The broader impacts of otitis media and sequelae for informing economic evaluations of pneumococcal conjugate vaccines.

INTRODUCTION: Otitis media (OM) is a common childhood infection. Pneumococcal conjugate vaccines (PCVs) prevent OM episodes, thereby reducing short- and long-term clinical, economic, humanistic, and societal consequences. Most economic evaluations of PCVs focus on direct health gains and cost savings from prevented acute episodes but do not fully account for the broader societal impacts of OM prevention. AREAS COVERED: This review explores the broader burden of OM on children, caregivers, and society to better inform future economic evaluations of PCVs. EXPERT OPINION: OM causes a substantial burden to society through long-term sequelae, productivity losses, reduced quality of life for children and caregivers, and contribution to antimicrobial resistance from inappropriate antibiotic use. The effect of PCVs on acute OM has been recognized globally, yet the broader impact has not been consistently quantified, studied, or communicated. Economic evaluations of PCVs must evolve to include broader effects for patients, caregivers, and society from OM prevention. Future PCVs with broader coverage may further reduce OM incidence and antimicrobial resistance, but optimal uptake will depend on increasing the recognition and use of novel frameworks that include broader benefits. Communicating the full value of PCVs to decision makers may result in wider access and positive societal returns.

Clinical and Economic Burden of Pneumococcal Disease Due to Serotypes Contained in Current and Investigational Pneumococcal Conjugate Vaccines in Children Under Five Years of Age.

INTRODUCTION: The widespread implementation of pneumococcal conjugate vaccines (PCVs) has significantly reduced the burden of pneumococcal disease around the world. Although licensed 10-valent (PCV10) and 13-valent (PCV13) vaccines have considerably reduced mortality and morbidity, a sizeable disease burden attributable to serotypes not contained in these PCVs remains. This study aimed to estimate the annual clinical and economic burden of pneumococcal disease attributable to licensed (PCV10 and PCV13) and investigational PCVs, notably 15-valent (PCV15) and 20-valent (PCV20) vaccines, in 13 countries in children under 5 years of age. METHODS: A decision-analytic model was created to aggregate total cases [inclusive of invasive pneumococcal disease (IPD), pneumonia, and otitis media (OM)], deaths, and direct costs in each country of interest [stratified by PCV10/PCV13 countries, depending on national immunization programs (NIPs)] over 1 year, using up to the three most recent years of available serotype coverage data. Data inputs were sourced from local databases, surveillance reports, and published literature. RESULTS: In 5 PCV10 NIPs (Austria, Finland, Netherlands, New Zealand, Sweden), most remaining PCV20-type disease was due to PCV13-unique serotypes (30-85%), followed by PCV20-unique (9-50%), PCV15-unique (4-15%), and PCV10-unique (2-14%) serotypes. In 8 PCV13 NIPs (Australia, Canada, France, Germany, Italy, South Korea, Spain, United Kingdom), most remaining PCV20-type disease was caused by PCV20-unique serotypes (16-69%), followed by PCV13-unique (11-54%), PCV15-unique (2-33%), and PCV10-unique serotypes (3-19%). Across all countries, PCV20 serotypes caused 3000 to 345,000 cases of disease and cost between $1.3 and $44.9 million USD annually with variability driven by population size, NIP status, and epidemiologic inputs. In aggregate, PCV20 serotypes caused 1,234,000 cases and $213.5 million in annual direct medical costs in children under 5 years of age. CONCLUSION: Despite the success of PCV10 and PCV13 in reducing pneumococcal disease, a substantial clinical and economic burden remains due to serotypes contained in investigational vaccines.

Public health impact of pneumococcal conjugate vaccination: a review of measurement challenges.

INTRODUCTION: Modeling analyses have attempted to quantify the global impact of pneumococcal conjugate vaccines (PCVs) on pneumococcal disease (PD), however these pediatric models face several challenges in obtaining comprehensive impact measurements. AREAS COVERED: We present several measurement challenges and discuss examples from recently published pediatric modeling evaluations. Challenges include estimating the number of infants fully or partially vaccinated with PCVs, inclusion of indirect effects of vaccination, accounting for various dosing schedules, capturing effect of PCVs on nonspecific, noninvasive PD, and inclusion of adult PCV use. EXPERT OPINION: The true impact of PCVs has been consistently underestimated in published analyses due to multiple measurement challenges. Nearly 100 million adults are estimated to have received PCV13 over the last decade globally, potentially preventing up to 662 thousand cases of PD. Approximately 4.1 million cases of invasive PD alone may have been averted through indirect protection. Estimates of PCV impact on noninvasive PD remain a challenge due to altered epidemiology. Program switches, incomplete vaccination, and private market uptake among children also confound PD impact estimates. Taken together, the number of averted PD cases from PCV use in the last ten years may be up to three times higher than estimated in previous studies.

Estimating the Public Health and Economic Impact of Introducing the 13-Valent Pneumococcal Conjugate Vaccine or 10-Valent Pneumococcal Conjugate Vaccines into State Immunization Programs in India.

