Exploring the ethics of tuberculosis human challenge models.

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 attenuated Mycobacterium tuberculosis.

A new day for human challenge trials?

Two years into the coronavirus disease 2019 (COVID-19) pandemic and following several hot debates, the world's first COVID-19 human challenge trial has recently been published by Killingley et al. We review its findings and explain why this particular juncture in time makes additional challenge trials for COVID-19 and for other diseases justified and important.

The Ethics of Human Challenge Trials Using Emerging Severe Acute Respiratory Syndrome 2 Variants.

The world's first coronavirus disease 2019 human challenge trial using the D614G strain of severe acute respiratory syndrome 2 (SARS-CoV-2) is underway in the United Kingdom. The Wellcome Trust is funding challenge stock preparation of the Beta and Delta variant for a follow-up human challenge trial, and researchers at hVIVO are considering conducting these trials. However, little has been written thus far about the ethical justifiability of human challenge trials with SARS-CoV-2 variants of concern. We explore 2 specific characteristics of some variants that may initially be thought to make such trials unethical and conclude that SARS-CoV-2 variant challenge trials can remain ethical.