Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000117516
Ethics application status
Approved
Date submitted
11/01/2024
Date registered
8/02/2024
Date last updated
8/02/2024
Date data sharing statement initially provided
8/02/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
What is the uptake of the COVID-19 and influenza vaccines in people with severe mental illness?
Scientific title
What is the uptake of the COVID-19 and influenza vaccines in people with severe mental illness?
Secondary ID [1] 311305 0
GNT1194635
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe mental illness 332551 0
COVID-19 332552 0
Influenza 332553 0
Vaccination 332554 0
Condition category
Condition code
Mental Health 329241 329241 0 0
Schizophrenia
Mental Health 329242 329242 0 0
Psychosis and personality disorders
Mental Health 329243 329243 0 0
Depression
Public Health 329244 329244 0 0
Epidemiology
Mental Health 329245 329245 0 0
Other mental health disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is a cohort study where we are investigating differences in vaccination rates for COVID-19 and influenza for Australian's with and without severe mental illness (SMI). We will also investigate whether vaccination has any effect on differences in COVID-19 and influenza-related morbidity and mortality between groups.

We will identify two exposure cohorts: (i) COVID-19 exposure cohort; (ii) influenza exposure cohort. Both will be identified using Pharmaceutical Benefits Scheme (PBS) data. Members of the cohorts may overlap (i.e., individuals in the COVID-19 exposure group may also have received the influenza vaccination and vice versa).

(i) COVID-19 exposure cohort: All individuals with SMI who were aged 18 years and over at 22/02/2021. We will define people as having SMI if they have been dispensed two prescriptions within 12 months for authority-only medications used specifically for SMI (ATC codes N05AH, N05AX, N05AE, N06AX) since 22/02/2019 (2 years prior to the period of interest of this study), or 2 prescriptions for lithium within 12 months. Authority-only medications will include all that were listed on the PBS during the time period (and subsequently may now be discontinued). In the case of quetiapine (ATC Code NO5AH04), we will only include anyone prescribed at least 100mg on those two occasions, to minimise the influence of off-label use. Individuals may have had the COVID-19 disease, but the cohort will not be restricted to just these individuals as we are interested in vaccination rates.

(ii) Influenza exposure cohort: All individuals with SMI aged 18 years and over on 01/01/2018. We will define people as having SMI if they have been dispensed two prescriptions within 12 months for authority-only medications used specifically for SMI (ATC codes N05AH, N05AX, N05AE, N06AX) since 01/01/2016 (2 years prior to the period of interest of this study), or 2 prescriptions for lithium within 12 months. In the case of quetiapine (ATC Code NO5AH04), we will only include anyone prescribed at least 100mg on those two occasions, to minimise the influence of off-label use. Individuals may have had influenza, but the cohort will not be restricted to just these individuals as we are interested in vaccination rates.

We are linking the following Commonwealth data sources: PBS, the Australian Immunisation Register (AIR), Medicare Benefits Schedule (MBS), Admitted Patient Care Database (APDC), and National Death Index (NDI). We will be using data collected between January 2016 - latest available. There is no direct participant involvement; information will only be collected through the above Commonwealth data sources.
Intervention code [1] 327751 0
Diagnosis / Prognosis
Comparator / control treatment
The comparator group will comprise Australian's without SMI. As per the exposure cohorts, we will identify two comparator cohorts: (i) COVID-19 comparator cohort; (ii) influenza comparator cohort.

(i) COVID-19 comparator cohort: A random sample of people on the Medicare Consumer Directory, randomly selecting a ratio of 4 random controls to every case from the entire population aged 18 years and over at 22/02/2021. This group will consist of people who have not been dispensed a prescription for one of the specified PBS medicines (ATC codes N05AH, N05AX, N05AE, N06AX) between 22/02/2019 to latest available. Individuals may have had the COVID-19 disease, but the cohort will not be restricted to just these individuals as we are interested in vaccination rates.

(ii) Influenza comparator cohort: A random sample of people on the Medicare Consumer Directory, randomly selecting a ratio of 4 random controls to every case from the entire population aged 18 years and over on the 1st January in each of the years 2018 and 2019. This group will consist of people who have not been dispensed a prescription for one of the specified PBS medicines (ATC codes N05AH, N05AX, N05AE, N06AX) between 1/1/2016 to latest available. Individuals may have had influenza, but the cohort will not be restricted to just these individuals as we are interested in vaccination rates.


The Medicare Consumer Directory appears to hold the most comprehensive set of those who would be eligible for our study. Selection of the comparator group from this dataset is least likely to introduce bias.
Control group
Active

Outcomes
Primary outcome [1] 337076 0
The proportion of individuals who received one dose of COVID-19 vaccine by 15/12/2021 (the date by which all Australian states & territories except WA opened their borders to domestic travellers).
Timepoint [1] 337076 0
Between 22/02/2021 - 15/12/2021.
Primary outcome [2] 337077 0
The proportion of individuals who received two doses of COVID-19 vaccine by 15/12/2021 (the date by which all Australian states & territories except WA opened their borders to domestic travellers).
Timepoint [2] 337077 0
Between 22/02/2021 - 15/12/2021.
Primary outcome [3] 337230 0
The proportion of individuals who received at least one COVID-19 booster vaccine by 15/12/2021 (the date by which all Australian states & territories except WA opened their borders to domestic travellers).
Timepoint [3] 337230 0
Between 22/02/2021 - 15/12/2021.
Secondary outcome [1] 430588 0
Differences in the proportion of COVID-19-related hospital admissions according to SMI and vaccination status.
Timepoint [1] 430588 0
Between 22/02/2021 - 15/12/2021.
Secondary outcome [2] 430589 0
Differences in the proportion of COVID-19-related deaths according to SMI and vaccination status.
Timepoint [2] 430589 0
Between 22/02/2021 - 15/12/2021.
Secondary outcome [3] 431131 0
Differences in the proportion of influenza-related hospital admissions according to SMI and vaccination status,
Timepoint [3] 431131 0
Between 22/02/2021 - 15/12/2021.
Secondary outcome [4] 431132 0
Differences in the proportion of influenza-related deaths according to SMI and vaccination status.
Timepoint [4] 431132 0
Between 22/02/2021 - 15/12/2021.

