Rates, Risks and Routes to Reduce Vascular Dementia

University of Edinburgh requires access to NHS England Data for the purpose of the following research project:

Rates, Risks and Routes to Reduce Vascular Dementia (R4VaD)

The following is a summary of the aims of the research project provided by University of Edinburgh:

“This is a UK-wide observational study of cognitive, physical and neuropsychiatric complications after stroke. Patients can experience memory, thinking or mood changes, or dementia, after a stroke but enough is not yet known about how to treat these conditions. R4VaD are looking at these conditions to help more people to make a better recovery.

Stroke is a highly prevalent disease and is known to be a cause of cognitive impairment and vascular dementia. The aim of R4VaD is to improve understanding of the rates of and risk factors for post-stroke cognitive impairment (PSCI), while informing patient services, intervention targets and research into mechanisms. The study team will use information on pre-morbid and pre-stroke cognition, medical, lifestyle and socioeconomic factors collected in the main study and via data linkage to this end. The fundamental questions are: who will develop memory and thinking problems after stroke, why does this happen, how can we treat it?

The aims of the main study are:

1. R4VaD aims to determine rates of cognitive impairment after stroke and risk factors for cognitive impairment occurring.

2. Examine the effects of stroke on cognition, recurrent vascular events and other clinical, cognitive, functional and neuropsychiatric outcomes.

3. Identify key risk predictors and develop better risk prediction models for individual patients;

4. Perform studies to improve cognitive testing and mechanistic understanding of PSCI

5. Establish a well phenotyped population, in follow-up, with consent for re-contact for future trials

6. Provide data to plan future RCTs and services for patients with PSCI.

The aims of the sub-study are:

7. Determine links between stroke and covid-19

8. Determine the number and proportion of patients recruited in R4VaD who developed SARS-CoV- infection.

9. Compare outcomes (recurrent stroke, functional outcome, death) in patients with and without SARS-CoV-19.

10. Examine cognitive and neuropsychological impacts of the COVID-19 outbreak.

11. In patients with both acute stroke and COVID-19 infection, to explore the relationship between the onset times of the symptoms related to these two illnesses.

12. To compare the clinical and laboratory features, stroke mechanism and phenotypes of patients with acute stroke and acute COVID-19 infection to those of patients with acute stroke without COVID-19 infection, and between mild and severe COVID-19 disease.

The NHS England Data will be used for the main study and the sub-study.””

The following NHS England Data will be accessed:

• Civil Registration Mortality – necessary to identify patients who die during follow up and the cause of death.

• Hospital Episode Statistics (HES) Admitted Patient Care (APC) – necessary to ascertain long term outcomes (recurrent stroke, dementia, myocardial infarct, place of residence) to supplement follow-up information and to identify if participants have been hospitalised with Covid19.

• Medicines dispensed in Primary Care (NHSBSA data) – Processing of the Medicines Dispensed in Primary Care (NHSBSA Data) dataset is only permitted to provide intelligence about the safety and effectiveness of medicines, as specified by the NHS Business Services Authority (NHSBSA) Medicines Data Directions 2019. Dissemination of this dataset is necessary to establish if the participant is on any drugs related to dementia, to assess their effectiveness, as well as the prescribing practise for medications relating to cognitive impairment and patient safety.

The level of Data will be identifiable. Although the University of Nottingham will receive pseudonymised data (along with their study ID) from NHS England, the University of Nottingham hold the cohort identifiers.

The data will be minimised as follows:

• Limited to a study cohort of 1753 participants who have either consented (covered under DARS-NIC-568980-P9W7B-v0.7) or had a consultee agreement (covered under DARS-NIC-773720-X4Q2Q-v0.1) as per the study protocol and ethical and HRA approval (1728 in England and 25 in Wales).

• Limited to data from 2018/19 and latest available data.

• Limited to recruitment date (between September 2018 and September 2022). For each individual patient, data will only be provided from the date they were recruited until latest available data.

The University of Edinburgh is the research sponsor and the controller as the organisation 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.

This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care.

The funding comes from multiple sources. Current funders include:

• The Stroke Association, British Heart Foundation and Alzheimer’s Society, joint call Advancing Care and Treatment of Vascular Dementia (ACT-VAD) – funding is in place until 31st December 2023.

The funding is specifically for the study described.

Funding to continue the work described will be sought on an ongoing basis.

The funders will have no ability to suppress or otherwise limit the publication of findings.

University of Nottingham is a processor acting under the instructions of University of Edinburgh. University of Nottingham’s role is limited to submitting the cohort data to NHS England, receiving the NHS England Data and processing the Data.

Accord, NHS Lothian, University of Cambridge, University of Oxford, University of Manchester, Stroke Research Centre, Centre for Clinical Brain Sciences, Glasgow Royal Infirmary, University of Leicester, St Thomas’ Hospital, Nottingham City Hospital, BHF Glasgow Cardiovascular Research Centre and Centre for Neuroimaging Sciences are all organisations which have acted in an advisory capacity for the R4VaD study. They do not determine the means and purpose of processing for this study. All final decisions are made by the controller, University of Edinburgh.

A Public and Patient Involvement and Engagement group helped refine the purpose of the research. The group supported the design of the study for the purposes described above.

The study team formed a Steering Committee with an independent chair, funders, an external expert, and user representatives who will be consulted throughout. The work is organised in Work-packages (Study Management including eCRF, Cognition, Imaging, Vascular function, Inflammation, Genetics, Statistical analysis) to share responsibilities, with Service User input.

