Abie Rohrig

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.

TB human challenge studies could accelerate TB vaccine development by reducing uncertainty in early-stage vaccine testing, selecting promising vaccine candidates for large-scale field trials, and identifying an immune correlate of protection. However, ethical concerns regarding the exposure of trial participants and bystanders to significant risk have been a limiting factor for TB human challenge models. We analyze the expected social value and risks of different types of TB human challenge models, and conclude that given the massive public health burden of TB, challenge models with even scant probabilities of expediting TB vaccine authorization have enormous expected humanitarian value, saving between 33,000 and 1,375,000 lives over the next ten years. We argue that attenuated M.tb challenge trials can be conducted ethically, and discuss the benefits and drawbacks of conducting virulent M.tb challenge trials.