The Oxford Vascular Study (section 251 cohort)

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Datasets: + Cancer Registration Data; + Emergency Care Data Set (ECDS); + Hospital Episode Statistics Accident and Emergency (HES A and E); + Hospital Episode Statistics Admitted Patient Care (HES APC); + Hospital Episode Statistics Critical Care (HES Critical Care); + Hospital Episode Statistics Outpatients (HES OP) · − MRIS - Cause of Death Report; − MRIS - Cohort Event Notification Report; − MRIS - Flagging Current Status Report; − MRIS - List Cleaning Report; − MRIS - Members and Postings Report

Objective for processing

The following provides background information on the purpose of the original study: University of Oxford requires access to NHS England data for the purpose of the following research project: The Oxford Vascular Study(OxVasc) (section 251 cohort) The following is a summary of the aims of the research project provided by University of Oxford: [1 paragraph unchanged] ACS is the leading cause of death in the developed world, causing [50 words unchanged] have never been measured in the same population at the same time. Comparison of OCSP (Oxford Community Stroke Project) and OXMIS (Oxford Myocardial Infarction Study) which took place in the early 1980s suggests that mortality due to stroke is lower than that due to ACS, but overall incidence is similar, and the total clinical instance of stroke may be greater. There are no data from the UK on recent time trends in [58 words unchanged] clinical services and limited governmental funding for medical research could be made. [1 paragraph unchanged] The GDPR legal bases for processing the data held under this Agreement are 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) and Article 9(2)(j) (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes). This research into the health outcomes for people who have suffered from stroke or other vascular events is a task in the public interest under General Data Protection Regulation (GDPR) as it aims to improve care for all patients considering undergoing this type of process – informing clinicians and commissioners of variation and outcomes and complications to support work to improve and standardise treatment selection choices. The protocol has had appropriate ethics committee approval and CAG support (all documentary evidence is included in this application. The following NHS England Data will be accessed: Since 2008, mortality and demographic data were supplied to the University of Oxford by ONS and subsequently the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of this research study. The overall aims of the study have not changed since 2002 and the benefits of a cohort study of this length and detail will continue to improve the public’s health through disease prevention, earlier disease diagnosis and better disease management. The study to date has had significant impacts (as described in the benefits section) and it is expected that further measurable benefits will be outputs that underpin NICE and other Department of Health strategies for detection, management and treatment of vascular disease. • Civil Registration Mortality data – necessary for survival after vascular event to evaluate treatment interventions, natural history of disease, to establish underlying and contributing factors to death and to stop further contact for follow up visits. The minimal information is requested under this agreement to meet the aims of the study and ensure integrity of study outputs, specifically: • Demographics – necessary for health economic analyses of recovery and use of assisted living/institutional care. Date of death-survival after vascular event to evaluate treatment interventions, natural history of disease and to stop further contact for follow up visits. • Cancer registrations - necessary to identify the interaction of the commonly prescribed treatments given as secondary prevention of vascular disease on the development and outcome of previously known and new cancers. This includes aspirin and some of the newly introduced antihypertensive agents. Place of normal residence and place of death-health economic analyses of recovery and use of assisted living/institutional care. • Hospital Episode Statistics - Admitted Patient Care (APC), Emergency Care Data Set (ECDS), Critical Care (CC) and Outpatients(OP) - necessary to evaluate the full cost of acute vascular events and the cost savings with the introduction of new treatments i.e. thrombolysis, mechanical thrombectomy Cause of death (including ICD10 codes and free text) to establish underlying and contributing factors to death. The level of the Data will be: The University of Oxford previously flowed identifying information to NHS Digital for the purpose of list cleaning. The University of Oxford used the list cleaning service to provide a newsletter to participants. Upon receipt of the Demographics data, University of Oxford will destroy this data and provide a data destruction certificate to NHS Digital as it will no longer be required. • Identifiable No attempt is made to contact families after the death of a participant notified to the study team through this process. The Data will be minimised as follows: The analyses are determined by the Principal Investigator (PI) and the study statistician and performed by the University of Oxford research team to support the aims and objectives of the study. Ethical approval and grant funding from the Wellcome Trust and the NIHR Oxford Biomedical Research Centre have been granted for the study, for the same purposes as described in this Agreement. • Limited to a study cohort of 11,940 participants. These participants are the under s251 subset of the cohort The progress is evaluated annually and new analyses are added or completed based on findings to date and the length of time required to collect outcomes (cause of death) to determine the prognosis of different presentations of vascular disease and/or achieve statistical power to answer the research question. For