COVID-19NCT04848584
Pfizer-BioNTech COVID-19 Vaccine Effectiveness Study - Kaiser Permanente Southern California
An observational study of COVID-19, run by Pfizer at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 0 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine, BNT162b2 BA.4/5 bivalent and XBB.1.5-adapted vaccinated
- Type of treatment
- Vaccines
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 15 May 2021to 30 Apr 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: All members of KPSC who are eligible based on vaccination status and age.
Who may be able to join
- 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.
- 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.
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- 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
- XBB.1.5-adapted monovalent vaccine eligibility analyses:
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Kaiser Permanente Southern California
Pasadena, California, 91101
About this study
Official title: Pfizer-BioNTech COVID-19 BNT162b2 Vaccine Effectiveness Study - Kaiser Permanente Southern California
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.
Read the 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.
- Conditions
- COVID-19
- Being tested
- Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine, BNT162b2 BA.4/5 bivalent, XBB.1.5-adapted vaccinated
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Primary Exposure Status of Pfizer-BioNTech COVID-19 VaccineBiological
Also called COVID VACCINE
prior administration of Pfizer-BioNTech COVID-19 vaccine; vaccine is not administered in this study
BNT162b2 BA.4/5 bivalentBiological
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.
XBB.1.5-adapted vaccinatedBiological
Vaccinated with XBB.1.5-adapted vaccine
| Study group | Role | What they receive |
|---|---|---|
| Fully vaccinated | 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. Receives: Biological: Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine; Biological: BNT162b2 BA.4/5 bivalent | |
| Partially vaccinated | Prior receipt of 1 dose (only) of BNT162b2 received with ≥14 days between receipt of the 1st dose and the index date. Receives: Biological: Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine; Biological: BNT162b2 BA.4/5 bivalent | |
| Ever vaccinated | Prior receipt ≥1 dose of BNT162b2 received with ≥14 days between index date and receipt of the 1st dose Receives: Biological: Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine | |
| Never vaccinated | never received BNT162b2. This group will serve as the reference exposure group (i.e., 'unexposed' group) in all VE analyses Receives: Biological: Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine; Biological: BNT162b2 BA.4/5 bivalent | |
| Bivalent vaccinated | 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 Receives: Biological: BNT162b2 BA.4/5 bivalent | |
| XBB.1.5 vaccinated | Receipt of XBB.1.5-adapted monovalent vaccine with greater than or equal 14 days between receipt of vaccine and the event date. Receives: Biological: XBB.1.5-adapted vaccinated | |
| Unexposed to XBB.1.5 | Unvaccinated with XBB.1.5-adapted monovalent vaccine or any other manufacturer's XBB-adapted formulation. Receives: Biological: XBB.1.5-adapted vaccinated |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: up to three years
VE of XBB.1.5-adapted monovalent vaccine against hospitalization
chart reviews focused on the identification of hospitalizations that are clearly not for COVID-19.
Measured: up to three years
VE of XBB.1.5-adapted monovalent vaccine against critical illness
Chart confirmed COVID-19 related to critical illness (death, mechanical ventilation, ICU)
Measured: up to three years
VE of XBB.1.5-adapted monovalent against outpatient visits
Number of patients with identified acute respiratory illness (ARI) diagnosis
Measured: up to three years
VE of XBB.1.5-adapted monovalent vaccine against UC/ED visits.
Number of patients with identified acute respiratory illness (ARI) diagnosis
Measured: up to three years
Secondary outcomes (21)
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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: up to three years
XBB.1.5 -adapted monovalent vaccine against critical illness
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.
Measured: up to three years
XBB.1.5-adapted monovalent vaccine against outpatient encounters
To describe the effectiveness of XBB.1.5-adapted monovalent vaccine against outpatient encounters.
