Pneumococcal conjugate vaccination for older adults: Reply letter to Hollingsworth et al

Hollingsworth and Isturiz (1) have raised several questions about our earlier review of the use of pneumococcal conjugate (PCV) or polysaccharide (PPV) vaccine for older adults (i.e., ≥65 y of age). (2) They begin by citing two metaanalyses published in 2009 and 2013 that concluded that prevention of pneumococcal pneumonia could not be demonstrated for PPV. (3)(,) (4) They overlook my earlier review of five metaanalyses that was published in 2004. (5) This review showed that the study populations in prospective trials of PPV were often not representative of the populations of elderly and high-risk adults for whom PPV is recommended. Furthermore, the five metaanalyses often omitted clinical trials that should have been evaluated, included trials that should have been omitted, and frequently miscounted the numbers of subjects and outcome events in the individual clinical trials. More important, retrospective sample size calculations showed that none of the five metaanalyses included an adequate number of person years of observation to rule out false-negative results. The numbers speak for themselves and cannot be ignored. Simply put, metaanalyses of the PPV clinical trials will never tell us whether the vaccine prevents pneumococcal pneumonia or all-cause pneumonia in elderly and high-risk adults, and consequently they must be regarded as inconclusive and uninformative. Since 2004, only one small prospective clinical trial of PPV has been published (reviewed in 6). Nothing new has been added to our knowledge of PPV efficacy by the more recent metaanalyses. (3)(,) (4) Epidemiologists have reminded us that the lack of evidence of PPV efficacy is not evidence of its absence. The conclusions of our earlier review still stand. (5.)