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Trial registered on ANZCTR


Registration number
ACTRN12622001238763
Ethics application status
Approved
Date submitted
29/08/2022
Date registered
14/09/2022
Date last updated
14/09/2022
Date data sharing statement initially provided
14/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A UK Biobank analysis to assess the outcomes of frailty in people with severe mental illness
Scientific title
Towards a better understanding of frailty in people with severe mental illness: a longitudinal analysis of the UK Biobank
Secondary ID [1] 307354 0
81605
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
frailty 326651 0
schizophrenia 326652 0
bipolar disorder 326653 0
major depressive disorder 326654 0
anxiety disorders 326655 0
multimorbidity 326665 0
mortality 326666 0
Condition category
Condition code
Public Health 323892 323892 0 0
Epidemiology
Mental Health 323894 323894 0 0
Schizophrenia
Mental Health 323895 323895 0 0
Other mental health disorders
Mental Health 323896 323896 0 0
Depression
Mental Health 323904 323904 0 0
Anxiety
Metabolic and Endocrine 323905 323905 0 0
Diabetes
Cardiovascular 323906 323906 0 0
Coronary heart disease
Respiratory 323907 323907 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Participants include all 502,412 subjects assessed at the baseline phase of the UK Biobank study. Baseline assessment occurred from 13 March 2006 to 1 October 2010.

For time-to-event analyses, we will obtain data on all-cause mortality from Data-Field 40000 of the UK Biobank study: https://biobank.ctsu.ox.ac.uk/crystal/field.cgi?id=40000. Data on the deaths of UK Biobank participants comes from NHS Digital for participants in England & Wales and from the NHS Central Register, part of the National Records of Scotland, for participants in Scotland (see https://biobank.ctsu.ox.ac.uk/crystal/ukb/docs/DeathLinkage.pdf).

In the time-to-event analysis of all-cause mortality, we will left-censor three subjects who have a date of death before study entry. We will right censor at 12 November 2021, which is the last date of death in the dataset.

We will derive information on mental and behavioural disorders, subjects' Hospital Frailty Risk Score, and subjects' Charlson Comorbidity Index Score, from record-level inpatient data on ICD-10 Diagnosis codes (ICD-9 or ICD-10) relating to the inpatient episode of
care for England, Wales and Scotland.

Data on diagnoses occurring during hospital inpatient admissions in England come from the Data Access Request Service, managed by NHS Digital. The dataset is called Hospital Episode Statistics Admitted Patient Care (see page 3 of https://biobank.ctsu.ox.ac.uk/crystal/ukb/docs/DeathLinkage.pdf).

Data on diagnoses occurring during hospital inpatient admissions in Wales comes from the Secure Anonymised Information Linkage Databank at the University of Swansea, managed by
NHS Wales Informatics Service's Information Services Division. The dataset is called
Patient Episode Database for Wales Admitted Patient Care (see https://biobank.ctsu.ox.ac.uk/crystal/refer.cgi?id=138483).

Data on diagnoses occurring during hospital inpatient stays in Scotland come from the electronic Data Research and Innovation Service, managed by Information Services Division Scotland part of NHS National Services Scotland. This dataset is called General Acute Inpatient and Day Case - Scottish Morbidity Record (see https://biobank.ctsu.ox.ac.uk/crystal/refer.cgi?id=138483).

We will not left-censor any of these conditions, but will right-censor them at 1 October 2010, the last date of assessment for any UK Biobank participant in the baseline assessment period.

The UK Biobank study has a protocol available for viewing online at https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/about-us

We will observe in participants mental and behavioural disorders, frailty (using three measures) and comorbidity (using one measure) and mortality.

This study involves no active participation for participants, as all data comes from previous UK Biobank assessments or hospital episode or death register records linked to UK Biobank.

After baseline observation from 13 March 2006 to 1 October 2010, there will only be follow-up data on all-cause mortality as deaths occur.
Intervention code [1] 323785 0
Diagnosis / Prognosis
Comparator / control treatment
Comparison groups will include:

Participants who did enrol into the UK Biobank study but who do not have an ICD-10 diagnosis of a severe mental illness (schizophrenia, bipolar or moderate to severe single or recurrent depressive episodes).

Participants who did enrol into the UK Biobank study but who do not have an ICD-10 diagnosis of a mental or behavioural disorder.