example, mortality data is required to determine the outcome (disability or death) and time course of bleeding requiring medical attention in patients taking long-term antiplatelet treatment after acute vascular events. This is then used to estimate the age-specific numbers needed to treat to prevent upper gastrointestinal bleeding with routine proton-pump inhibitor co-prescription. • Limited to the following geographic areas - eight GP practices in Oxfordshire Not all of the work of the Oxford Vascular Study involve use of data on mortality obtained from NHS Digital but use of the data will be important in some analyses in order to determine firstly the impact of any treatment on survival and secondly the health economic value of any intervention e.g. prevention of recurrent stroke and subsequent health resource use. • Limited to data between 1997 and latest available The data subjects are patients registered in one of eight GP practices in Oxfordshire who have had a stroke, transient ischaemic attack (TIA), Acute Coronary Syndrome (ACS) or acute peripheral vascular events. These are the same practices (and associated demographic characteristics of the previous studies-OCSP/OXMIS) allowing valid comparisons over time. Since 2002, participants have been recruited from hospital, outpatients’ clinics or home following referral from a collaborating GP and interviewed by a researcher following written consent. Clinical information is gathered from participants about their health, medical history, family history and current treatment. The study team extract information about their vascular event and related conditions from health records for the duration of the study in order to follow up on participants health status. Regular face-to-face or telephone contact is maintained with participants and their GPs over the first two years and they are contacted again at five and ten years after entering the study. However, over this period participants may move out of Oxfordshire or register with a different GP. In order to achieve the study aims, accurate information on the date and cause of death of participants in the cohort to evaluate long term morbidity and mortality for the study population is required. For this reason, national data is required. Data will need to be shared at a record level as agreed between the University of Oxford and NHS Digital to flag and receive date and cause of death for each individual cohort member and in order to produce accurate matching. There is no alternative way to obtain all cause mortality data sufficiently robust to achieve the aims of the study. All results will be presented as aggregated data. University of Oxford 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 earliest participants were recruited while the study was in a pilot phase and they were all asked to re-consent to participate in the full study when version 2 of the consent form (dated 28/12/2006) came into use. Under a separate Agreement, DARS-NIC-653950-W8D4Z, the University of Oxford is permitted to share with NHS Digital details of participants who gave consent using version 2 of the consent form or any subsequent version. The DARS-NIC-653950-W8D4Z Agreement does not permit the processing of data relating to any participant who was recruited using an earlier version - which did not include a declaration of consent for "information held by the NHS and records maintained by the General Register Office" to be used to maintain contact and follow up their health status - and did not re-consent using version 2 or a subsequent version. However, processing of data relating to participants recruited using an earlier version is permitted under this Agreement using section 251 support granted from CAG to meet the Common Law Duty of Confidentiality. The lawful basis for processing personal data under the UK GDPR is: The University of Oxford is the sole data controller who also process the data supplied by NHS Digital under this Agreement. No other organisation determines the purpose for data processing or has any access to the data. Funding for OxVasc is provided by the Wellcome Trust and the NIHR Oxford Biomedical Research Centre. Past funding has been provided by the Stroke Association which is still acknowledged on some of the study outputs. The funders expect the Nuffield Department of Clinical Neurosciences to undertake research such as this but the funding body can not access data nor has a role in analysis or interpretation. 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 in the public interest because it adheres to the UK Policy Framework and Social Care Reearch, as it aims to improve care for all patients considering undergoing this type of process – informing clinicians and commissioners of variation and outcomes and complications to support work to improve and standardise treatment selection choices. The funding is provided by National Institute for Health and Care Research (NIHR). The funding is specifically for the OxVasc study described. The earliest participants were recruited while the study was in a pilot phase and they were all asked to re-consent to participate in the full study when version 2 of the consent form (dated 28/12/2006) came into use. Under a separate Agreement, DARS-NIC-653950-W8D4Z, the University of Oxford is permitted to share with NHS England details of participants who gave consent using version 2 of the consent form or any subsequent version. The DARS-NIC-653950-W8D4Z Agreement does not permit the processing of data relating to any participant who was recruited using an earlier version - which did not include a declaration of consent for "information held by the NHS and records maintained by the General Register Office" to be used to maintain contact and follow up their health status - and did not re-consent using version 2 or a subsequent version. However, processing of data relating to participants recruited using an earlier version is permitted under this Agreement using section 251 support granted from CAG to meet the Common Law Duty of Confidentiality.

