary care for five years in San Diego, California, US. He also served as a medical consultant to the University of California, San Diego, US on a groundbreaking prisoner healthcare reform project. 

Tara B. Coffin, PhD, MEd, CIP, is regulatory chair at WCG. Dr Coffin is a qualitative research and health communication consultant. Trained in public health genetics and education, her work centres on improving equitable access to genetic testing, early cancer detection, and clinical research participation. She has collaborated on multi‑institutional studies with leading cancer centres, including Dana‑Farber, MD Anderson, and Brigham and Women’s Hospital, with a focus on recruitment, usability testing, and participant‑centred communication. Dr Coffin has published extensively on genetic education, research ethics, and health equity, and brings regulatory expertise to advancing ethical, inclusive research practices.

Ranga Venkatesan, PhD, MS, RAC, is IRB chair at WCG. Dr Venkatesan is a regulatory IRB chair at WCG, with expertise in regulatory affairs. Before transitioning to regulatory affairs, he conducted preclinical oncology and drug development research in the biotechnology industry and in academia. His professional interests include preclinical drug discovery, clinical development, and regulatory affairs.