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Aurum institute

Measuring indirect transmission-reducing effects in tuberculosis vaccine efficacy trials: why and how?

Tuberculosis is the leading bacterial cause of death globally. In 2021, 10·6 million people developed symptomatic tuberculosis and 1·6 million died. Seven promising vaccine candidates that aim to prevent tuberculosis disease in adolescents and adults are currently in late-stage clinical trials. Conventional phase 3 trials provide information on the direct protection conferred against infection or disease in vaccinated individuals, but they tell us little about possible indirect (ie, transmission-reducing) effects that afford protection to unvaccinated individuals. As a result, proposed phase 3 trial designs will not provide key information about the overall effect of introducing a vaccine programme. Information on the potential for indirect effects can be crucial for policy makers deciding whether and how to introduce tuberculosis vaccines into immunisation programmes. We describe the rationale for measuring indirect effects, in addition to direct effects, of tuberculosis vaccine candidates in pivotal trials and lay out several options for incorporating their measurement into phase 3 trial designs

What do people want?

Investigate current TB prevention modalities vs vaccine. We lack understanding of preferences and trade offs people would be willing to make across a spectrum of issues related to study design, type of vaccines, how they are given, how often, where they are given, to whom, efficacy estimates and side effects etc.

TPTVaxx

Vaccines will be introduced in contexts where TPT already exists. Exploration of possible study designs, expected effectiveness, feasibility of integrated approaches is key.
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