Community-acquired pneumonia (CAP) is pneumonia acquired outside of a hospital or within the first 48 hours of hospitalization. It is one of the most common reasons for hospitalization in the US, with up to 10% of patients requiring hospitalization and is the leading cause of infectious disease-related death in the US. Streptococcus pneumoniae remains the leading bacterial cause of CAP, although its incidence has declined over time due to vaccination. Streptococcus pneumoniae is also responsible for Invasive Pneumococcal Disease (IPD).
In 2014, the Advisory Committee in Immunization Practices (ACIP) recommended routine use of the 13-valent pneumococcal conjugate vaccine (PCV13) in series with PPSV23 for all adults aged ≥65 years based on the evidence of PCV13's safety and efficacy against PCV13-type IPD and pneumonia in this age group. A higher valency, 20-valent pneumococcal conjugate vaccine (PCV20) builds on the PCV13 vaccine, and includes seven additional serotypes that cause pneumococcal disease. On October 20, 2021, the ACIP recommended that adults ≥65 years, who had not previously received pneumococcal conjugate vaccine or whose previous vaccination history is unknown may receive PCV20 alone or 15-valent pneumococcal conjugate vaccine (PCV15) in series with PPSV23. On October 19, 2022, the ACIP updated the previous recommendation, recommending that adults who have previously received PCV13 should receive either a dose of the PCV20 or PPSV23.
As a condition of the accelerated approval for PCV20 in June 2021, Pfizer is currently conducting a post-approval confirmatory study to verify and describe the clinical benefit of PCV20 in adults ≥65 years (NCT05452941). In the interim, this study will evaluate the real-world vaccine effectiveness (VE) of PCV20 against IPD, PP, all-cause pneumonia (ACP), and Lower Respiratory Tract Infection (LRTI) among adults aged ≥65 years in Medicare Fee-for-Service (FFS) Parts A, B, and D.
This structured secondary data collection study is a retrospective cohort study using Medicare FFS claims data to estimate real-world PCV20 VE against IPD, PP, ACP, and LRTI among adults aged ≥65 years in the US.
Study analyses will be conducted at the time-segment level, where PCV20 vaccination is a time-varying exposure. In this time-segment design, individuals who receive a PCV20 vaccine during the patient identification period can contribute up to two time segments during the follow-up period: a PCV20 unvaccinated time segment and a PCV20 vaccinated time segment. Each segment will be attributed to the appropriate vaccination exposure status cohort.
Individuals who do not receive a PCV20 vaccine during the patient identification period can contribute a maximum of 1 time segment to the analysis, which will be attributed to the PCV20 unvaccinated cohort. All analyses will be conducted based on time-segment level data.
For PCV20 unvaccinated time segments, individuals will be followed from their unvaccinated index date until the earliest of the following: 1) PCV20 vaccination, 2) PCV13 vaccination, 3) PPSV23 vaccination, 4) PCV15 vaccination, 5) outcome of interest, 6) disenrollment from Medicare FFS Parts A or B, 7) enrollment in Medicare Part C, 8) death, or 9) end of the study period. For PCV20 vaccinated time segments, individuals will be followed from their PCV20 vaccinated index date until the earliest of the following: 1) PCV13 vaccination, 2) PPSV23 vaccination, 3) PCV15 vaccination, 4) second PCV20 vaccination, 5) outcome of interest, 6) disenrollment from Medicare FFS Parts A or B, 7) enrollment in Medicare Part C, 8) death, or 9) end of the study period.
The primary objective is to estimate overall effectiveness of the PCV20 vaccine against three outcome events - first IPD, PP, and ACP due to any serotype - among adults aged ≥ 65 years.
The secondary objective focuses on estimating the overall VE and absolute difference in incidence of PCV20 against LRTI and subgroup VE and absolute difference in incidence stratified by age groups and risk groups. This will involve comparing the time-to-event for LRTI between the vaccinated and unvaccinated using similar methods as described for the primary outcome.
