Cost effectiveness of pneumococcal vaccination among Dutch infants: economic analysis of the seven valent pneumococcal conjugated vaccine and forecast for the 10 valent and 13 valent vaccines

Hausdorff and colleagues invite us to elaborate more on the assumed
estimates regarding the efficacy against acute otitis media (AOM) in our
cost-effectiveness analysis of a pneumococcal vaccine program among
infants. In contrast to what Hausdorff et al. state we did not use a 7%
efficacy against AOM in the base case for all three vaccines, but assumed
higher efficacy against AOM for the higher-valent vaccines. The efficacy
was based on the added serotype coverage for invasive pneumococcal
disease. In particular, an increase in efficacy was assumed proportionally
with the number of serotypes included in the vaccine considered, compared
to the 7% reduction previously shown in trials using the seven-valent
pneumococcal conjugate vaccine (PCV-7)(1). Regarding the efficacy of the
Pneumococcal Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV)
against OAM, we are certainly aware that, a PHiD-CV precursor vaccine
showed an efficacy of 34% against all clinical AOM episodes (2). We
however felt that this efficacy estimate cannot directly be transferred to
the registered PhiD-CV because (1) the licensed vaccine differs from the
vaccine used in the trial (for example, 11- vs. 10-valent); and (2) the
efficacy in this specific trial was based on inclusion of more severe
cases of AOM with potentially different pathogens compared with less
severe AOM (3). We do, however, agree with Hausdorff et al. that the
observed overall differences in clinical AOM vaccine efficacies of the
vaccines cannot solely be differences in case definitions or pathogen
distributions in the respective trial settings. Importantly, de Wals et
al. (4) concluded that the most important factor, explaining variation in
VE estimates was bacterial replacement, which reduced the efficacy in the
in the trials for PCV-7 but not in the POET study for PHiD-CV (which might
however be related to the vaccine composition).
Additionally, one could argue that also for the other multivalent vaccines
higher efficacies might be applicable. For example, post-marketing studies
suggest that the impact of PCV-7 on AOM is much greater than was shown in
clinical trials(5). After the implementation of widespread vaccination the
risk of developing frequent OM was reduced with 17% to 28% in young
children(6). Furthermore, similar and larger reductions were found for
both ambulatory and outpatient visits and AOM-related antibiotic
prescriptions(7;7-9). Again, however, various aspects are still unclear
here. For example, the role of PCV-7 vaccination here might be limited as
several other explanations could also be hypothesized such as
recommendation of influenza vaccination of young children(3;10). Yet, we
included scenario analyses increasing the vaccine efficacies for all three
vaccines considered (7-, 10- and 13-valent) to potentially cover this
trend. In our aim to estimate cost-effectiveness based on the best
available evidence, we decided to use overall conservative estimates on
efficacy in the base case.
Finally, we agree that there is strong influence of a few key assumptions
on the overall projected cost- effectiveness. These do not include the
efficacy estimates for AOM. In fact, we show that our conclusions
regarding the incremental cost effectiveness ratios for all three vaccines
are quite robust across a range of assumptions.

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