Human challenge trials in vaccine development, Rockville, MD, USA, September 28–30, 2017

Abstract

The International Alliance for Biological Standardization organized the second workshop on human challenge trials (HCT) in Rockville, MD, in September 2017. The objective of this meeting was to examine the use of HCT, in response to the continuing human suffering caused by infectious diseases, preventable by the development of new and improved vaccines. For this, the approach of HCT could be valuable, as HCT can provide key safety, tolerability, immunogenicity, and efficacy data, and can be used to study host-pathogen biology. HCT can generate these data with speed, efficiency and minimal expense, albeit not with the same level of robustness as clinical trials. Incorporated wisely into a clinical development plan, HCT can support optimization or down-selection of new vaccine candidates, assuring that only the worthiest candidates progress to field testing. HCT may also provide pivotal efficacy data in support of licensure, particularly when field efficacy studies are not feasible. Many aspects of HCT were discussed by the participants, including new and existing models, standardization and ethics. A consensus was achieved that HCT, if ethically justified and performed with careful attention to safety and informed consent, should be pursued to promote and accelerate vaccine development.

Stakeholder views on the acceptability of human infection studies in Malawi

“…The growing literature on HIS ethics suggests a range of ethical principles, including a strongly justified research question that can only be answered through HIS, independent review, qualified and experienced researchers, rigorous informed consent, safe selection of participants, minimisation of risks and no irreversible harm, protection of contacts and the environment, compensation that avoids undue influence, compensation for harm, and public involvement [4,6,8]. However, further evidence is needed to guide researchers and ethics committees on appropriate frameworks for HIS, particularly in LMICs [10,11].…”

Back to WHAT? The role of research ethics in pandemic times

“…But humans do many important things out of altruism t Volunteers who participate in the challenge trials should be motivated to advance human health and wellbeing rather than driven by their economic needs u The social value argument Benefits to the subject + benefits to society > risks to the subject v,w Given the risks to participants, SARS-CoV-2 challenge studies would need to demonstrate very substantial social value before proceeding. Arguably, this bar might already be met given the high death toll and severe disruption caused by the pandemic x Covid-19 CHIs could help prioritize among the almost 100 investigational vaccines and over 100 experimental treatments for COVID-19 currently in development y Young healthy adults may not generalize to older individuals and those with comorbidities who would most benefit from effective vaccines z a Eyal ( 2020 ) and Callaway ( 2020 ) b The International Alliance for Biological Standardization ( 2019 ), Jamrozik and Selgelid ( 2020a , b ), Menikoff ( 2020 ), Eyal et al ( 2020 , pp. 1753–1754) c Deming et al ( 2020 ) d The International Alliance for Biological Standardization ( 2019 ), Jamrozik and Selgelid ( 2020a ) e Bambery et al ( 2020 , pp.…”

“…20–22), Jamrozik and Selgelid ( 2020b , pp. 602–603), Shah et al ( 2020 , p. 2) and Wolemonwu ( 2020 , p. 2) f Deming et al ( 2020 ) g Schaefer et al ( 2020 ) h The International Alliance for Biological Standardization ( 2019 ), Jamrozik and Selgelid ( 2020a ) i Stoeklé and Hérve ( 2020 ), Plotkin and Caplan ( 2020 ) j Schaefer et al ( 2020 ) k Eyal ( 2020 , p. 26) l Jamrozik and Selgelid ( 2020a , p. 3) m WHO ( 2020 , p. 9) n Eyal et al ( 2020 , pp. 1754–1755) o Eyal ( 2020 , p. 25) p WHO ( 2020 , p. 10) q Eyal ( 2020 , p. 24) r Deming et al ( 2020 ) s Eyal ( 2020 , p. 27) t Callaway ( 2020 ) u Wolemonwu ( 2020 ) v Menikoff ( 2020 , p. 81) w Eyal et al ( 2020 , p. 1754) x Schaefer et al ( 2020 ) y Shah et al ( 2020 , p. 2) z Schaefer et al ( 2020 )…”

“… a Eyal ( 2020 ) and Callaway ( 2020 ) b The International Alliance for Biological Standardization ( 2019 ), Jamrozik and Selgelid ( 2020a , b ), Menikoff ( 2020 ), Eyal et al ( 2020 , pp. 1753–1754) c Deming et al ( 2020 ) d The International Alliance for Biological Standardization ( 2019 ), Jamrozik and Selgelid ( 2020a ) e Bambery et al ( 2020 , pp. 93–94), Shah et al ( 2017 , pp.…”

“…b The International Alliance for Biological Standardization ( 2019 ), Jamrozik and Selgelid ( 2020a , b ), Menikoff ( 2020 ), Eyal et al ( 2020 , pp. 1753–1754)…”