This is part two of a multi-part post on the ethical and practical considerations of mandating vaccines for participation in (or conduct of) research. Read part one here.

On the SBER Network, a PRIM&R Online Community, discussion emerged (PRIM&R Membership required to view the link) about whether institutions could mandate COVID-19 vaccinations, what role IRBs might play in that conversation, and the principles we should take into account as we consider the question. Below, we share key points from that conversation and some further discussion from the participants:

• Nicole Ferrari, IRB Administrator at Central Connecticut State University
• Curt Naser, Chief Product Officer at Axiom Mentor
• An IRB Administrator working in public health, participating anonymously (IRB Administrator)
• An IRB Director working in public health, participating anonymously (IRB Director)

Part one tackled the appropriateness (and potential downsides) of vaccine mandates. This post addresses the core principles behind these decisions, and what IRBs should do when presented with these challenging questions at their institutions.

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The views presented are those of our featured participants, and shouldn’t be understood as positions taken by their institutions or PRIM&R as a whole.

How do the Belmont principles inform this discussion?

IRB Director: With all the attention on social justice issues relative to both COVID-19 outcomes and vaccination rates, it’s clear that there’s a disparate impact on minority groups. Excluding people from studies based on vaccination status is likely to disfavor those same groups, which contradicts the ethical principle of Justice.

Curt Naser: I think there are two questions or situations here: 1) when the research presents the possibility of direct benefit; and 2) when the results of research are skewed by exclusion/inclusion criteria that disproportionately disadvantage sub-populations. In both cases, we must weigh the risk of infection to subjects against the benefits of participation, either direct or indirect. I would want to see the specific protocols and make a judgment on a case by case basis and would treat medical reasons for not being vaccinated separately from the choice of individuals not to be vaccinated. In both cases, we have to balance beneficence considerations (avoiding harm) against justice considerations of equitable distribution of benefits and harms.

In general, those who are delaying or refusing to be vaccinated will come from a variety of different perspectives. There are those who are generally against vaccination, claiming risks that simply have not been proven. There are those who refuse out of political allegiance in our current partisan divide on all things government. There are also those populations that have been underserved and discriminated against by the health care system. The impact of Tuskegee and other abuses of vulnerable populations in our history cannot be underestimated. On the other hand, we have very clear evidence of the effectiveness of the vaccines and their risks. We don’t know the long-term risks yet, but we do know the immediate- and medium-term risks of COVID-19 infection (and learning more that is not good every week). Individuals may make their own judgments, but in cases where those judgments fly in the face of overwhelming scientific evidence, it is one thing to risk harm to yourself; it is quite another to risk harm to others because of your refusal to be vaccinated. I am not sure that we serve the public well by playing into the failure of individuals who think they can make better medical decisions than the community of public health physicians and researchers. Participation in research is not a right. The research community has an obligation to be fair and equitable in the conduct of research, but it is not obligated to put subjects and the population at risk for the sake of “fair” treatment of those who make medical judgments contrary to overwhelming scientific evidence.

Nicole Ferrari: In addition to Justice, I would say Beneficence is extremely relevant to the discussion as it is difficult to accurately determine risks and benefits without understanding the risk of COVID-19 exposure if we are not allowed to screen for vaccination status. And without fully understanding the risks of a study, how can researchers provide a fully informed consenting process (which addresses Respect for Persons)?

IRB Administrator: The Belmont Principles of respect for persons, beneficence, and justice should always be considered when reviewing human subjects research and impact any IRB’s decision to approve research as it is part of the approval criteria for human subjects research. If any of the criteria is not met, the research should not be approved (45 CFR 4.111). Risks to participants must be minimized by using procedures which are consistent with sound research design and which do not unnecessarily expose participants to risk, as well as use procedures already being performed on the participants for diagnostic or treatment purposes when appropriate. The risks to participants must be reasonable in relation to anticipated benefits, if any, to participants, and the importance of the knowledge that may reasonably be expected to result.

Is vaccination the only way to minimize risk from COVID-19? I think we have proven it is not. The selection of participants must be equitable. Excluding individuals because they are not vaccinated against COVID-19 is not creating a selection of individuals that is equitable. If any of these requirements to approve human subjects research are not met, the research should not be approved.