The data on hospital episode statistics recording mental and behavioural disorders come from these data sources:

Those occurring during hospital inpatient admissions in England come from the Data Access Request Service, managed by NHS Digital. The dataset is called Hospital Episode Statistics Admitted Patient Care (see page 3 of https://biobank.ctsu.ox.ac.uk/crystal/ukb/docs/DeathLinkage.pdf). The time period starts on 1 January 1997 and ends on 1 October 2010.

Data on diagnoses occurring during hospital inpatient admissions in Wales comes from the Secure Anonymised Information Linkage Databank at the University of Swansea, managed by NHS Wales Informatics Service's Information Services Division. The dataset is called
Patient Episode Database for Wales Admitted Patient Care (see https://biobank.ctsu.ox.ac.uk/crystal/refer.cgi?id=138483). The time period starts on 1 January 1998 and ends on 1 October 2010.

The Scottish Morbidity Record does not yet have mental health hospital admissions.
Control group
Active

Outcomes
Primary outcome [1] 331709 0
Frailty, assessed with:

The 49-item Frailty Index, as derived in Williams, D. M., Jylhävä, J., Pedersen, N. L., & Hägg, S. (2019). A frailty index for UK Biobank participants. The Journals of Gerontology: Series A, 74(4), 582-587.
Timepoint [1] 331709 0
Baseline: Initial assessment visit (2006-2010) at which participants were recruited and consent given. This is the cross-sectional component of this project, which will right-censor the Hospital Frailty Risk Score at 1 October 2010.
Primary outcome [2] 331710 0
Frailty, assessed with the 109-item Hospital Frailty Risk Score, as derived in Mak, J. K., Kuja-Halkola, R., Wang, Y., Hägg, S., & Jylhävä, J. (2021). Frailty and comorbidity in predicting community COVID-19 mortality in the UK Biobank: The effect of sampling. Journal of the American Geriatrics Society, 69(5), 1128-1139.
Timepoint [2] 331710 0
Baseline: Initial assessment visit (2006-2010) at which participants were recruited and consent given. This is the cross-sectional component of this project, which will right-censor the Hospital Frailty Risk Score at 1 October 2010.
Primary outcome [3] 332534 0
Frailty, assessed with:

The 5-item Physical Frailty Phenotype, as derived in Mak, J. K., Kuja-Halkola, R., Wang, Y., Hägg, S., & Jylhävä, J. (2021). Frailty and comorbidity in predicting community COVID-19 mortality in the UK Biobank: The effect of sampling. Journal of the American Geriatrics Society, 69(5), 1128-1139
Timepoint [3] 332534 0
Initial assessment visit (2006-2010) at which participants were recruited and consent given. This is the cross-sectional component of this project, which will right-censor the Hospital Frailty Risk Score at 1 October 2010.
Secondary outcome [1] 410835 0
An ICD-10 diagnosis of diabetes, as derived from hospital episode statistics on ICD-10 diagnoses assigned in the primary or secondary position during hospital admissions.
Timepoint [1] 410835 0
As diabetes diagnoses occurred, using linked hospital admissions data. UK Biobank receives hospital inpatient data from each data provider approximately annually (https://biobank.ctsu.ox.ac.uk/crystal/ukb/docs/HospitalEpisodeStatistics.pdf). The data linkage means that our investigatory team will assess these once, when UK Biobank data is extracted, and include diagnoses occurring up to and including the 30 September 2021.
Secondary outcome [2] 410836 0
An ICD-10 diagnosis of cardiovascular disease, as derived from hospital episode statistics on ICD-10 diagnoses assigned in the primary or secondary position during hospital admissions.
Timepoint [2] 410836 0
As cardiovascular disease diagnoses occurred, using linked hospital admissions data. UK Biobank receives hospital inpatient data from each data provider approximately annually (https://biobank.ctsu.ox.ac.uk/crystal/ukb/docs/HospitalEpisodeStatistics.pdf). The data linkage means that our investigatory team will assess these once, when UK Biobank data is extracted, and include diagnoses occurring up to and including the 30 September 2021.
Secondary outcome [3] 410837 0
An ICD-10 diagnosis of chronic lung disease, as derived from hospital episode statistics on ICD-10 diagnoses assigned in the primary or secondary position during hospital admissions.
Timepoint [3] 410837 0
As chronic lung disease diagnoses occurred, using linked hospital admissions data. UK Biobank receives hospital inpatient data from each data provider approximately annually (https://biobank.ctsu.ox.ac.uk/crystal/ukb/docs/HospitalEpisodeStatistics.pdf). The data linkage means that our investigatory team will assess these once, when UK Biobank data is extracted, and include diagnoses occurring up to and including the 30 September 2021.
Secondary outcome [4] 413838 0
All-cause mortality
Timepoint [4] 413838 0
As death occurred, using linked data from National Death Registries in England, Scotland and Wales. UK Biobank currently receives new data on mortality from NHS Digital and the NHS Central Register every month (https://biobank.ctsu.ox.ac.uk/crystal/ukb/docs/DeathLinkage.pdf). The last date of death in the dataset is the outcome endpoint. The data linkage means that our investigatory team will assess these once, when UK Biobank data is extracted, and include deaths occurring up to and including the 12 November 2021: https://biobank.ctsu.ox.ac.uk/crystal/field.cgi?id=40000

