Pfizer-BioNTech COVID-19 Vaccine Effectiveness Study - Kaiser Permanente Southern California

Recruiting

• Conditions: COVID-19
• Interventions: Biological: XBB.1.5-adapted vaccinated; Biological: Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine; Biological: BNT162b2 BA.4/5 bivalent

• Registration Number: NCT04848584
• Lead Sponsor: Pfizer

Brief Summary

The primary objective of this study is to determine the vaccine effectiveness of 2 doses of Pfizer-BioNTech BNT162b2 vaccine against COVID-19-associated hospitalization. There will be a large retrospective database study using two parallel study designs: a test-negative case-control design and a retrospective cohort design. VE estimates by various strata and strain type will be conducted.

Detailed Description

The primary objective of the study is to estimate vaccine effectiveness (VE) of 2 doses of Pfizer's BNT162b2 vaccine against acute respiratory illness (ARI) requiring hospitalization due to SARS-CoV-2 infection among KPSC members eligible for vaccination. VE will be evaluated using a test-negative design (TND), including all KPSC patients eligible for vaccination who are admitted to the hospital with (ARI) after 14 December 2020 (date of first vaccinations at KPSC), and who receive a PCR test for SARS-CoV-2. Secondary and exploratory objectives may examine VE for 1 dose vaccination, at least 1 dose, \>2 doses, monovalent, bivalent or mixed dosing schedules as well as against ED admission, specific variants, mixed dosing schedules, durability, age cut-offs to align with regulatory authorizations/approvals and other populations of interest. Additionally, we will estimate VE using a full cohort design, including all KPSC members eligible for vaccination.

To assess VE, we propose a large retrospective database study using two parallel study de-signs: a test-negative case-control design and a retrospective cohort design. The TND will assess VE against COVID-19 hospitalization (primary endpoint) and ED admission. The retrospective cohort analysis may assess VE against COVID-19 hospitalization (primary), ICU admission, death, ED admission, and outpatient disease (with no subsequent hospitalization within 14 days). The BNT162b2 BA.4/BA.5 bivalent vaccine effectiveness will only be assessed via a test negative design due to the limitations regarding testing bias. As the pandemic evolved PCR-confirmed testing and reporting became less routine and differences in health care seeking behaviors were seen based on vaccination status.

VE for the XBB1.5-adapted monovalent vaccine will be defined as receipt of Pfizer -BioNTech XBB1.5-adapted monovalent vaccine with greater than or equal to 14 days between receipt of vaccine and the event date.

We will further conduct additional analyses of VE estimates by various patient characteristics and strain types.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2021-03-30
• Study First Submitted QC: 2021-04-15
• Study First Posted: 2021-04-19
• Study Start: 2021-05-15
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-06
• Last Update Posted: 2025-01-08
• Primary Completion: 2025-06-15
• Study Completion: 2025-06-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 999

Inclusion Criteria

• KPSC membership for a minimum of 1 year prior to index date, allowing a 30-day gap in membership to allow for delays in renewal. Participants <1 year did not have a membership requirement.≥6 months of age as of index date
• Admitted to the hospital or had an encounter in the ED, UC, or OP setting with a diagnosis of acute respiratory infection (ARI; defined based on International Classification of Diseases (ICD) codes listed in Appendix Table 1) after 25 September 2023
• Received a SARS-CoV-2 PCR or rapid antigen test

Exclusion criteria:

• Individuals who received a non-Pfizer-BioNTech XBB.1.5-adapted monovalent vaccine
• Individuals with an index event <14 days after vaccination with Pfizer-BioNTech XBB.1.5-adapted monovalent vaccine
• Individuals receiving a mRNA bivalent BA4.5 booster ≤ 8 weeks (≤ 56 days) since receiving last wild type dose
• Individuals with <28 days between a second and subsequent wild type dose
• Individuals receiving a XBB.1.5-adapted monovalent vaccine ≤ 8 weeks (≤ 56 days) since receiving a mRNA bivalent BA4.5 booster
• Individuals receiving oral COVID-19 antiviral OP treatments within 30 days of index event (will be excluded for primary analysis, but included in sensitivity analyses)

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Unexposed to XBB.1.5	XBB.1.5-adapted vaccinated	Unvaccinated with XBB.1.5-adapted monovalent vaccine or any other manufacturer's XBB-adapted formulation.
Fully vaccinated	Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine	Prior receipt of 2 doses of BNT162b2 received with ≥7 days between receipt of the 2nd dose and the index date. This group will serve as the 'exposed' group evaluated in the primary objective.
Fully vaccinated	BNT162b2 BA.4/5 bivalent	Prior receipt of 2 doses of BNT162b2 received with ≥7 days between receipt of the 2nd dose and the index date. This group will serve as the 'exposed' group evaluated in the primary objective.
Partially vaccinated	Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine	Prior receipt of 1 dose (only) of BNT162b2 received with ≥14 days between receipt of the 1st dose and the index date.
Ever vaccinated	Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine	Prior receipt ≥1 dose of BNT162b2 received with ≥14 days between index date and receipt of the 1st dose
Never vaccinated	BNT162b2 BA.4/5 bivalent	never received BNT162b2. This group will serve as the reference exposure group (i.e., 'unexposed' group) in all VE analyses
Never vaccinated	Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine	never received BNT162b2. This group will serve as the reference exposure group (i.e., 'unexposed' group) in all VE analyses
Partially vaccinated	BNT162b2 BA.4/5 bivalent	Prior receipt of 1 dose (only) of BNT162b2 received with ≥14 days between receipt of the 1st dose and the index date.
Bivalent vaccinated	BNT162b2 BA.4/5 bivalent	Receipt of the BNT162b2 BA.4/5 bivalent vaccine ≥8 weeks (≥56 days) since the most recent dose of wild-type COVID-19 mRNA vaccine (BNT162b2 or mRNA-1273) received
XBB.1.5 vaccinated	XBB.1.5-adapted vaccinated	Receipt of XBB.1.5-adapted monovalent vaccine with greater than or equal 14 days between receipt of vaccine and the event date.