Principal Investigators (PI)s should be able to provide a fully informed consent process if including all participants/subjects. Why is COVID-19 making this difficult? The risk of contracting COVID-19 by participating in a research study is minimal if the PI follows the guidance provided by the CDC and local health departments. If guidance is followed, participants/subjects should be at less risk for COVID-19 than if they went to their local grocery store. We recently had an outbreak of measles in three counties involving academic institutions. Is it fair to have researchers at those institutions require a Measles vaccination to participate in a research study because others might be at risk for contracting the measles if they participate? What about during flu season—are PIs including statements in the informed consent that participants/subjects are at a higher risk for contracting flu because you used the same pen as someone else?

Before COVID-19, researchers were not washing down community areas being used by participants/subjects and pens to minimize the risk of flu or any other contractable disease. Has any researcher ever included in their informed consent under risks that you may catch a contractable disease (cold/flu/measles/chicken pox, etc.) by using the same pen or equipment as other participants/subjects? Where does this vaccination requirement stop? It is opening up the opportunity for legal action to include only those individuals that are vaccinated to participate in research. What if someone really wants to participate in the study and is excluded because they are not vaccinated? It is not a right to participate in a research study, but isn’t it discriminatory to exclude for a personal choice? There is a reason Belmont Principles are part of the criteria to approve human subjects research: so that history does not repeat itself.  

IRB Director: I think another angle to consider (in terms of both Respect for Persons and Nicole’s point about Beneficence) is whether an unvaccinated subject could be given “reasonable accommodation” to participate without putting themselves or others at risk. For example, could they participate remotely or in isolation? If not, then the PI could list vaccination status as one of the Inclusion/Exclusion Criteria and provide a scientific justification for that requirement (i.e., explain the methods/study design factors that don’t allow reasonable accommodation for non-vaccinated participants). The Employment Opportunity Commission recently tackled the reasonable accommodation issue (see item K5) with regard to Americans with Disabilities Act accommodations in the workplace, stating that disability-based exceptions to vaccination requirements are also subject to reasonable accommodation provisions. But they also don’t rule out excluding someone from the workplace if accommodations can’t be made. Perhaps there’s a lesson there for investigators and IRBs.

Do you have advice for IRB administrators, members, or other staff who are currently being confronted with this question?

IRB Directors: I encourage investigators to minimize the collection of specific health/medical data when a more general screening approach is possible. I think the same principle can be applied to vaccine status. For example, instead of asking “have you been vaccinated for COVID-19?” list all Inclusion Criteria and ask, “do you meet all requirements for participation in this study?” Whenever possible, SBER researchers should avoid collecting health/medical data if the study team doesn’t include qualified medical personnel.

Nicole Ferrari: I have no advice (I wish I had enough clarity on this to offer advice!). This is an interesting topic that gets at the heart of what we do, and while there are not any clear answers right now, it has been rewarding to exchange ideas with other HRPP professionals as we all figure out how to safely conduct research in our current COVID-19 environment.

Curt Naser: I would advise that IRB administrators seek out public health, occupational safety, and legal consultation within their institutions or outside if necessary. Any policy should be developed and promulgated through normal institutional governance procedures. However, the IRB has to make judgments on the safety and the risks and benefits of individual protocols. Institutional policies can guide those judgments but cannot replace them.

IRB Administrator: For those that are currently being confronted with this question, my advice is to defer to the Belmont Principles and the eligibility criteria for approval of human subjects research. It is important to always remain objective by constructing decisions on federal regulations, state laws, and local directives for human subjects research to ensure all risks are addressed. I do agree, medical information should not be collected for any study unless it is directly related to the aims of the protocol. SBER staff should have the expertise and credentials to ask medical questions and ensure HIPAA is being followed if appropriate to the aims of the study. Including the exclusion criteria up front, as does the American Red Cross before someone donates blood, would be a valid suggestion. Another suggestion would be if researchers are asking the question regarding vaccination, they provide a choice for participants to check that they prefer not to answer.