INTRODUCTION: Although the pneumococcal conjugate vaccine (PCV) has been introduced into select state immunization programs (SIPs) in India, many children remain unvaccinated. Recently, India's Advisory Committee on Vaccines & Immunization Practices recommended PCV on the pediatric immunization schedule nationally. This study estimates the public health and economic impact of introducing either Pfizer's 13-valent PCV (PCV13-PFE), GlaxoSmithKline's 10-valent PCV (PCV10-GSK), or Serum Institute of India's 10-valent PCV (PCV10-SII) into every pediatric SIP. METHODS: A model was developed to predict the disease cases, deaths, and costs associated with implementing PCV13-PFE, PCV10-GSK, or PCV10-SII in SIPs compared to no vaccination program across a 5-year period (2021-2025). State and national-level uptake rate and clinical and economic input parameters were collected from published literature. Disease outcomes included invasive pneumococcal disease, inpatient and outpatient pneumonia, and otitis media. Costs were estimated as vaccine-related costs and direct medical costs incurred to the healthcare system. Results were reported by individual state and aggregated nationally. RESULTS: Estimated over 5 years, implementing PCV13-PFE in SIPs could avert 12.1 million cases and save 626,512 lives among children under 5 years old compared to no vaccination. This corresponds to net national cost savings of over $1.0 billion. Both lower-valent PCVs are estimated to provide less economic savings than PCV13-PFE inclusive of vaccine-related costs. Compared with PCV13-PFE, implementing PCV10-GSK or PCV10-SII nationally is estimated to have a smaller public health impact, with PCV10-GSK averting 8.4 million cases (436,577 deaths) and PCV10-SII preventing 10.3 million cases (531,545 deaths) in India compared to no vaccination, respectively. CONCLUSION: Implementation of PCV13-PFE throughout India is estimated to provide greater public health and economic benefits than PCV10-GSK or PCV10-SII SIPs. Our analysis highlights the substantial disease cases, deaths, and health system cost savings that may be realized from implementing PCV programs throughout India.

Validation of a Novel Forecasting Method for Estimating the Impact of Switching Pneumococcal Conjugate Programs: Evidence from Belgium.

INTRODUCTION: Since 2010, 10-valent (PCV10) and 13-valent pneumococcal conjugate vaccines (PCV13) have been available as part of infant national immunization programs. Belgium is as one of the few countries that implemented PCV13 (2007-2015), switched to PCV10 (2015-2018) and then switched back to PCV13 (2018-present) after observing increases in disease. We assessed the impacts of both historical and prospective PCV choice in the context of the Belgian health care system and used this experience to validate previously developed economic models. METHODS: Using historical incidence (2007-2018) of pneumococcal disease for Belgian children aged < 16 years, observed invasive pneumococcal disease (IPD) trends from surveillance data were used to estimate future disease in a given PCV13- or PCV10-based program. We compared observed incidence data with two modeled scenarios: (1) the 2015 switch to PCV10 and (2) a hypothetical continuation of PCV13 in 2015. Finally, we explored the potential impact of PCV choice from 2019 to 2023 by comparing three scenarios: (3) continued use of PCV10; (4) a switch back to PCV13; (5) a hypothetical scenario in which Belgium never switched from PCV13. RESULTS: Model predictions underestimated observed data from 2015 to 2018 by 100 IPD cases among ages < 16 years. Comparing observed data with scenario 2 suggests that PCV13 would have prevented 105 IPD cases from 2015 to 2018 compared with PCV10. Switching to PCV13 in 2019 would avert 625 IPD cases through 2023 compared with continuing PCV10. Scenario never switching from PCV13 would have resulted in a reduction of 204 cases from 2016 to 2023 compared with switching to PCV10 and switching back to PCV13. CONCLUSION: The findings from this study suggest that previously published modeling results of PCV13 versus PCV10 in other countries may have underestimated the benefit of PCV13. These results highlight the importance of continually protecting against vaccine-preventable pneumococcal serotypes.

Pneumococcal Conjugate Vaccine Impact on Serotype 3: A Review of Surveillance Data.

INTRODUCTION: Limited changes in serotype 3 invasive pneumococcal disease (IPD) incidence rates after a decade of 13-valent pneumococcal conjugate vaccine (PCV13) introduction into several national immunization programs (NIP) have raised questions about PCV13's effectiveness against this serotype. METHODS: We analyzed the impact of pediatric PCV programs on serotype 3 IPD with two approaches. First, we reviewed the publicly available surveillance data from countries identified in two recently published reviews to describe the population impact of pediatric PCV13 or PCV10 vaccination programs on serotype 3 IPD. We then compared the observed trends in PCV10 and PCV13 countries to a previously described dynamic transmission model that simulates the spread of pneumococcal carriage and development of IPD in a population over time. RESULTS: When serotype 3 disease rates are compared from countries that have introduced either a 10-valent (PCV10) vaccine that does not contain serotype 3 in its formulation or PCV13 in their pediatric NIP, over time, serotype 3 incidence rate trends are markedly different. Countries with a PCV10 NIP showed a substantial linear increase in serotype 3 pneumococcal disease among all age groups since the time of PCV10 introduction, whereas countries with a PCV13 NIP experienced a modest decline during the 3-4 years after vaccine introduction followed by an inflection upward in subsequent years. CONCLUSION: These data suggest that PCV13 provides a certain degree of direct and indirect protection against serotype 3 at the population level and direct adult vaccination with a serotype 3-containing vaccine is likely to provide substantial benefit in the context of a pediatric PCV NIP. Further research around serotype 3 transmission patterns and epidemiology is nonetheless warranted.