Rethinking results from the Japanese 23-valent pneumococcal polysaccharide vaccine randomized clinical trial

We review a previously published randomized clinical trial of 23-valent pneumococcal polysaccharide vaccine (PPSV23) that has been used extensively globally to support PPSV23 use among adults. We argue that serious issues with internal and external validity exist that affect the usefulness of these data when evaluating pneumococcal vaccines for the general adult population. As one example of internal data inconsistency, the values reported for the percent of all pneumonia cases due to pneumococcus and the vaccine efficacy (VE) for all cause pneumonia are mutually inconsistent, even based on unrealistically high values for PPSV23 VE against vaccine serotypes and the proportion of pneumococcal pneumonias due to vaccine serotypes.