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The most commonly evaluated and clinically relevant outcome measures include IPD, all-cause pneumonia, pneumococcal pneumonia and mortality (all-cause or pneumonia-related). All-cause pneumonia rates are often used as a surrogate marker for pneumococcal pneumonia given the low yield of diagnostic tests for definitive identification of S.?pneumoniae as the aetiological agent. All told, there seems to be little doubt regarding the protective action of the polysaccharide vaccine against IPD in healthy adults and, to a lesser extent, among elderly individuals. For example, the 2008 Cochrane review [45] analysed 15 RCTs (involving >48?000 participants) and included seven observational studies (involving >62?000 subjects) that provided adjustment for important [http://www.selleckchem.com/products/birinapant-tl32711.html learn more] confounding factors. Meta-analysis of the RCTs found that the polysaccharide vaccine reduced the risk of IPD with an OR of 0.26 (95% CI 0.15�C0.46). This correlated with a protective vaccine efficacy of 74% (95% CI 56�C85%). The protective effect does not seem to apply to patient subgroups because it was absent in adults with chronic illness, a vulnerable population for pneumococcal disease. Meta-analysis of the seven non-RCTs showed vaccine protective efficacy towards IPD of 52% (95% CI 37�C61%), which was maintained in the subgroup of elderly immunocompetent patients. Polysaccharide vaccine efficacy against other outcomes such as pneumonia or mortality is less clear. In the Cochrane 2008 meta-analysis [45], efficacy [http://www.selleckchem.com/products/dinaciclib-sch727965.html http://www.selleckchem.com/products/dinaciclib-sch727965.html] against all-cause pneumonia among RCTs gave an OR of 0.71 (95% CI 0.52�C0.97), which was judged as inconclusive because of substantial heterogeneity among the included studies. Likewise, the study failed to demonstrate evidence for polysaccharide vaccination effectiveness against all-cause mortality. The most recently published meta-analysis in the field is noteworthy in that data were analysed according to the methodological quality of the trials [44]. Once again, the authors found no [http://en.wikipedia.org/wiki/Terminal_deoxynucleotidyl_transferase Terminal deoxynucleotidyl transferase] apparent efficacy of polysaccharide vaccines for presumptive pneumococcal pneumonia, all-cause pneumonia or mortality. One observational study that reported some benefit in preventing pneumococcal pneumonia found that best efficacy was registered in healthy adults, but PPV23 failed to protect the elderly and populations at risk such as patients with chronic illness and immune suppression [46]. The latest RCT using PPV23 was conducted among 1006 elderly nursing home residents (mean age 85?years) in Japan [47]. The authors found a protective vaccine efficacy of 44.85% (95% CI 22.4�C60.8, p?