Document text
Update on Original COVID -19 Vaccine and COVID -19
Vaccine, Bivalent Safety
Richard Forshee
Deputy Director, FDA/CBER/OBPV
Advisory Committee on Immunization Practices
February 24, 2023
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•CBER Active Surveillance Program (BEST Initiative)
•Bivalent COVID - 19 mRNA Vaccines Safety Surveillance
•ConclusionOutline
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*Data lag varies based on data source, ranges from a few days to a few months.
BEST Initiative Data Sources
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Claims Data Source Age (years)Population Enrolled
(million)
CMS Medicare 65+ 36
DP 10-4
5-17
18-641.2
3.1
14.8
DP 20-4
5-17
18-641.02.6
11.6
DP 30-4
5-17
18-641.43.7
17.1Rapid Cycle Analysis (RCA) Data Sources
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•Confidential, population- b ased, computerized
databases that record immunization doses
administered by participating providers to persons in U.S. public health jurisdictions
•Supplements claims- b
ased COVID-19 vaccine
administration data
•Undercapture o f COVID-19 vaccines in claims
databases due to vaccines administered without insurance reimbursementImmunization Information Systems (IIS)
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Descriptive Monitoring provides descriptive statistics of
vaccine doses and selected adverse events.
Signal Detection performs sequential testing, while
vaccine doses accumulate, to identify potential safety
risks early; does not prove causal relationship.
Signal Evaluation uses more robust study designs to
evaluate potential safety signals.Phases of Vaccine Active Surveillance
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•CBER Active Surveillance Program (BEST Initiative)
•Bivalent COVID-19 mRNA Vaccines Safety Surveillance
•ConclusionOutline
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COVID-19 Bivalent mRNA Vaccines Rapid Cycle Analyses
Administered Doses By Age Group
1. Data cuts: CVS data through 10/2022, HealthCore data through 11/2022, Optum data through 12/2022
2. Data cuts: CMS data through 12/2022Age Groups
(years)BNT162b2
(# vaccinations)mRNA-1273
(# vaccinations)Total
(# vaccinations)
5/6-171196,992 13,016 210,008
18-351442,870 211,694 654,564
36-641 1,248,430 654,220 1,902,650
65+2 4,265,244 3,042,074 7,307,318
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•FDA Study Design: Rapid Cycle Analysis (RCA) near real-time
surveillance
•No causal association established
•Population: 6 month-4/5 years, 5/6-17 years, 18-64 years*, ≥65
years
•Exposure: mRNA -1273.222 and BNT162b2 COVID -19 vaccines
•Bivalent booster: original SARS-CoV -2 virus and Omicron
variants BA.4 and BA.5.
•Statistical Method : MaxSPRT
•Comparator: Historical rates
*For the myocarditis/pericarditis outcome, the study population was additionally split into 18- 35 and 36 -64year age groups.COVID- 19 Bivalent mRNA Vaccines Safety Monitoring
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Adverse Events Monitored in Adult and Pediatric Populations
Acute Myocardial Infarction Hemorrhagic Stroke
Anaphylaxis Immune Thrombocytopenia
Appendicitis Multisystem Inflammatory Syndrome
Bell’s Palsy Myocarditis/Pericarditis (Myo- /Pericarditis)*
Common Site Thrombosis with
ThrombocytopeniaNarcolepsy
Disseminated Intravascular Coagulation Non- hemorrhagic Stroke
Deep Vein Thrombosis Pulmonary Embolism
Encephalitis/Encephalomyelitis Transverse Myelitis
Guillain -Barre Syndrome Unusual Site Thrombosis (Broad) with
Thrombocytopenia
*This includes 4 myo -/pericarditis outcome definitions varying care settings (all settings vs. IP/OP -ED) and risk windows (1 -7 vs. 1-21 days)
These AEs have not been associated with COVID- 19 vaccines based on available pre- licensure evidence.Adverse Events Monitored in
Pediatric Populations Only
Seizure/Febrile Seizure
Kawasaki Disease
Multisystem Inflammatory Syndrome in children
(MIS -C) FDA Adverse Events Monitored
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Adverse Event (AE)Medicare Population1
(Ages 65+)Adult Population2
(Ages 18-64)Pediatric Population2
(Ages 5-17/6-17)
Acute Myocardial Infarction No No Descriptive Only
Anaphylaxis No No No
Appendicitis No No No
Disseminated Intravascular Coagulation No No No
Deep Vein Thrombosis No No No
Bell’s Palsy No No No
Encephalomyelitis/Encephalitis No No No
Guillain -Barré Syndrome No No Descriptive Only
Hemorrhagic Stroke No No Descriptive Only
Myocarditis/Pericarditis NoBNT162b2 Bivalent
(18-35)No
Common Site Thrombosis with
ThrombocytopeniaNo No No
Uncommon Site Thrombosis with Thrombocytopenia SyndromeNo No Descriptive Only
Narcolepsy No No No
Non-Hemorrhagic Stroke No No No
Pulmonary Embolism No No No
Transverse Myelitis No No Descriptive Only
Immune Thrombocytopenia No No No
Febrile Seizures N/A N/A Descriptive Only
Seizures/Convulsions N/A N/A No
Kawasaki disease N/A N/A Descriptive Only
Multisystem Inflammatory Syndrome Descriptive Only Descriptive Only Descriptive Only
1. Data cuts: CMS 12/2022
2. Data cuts: CVS Health data through 10/2022; HealthCore data through 11/2022, Optum data through 12/2022
A
Es and the associated vaccine brand with a safety signal are noted.