Measured: up to three years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2021
- Study start15 May 2021
- Primary completion30 Apr 2025
- Study completion30 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04848584
- Sponsor's protocol ID
- C4591014
- Other IDs
- NCT04848584
- Status last verified
- Jul 2025
- First submitted
- 30 Mar 2021
- Last updated
- 29 Jul 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Publications
Tartof SY, Slezak JM, Puzniak L, Hong V, Frankland TB, Ackerson BK, Xie F, Takhar H, Ogun OA, Simmons S, Zamparo JM, Valluri SR, Jodar L, McLaughlin JM. Effectiveness of BNT162b2 BA.4/5 bivalent mRNA vaccine against a range of COVID-19 outcomes in a large health system in the USA: a test-negative case-control study. Lancet Respir Med. 2023 Dec;11(12):1089-1100. doi: 10.1016/S2213-2600(23)00306-5. Epub 2023 Oct 25.
PubMed 37898148Tartof SY, Slezak JM, Puzniak L, Hong V, Frankland TB, Xie F, Ackerson BK, Valluri SR, Jodar L, McLaughlin JM. Effectiveness and durability of BNT162b2 vaccine against hospital and emergency department admissions due to SARS-CoV-2 omicron sub-lineages BA.1 and BA.2 in a large health system in the USA: a test-negative, case-control study. Lancet Respir Med. 2023 Feb;11(2):176-187. doi: 10.1016/S2213-2600(22)00354-X. Epub 2022 Oct 7.
PubMed 36216013Tartof SY, Slezak JM, Puzniak L, Hong V, Xie F, Ackerson BK, Valluri SR, Jodar L, McLaughlin JM. Durability of BNT162b2 vaccine against hospital and emergency department admissions due to the omicron and delta variants in a large health system in the USA: a test-negative case-control study. Lancet Respir Med. 2022 Jul;10(7):689-699. doi: 10.1016/S2213-2600(22)00101-1. Epub 2022 Apr 22.
PubMed 35468336Tartof SY, Slezak JM, Fischer H, Hong V, Ackerson BK, Ranasinghe ON, Frankland TB, Ogun OA, Zamparo JM, Gray S, Valluri SR, Pan K, Angulo FJ, Jodar L, McLaughlin JM. Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study. Lancet. 2021 Oct 16;398(10309):1407-1416. doi: 10.1016/S0140-6736(21)02183-8. Epub 2021 Oct 4.
PubMed 34619098
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pfizer-BioNTech COVID-19 BNT162b2 Vaccine Effectiveness Study - Kaiser Permanente Southern California
- ClinicalTrials.gov ID
- NCT04848584
- Acronym / sponsor ID
- C4591014
- Conditions
- COVID-19
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 15 May 2021 (actual)
- Primary completion
- 30 Apr 2025 (actual)
- Study completion
- 30 Apr 2025 (actual)
- First posted
- 19 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Fully vaccinated | – | Biological: Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine, Biological: BNT162b2 BA.4/5 bivalentPrior 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 | – | Biological: Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine, Biological: BNT162b2 BA.4/5 bivalentPrior receipt of 1 dose (only) of BNT162b2 received with ≥14 days between receipt of the 1st dose and the index date. |
| Ever vaccinated | – | Biological: Primary Exposure Status of Pfizer-BioNTech COVID-19 VaccinePrior receipt ≥1 dose of BNT162b2 received with ≥14 days between index date and receipt of the 1st dose |
| Never vaccinated | – | Biological: Primary Exposure Status of Pfizer-BioNTech COVID-19 Vaccine, Biological: BNT162b2 BA.4/5 bivalentnever received BNT162b2. This group will serve as the reference exposure group (i.e., 'unexposed' group) in all VE analyses |
| Bivalent vaccinated | – | Biological: BNT162b2 BA.4/5 bivalentReceipt 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 | – | Biological: XBB.1.5-adapted vaccinatedReceipt of XBB.1.5-adapted monovalent vaccine with greater than or equal 14 days between receipt of vaccine and the event date. |
| Unexposed to XBB.1.5 | – | Biological: XBB.1.5-adapted vaccinatedUnvaccinated with XBB.1.5-adapted monovalent vaccine or any other manufacturer's XBB-adapted formulation. |
Who may qualify
- Ages
- 0 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- All members of KPSC who are eligible based on vaccination status and age.
Key inclusion criteria (11 listed)
- 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.
