Pfizer-BioNTech COVID-19 BNT162b2 Vaccine Effectiveness Study - Kaiser Permanente Southern California

Study Overview
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Brief Summary
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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. Exploratory analyses of VE estimates by strain type will be conducted.

Detailed Description
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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. We may further conduct additional analyses of VE estimates by various patient characteristics and strain type.

Official Title
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Pfizer-BioNTech COVID-19 BNT162b2 Vaccine Effectiveness Study - Kaiser Per-manente Southern California

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine
* Biological: Bivalent vaccinated


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Test Negative Design KPSC patients eligible to receive BNT162b2 who are admitted to the hospital (primary objective and some secondary objectives) with acute respiratory infection (ARI; International Classification of Diseases (ICD) codes) after 14 December 2020 (date of first vaccinations at KPSC), and who receive a PCR test for SARS-CoV-2. For secondary objectives estimating VE against ED admission, the TND will include KPSC patients eligible to receive BNT162b2 who present to the ED with ARI after 14 December 2020, and who receive a PCR test for SARS-CoV-2. We will include membership requirement of 1 year prior to index date, which is defined as the date of hospitalization or ED admission (allowing 31-day administrative gap), to facilitate accurate capture of comorbid conditions. Inclusion Criteria for Cohort Design- All KPSC members as of 14 December 2020 (date of first Pfizer vaccination at KPSC) eligible to receive BNT162b2. For the cohort study, patients must have at least 1 year of membership (allowing 31-day administrative gap) prior to 14 December 2020 (index date, date vaccinations first began at KPSC) to facilitate accurate capture of comorbid conditions. Exclusion Criteria Test Negative Design Patients who receive only another newly licensed or investigational SARS-CoV-2 vaccine or COVID-19 prophylactic agent other than Pfizer's COVID-19 vaccine prior to hospitalization (or ED, for secondary objective) will be excluded from the study population When estimating VE for BNT162b2 vaccination, patients receiving another newly licensed or investigational SARS-CoV-2 vaccine or COVID-19 prophylactic agent other than Pfizer's COVID-19 vaccine prior to hospitalization or ED will be excluded from the analysis. Patients will also be excluded if the index date is within certain time windows from vaccination date, outlined further in the exposure section below. Exclusion Criteria for Cohort Design There will be no exclusion criteria for the cohort design, however patients will be censored for receiving any other newly licensed or investigational SARS-CoV-2 vaccine or COVID-19 prophylactic agent other than Pfizer's COVID-19 vaccine
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Fully vaccinated<br>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. | Biological: Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine<br>* prior administration of Pfizer-BioNTech COVID-19 vaccine; vaccine is not administered in this study<br>* Other names: COVID VACCINE;|
| Partially vaccinated<br>Prior receipt of 1 dose (only) of BNT162b2 received with ≥14 days between receipt of the 1st dose and the index date. | Biological: Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine<br>* prior administration of Pfizer-BioNTech COVID-19 vaccine; vaccine is not administered in this study<br>* Other names: COVID VACCINE;|
| Ever vaccinated<br>Prior receipt ≥1 dose of BNT162b2 received with ≥14 days between index date and receipt of the 1st dose | Biological: Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine<br>* prior administration of Pfizer-BioNTech COVID-19 vaccine; vaccine is not administered in this study<br>* Other names: COVID VACCINE;|
| Never vaccinated<br>never received BNT162b2. This group will serve as the reference exposure group (i.e., 'unexposed' group) in all VE analyses | Biological: Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine<br>* prior administration of Pfizer-BioNTech COVID-19 vaccine; vaccine is not administered in this study<br>* Other names: COVID VACCINE;|
| Bivalent vaccinated<br>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 | Biological: Bivalent vaccinated<br>* Vaccination with a bivalent booster was defined as 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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%. | To estimate the effectiveness of 2 doses of BNT162b2 against hospitalization for Acute Respiratory Infection due to SARS-CoV-2 infection | up to three years | 
| 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%. | To estimate the effectiveness of 2 doses of BNT162b2 against hospitalization due to SARS-CoV-2 infection | up to three years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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% | To estimate the effectiveness of 2 doses of BNT162b2 against ED admission (without subsequent hospitalization) for ARI due to SARS-CoV-2 infection | up to three years | 
| 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%. | To describe the effectiveness of only 1 dose of BNT162b2 (i.e., partially vaccinated) against hospitalization for ARI due to SARS-CoV-2 infection. | up to three years | 
| 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%. | 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 | up to three years | 
| 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%. | To describe the effectiveness of ≥1 dose of BNT162b2 (i.e., ever vaccinated) against hospitalization for ARI due to SARS-CoV-2 infection | up to three years | 
| 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%. | 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 | up to three years | 
| 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%. | To describe the effectiveness of >2 doses of BNT162b2 against hospitalization for ARI due to SARS-CoV-2 infection | up to three years | 
| 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%. | To describe the effectiveness of >2 doses of BNT162b2 against ED admission (without subsequent hospitalization) for ARI due to SARS-CoV-2 infection | up to three years | 
| 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 | To further describe the effectiveness of BNT162b2 against hospitalization and ED admission stratified by prevalent or important viral strains | up to three years | 
| Test Negative Design Outcome: BNT162b2 VE estimates against severe outcomes including ICU admission, mechanical ventilation, and death by number of doses received. | To evaluate the effectiveness of BNT162b2 against severe hospitalization-related outcomes (e.g., ICU admission, mechanical ventilation, and death) | up to three years | 
| Test Negative Design Outcome: Monthly VE estimates between variants of interest using independent Z tests of log hazard ratios. | 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) | up to three years | 
| 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%. | To estimate the effectiveness of the BNT162b2 BA.4/BA.5 bivalent booster against hospitalization for ARI due to SARS-CoV-2 infection. | up to three years | 
| 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%. | 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. | up to three years | 
| 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%. | To estimate the effectiveness of 2 doses of BNT162b2 against ED admission (without subsequent hospitalization) ED admission due to SARS-CoV-2 infection | up to three years | 
| 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%. | To estimate the effectiveness of 2 doses of BNT162b2 against ICU admission due to SARS-CoV-2 infection | up to three years | 
| 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%. | To estimate the effectiveness of 2 doses of BNT162b2 against death due to SARS-CoV-2 infection | up to three years | 
| 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%. | 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 | up to three years | 
| 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%. | 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 | up to three years | 
| 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%. | 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 | up to three years | 
| 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%. | 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. | up to three years |