Title: The immunogenicity and efficacy of pneumococcal vaccines: a systematic review and network meta-analysis of individual participant data
Funder: Department of Health and Social Care

Abstract: Decisions about which vaccines to use in the UK should be made based on good data to make sure we are protected against disease. _x000D_ Pneumococcal disease is a serious illness caused by a bacterial infection that can result in death. Children in the UK receive one type of pneumococcal vaccine to prevent this disease and the vaccine in use has been very successful. Another vaccine is used in other countries, and might be a good option for the UK as it is cheaper. From studies in this area, however, there is very little information directly comparing these two vaccines, so it is difficult to know which is best. _x000D_ We plan to do a large analysis combining all pneumococcal vaccine studies. We will use information from studies published in medical journals, but we will also include data from studies done by the companies that own the vaccines. We have used this sort of company data before and are experienced in analysing it. We aim to show which vaccine produces the highest responses when measured in blood samples in infants and also to show which vaccine protects infants best against infection. _x000D_ Our results will provide the best comparison of pneumococcal vaccines done so far. This will help the UK to decide whether to keep the current vaccine or to change. In turn, this will help to continue to protect the population against disease.

Lay abstract: Streptococcus pneumoniae (pneumococcus) is a leading cause of bacterial pneumonia, meningitis, sepsis, and otitis media in children.(1) Pneumococcal disease can be prevented by vaccination. In the UK, infants are vaccinated against pneumococcal disease using a pneumococcal conjugate vaccine containing 13 serotypes (strains) of pneumococcus (PCV13, “Prevenar 13”, Pfizer). Public Health England estimate that pneumococcal vaccination has prevented 40,000 cases of invasive pneumococcal disease in England and Wales.(2) _x000D_ There is a different pneumococcal vaccine used in many countries that contains 10 serotypes (PCV10, “Synflorix”, GSK). _x000D_ It is important that policy makers know whether one vaccine is superior to the other when deciding on the right vaccine for the UK. If both vaccines are equally efficacious then the vaccine tendering process can be opened up to both suppliers, likely resulting in competition in the market and cost-savings to the NHS. _x000D_ Very few studies have directly compared these two vaccines so data are limited. Trials that have compared them have only looked at immunogenicity (antibody production induced by vaccination) which is not the same as comparing efficacy (actual disease prevention). However, large randomised efficacy trials with a placebo control are no longer possible now that licensed vaccines are in routine use. Previous reviews to determine which vaccine is more immunogenic only looked at published estimates and only for trials that directly compared the two licensed vaccines. No meta-analyses were possible in these reviews. _x000D_ We will conduct a wider systematic review and an individual participant data network meta-analysis to fully answer the question of which vaccine has better immunogenicity, as well as superior efficacy. We will incorporate additional trials published since the last review as well as unpublished data that is available on company websites. We will access the individual participant data rather than relying on published estimates alone, and use novel methods to derive estimates of efficacy based on the individual infant’s serology data (‘sero-efficacy’). Our methods for determining sero-efficacy have successfully been used before to estimate the efficacy of vaccines for which no large randomised trials have been completed._x000D_ Our review will be substantially larger than previous reviews as we will not only include direct head-to-head studies of PCV10 vs PCV13 but also include a large number of trials that compared one of the two vaccines to the older vaccine (PCV7) that is no longer in use. The studies of these three vaccines form a ‘network’ that can then be analysed together. The additional trials and the connections within the network will add a large amount of statistical power and precision to the analysis and enable us to fill in the gaps where data are limited for the direct comparisons of PCV10 vs PCV13. _x000D_ Our results will provide robust estimates of the comparative immunogenicity and efficacy of licensed pneumococcal conjugate vaccines, enabling economic modellers and policy-makers in the UK and worldwide to make informed evidence-based decisions to protect the population from disease.

Research activity codes: 3.4 VACCINES
Health categories: RESPIRATORY