Abstract

The efficacy of PPV-23 vaccine on outcomes of pneumococcal disease in adults still remains controversial due mainly to the lack of consistency between the results obtained from observational studies(OSs) and those obtained from randomized controlled trials(RCTs). As a consequence, the complexity in the structure of evidence available, in turn, generates a challenge for combining disparate pieces of evidence quantitatively. In this regard, we used a hierarchical Bayesian inference-based evidence synthesis of RCTs and observational data using a two-stage approach (in addition to a traditional random-effects meta-analysis) to examine the effectiveness of PPV-23 in adults. To this end, 21 studies were included involving 826109 adult participants. By a two-stage Bayesian metaanalysis, which was directly used for combining studies of different designs, the overall log OR (95 credible interval) for IPDs was -0.1048 (-0.3920,-0.0250), indicating a significant protective effect of the vaccination against IPDs. No significant effect of PPV-23 was found on all-cause pneumonia, pneumococcal pneumonia, and death from pneumonia, which confirmed the results obtained by a traditional method followed by stratified and sensitivity analyses. The estimated overall log OR (95 credible interval) was -0.0002 (-0.0241,0.0142), -0.0002 (-0.0110,0.0122), and -6.3912 x 10(-5) (-0.0219,0.0131), respectively. The PPV-23 vaccine might be effective in preventing the most severe invasive forms of pneumococcal diseases, but not effective in preventing other clinical outcomes, in the adult population of 18 years and older.