Ethical Excellence in Vaccine Clinical Trials: 5 Key Principles for Protecting Research Integrity and Research Participant Rights

Since Dr. Edward Jenner’s smallpox vaccine in 1796, vaccines have driven the eradication of many deadly diseases, including smallpox and polio. More recently, COVID-19's impact was mitigated by the rapid development and rollout of mRNA vaccines, averting what could have been a crisis comparable to the 1918 influenza pandemic. However, vaccine research has also faced setbacks, such as adverse events in trials for diseases like swine flu, dengue fever, and H1N1, which halted development. These incidents, compounded by widespread misinformation —particularly the discredited claims linking vaccines to autism — have contributed to public distrust and fueled the rise of organized anti-vaccination movements.

In Canada today, according to clinicaltrials.gov, there are currently over 50 active vaccine studies underway, reflecting the continued importance of clinical trials to ensure vaccine safety and efficacy. However, such trials also raise substantial ethical considerations. These challenges—focused on protecting research participants, ensuring transparency, promoting fairness, and balancing public health needs with individual rights—are best understood through the ethical principles of beneficence, non-maleficence, autonomy, justice, and transparency.

Here are five key ethical issues in vaccine clinical trials.

1. Beneficence: Prioritizing Public Good and Participant Welfare

The principle of beneficence underscores the need for vaccine trials to maximize public health benefits while minimizing risks. This involves creating study designs that account for diverse populations, ensuring that trial outcomes are meaningful and broadly applicable. Inclusivity across race, ethnicity, and other demographics strengthens a vaccine’s validation for all groups.

Beneficence also obligates vaccine manufacturers to maintain stringent safety and quality standards, especially with innovative technologies. Conducting thorough risk-benefit analyses and providing evidence on potential long-term effects ensures transparency and accountability. Thus, beneficence guides vaccine research by prioritizing public health and participant welfare.

2. Non-Maleficence: Avoiding Harm in Trial Design

The principle of non-maleficence, or "do no harm," requires rigorous oversight to prevent harm to participants. Vaccine trials must adhere to high safety standards and undergo thorough ethical review at every stage. Independent research ethics boards (REBs) assess study methodologies and participant protections, ensuring that trials are scientifically sound and ethically justified.

Placebo-controlled trials present specific ethical challenges under the principle of non-maleficence, particularly when effective vaccines already exist. Denying a proven preventive measure to control groups could increase risks of infection for these research participants. To address this, the Tri-Council Policy Statement and WHO guidance recommend exploring alternatives, such as using active comparators, delayed vaccination, or synthetic control groups, when feasible. In cases where placebos are necessary, ethical standards demand that research participants be given access to the vaccine once its efficacy is proven, minimizing harm associated with delayed protection.

3. Autonomy: Ensuring Informed Consent and Respect for Choices

Respecting autonomy, or the right of individuals to make informed decisions, is essential in vaccine trials. This principle is embodied through the voluntary nature of participation, informed decision-making, and the protection of privacy and confidentiality. Research participants must be fully informed of the risks, benefits, and procedures involved in the trial, as well as their rights in the event of adverse effects.

To further support participants’ right to make informed choices, researchers are encouraged to let participants know that they have the option to find out whether they received the vaccine or a placebo once they become eligible for a local vaccination program. This right, along with clear criteria for unblinding, should be included in informed consent documentation. Additionally, relevant trial documentation, such as standard operating procedures for unblinding, should be established to ensure transparency and consistency in respecting participants' right to know their treatment arm.

Privacy and confidentiality are central to autonomy, and vaccine trials must protect participants’ personal data to foster trust. Synthetic or external controls, which may use real-world data (RWD) such as electronic health records or insurance claims rather than new participant data, offer alternatives to placebo controls but raise privacy concerns, as RWD was not initially collected for research. When using secondary data, researchers must submit their protocols to a research ethics board (REB) for review, demonstrating that identifiable information is essential to the research and that privacy protections are in place. The REB will assess whether the use of data aligns with individuals’ previously expressed preferences and whether it is impractical to seek consent directly. These precautions, guided by REB oversight, help ensure adherence to privacy standards and respect for participants’ autonomy.

4. Justice: Promoting Fairness and Avoiding Exploitation

The ethical principle of justice emphasizes fair treatment, respect for human rights, and equitable access to vaccine trials and their benefits. Justice ensures that vulnerable and underrepresented populations, such as racial and ethnic minorities who may face a higher burden of disease, are included in trials not only to benefit from research but without being exploited. Achieving equitable representation has been a challenge, as illustrated by the COVID-19 pandemic, where certain communities were disproportionately affected by the virus yet remained underrepresented in clinical trials. Addressing these disparities requires intentional and adaptive strategies, such as inclusive recruitment practices and outreach to communities historically hesitant to participate in medical research.

Efforts to ensure justice in vaccine trials involve transparent communication around trial benefits and risks, and offering advantages like priority access to an effective vaccine. This equitable approach respects participants as valued contributors, fostering trust and fair treatment throughout the research process.

5. Transparency: Building Trust and Accountability in Vaccine Development

Transparency throughout vaccine development is essential to ethical conduct. Manufacturers and research teams have a duty to provide clear, comprehensive information on vaccine production, methodologies, and outcomes. This openness is critical in addressing vaccine hesitancy and countering misinformation, which has intensified public distrust.

Transparent communication about trial results, adverse events, and vaccine efficacy is vital in maintaining public accountability and reinforcing ethical standards. By openly sharing information, researchers build a foundation of trust that supports public health initiatives and promotes informed, responsible participation in vaccine research.

Conclusion: Ensuring Ethical Integrity through Collaboration with REBs in Vaccine Trials

While vaccines are critical to public health, their development must prioritize ethical integrity to sustain public trust and deliver equitable health outcomes. The ethical principles of beneficence, non-maleficence, autonomy, justice, and transparency are foundational to conducting responsible vaccine research. To uphold these principles effectively, close collaboration with the research ethics board (REB) during the early stages of study design is essential.

Engaging the REB from the outset ensures that protocols address key ethical concerns, such as minimizing risks, protecting participant autonomy, promoting fairness, and safeguarding data privacy, particularly when using real-world data as alternatives to placebo-controlled trials. Early REB input also facilitates proactive consideration of diverse representation, informed consent, and data confidentiality measures, building a solid ethical foundation for the trial.

By partnering closely with the REB, researchers in Canada can reinforce the credibility of vaccine research, counter public skepticism, and align with the Tri-Council Policy Statement (TCPS2). This collaborative approach ultimately strengthens the vaccine development process, supporting a public health framework grounded in trust, transparency, and respect for participant rights.

Designing a vaccine trial and need ethical guidance? Contact us today. Our team is here to help ensure your study meets the highest ethical standards and aligns with all normative requirements.