Field trials of tuberculosis vaccines: how could we have done them better?

Nineteen controlled trials of vaccination against tuberculosis are reviewed. Most involved very large numbers of participants and represented a wide variety of geographic and socioeconomic conditions. The trials were conducted under field conditions that sometimes verged on the primitive. Length of follow-up for tuberculosis ranged from 3 to 23 years, and up to 28 years for cancer. Under these circumstances, compromises and mistakes were made along with notable successes. With the current interest in the immunology of tuberculosis and other chronic infectious diseases giving rise to renewed hope for more efficacious vaccines, lessons from the past can be useful in planning the long-term evaluations that will be needed as these hoped-for vaccines become available.