There are currently no head-to-head trials comparing pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccination (PHiD-CV) with 13-valent pneumococcal conjugate vaccine (PCV-13). This study investigated the possibility of utilizing network meta-analysis (NMA) to undertake an indirect assessment of the two vaccines’ relative efficacy or effectiveness. A systematic review of the literature was conducted to find 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 who received 7-valent pneumococcal conjugate vaccine (PCV-7), PHiD-CV, or PCV-13. The study’s quality was assessed using established measures. The practicality of NMA was determined by evaluating published research for variations in study or patient factors that might function as possible treatment effect modifiers or confounding variables. A total of 26 articles were considered, including two randomized controlled trials, seven indirect cohort studies, and fourteen case-control studies. The study’s overall quality was high. Because there was no common comparator, the RCTs could not be linked in a network. The trials vary greatly in terms of design, dosage number, administration schedules, and subgroups studied.

Due to the lack of a linked network among the two RCTs and significant heterogeneity between trials, NMA to assess the relative efficacy or effectiveness of PHiD-CV and PCV-13 is not possible on the existing evidence base. NMA may be viable in the future if enough RCTs become available to build a linked network.