Primary Outcome Measures

Name	Time	Method
Cohort Design Outcome: VE calculated as 1 minus the hazard ratio (HR) comparing the incidence of 2 doses with BNT162b2 for hospitalization due to SARS-CoV-2 infection and not, multiplied by 100%.	up to three years	To estimate the effectiveness of 2 doses of BNT162b2 against hospitalization due to SARS-CoV-2 infection
VE of XBB.1.5-adapted monovalent vaccine against hospitalization	up to three years	chart reviews focused on the identification of hospitalizations that are clearly not for COVID-19.
VE of XBB.1.5-adapted monovalent vaccine against critical illness	up to three years	Chart confirmed COVID-19 related to critical illness (death, mechanical ventilation, ICU)
Test Negative Design Outcome: VE calculated as 1 minus the odds ratio (OR) comparing the odds of being vaccinated with 2 doses with BNT162b2 for hospitalized cases and controls, multiplied by 100%.	up to three years	To estimate the effectiveness of 2 doses of BNT162b2 against hospitalization for Acute Respiratory Infection due to SARS-CoV-2 infection
VE of XBB.1.5-adapted monovalent against outpatient visits	up to three years	Number of patients with identified acute respiratory illness (ARI) diagnosis
VE of XBB.1.5-adapted monovalent vaccine against UC/ED visits.	up to three years	Number of patients with identified acute respiratory illness (ARI) diagnosis

