How to compare the efficacy of conjugate vaccines to prevent acute otitis media?

Abstract

Although the currently available 7-valent pneumococcal conjugate vaccine (PCV7-CRM 197) has been primarily designed for the prevention of invasive pneumococcal disease, it has also demonstrated the potential to prevent acute otitis media (AOM) and its associated complications. A candidate 11-valent pneumococcal conjugate vaccine (PCV11- HiD), which utilizes Haemophilus influenzae ( Hi)-derived protein D as a carrier has demonstrated the ability to prevent AOM caused by not only vaccine serotypes of Streptococcus pneumoniae ( Sp), but also those caused by Hi. The methodological, clinical, and epidemiological factors influencing results of vaccine trials for AOM prevention were reviewed and a model-based approach was developed, in order to assess the relative efficacy of different vaccine formulations. Six randomized trials having AOM as a measured outcome were identified. Vaccine efficacy (VE) ranged from −1% to 34% for all-cause AOM and between 56% and 64% for AOM caused by vaccine-type Sp. Using otopathogen-specific VE rates from the FinOM and POET trials and otopathogen distributions observed in three relatively unbiased studies, VE against all-cause AOM episodes under different scenarios was modeled. The most important factor explaining variation in VE estimates was bacterial replacement, which was present in the PCV7-CRM 197 FinOM study but not in the PCV11- HiD POET study. Another contributing factor was increased protection conferred against Hi AOM by protein D. Geographical variation in the distribution of otopathogens was a third factor explaining differences between trials. More studies on the current aetiology of AOM need to be performed to accurately predict the marginal benefit of a switch from PCV7-CRM 197 to the newly licensed PCV10- HiD-DiT or to the future PCV13-CRM 197.