Does POI predict POD?
Does POI predict POD following BCG?
This study evaluates the extent to which prevention of M. tuberculosis infection can serve as a surrogate indicator for prevention of TB disease. It does so through individual participant data meta-analyses of existing data.
The endpoint for regulatory phase III trials of new TB vaccines developed for preventing TB in adolescents and adults is prevention of disease (PoD), requiring large trials with prolonged follow-up. A major impediment to acceleration of clinical development of new TB vaccine candidates is the lack of validated surrogate efficacy endpoints that can be used to establish proof-of-principle in phase IIb trials. One proposed surrogate endpoint is prevention of M. tuberculosis infection (PoI). The PoI endpoint has however not been validated against the PoD endpoint, i.e. we do not know how well PoI predicts PoD. There are concerns that the infections prevented by TB vaccination may be those that do not progress to TB disease.
In addition to this generic dilemma, there is a need to understand the PoI-to-PoD translation to inform policy around BCG revaccination. While the initial understanding was that BCG protects mainly against disease, several observational studies have indicated that BCG may protect against infection as well.
This study re-analyzes existing datasets to quantify the extent to which PoI due to BCG vaccination predicts PoD.
AIGHD Research Lead
Gerton Rongen (G.Rongen@aighd.org)
Bill and Melinda Gates Foundation
The Netherlands, United Kingdom