Secondary Outcome Measures

Name	Time	Method
Cohort Design Outcome: VE = 1 minus the HR comparing the incidence of >2 doses of BNT162b2 for hospitalization, ED visit, death, and COVID-19 outpatient visits (without subsequent hosp. within 14 days) due to SARS-CoV-2, multiplied by 100%.	up to three years	To describe the effectiveness of \>2 doses of BNT162b2 against hospitalization, ED admission, ICU admission, death, and outpatient visits (without subsequent hospitalization within 14 days) due to SARS-CoV-2 infection.
XBB.1.5-adapted monovalent vaccine against outpatient encounters	up to three years	To describe the effectiveness of XBB.1.5-adapted monovalent vaccine against outpatient encounters.
Cohort Design Outcome: VE calculated as 1 minus the HR comparing the incidence of 2 doses with BNT162b2 for ED admission due to SARS-CoV-2 infection and not, multiplied by 100%.	up to three years	To estimate the effectiveness of 2 doses of BNT162b2 against ED admission (without subsequent hospitalization) ED admission due to SARS-CoV-2 infection
XBB.1.5 -adapted monovalent vaccine against critical illness	up to three years	To describe the effectiveness of XBB.1.5-adapted monovalent vaccine against critical illness (intensive care unit admissions, mechanical ventilation, or inpatient death confirmed by chart review to be COVID-19 related), emergency department, and urgent care visits.
Cohort Design Outcome: VE calculated as 1 minus the HR comparing the incidence of (2 doses with BNT162b2 for death due to SARS-CoV-2 infection and not, multiplied by 100%.	up to three years	To estimate the effectiveness of 2 doses of BNT162b2 against death due to SARS-CoV-2 infection
Cohort Design Outcome: VE calculated as 1 minus the HR comparing the incidence of 2 doses with BNT162b2 for COVID-19 outpatient visits (without subsequent hospitalization within 14 days) due to SARS-CoV-2 infection and not, multiplied by 100%.	up to three years	To estimate the effectiveness of 2 doses of BNT162b2 against COVID-19 outpatient visits (without subsequent hospitalization within 14 days) due to SARS-CoV-2 infection
Cohort Design Outcome: VE = 1 minus the HR comparing the incidence of 1 dose of BNT162b2 for hospitalization, ED visit, death, and COVID-19 outpatient visits (without subsequent hosp. within 14 days) due to SARS-CoV-2 and not, multiplied by 100%.	up to three years	To describe the effectiveness of only 1 dose of BNT162b2 (i.e., partially vaccinated) against hospitalization, ED admission, ICU admission, death, and outpatient visits (without subsequent hospitalization within 14 days) due to SARS-CoV-2 infection
Test Negative Design Outcome: VE calculated as 1 minus the OR comparing the odds of being partially vaccinated with BNT162b2 (only 1 dose) for ED cases and controls, multiplied by 100%.	up to three years	To describe the effectiveness of only 1 dose of BNT162b2 (i.e., partially vaccinated) against ED admission (without subsequent hospitalization) for ARI due to SARS-CoV-2 infection
Test Negative Design Outcome: VE calculated as 1 minus the OR comparing the odds of ever being vaccinated (≥1 dose) with BNT162b2 for hospitalized cases and controls, multiplied by 100%.	up to three years	To describe the effectiveness of ≥1 dose of BNT162b2 (i.e., ever vaccinated) against hospitalization for ARI due to SARS-CoV-2 infection
Test Negative Design Outcome: VE calculated as 1 minus the OR comparing the odds of >2 doses with BNT162b2 for hospitalized cases and controls, multiplied by 100%.	up to three years	To describe the effectiveness of \>2 doses of BNT162b2 against hospitalization for ARI due to SARS-CoV-2 infection
Test Negative Design Outcome: VE calculated as 1 minus the OR comparing the odds of ever being vaccinated (≥1 dose) with BNT162b2 for ED cases and controls, multiplied by 100%.	up to three years	To describe the effectiveness of ≥1 dose of BNT162b2 (i.e., ever vaccinated) against ED admission (without subsequent hospitalization) for ARI due to SARS-CoV-2 infection
Test Negative Design Outcome: VE calculated as 1 minus the OR comparing the odds of >2 doses with BNT162b2 for ED cases and controls, multiplied by 100%.	up to three years	To describe the effectiveness of \>2 doses of BNT162b2 against ED admission (without subsequent hospitalization) for ARI due to SARS-CoV-2 infection
Test Negative Design Outcome: BNT162b2 VE estimates stratified by virus variant (as determined by genome sequencing) and select descriptive analyses described above by number of doses received	up to three years	To further describe the effectiveness of BNT162b2 against hospitalization and ED admission stratified by prevalent or important viral strains
Test Negative Design Outcome: BNT162b2 VE estimates against severe outcomes including ICU admission, mechanical ventilation, and death by number of doses received.	up to three years	To evaluate the effectiveness of BNT162b2 against severe hospitalization-related outcomes (e.g., ICU admission, mechanical ventilation, and death)
Test Negative Design Outcome: VE calculated as 1 minus the OR comparing the odds of being vaccinated with 2 doses BNT162b2 for ED cases and controls, multiplied by 100%	up to three years	To estimate the effectiveness of 2 doses of BNT162b2 against ED admission (without subsequent hospitalization) for ARI due to SARS-CoV-2 infection
Test Negative Design Outcome: VE calculated as 1 minus the OR comparing the odds of being partially vaccinated with BNT162b2 (only 1 dose) for hospitalized cases and controls, multiplied by 100%.	up to three years	To describe the effectiveness of only 1 dose of BNT162b2 (i.e., partially vaccinated) against hospitalization for ARI due to SARS-CoV-2 infection.
Test Negative Design Outcome: Monthly VE estimates between variants of interest using independent Z tests of log hazard ratios.	up to three years	To evaluate overall and variant-specific effectiveness of BNT162b2 against SARS-CoV-2 infections and COVID-19 related hospital admissions by time since vaccination (by month)
Test Negative Design Outcome: VE calculated as 1 minus the odds ratio (OR) comparing the odds of being vaccinated with BNT162b2 BA.4/BA.5 bivalent booster for hospitalized cases and controls, multiplied by 100%.	up to three years	To estimate the effectiveness of the BNT162b2 BA.4/BA.5 bivalent booster against hospitalization for ARI due to SARS-CoV-2 infection.
Test Negative Design Outcome: VE calculated as 1 minus the odds ratio (OR) comparing the odds of being vaccinated with BNT162b2 BA.4/BA.5 bivalent for emergency room admissions/urgent care visit cases and controls, multiplied by 100%.	up to three years	To estimate the effectiveness of the BNT162b2 BA.4/BA.5 bivalent booster against emergency room admissions/urgent care vists for ARI due to SARS-CoV-2 infection.
Cohort Design Outcome: VE calculated as 1 minus the HR comparing the incidence of 2 doses with BNT162b2 for ICU admission due to SARS-CoV-2 infection and not, multiplied by 100%.	up to three years	To estimate the effectiveness of 2 doses of BNT162b2 against ICU admission due to SARS-CoV-2 infection
Cohort Design Outcome: VE = 1 minus the HR comparing the incidence ≥1 dose of BNT162b2 (for hospitalization, ED visit, death, and COVID-19 outpatient visits (without subsequent hosp. within 14 days) due to SARS-CoV-2 and not, multiplied by 100%.	up to three years	To describe the effectiveness of ≥1 dose of BNT162b2 (i.e., ever vaccinated) against hospitalization, ICU admission, ED admission, death, and outpatient visits (without subsequent hospitalization within 14 days) due to SARS-CoV-2 infection

Trial Locations

Locations (1)

Kaiser Permanente Southern California; 🇺🇸 Pasadena, California, United States