Human challenge studies
Modern challenge studies may be ethically acceptable under certain conditions,
which are explained in the WHO document, Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies. There are eight ethical criteria to consider in the context of COVID-19, which are summarized here. See also Altered standards of review on this Dashboard, under Research Scope and Context.
- SARS-CoV-2 challenge studies must have strong scientific justification. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Scientific justification would be strongest where studies aim to produce results of public health importance, especially to the extent that similar results could not feasibly be obtained as efficiently or expediently in other designs involving less risk to human participants. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- The justification of challenge studies should include specification of their role in vaccine development pathways, broader research programs, and planning of public health responses. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- It must be reasonable to expect that the potential benefits of SARS-CoV-2 challenge studies outweigh risks. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Potential benefits and risks should be evaluated for each of three key groups: participants, society (in general), and third-party contacts of participants. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Potential public health benefits are greatest where there is a clear plan for relevant knowledge, tests, vaccines or other interventions to be made widely available to the global population. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Risks to participants should be carefully controlled and minimized. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Investigators should revise challenge study designs with further risk minimization strategies, including provision of specific, curative treatment or use of attenuated challenge strains if or when these become available. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- SARS-CoV-2 challenge research programmes should be informed by consultation and engagement with the public as well as relevant experts and policymakers. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Consultation and engagement activities should ideally be rapid, rigorous, and mutually informative, such that the views of the public and expert groups are updated in light of each other. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Consultation with local policymakers should aim to coordinate any proposed research with local public health policy and the pandemic response. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- SARS-CoV-2 challenge study research programmes should involve close coordination between researchers, funders, policy-makers and regulators. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Research should thus be coordinated with public health agencies in order to avoid unduly compromising the local public health response to COVID-19. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- If multiple research groups conducts SARS-CoV-2 challenge studies, these programmes should, as far as possible, be (a) standardized (in order to maximize benefits by obtaining comparable results in larger numbers of participants), including by sharing of challenge strains and vaccine candidates, and (b) designed so as to avoid unnecessary duplication. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- SARS-CoV-2 challenge studies should be situated where the research can be conducted to the highest scientific, clinical and ethical standards. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Decision-makers will thus need to balance competing considerations, for example reduction of marginal risk for participants versus the coordination of research with the public health response. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- SARS-CoV-2 challenge study researchers should ensure that participant selection criteria limit and minimize risk. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Participant selection criteria must be designed so that there is a high level of confidence that participation is as safe as possible. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Initial studies should thus be limited to young healthy adults. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Those whose background risk if high as a result of social injustice should be excluded from participation because their inclusion could be considered unethical exploitation. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Selection criteria should thus be updated promptly in light of emerging evidence that would help to stratify prospective participants further and thus enable selection of those at (even) lower risk. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Essential workers should not be recruited to challenge studies where this would unduly compromise the pandemic public health response. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- SARS-CoV-2 challenge studies should be the subject of specialized independent review in addition to or in conjunction with a standard local ethics review. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Review procedures should involve high levels of expertise and be conducted rapidly (potentially in parallel) without compromising the stringency of review. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Even where a local (that is, institutional) ethics committee has relevant specialized expertise, there should be independent review of initial SARS-CoV-2 challenge studies, as such studies may be particularly controversial and their conduct may have implications beyond the local setting. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- SARS-CoV-2 challenge studies must involve rigorous informed consent. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies
- Consent processes and participant selection criteria should be such that there is virtually no doubt that participants comprehensively understand the potential risks of participation and that consent is voluntary. WHO Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies