Applying experiences from trials of bacille Calmette-Guérin vaccine.

Bacille Calmette-Guérin (BCG) vaccine, a live vaccine developed to prevent tuberculosis (TB), has been given to billions of persons over more than 7 decades. Studies of the efficacy of BCG vaccine have had widely divergent results, underscoring the complexity of the biology and immunology of TB. The long duration of TB infection, the heterogeneity of its clinical expression, and lack of inexpensive, reliable markers of infection and disease have made it difficult to study the impact of a vaccine, especially in resource-poor areas. A meta-analysis of data from trials of BCG vaccine found that studies conducted at sites that are a greater distance from the equator are associated with better vaccine efficacy, a finding that needs fuller study. BCG vaccine trials with higher validity scores showed higher rates of protection. Ongoing changes, including human immunodeficiency virus infection and demographic shifts, should be considered when developing trials of future vaccines. Analyses of past studies of BCG vaccine can identify sources of variation that may guide the design of studies of new vaccines. Rigorous study design and new tools are needed if studies are to provide clear, useful answers about new vaccines.