N/A indicates neither descriptive monitoring nor sequential testing is being conducted in the indicated age group for a given AE . NOindicates that a safety signal has
not been detected. Descriptive Only indicates sequential testing is not being conducted in the indicated age group for a given AE.Signals Detected
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Adverse Event (AE) Ages 65+ years
Acute Myocardial Infarction BNT162b2, mRNA- 1273
Deep Vein Thrombosis BNT162b2, mRNA- 1273
Bell’s Palsy BNT162b2
Common Site Thrombosis with
ThrombocytopeniaBNT162b2
Non-Hemorrhagic Stroke BNT162b2, mRNA- 1273
Pulmonary Embolism BNT162b2Adverse Events that Completed Surveillance Period
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Risk Ratio Non -hemorrhagic Stroke for Pfizer
Bivalent Compared to Historical Rates (2019)
We reached the maximum length of surveillance without a signal
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•Approximately 4. 25 million doses of the Pfizer -BioNTech bivalent vaccine have
been administered in the CMS database in individuals 65 years and older
•38% of the Medicare recipients who received a Pfizer bivalent COVID-19
b
ooster received a seasonal influenza vaccination on the same day
•78% received a seasonal influenza vaccination within +/- 4 2 days
•Further work to be done to segment out the different influenza vaccine types
adm
inistered with the COVID-19 vaccines
•No signal seen at this time for non-hemorrhagic strokeConcomitant Influenza Vaccination
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•This is a large-scale signal detection study of two COVID-19 mRNA bivalent
vaccines conducted in multiple claims databases.
•RCA surveillance detected a signal for myocarditis/pericarditis following BNT162b2 bivalent vaccine doses among 18-35 year olds.
•Among adults 65 years and older, several AEs have completed the surveillance period.
•Signal detection studies do not establish a causal relationship and further evaluation of signals is required in more robust studies.
•Surveillance is ongoing and expanded to < 5 year olds. COVID- 19 Bivalent mRNA Vaccines RCA
Summary
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1)No excess reports of stroke from VAERS
2)CMS database with about 4.25 million doses shows no increase in stroke
3)VA database run shows no increase in stroke on preliminary query
4)Various countries in Europe as well as Israel indicate no increased risk of stroke in
their surveillance systems
5)Pfizer notes no increase in signal in their global safety database or when comparing the monovalent to bivalent vaccines
In any case, a formal epidemiologic study is being initiated by FDA to
prepare for potential vaccine coadministration in 2023-2024Data Suggesting Absence of Safety Risk for the
Bivalent Boosters in Age 65y+
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Acknowledgements
•Steven A. Anderson
•CBER Surveillance T eam: Azadeh Shoaibi, Hui-Lee Wong, Tainya C. Clarke,
Joyce Obidi, Joann F. Gruber, Patricia C. Lloyd, Sylvia Cho
•CBER OBPV
•Federal Partners: CMS, VA, CDC
•FDA Partners: Acumen, Blue Health Intelligence, CVS Health, Healt hCore,
IBM, IQVIA, OHDSI, Optum, RTI Health Solutions
www.bestinitiative.org