HERO (Home-based Extended Rehabilitation of Older people) trial.

Bradford Teaching Hospitals NHS Foundation Trust (BTHFT) and the University of Leeds require access to NHS England data for the purpose of the following research project: "Home-based Extended Rehabilitation for Older people (HERO)" - Individually randomised controlled multi-centre trial to determine the clinical and cost effectiveness of a home- based exercise intervention for older people with frailty as extended rehabilitation following acute illness or injury, including embedded process evaluation

The following is a summary of the aims of the research project provided by the BTHFT and University of Leeds:

"The majority of older people (>65 years) in hospital have frailty and are at increased risk of readmission or death following discharge home. In the UK, following acute hospitalisation, around one third of older people with frailty are referred on for rehabilitation. Although this rehabilitation can reduce early readmission to hospital, recipients often do not feel ready to leave the service on discharge, suggesting possible incomplete recovery. Limited evidence suggests extended rehabilitation is of benefit in several conditions and there is preliminary evidence that progressive physical exercise can improve mobility and function for older people with frailty, and slow progression to disability. The HERO study aim is to evaluate the clinical and cost effectiveness of the Home-based Older People’s Exercise (HOPE) programme as extended rehabilitation for older people, in a multi-centre individually randomised controlled trial. HOPE is a individualised, graded and progressive 24 week exercise programme delivered by NHS physiotherapy."

The following NHS England data will be accessed: Hospital Episode Statistics (HES) Admitted Patient Care (APC), Outpatient Care (OC), Critical Care (CC), Accident and Emergency (A&E), Emergency Care Data Set (ECDS), and Civil Registration Deaths. This is necessary to establish whether the HOPE intervention: 1) reduces all-cause hospitalisation 2) reduces falls / hospitalisation due to falls; 3) reduces overall health and social care resource use; 4) intervention is cost-effective. The use of routinely collected administrative data is preferred to asking participants or hospital staff to retrospectively account for resource use as the data are detailed, complete, are amenable to costing and much less likely to be missing due to non-response.

Identifiable data will be submitted to NHS England. This is necessary to enable linkage of data with the clinical data (from hospitals) and patient reported outcomes (for the cohort of participants) to derive an analysis dataset for the HERO study. Pseudonymised data will be disseminated back to the Clinical Trials Research Unit (CTRU) at the University of Leeds.

The data will be minimised as follows:

Limited to data for the cohort - approx. 700 participants recruited to the HERO study as identified by BTHT and the University of Leeds. Participants were eligible if they were aged over 65 and admitted to general medicine / elderly medicine or trauma and orthopaedics care following acute illness or injury, who were then discharged home. People had to have mild, moderate or severe frailty, defined using the Clinical Frailty Scale (CFS) and had to be able to provide informed consent.

People were excluded if they were permanent care home residents, had significant cognitive impairments or other medical conditions to preclude participation in the HOPE programme. These included:

- Moderate/severe dementia at baseline* (defined as Montreal Cognitive Assessment test <20).

- Recent (<3 months prior randomisation) myocardial infarction, or unstable angina

- Very severe frailty (defined as score of 8 on CFS).

- Terminally ill (defined as score of 9 on CFS).

- Receiving palliative care

Recruitment took place from between December 2017 and August 2021, from 15 NHS Trusts across Yorkshire and the South-West of England. The NHS Trusts are based in 2 geographical hubs in Yorkshire and the Southwest of England. The trial team are based in these regions and have strong working relationships with the NHS Trusts locally, existing partnerships and shared interest/ expertise in this area of research. The hubs provide scope for diversity in the population recruited to the trial and cover urban and rural areas with different population profiles. This is important to ensure the trial population is representative of the general population to ensure generalisable results.

Data will be provided for each participant from date of randomisation to 12 month + 30 days post randomisation. The additional 30 days will capture NHS activity/discharge date for those participants who were admitted / received care towards the end of the 12 month post-randomisation time window and collect all relevant data relating to the admission to minimise missing/unknown outcomes.

BTHFT and University of Leeds are joint controllers and are responsible for ensuring that the data will only be processed for the purpose described above. BTHFT is the research sponsor. This study is multidisciplinary academic collaboration between the Academic Unit for Ageing & Stroke Research (ASR) based at BTHFT and part of the University of Leeds, the Clinical Trials Research Unit (CTRU) and Academic Unit of Health Economics (AUHE) at the University of Leeds, and the University of Exeter.