Eligibility
Key inclusion criteria
Participants in the UK Biobank study, as this is a secondary data analysis of that dataset. The UK Biobank Study Protocol is available at https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/about-us
Minimum age
37 Years
Maximum age
73 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
None.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Both
Statistical methods / analysis
The prevalence of frailty will be reported using descriptive statistics as means and standard deviations or numbers and percentages as appropriate. Sociodemographic characteristics and long-term conditions will be examined across frail, pre-frail, and non-frail participants using chi-square (or Fisher’s exact) test for categorical variables and Kruskal-Wallis test for continuous variables. Subsequently, all significant variables from the descriptive analysis will be entered into multinomial logistic regression to assess the probability of a specific outcome. Odds ratios for pre-frail and frail group will be compared separately with that of the non-frail participants. This analysis will be conducted for participants with severe mental illness and for each group of mental disorders separately. Association of frailty status with the risk time of to developing any of the long-term conditions and of or all-cause mortality will be measured using Kaplan–Meier survival curves and Cox regression to calculate adjusted hazard ratios. was assessed using Cox proportional hazards regression models . The models will be adjusted for relevant variables, including sex, age, ethnicity, employment, income, smoking status, body mass index (BMI), and being born overseas, which are known to impact either the prevalence of mental disorder or frailty.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/09/2022
Actual
Date of last participant enrolment
Anticipated
30/09/2022
Actual
Date of last data collection
Anticipated
30/09/2022
Actual
Sample size
Target
500000
Accrual to date
Final
Recruitment outside Australia
Country [1] 24838 0
United Kingdom
State/province [1] 24838 0

Funding & Sponsors
Funding source category [1] 311640 0
University
Name [1] 311640 0
The University of Queensland (UQ) Academy of Psychiatry top-up research funds
Country [1] 311640 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
Sir Fred Schonell Dr., Brisbane, Queensland 4072
Country
Australia
Secondary sponsor category [1] 313083 0
None
Name [1] 313083 0
Address [1] 313083 0
Country [1] 313083 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311096 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 311096 0
Ethics committee country [1] 311096 0
Australia
Date submitted for ethics approval [1] 311096 0
Approval date [1] 311096 0
01/01/2022
Ethics approval number [1] 311096 0

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

Contacts
Principal investigator
Name 119930 0
Prof Dan Siskind
Address 119930 0
Woolloongabba Community Health Centre
Level 2 Mental Health, 228 Logan Rd
Woolloongabba, QLD, 4102 AUSTRALIA
Country 119930 0
Australia
Phone 119930 0
+61733171040
Fax 119930 0
+61733171298
Email 119930 0
d.siskind@uq.edu.au
Contact person for public queries
Name 119931 0
Dan Siskind
Address 119931 0
Woolloongabba Community Health Centre
Level 2 Mental Health, 228 Logan Rd
Woolloongabba, QLD, 4102 AUSTRALIA
Country 119931 0
Australia
Phone 119931 0
+61733171040
Fax 119931 0
+61733171298
Email 119931 0
d.siskind@uq.edu.au
Contact person for scientific queries
Name 119932 0
Dan Siskind
Address 119932 0
Woolloongabba Community Health Centre
Level 2 Mental Health, 228 Logan Rd
Woolloongabba, QLD, 4102 AUSTRALIA
Country 119932 0
Australia
Phone 119932 0
+61733171040
Fax 119932 0
+61733171298
Email 119932 0
d.siskind@uq.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.