RESUMEN
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.
RESUMEN
Human challenge trials provide a promising route to cut down on the high, sometimes prohibitive, costs of vaccine development. By requiring fewer participants than a conventional clinical trial and reducing the time required for a trial, human challenge trials improve economic feasibility and reduce the risk of vaccine development. Tuberculosis is one disease where challenge trials could be very impactful, given that it is a widespread and dangerous disease that is nonetheless difficult to track in a standard clinical vaccine trial. Various attenuated strains of Mycobacterium tuberculosis are in development and can be used in a challenge trial in order to reduce the risk to challenge trial participants and their surrounding communities.