The Chief Investigator is Chair of Geriatric Medicine and his substantive employer is the University of Leeds. The CTRU is co-coordinating the trial and is responsible for trial design and conduct, including protocol development, ethics approval, trial monitoring, data collection and ongoing management, and statistical analysis and reporting. The AUHE will perform the cost effectiveness analysis. The geographical hubs are led by ASR and University of Exeter. Each hub has trial managers and clinical co-applicants to co-ordinate set-up, recruitment, data collection and ongoing liaison with sites through the course of the trial.

A contract is in place between the funder (Department of Health) and BTHFT (NHS Lead and sponsor), and a collaboration agreement is in place between the BTHT (Sponsor), the University of Leeds, and the University of Exeter. University of Exeter is neither a controller, nor a processor in regard to data requested under this application and the data controllers are the organisations responsible for ensuring that the data will only be processed for the purpose described above.

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller.

The lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

The trial is funded by the NIHR Heath Technology Assessment (15/43/07). The trial funder does not make decision on the processing of personal data, and has no role in study design, data collection, data analysis, data interpretation, or writing of the final report. The funding is specifically for the HERO trial and funding is in place until May 2023.

Patient and Public Involvement and Engagement (PPIE) is provided via representation on oversight groups, and the NIHR Applied Research Collaboration (ARC) Frailty Oversight Group (FOG). The data collection processes were discussed at the grant application stage, and this was scrutinised by the Frailty Oversight Group (FOG) at NIHR ACR which includes PPIE representation. The protocol was finalised in collaboration between the Trial Management Group (TMG) and Trial Steering Committee (TMC), both committees include PPIE representation. The PPIE representatives on the TMG have included a patient representative who was in her late 70's and frail herself, and 2 representatives from Carers' resource, both professionals working very closely with carers whom are frequently adults caring for older adults with frailty. Our TSC PPIE representatives included an older adult with frailty, and a director from a local branch of Age UK. FOG meet at least quarterly and is made up of older adults and carers, many of whom have varying degrees of frailty.

The trial statistician at the CTRU will provide the following identifier for each participant:

NHS Number.

Study ID

Gender

Date Of Birth

Postcode

For each participant, the data request will be for a date the participants were randomised up until 12 months and 30 days post randomisation. This will provide assurance that minimum data required is obtained. The last randomisation was August 2021, and therefore the data request will be up to and including September 2022 for the last participant randomised to the trial.

NHS England will perform an automatic cohort tracing system to search the data provided against existing electronic records to generate a set of records that belong the cohort of 701 trial participants. This will include linkage of data from Hospital Episode Statistics (HES) Admitted Patient Care (APC), HES Critical Care (CC), HES Outpatients, Emergency Care Data Set (ECDS), HES Accident & Emergency (A&E) and Civil Registration (Deaths) Secondary Care Cut. The period request for the HES data will be from 17/18 annual data, up until September 2022 data, in addition to Civil Registration Deaths. This will be be provided to allow linkage of the NHS England data to the trial data held by the CTRU. NHS England will return pseudonymised data linked using the CTRU supplied Study ID.

To enable the analysis to take place the data will be identified by Study ID number but will be stored separately to other patient identifiable data. The data therefore is pseudonymised.

Data flowing from NHS England will include, Study ID, HES and mortality record level data to the trial statistician, via a Secure Electronic File Transfer (SEFT). On receipt of data from NHS England, the trial statistician will transfer the data into a secure folder prior to using in statistical software for analysis. Pseudonymised data are made available on the CTRU secured servers for processing by the Health Economist.

The statistical analysis will be conducted within a statistical software package in accordance with a Statistical Analysis Plan which will be finalised and agreed by the TMG. For the analysis of the outcome related to hospital readmission an indicator will be derived for each participant to indicate whether or not they experienced a readmission. The number (proportion) of participants experiencing readmission will be compared between study arms using a partially nested logistic regression mixed effects model (accounting for clustering in the intervention arm only) which will include trial data held by CTRU.

A similar approach will be used to analyse outcomes related to all-cause hospitalisation and hospitalisation due to falls. The Health Economics Analysis Plan will be conducted in accordance with the Health Economic Analysis Plan (HEAP) which will be agreed by the lead health economist on the trial. The health economic evaluation will involve a within-trial cost-effectiveness analyses and long-term decision-analytical model. Information on health resource use and mortality will be sourced from NHS England data.