Eligibility
Key inclusion criteria
Eligibility for exposure cohorts:

(i) COVID-19 exposure cohort: All individuals with SMI who were aged 18 years and over at 22/02/2021. We will define people as having SMI if they have been dispensed two prescriptions within 12 months for authority-only medications used specifically for SMI (ATC codes N05AH, N05AX, N05AE, N06AX) since 22/02/2019 (2 years prior to the period of interest of this study), or 2 prescriptions for lithium within 12 months. Authority-only medications will include all that were listed on the PBS during the time period (and subsequently may now be discontinued). In the case of quetiapine (ATC Code NO5AH04), we will only include anyone prescribed at least 100mg on those two occasions, to minimise the influence of off-label use.

(ii) Influenza exposure cohort: All individuals with SMI aged 18 years and over on 01/01/2018. We will define people as having SMI if they have been dispensed two prescriptions within 12 months for authority-only medications used specifically for SMI (ATC codes N05AH, N05AX, N05AE, N06AX) since 01/01/2016 (2 years prior to the period of interest of this study), or 2 prescriptions for lithium within 12 months. In the case of quetiapine (ATC Code NO5AH04), we will only include anyone prescribed at least 100mg on those two occasions, to minimise the influence of off-label use.

Eligibility for comparator cohorts:

(i) COVID-19 comparator cohort: A random sample of people on the Medicare Consumer Directory, randomly selecting a ratio of 4 random controls to every case from the entire population aged 18 years and over at 22/02/2021. This group will consist of people who have not been dispensed a prescription for one of the specified PBS medicines (ATC codes N05AH, N05AX, N05AE, N06AX) between 22/02/2019 to latest available.

(ii) Influenza comparator cohort: A random sample of people on the Medicare Consumer Directory, randomly selecting a ratio of 4 random controls to every case from the entire population aged 18 years and over on the 1st January in each of the years 2018 and 2019. This group will consist of people who have not been dispensed a prescription for one of the specified PBS medicines (ATC codes N05AH, N05AX, N05AE, N06AX) between 1/1/2016 to latest available.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
None.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Case control
Timing
Both
Statistical methods / analysis
We will use proportional hazards regression models to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals for each outcome (1st, 2nd and booster COVID-19 vaccination rates, annual influenza vaccination and cause-specific mortality), comparing those with and without SMI and the effects of vaccination on these outcomes. We will compare vaccination rates for both groups according to location – metropolitan, regional, and remote. We will undertake a sensitivity analysis of the effect of excluding quetiapine to minimize the influence of off-label use.

Adjusting for confounders:

The models will be adjusted for age, area-level socio-economic status, indigenous status, rurality and state. We will also explore the possibility of adjusting for concessional status (holding a healthcare card or similar to receive further subsidisation on costs of medicines or health services) as a further marker of socio-economic status. In addition, we will consider the possible effects of concomitant comorbidities and risk factors (e.g., CVD, diabetes, etc) through PBS data on the prescription of statins and oral hypoglycaemics. We will also consider the potential confounding effect of nirmatrelvir & ritonavir Paxlovid® (ATC J05AE30) and molnupiravir Lagevrio® (ATC J05AB18) which are medications listed on the PBS for the management of SARS-CoV-2 infection that have demonstrated reductions in hospital admission in patients with mild-moderate COVID-19. Lastly, MBS data on the number and type of medical consultations for each person during the study period will be considered as mediators in the model.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
4/10/2023
Date of last participant enrolment
Anticipated
Actual
29/12/2023
Date of last data collection
Anticipated
1/07/2024
Actual
Sample size
Target
2000000
Accrual to date
Final
2000000
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 315559 0
Government body
Name [1] 315559 0
NHMRC
Country [1] 315559 0
Australia
Primary sponsor type
Government body
Name
NHMRC
Address
414 La Trobe St, Melbourne VIC 3000
Country
Australia
Secondary sponsor category [1] 317791 0
None
Name [1] 317791 0
Address [1] 317791 0
Country [1] 317791 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314458 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 314458 0
Ethics committee country [1] 314458 0
Australia
Date submitted for ethics approval [1] 314458 0
26/01/2023
Approval date [1] 314458 0
03/10/2023
Ethics approval number [1] 314458 0
HREC/2023/QMS/94167

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 131654 0
Prof Steve Kisely
Address 131654 0
Level 4, Building 1, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD 4102
Country 131654 0
Australia
Phone 131654 0
+61 7 3176 9568
Fax 131654 0
Email 131654 0
[email protected]
Contact person for public queries
Name 131655 0
Steve Kisely
Address 131655 0
Level 4, Building 1, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD 4102
Country 131655 0
Australia
Phone 131655 0
+61 7 3176 9568
Fax 131655 0
Email 131655 0
[email protected]
Contact person for scientific queries
Name 131656 0
Steve Kisely
Address 131656 0
Level 4, Building 1, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD 4102
Country 131656 0
Australia
Phone 131656 0
+61 7 3176 9568
Fax 131656 0
Email 131656 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This is a data linkage study using large datasets with de-identified data under the jurisdiction of data custodians.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.