The lay advisory panel reviewed consent materials for the study and have unanimously acknowledged the importance of data linkage for the study.

The data linkage committee, made up from members of the study steering committee with experience of data linkage, have reviewed the requested datasets and helped to minimise the request and ensure it is the minimum required and appropriate to the study aims.

The wider steering committee Includes a funder representative from The Stroke Association (TSA) who represents not only TSA but also The Alzheimer’s Society and the British heart foundation.

A sub-studies sub-Committee of the R4VaD SSC considers proposals for sub-studies. There are currently no sub-studies that access NHS England data under this Agreement.

The University of Nottingham will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number, Date of Birth, surname, forename, gender, postcode, recruitment date and a unique person ID) for the cohort to be linked with NHS England Data.

NHS England will provide the relevant records from the following datasets to the University of Nottingham.

• Civil Registration Mortality

• Hospital Episode Statistics Admitted Patient Care

• Medicines dispensed in Primary Care (NHSBSA data)

The Data will contain no direct identifying data items but will contain a unique person ID which can be used to link the Data with other record level data already held by the recipient.

The Data will not be transferred to any other location.

The Data will be stored on servers at the University of Nottingham. University of Nottingham also uses their own offsite back-up services within the UK (University of Nottingham servers).

The Data will be accessed by authorised personnel via remote access.

The Controller(s) must confirm and provide evidence upon audit by NHS England that access via any remote device complies with the data security obligations within this DSA and the Data Sharing Framework Contract.

For remote access:

- Remote access will only be from secure locations situated within the territory of use (as further restricted elsewhere within the DSA if so done) stated within this DSA;

- Personnel are both prohibited and technically prevented from downloading or copying NHSE data to local devices;

- Access controls granting users the minimum level of access required are in place;

- Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data;

- Multifactor authentication (MFA) is required for remote access;

- Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access;

- All remote access is undertaken within the scope of the organisation’s DSPT (or other security arrangements as per this agreement) and complies with the organisation’s remote access policy.

The above applies in addition to any condition set out elsewhere within the DSA (e.g. who may carry out processing, and for what purpose).

Remote processing will be from secure locations within the UK. The data will not leave the UK at any time.

Access is restricted to employees or agents of University of Nottingham who have authorisation from the Chief Investigator. All such individuals are substantive employees of University of Nottingham.

Funding co-applicants for the study that are not listed as a controller or processor in this data sharing agreement are not permitted to access the Data.

All personnel accessing the Data have been appropriately trained in data protection and confidentiality.

The Data will be linked at person record level with the cohort data held by University of Nottingham.

The identifying details will be stored in a separate database to the linked dataset used for analysis. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset.

Researchers from the University of Nottingham will process the Data for the purposes described above.

The medicines data is not deemed disclosive and information on a GP level is available in the public domain. However, should the published information pose a risk of re-identification, the following suppression methodology should be applied:

· Zeros should be shown.

· 1-7 to be rounded to 5.

· Any other numbers rounded to nearest 5.

· Rounding unnecessary for averages etc.

· Percentages calculated from rounded values.

· If zeros need to be suppressed, round to 5

The expected outputs of the processing will be:

• Submissions to peer reviewed journals. Previous studies have been published in journals such as The European Stroke Journal and JAMA neurology. The baseline results paper is expected to be published in 2024, with outcomes from follow ups and data linkage published later.

• Presentations at conferences such as UK Stroke Forum and European Stroke Organisation conference.

• Results will be shared via a newsletter to the lay panel.

The outputs will not contain NHS England Data and 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.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Social media

• Public reports

• Industry newsletters

• Posters displayed at conferences

• Public promotion of the research

• Lay Panel Newsletters

The target dates for production and dissemination of all the outputs is 2027, with outputs expected to start from 2024 onwards.

The findings of this research study are expected to contribute to evidence-based decision-making for policy-makers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of health care users relevant to the subject matter of the study.

The use of the data could:

• help the system to better understand the health and care needs of populations.

• lead to the identification or improvement of treatments or interventions, or health and care system design to improve health and care outcomes or experience.

• advance understanding of regional and national trends in health and social care needs.

• advance understanding of the need for, or effectiveness of, preventative health and care measures for particular populations or conditions

• inform planning health services and programmes, for example to improve equity of access, experience and outcomes.

• support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work).

It is hoped that through publication of findings in appropriate media, the findings of this research will add to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients.

Stroke increases risk of cognitive impairment and dementia, however risk prediction for individual patients is difficult as there is limited supporting data. Patients have reported cognitive impairment as one of their biggest concerns following stroke. By obtaining long term data on cognitive function the study team hope to be able to benefit patients by providing more concrete prediction models and information on what happens to memory and thinking after stroke. This aims to enable patients to be better informed and hopefully access earlier treatment and care services. Benefits may be in tractable changes to health care provision and information for participants about cognition after stroke. The Covid-19 infection data will be used to support the aims to determine the impact of Covid-19 on stroke patients, benefitting patients, and care-givers, who can provide further information on the impact of this infection on this cohort potentially resulting in tailored care and advice for patients.

The outcomes of this study may also fuel further work into this area and provide a platform for further funding.

Participants may be consented for re-contact, facilitating future clinical trials and providing a resource for the stroke and dementia research communities. This is particularly important given difficulties in recruiting patients with vascular cognitive impairment into trials.

Members of the study team have been responsible for publication of guidelines for stroke care and it is likely that the outcomes of this study may be used to help revise guidelines in the future.

Not stated in the register.