Processing activities

The following provides background on the processing activities undertaken for the original study: University of Oxford will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number, Date of Birth, Surname, First name, and a unique person ID) for the cohort to be linked with NHS England data. The study data, including data provided by NHS Digital under previous versions of this Agreement, are held by the University of Oxford in the Nuffield Department of Clinical Neurosciences Medical Sciences Division, based within the West Wing of John Radcliffe Hospital Oxford. The data are stored electronically on University of Oxford central servers which are connected to the main University of Oxford’s network. At no time will sole employees of John Radcliffe Hospital have access to the data held on the server for University of Oxford. NHS England will provide the relevant records from the Civil Registration Mortality Data, Demographics, HES data, Cancer Registrations datasets to University of Oxford. The Data will contain directly identifying data items including date of birth and NHS number to link the Data at record level with data already held by the recipient Identifying details of participants have previously been supplied to ONS and subsequently NHS Digital so that their patient records could be flagged and mortality data could be reported to the study. The University of Oxford will flow identifiers (Surname, First name, NHS number, date of birth, study ID) to NHS Digital to update the cohort to flag participants recruited after 2018. The Data will not be transferred to any other location. The data disseminated under this Agreement will only cover participants where section 251 support has been granted to meet the Common Law Duty of Confidentiality. Data of participants recruited via consent is disseminated under a separate Agreement for this study: DARS-NIC-653950-W8D4Z. The data provided under DARS-NIC-148369-8PPWK and DARS-NIC-653950-W8D4Z will be combined and analysed as one study. The Data will be stored in an access-controlled server room within the University of Oxford Medical Sciences Division, situated on the Old Road Campus and connected to the main University network, located behind a firewall. The following datasets are processed by the study: The Data will be accessed onsite at the premises of University of Oxford only. Physical access is limited to Computer Services Department staff. i. Civil Registration Mortality data – details of participants’ deaths including date and cause; Access is restricted to individuals within the Oxford Vascular study team of University of Oxford who have authorisation from the Principal Investigator. All such individuals are substantive employees of University of Oxford. ii. Demographics – details of embarkations or lost to follow up All personnel accessing the Data have been appropriately trained in data protection and confidentiality. Data received from NHS Digital will be linked to unique study ID using date of birth and NHS number to ensure a perfect match to each participant’s date of vascular event to calculate outcomes (Kaplan-Meier survival analyses). All data supplied by NHS Digital will be used only for the approved Medical Research Project MR1086-The Oxford Vascular Study. No data will be shared with any individuals or agencies outside of the study team and all study staff are substantive employees of the University of Oxford. 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. The data is stored in an access-controlled server room within the University of Oxford Medical Sciences Division, situated on the Old Road Campus and connected to the main University network, located behind a firewall. Physical access is limited to Computer Services Department staff. Data will be encrypted using industry standard techniques meeting the Information Governance Toolkit standard (RBQ). Analyst from the University of Oxford will analyse the Data for the purposes described above. Data of participants recruited via consent is disseminated under a separate Agreement for this study: DARS-NIC-653950-W8D4Z. The data provided under DARS-NIC-148369-8PPWK and DARS-NIC-653950-W8D4Z will be combined and analysed as one study.

