A systematic literature review and network meta-analysis feasibility study to assess the comparative efficacy and comparative effectiveness of pneumococcal conjugate vaccines

Background: No head-to-head studies are currently available comparing pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with 13-valent pneumococcal conjugate vaccine (PCV-13). This study explored the feasibility of using network meta-analysis (NMA) to conduct an indirect comparison of the relative efficacy or effectiveness of the two vaccines. Methods: A systematic literature search was conducted for published randomized controlled trials (RCTs) and non-RCT studies reporting data on vaccine efficacy or effectiveness against invasive pneumococcal disease in children aged <5 years receiving 7-valent pneumococcal conjugate vaccine (PCV-7), PHiD-CV or PCV-13. Study quality was evaluated using published scales. NMA feasibility was assessed by considering whether a connected network could be constructed by examining published studies for differences in study or patient characteristics that could act as potential treatment effect modifiers or confounding variables. Results: A total of 26 publications were included; 2 RCTs (4 publications), 7 indirect cohort studies, and 14 case-control studies (15 publications). Study quality was generally good. The RCTs could not be connected in a network as there was no common comparator. The studies differed considerably in design, dose number, administration schedules, and subgroups analyzed. Reporting of exposure status and subject characteristics was inconsistent. Conclusion: NMA to compare the relative efficacy or effectiveness of PHiD-CV and PCV-13 is not feasible on the current evidence base, due to the absence of a connected network across the two RCTs and major heterogeneity between studies. NMA may be possible in future if sufficient RCTs become available to construct a connected network.