Fluad vs. Fluzone High-Dose Vaccine Effectiveness Among Adults ≥65 Years

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the relative vaccine effectiveness of quadrivalent adjuvanted inactivated influenza vaccine (aIIV4) versus quadrivalent high-dose inactivated influenza vaccine (HD-IIV4) in preventing polymerase chain reaction (PCR)-confirmed influenza and influenza-related outcomes in adults ≥65 years of age during the 2023/24 and 2024/25 influenza seasons. The study is an observational study conducted at Kaiser Permanente Northern California (KPNC), an integrated health care system in the United States.

Official Title
-----------------
Relative Vaccine Effectiveness of Adjuvanted Quadrivalent Inactivated Influenza Vaccine vs High-Dose Quadrivalent Inactivated Influenza Vaccine Among Adults ≥65 Years for the 2023-24 and 2024-25 Seasons

Conditions
-----------------
Influenza, Community-acquired Pneumonia, Cardiovascular Events

Intervention / Treatment
-----------------
* Biological: Adjuvanted Quadrivalent Inactivated Influenza Vaccine (aIIV4)
* Biological: High-Dose Quadrivalent Inactivated Influenza Vaccine (HD-IIV4)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥65 years at the time of influenza vaccination KPNC member at the time of vaccination Receive either aIIV4 or HD-IIV4 at a KPNC facility during the 2023/24 and/or 2024/25 influenza seasons Exclusion Criteria: Age <65 years at the time of influenza vaccination Received either aIIV4 or HD-IIV4 in the inpatient setting Receive more than one influenza vaccination during a single season period (i.e., 2023/24 or 2024/25 influenza seasons) Receive an influenza vaccination outside of KPNC

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Fluad Recipients<br>Kaiser Permanente Northern California members aged ≥65 years who receive Adjuvanted Quadrivalent Inactivated Influenza Vaccine (aIIV4) | Biological: Adjuvanted Quadrivalent Inactivated Influenza Vaccine (aIIV4)<br>* Fluad Quadrivalent vaccine is an inactivated influenza vaccine formulated to contain 60 mcg of hemagglutinin (HA) total, with 15 mcg from each of the four recommended influenza strains and the MF59 adjuvant in single-dose prefilled 0.5 mL syringes. Kaiser Permanente Northern California members ≥65 years may receive Fluad as part of routine clinical care during the influenza season.<br>* Other names: Fluad;|
| Fluzone High-Dose Recipients<br>Kaiser Permanente Northern California members aged ≥65 years who receive High-Dose Quadrivalent Inactivated Influenza Vaccine (HD-IIV4) | Biological: High-Dose Quadrivalent Inactivated Influenza Vaccine (HD-IIV4)<br>* Fluzone High-Dose Quadrivalent vaccine is an inactivated split virion influenza vaccine formulated to contain 240 mcg of HA total, with 60 mcg from each of the four recommended influenza strains in single-dose prefilled 0.7 mL syringes. Kaiser Permanente Northern California members ≥65 years may receive Fluzone High-Dose as part of routine clinical care during the influenza season.<br>* Other names: Fluzone High-Dose;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PCR-confirmed influenza | KPNC members ≥65 years who receive Fluad or Fluzone High-Dose will be retrospectively assessed for the presence of PCR-confirmed influenza. This outcome will be assessed in single-season analyses (2023/24 and 2024/25 separately) and a pooled 2-seasons analysis (2023/24 and 2024/25 combined). | ≥14 days after vaccination until date of outcome, death, loss-to-follow-up, or end of each season (estimated May 2024 or May 2025) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Emergency department visit or hospitalization for PCR-confirmed influenza | KPNC members ≥65 years who receive Fluad or Fluzone High-Dose will be retrospectively assessed for an emergency department visit or hospitalization for PCR-confirmed influenza. This outcome will be assessed in single-season analyses (2023/24 and 2024/25 separately) and a pooled 2-seasons analysis (2023/24 and 2024/25 combined). | ≥14 days after vaccination until date of outcome, death, loss-to-follow-up, or end of each season (estimated May 2024 or May 2025) | 
| Hospitalization for PCR-confirmed influenza | KPNC members ≥65 years who receive Fluad or Fluzone High-Dose will be retrospectively assessed for hospitalization for PCR-confirmed influenza. This outcome will be assessed in a pooled 2-seasons analysis (2023/24 and 2024/25 combined). | ≥14 days after vaccination until date of outcome, death, loss-to-follow-up, or end of each season (estimated May 2024 or May 2025) | 
| Hospitalization for all-cause community-acquired pneumonia | KPNC members ≥65 years who receive Fluad or Fluzone High-Dose will be retrospectively assessed for hospitalization for all-cause community-acquired pneumonia. This outcome will be assessed in single-season analyses (2023/24 and 2024/25 separately) and a pooled 2-seasons analysis (2023/24 and 2024/25 combined). | ≥14 days after vaccination until date of outcome, death, loss-to-follow-up, or end of each season (estimated May 2024 or May 2025) |