There will be no record level data transferred from CTRU for the purpose of economic evaluation. The within-trial and decision analytic model require only population-averaged expectations of Health Related Quality of Life (HRQoL) and cost generation over time. These parameters will be estimated within CTRU and provided to the health economic modelling team. These parameters are those that would be typically presented in a report and would be acceptable to be placed in the public domain. The outputs will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

Data will only be accessed and processed by substantive employees of the University of Leeds and will not be accessed or processed by any other third parties not mentioned in this agreement. Data will be stored at the CTRU (Organisation Data Service (ODS) is ECC0010). No record level data disseminated via NHS England for this application will flow from the University of Leeds.

The CTRU server infrastructure is split between two data centres on the main University of Leeds campus. Data on CTRU servers is encrypted to AES 256 with access restricted to just CTRU server admins. The ability to decrypt is only held by the CTRU.

Only aggregated data with small numbers suppressed will be made publicly available. No third party will have access to the data. Data will not be used for any other purposes, and it will not be used for commercial purposes, nor for direct marketing purposes.

Following analysis, publication and dissemination, if needed, the data will be retained, under a valid Data Sharing Agreement, with no further data being requested, to allow compliance with good clinical practice and regulations. This will allow verification of results or audit by the sponsor (or delegate).

There will be no data linkage undertaken with NHS England data provided under this agreement that is not already noted in the agreement.

The analysis and publication is due to be completed by Summer 2023 (subject to availability of data). The dissemination strategy will be co-developed by the research teams patient/carer led Frailty Oversight Group;

Specific planned outputs include:

•Publication(s) in open access journals, including the NIHR journal series and peer reviewed international general medical journal(s);

•Press releases, for example through the British Geriatrics Society press office;

•Presentations and local and international conferences;

•Presentations and informal discussion at voluntary agency events, and contributions to local community group newsletters,

•A lay summary to be provided to all participants, and their carers;

•A lay summary for the trial website, and other platforms, including Twitter;

•Summaries for therapists and participating research teams;

•Resource to support commissioning, including an Implementation toolkit consisting of intervention materials, training materials, and a mechanism to measure impact.

• A derived dataset, for evaluation, teaching and training purposes relating to the provision of NHS care and treatment, and for academic and non-commercial research purposes (subject to further approval from NHS England).

The majority of older people (>65 years) in hospital have frailty and are at increased risk of readmission or death following discharge home. In the UK, following acute hospitalisation, around one third of older people with frailty are referred on for rehabilitation, termed ‘intermediate care’ services (Reference: A whole system study of intermediate care service for older people. Age Ageing. 2005;34(6):577–83).

Although this rehabilitation can reduce early readmission to hospital (<30 days), recipients often do not feel ready to leave the service on discharge, suggesting possible incomplete recovery. Limited evidence suggests extended rehabilitation is of benefit in several conditions and there is preliminary evidence that progressive physical exercise can improve mobility and function for older people with frailty, and slow progression to disability.

HERO will evaluate the effectiveness of the Home-based Older People’s Exercise (HOPE) programme as extended rehabilitation for older people with frailty discharged home from hospital or intermediate care services after acute illness or injury. If HOPE is found to be effective, it could be used to inform policy changes to improve mobility and function for older people with frailty. The trial team will development an implementation pack or toolkit to support the implementation of the trial findings. This would be communicated to NHS England, through the National Clinical Director for Frailty and disseminated to Integrated Care Boards to support future commissioning of services for older people in the UK. This has the potential to improve care & quality of life of older people and if shown to be cost-effective, reduce the cost burden for the NHS & social care. The anticipated date of this benefit is late 2023 when the analysis completes. The cost consequences of different treatment decisions is a fundamental part of the health economic evaluation.  A requirement to understand the counterfactual cost expectations in absolute terms if one treatment is used compared to the other.  It will enable to explore the cost-consequences from both a payer (NHS and PSS) and wider-societal perspective and this will of course include secondary care costs which are derived from combining HES and national cost data and primary care costs which include self-reported resource use combined with national sources of costing (e.g. PSSRU).  It will enable and hopefully result in the distribution of cost burden across the agents involved in the decision including patients, social care and the NHS.

Yielded Benefits is not a requirement for new applications.