We extend recent conversation about the ethics of human challenge trials to tuberculosis (TB). TB challenge studies could accelerate vaccine development, but ethical concerns regarding risks to trial participants and third parties have been a limiting factor. We analyse the expected social value and risks of different challenge models, concluding that if a TB challenge trial has between a 10% and a 50% chance of leading to the authorisation and near-universal delivery of a more effective vaccine 3–5 years earlier, then (...) the trial would save between 26 400 and 1 100 000 lives over the next 10 years. We also identify five important ethical considerations that differentiate TB from recent human challenge trials: an exceptionally high disease burden with no highly effective vaccine; heightened third party risk following the trial, and, partly for that reason, uniquely stringent biosafety requirements for the trial; risks associated with best available TB treatments; and difficulties with TB disease detection. We argue that there is good reason to consider conducting challenge trials with attenuated strains like Bacillus Calmette-Guérin or attenuatedMycobacterium tuberculosis. (shrink)

The COVID-19 pandemic has necessitated rapid research to aid in the understanding of the disease and the development of novel therapeutics. One option is to conduct controlled human infection trials (CHITs). In this article I examine the history of deliberate human infection and CHITs and their utilization prior to the COVID-19 pandemic, key ethical considerations of CHITs in the COVID-19 setting, an analysis of the World Health Organization’s (WHO) Key criteria for the ethical acceptability of COVID-19 human challenge studies, and (...) a review of the two COVID-19 CHITs that have already commenced, their compliance with the WHO criteria and other ethical considerations. (shrink)

That they are ‘following the science’ has become the watchword of many politicians during the present pandemic, especially when imposing or prolonging lockdowns or other liberty-restricting regulations. The scientists who advise politicians however are usually careful to add that the decision what to restrict and when is ultimately a political one. In science, as in medical practice, there is a delicate balance to be maintained between confidence in the best available information, and the necessary caveat that the assumptions and calculations (...) on which that information is based are subject to further scientific enquiry. For politicians and the public, moreover, as for patients, whether those informing them are judged to be trustworthy is a necessary consideration, a judgement determined by a variety of personal and political contingencies and circumstances. Ethics, by contrast, unable to appeal to scientific consensus or political authority, let alone a confidence-inspiring bedside manner, must rest the case for its essentially contestable assumptions and arguments being judged trustworthy, on its willingness to admit all reasoned voices to a conversation that is potentially unending, but in the process often highly enlightening. That conversation is contributed to in this issue of the Journal by several reasoned voices, mostly on ethical aspects of the COVID-19 pandemic. Relevant to issues on which politicians claim to be ‘following the science’, but also raising fundamental ethical questions, is this month’s feature article. In Ethics of Selective Restriction of Liberty in a Pandemic, 1 Cameron and colleagues consider ‘if and when it may be ethically acceptable to impose selective liberty-restricting measures in order to reduce the negative impacts of a pandemic by preventing particularly vulnerable groups [for example, the elderly in COVID-19] of the community from contracting the disease’ [and thereby, for example, increasing …. (shrink)

Ongoing and anticipated COVID-19 human challenge studies in the UK may advance our understanding of COVID-19 and facilitate the licensure of safe, effective, and easily deployable next-generation COVID-19 vaccines and boosters. We argue that international volunteer recruitment for COVID-19 human challenge trials can help promote diversity in these trials and ensure a sufficient number of eligible volunteers, both of which will increase the benefits of challenge research. We explore the ethical ramifications of dealing with unfair background conditions of global vaccine (...) injustice to expand medical research, and conclude that international recruitment for COVID-19 human challenge trials can be conducted ethically provided that several robust protections are in place for volunteers. (shrink)