Cost-Effectiveness of the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Versus Lower-Valent Alternatives in Filipino Infants.

Key Summary Points

To the Editor,

We would like to comment on a recent article published in your journal authored by Johnna Perdrizet et al., titled “Cost-Effectiveness of the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Versus Lower-Valent Alternatives in Filipino Infants" [1].

The authors reported having performed this cost-effectiveness exercise on a model that leverages real-world surveillance data from the Philippines, based on which they conclude the use of the Pfizer vaccine (PCV13-PFE/PCV-13/PCV13) with favorable outcomes. The model structure attributes the source of invasive pneumococcal disease (IPD) serotype distribution to a pooled (2012–2019) set of passive laboratory-based surveillance data from the Research Institute for Tropical Medicine [RITM] referencing the 2020 Health Technology Assessment Council (HTAC) report [2]. We could not find relevant details or references in the paper with respect to the pooled sample sizes taken up for IPD serotyping, so we looked instead at the referenced 2020 HTAC report. This report also makes no mention of the sample sizes but does clearly state that “only relatively small number of isolates were reported owing to the passive nature of the surveillance, variability in specimen collection, laboratory processing, and reporting,” and goes on to say that “in case-ascertainment practices within sentinel sites, the serotype percentage as reported may not reflect the true prevalence of individual serotypes causing IPD.”

We therefore question the authors’ use of this limited real-world surveillance data to arrive at serotype coverage in the Philippines for PCV13-PFE, GlaxoSmithKline (PCV10-GSK), and Serum Institute of India (PCV10-SII), and its use as the basis to determine the cost-effectiveness of various PCVs in the Philippines.

Furthermore, we notice that age group stratification is done up to 65+ years in this modeling exercise (meant for infants). This seems irrelevant, with a possibility of arriving at skewed conclusions.

As manufacturers of PCV-10SII, we want to offer clarity on inaccurate statements towards “clinical uncertainties” around this vaccine by the authors.

Similar to licensure of both PCV10-GSK and 13-valent PCV13, PCV-10SII has been WHO-prequalified, after demonstration of vaccine efficacy based on proven immunologic non-inferiority to a licensed and prequalified comparator vaccine (WHO Technical Report Series [TRS] 927/977). The serotype-specific functional antibody response opsonophagocytic assay (OPA) responders in the PCV10-SII group exceeded 92% for all serotypes [2, 3].

In addition to head-to-head study comparisons of PCV10-SII with PCV13-PFE, the choice of PCV10-GSK as the clinical comparator in the pivotal study was strategic, since PCV10-GSK has been evaluated in randomized controlled trials for efficacy and effectiveness for both IPD and pneumonia in infants and children. [2, 4].

Overall, the efficacy/effectiveness of PCV10-SII is expected to be equivalent to PCV13 and PCV10-GSK based on immunogenicity data showing non-inferiority [5]. Several real-world surveillance studies using PCV10-SII are under initiation [6].

The suggestions from authors that switching from a higher-valent to a lower-valent PCV in the Philippines can result in an increase in pneumococcal disease from the re-emergence of newly unprotected serotypes seem unfounded, since in fact we note that a comparison of serotype distribution pre-and-post-PCV13 introduction in the Philippines since 2015–2019 (up to 60% uptake) suggests a rise in several vaccine type serotypes (4,6B, 7, 9V,18C, 19A, 19F) [2].

It is also of relevance to mention here that data on the impact of PCV13-PFE on serotype 3 are inconclusive, with most global studies showing no impact of this serotype [5].

The real-world surveillance data to determine serotype prevalence and cost-effectiveness in the Philippines is unsubstantiated.

Age group stratification up to 65+ years adapted into the modeling exercise appears irrelevant.

PCV-10SII has well-established clinical endpoints showing strong immune and safety responses.