Ethical Considerations in Vaccine Trials in Resource-Limited Settings

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Introduction

This chapter focuses on ethical concerns early in the life cycle of vaccines, namely trials designed to test safety, immunogenicity, and efficacy of vaccines in human participants. Vaccine trials involve many ethical complexities that stem from several features. These include that vaccine trials are frequently international projects involving organizations in high-income countries collaborating with those in low-resource settings; such trials are often implemented in settings with constrained healthcare systems; they involve multiple sites within and across host countries; and they involve complex trial designs and sometimes highly stigmatized conditions.

Furthermore, such trials may enroll participants considered vulnerable, that is, where intraindividual, interpersonal, or contextual factors elevate research risks, or undermine consent. Very often, participants are infants or children, recognized as among the most vulnerable of participants. In addition, vaccine trials may be reviewed by research ethics committees (RECs) with variable review capacity and be implemented in host countries with diverse and sometimes weak ethico-legal frameworks. Also, enrolled participants may be “healthy yet at-risk” of acquiring the medical condition that is the vaccine target, at least for late-stage trials, and reside in settings with inadequate health care. Last, vaccine trials require participants (sometimes in their thousands) to be retained over several years, to attend many visits and to undergo several procedures, some of which may be burdensome.

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Ethical considerations

The ethics of vaccine trials are concerned with promoting the rights and welfare of participants while participants are contributing to the social good of evaluating vaccines designed to impact public health. There are several ethical resources to assist vaccine stakeholders to respond to ethical complexities in vaccine trials. Such resources comprise of broad ethical principles, ethical guidelines, ethical frameworks or models, and, in some instances, empirical data—the latter likely to be ethically relevant if not definitive.

Several broad principles are held to apply to research including vaccine trials. First, respect for persons—researchers should respect people’s decisions and actions, and protect persons with impaired or diminished autonomy. Second, beneficence—researchers should maximize potential research-related benefits, minimize potential research-related risks, and ensure the potential risks are reasonable in light of expected benefits. Third, justice—there should be a fair distribution of research-related burdens and benefits among the collaborating parties, and no single group should bear a disproportionate share of the risks nor access a disproportionate share of the benefits.

Because ethical principles are formulated at a fairly abstract level, they must be specified and applied to actual cases, which can lead decision makers to reach different conclusions about what should be done. The ethical principles are generally held to be “universally germane” with expected variations in how they are interpreted, applied, and balanced with each other. Ethical standards operate at a less abstract level, such as the ethical standard that informed consent be obtained for trial participation. Several ethical complexities in vaccine trials are outlined here, informed by a popular framework for reviewing the ethics of research protocols, including vaccine trials.