A Novel Approach to Estimate the Impact of PCV20 Immunization in Children by Incorporating Indirect Effects to Generate the Number Needed to Vaccinate

Abstract

Background/Objectives: The number needed to vaccinate (NNV) is a metric commonly used to evaluate the public health impact of a vaccine as it represents the number of individuals that must be vaccinated to prevent one case of disease. Traditional calculations may underestimate vaccine benefits by neglecting indirect effects and duration of protection (DOP), resulting in NNV overestimation. This study evaluated the NNV for the pediatric 20-valent pneumococcal conjugate (PCV20) US immunization program, as compared to PCV13, with a unique approach to NNV. Methods: A multi-cohort, population-based Markov model accounting for indirect effects was employed to calculate the NNV of PCV20 to avert a case of pneumococcal disease, invasive pneumococcal disease (IPD), hospitalized non-bacteremic pneumonia (NBP), ambulatory NBP, and otitis media (OM), as well as to prevent antibiotic-resistant cases and antibiotic prescriptions. Results: The mean NNV over a 25-year time horizon to prevent one case of pneumococcal disease was 6, with NNVs of 854 for IPD, 106 for hospitalized NBP, 25 for outpatient NBP, and 9 for OM, 11 for a course of antibiotic, and 4 for resistant disease. The mean NNV per year decreased over time, reflecting the DOP and increasing indirect effects over time. Conclusions: This study presents a novel approach to NNVs and shows that relatively few vaccinations are required to prevent disease. The decrease in NNV over time highlights the necessity of including DOP and indirect effects in NNV calculations, ensuring a more realistic assessment of a vaccine's impact.

Keywords: PCVs; full value of vaccine assessment; number needed to vaccinate; pneumococcal; vaccination.

Figure 1

NNV for outcomes in the base case analysis. Abbreviations: IPD = invasive pneumococcal disease; OM = otitis media.

Figure 2

Annual number-needed-to-vaccinate (NNV) for PCV20 versus PCV13 under scenarios that include versus exclude indirect (herd) effects, by disease outcome, over a 25-year horizon. The x-axis shows calendar years following PCV20 introduction; the y-axis shows the NNV required to avert one additional case. For each outcome—(A) invasive pneumococcal disease (IPD), (B) hospitalized non-bacteremic pneumonia, (C) non-hospitalized pneumonia, and (D) otitis media (OM)—solid lines trace the base-case scenario that incorporates indirect protection, while dashed lines represent a counterfactual in which herd effects are set to zero. Abbreviations: IPD = invasive pneumococcal disease; OM = otitis media; NNV = number needed to vaccinate.

Figure 3

One-way deterministic sensitivity analysis (DSA) for the total-disease number-needed-to-vaccinate (NNV) when replacing PCV13 with PCV20 over a 25-year time horizon. The vertical gray line marks the base-case NNV (≈5.9). For each input, the model was rerun twice—once with the parameter set to its lower bound (salmon bars) and once with the upper bound (teal bars)—while all other inputs remained at their base-case values. Horizontal bar length therefore represents the absolute change in NNV attributable to that single parameter; longer bars denote greater influence. Parameters are ordered from top to bottom by decreasing impact. The x-axis shows the resulting NNV, ranging from 5.39 (most favorable) to 6.67 (least favorable). Abbreviations: NNV = number needed to vaccinate; PCV20 = 20-valent pneumococcal conjugate vaccine; SoC = standard of care.