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Primary Exposure Status of Pfizer-BioNTech COVID-19 VaccineAlso: COVID VACCINEprior administration of Pfizer-BioNTech COVID-19 vaccine; vaccine is not administered in this study | Biological | Ever vaccinated, Fully vaccinated, Never vaccinated, Partially vaccinated |
| BNT162b2 BA.4/5 bivalentVaccination 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. | Biological | Bivalent vaccinated, Fully vaccinated, Never vaccinated, Partially vaccinated |
| XBB.1.5-adapted vaccinatedVaccinated with XBB.1.5-adapted vaccine | Biological | Unexposed to XBB.1.5, XBB.1.5 vaccinated |
Primary outcome
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%.
Time frame: 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
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%.
Time frame: 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
Time frame: 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
Time frame: up to three years
Chart confirmed COVID-19 related to critical illness (death, mechanical ventilation, ICU)
VE of XBB.1.5-adapted monovalent against outpatient visits
Time frame: 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.
Time frame: up to three years
Number of patients with identified acute respiratory illness (ARI) diagnosis
21 secondary outcomes
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%
Time frame: 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%.
Time frame: 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%.
Time frame: 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%.
Time frame: 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%.
Time frame: 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%.
Time frame: 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%.
Time frame: 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
Time frame: 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.
Time frame: up to three years
Test Negative Design Outcome: Monthly VE estimates between variants of interest using independent Z tests of log hazard ratios.
Time frame: 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%.
Time frame: 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%.
Time frame: 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%.
Time frame: 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%.
Time frame: 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%.
Time frame: 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%.
Time frame: 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%.
Time frame: 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%.
Time frame: 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%.
Time frame: up to three years
XBB.1.5 -adapted monovalent vaccine against critical illness
Time frame: up to three years
XBB.1.5-adapted monovalent vaccine against outpatient encounters
Time frame: up to three years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2025.
- Derived from this study: PubMed 37898148Tartof SY, Slezak JM, Puzniak L, Hong V, Frankland TB, Ackerson BK, Xie F, Takhar H, Ogun OA, Simmons S, Zamparo JM, Valluri SR, Jodar L, McLaughlin JM. Effectiveness of BNT162b2 BA.4/5 bivalent mRNA vaccine against a range of COVID-19 outcomes in a large health system in the USA: a test-negative case-control study. Lancet Respir Med. 2023 Dec;11(12):1089-1100. doi: 10.1016/S2213-2600(23)00306-5. Epub 2023 Oct 25.
- Derived from this study: PubMed 36216013Tartof SY, Slezak JM, Puzniak L, Hong V, Frankland TB, Xie F, Ackerson BK, Valluri SR, Jodar L, McLaughlin JM. Effectiveness and durability of BNT162b2 vaccine against hospital and emergency department admissions due to SARS-CoV-2 omicron sub-lineages BA.1 and BA.2 in a large health system in the USA: a test-negative, case-control study. Lancet Respir Med. 2023 Feb;11(2):176-187. doi: 10.1016/S2213-2600(22)00354-X. Epub 2022 Oct 7.
- Derived from this study: PubMed 35468336Tartof SY, Slezak JM, Puzniak L, Hong V, Xie F, Ackerson BK, Valluri SR, Jodar L, McLaughlin JM. Durability of BNT162b2 vaccine against hospital and emergency department admissions due to the omicron and delta variants in a large health system in the USA: a test-negative case-control study. Lancet Respir Med. 2022 Jul;10(7):689-699. doi: 10.1016/S2213-2600(22)00101-1. Epub 2022 Apr 22.
- Derived from this study: PubMed 34619098Tartof SY, Slezak JM, Fischer H, Hong V, Ackerson BK, Ranasinghe ON, Frankland TB, Ogun OA, Zamparo JM, Gray S, Valluri SR, Pan K, Angulo FJ, Jodar L, McLaughlin JM. Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study. Lancet. 2021 Oct 16;398(10309):1407-1416. doi: 10.1016/S0140-6736(21)02183-8. Epub 2021 Oct 4.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: No. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19, run by Pfizer at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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%. (time frame: up to three years). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04848584, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2025.