Expected output

The study overall has produced over 250 300 peer reviewed publications on incidence of disease, risk factor management, prognosis and [82 words unchanged] and secondary prevention of vascular disease over a long period of time. Research aims and findings from the Oxford Vascular Study are summarised on the study website (www.ndcn.ox.ac.uk/research/oxvasc) and presented at open days organised by the NIHR Oxford Biomedical Research Centre (BRC), Nuffield Department of Clinical Neurosciences and public involvement and engagement groups. Talks on OxVasc and related topics (e.g., high blood pressure, vascular dementia) are also available on YouTube (https://oxfordbrc.nihr.ac.uk/research-themes-overview/stroke-and-vascular-dementia/videos-stroke-and-vascular-dementia). Selected results of the study have been reported in the local, national and international press. The outputs (presentations, posters, peer reviewed publications and oral presentations at conferences) 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: > The study website (www.ndcn.ox.ac.uk/research/oxvasc) > Public Events - Presented at open days organised by the NIHR Oxford Biomedical Research Centre (BRC), Nuffield Department of Clinical Neurosciences and public involvement and engagement groups. > Social Media - Talks on OxVasc and related topics (e.g., high blood pressure, vascular dementia) are also available on YouTube (https://oxfordbrc.nihr.ac.uk/research-themes-overview/stroke-and-vascular-dementia/videos-stroke-and-vascular-dementia). > Selected results of the study have been reported in the local, national and international press. [2 paragraphs unchanged] All outputs (presentations, posters, peer reviewed publications and oral presentations at conferences) report numbers at an aggregated level, with small numbers suppressed.

Expected measurable benefits

The overall aims of the Oxford Vascular Study are to improve the [56 words unchanged] how to effectively treat common risk factors such as high blood pressure. See how the research has impacted patient care here https://rdn.nihr.ac.uk/news/oxford-vascular-disease-study-celebrates-20-years [4 paragraphs unchanged] Mortality data from NHS Digital England also potentially reduces distress to participant’s relatives by attempting to contact them for follow up/information about circumstances of death. The OxVasc study has been running for over 20 years, during which [46 words unchanged] of how long term cohort studies like OxVasc can direct further research is in stoke on stroke incidence in younger age groups, which appears to be increasing. A new [48 words unchanged] study builds on OxVasc research to improve treatment for young stroke victims.

Benefits reported

[10 paragraphs unchanged] Outcome in stroke trials is often based on an assessment of 3-month [112 words unchanged] of outcomes used in clinical trials evaluating new treatments for acute stroke. The study was highlighted by the NIHR Research Delivery Network in 2022 rdn.nihr.ac.uk/news/oxford-vascular-disease-study-celebrates-20-years

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Datasets: + Civil Registrations of Death; + Demographics

Objective for processing

This Data Sharing Agreement permits the retention of the data provided under previous iterations of this Agreement for an interim period. This is a pragmatic approach to provide an active Agreement whilst enabling The University of Oxford to complete the necessary actions to enable a subsequent application to extend the Agreement meeting all applicable data sharing standards as published in NHS Digital’s website (see: https://digital.nhs.uk/services/data-access-request-service-dars/dars-guidance). Permission to retain the data is an interim measure to enable the study to complete the actions documented in the Special Conditions section below. If, for any reason, it is not possible for the study to meet the conditions, this Agreement will be terminated and destruction of the data will be required. [1 paragraph unchanged] The Oxford Vascular Study (OxVasc) began in April 2002 to determine mortality, disability, psychological morbidity, cognitive decline [18 words unchanged] events in patients registered in one of eight GP practices in Oxfordshire. The University of Oxford has deemed this research into the health outcomes for people who have suffered from stroke or other vascular events to be a task in the public interest under General Data Protection Regulation (GDPR) as it aims to improve care for all patients considering undergoing this type of process – informing clinicians and commissioners of variation and outcomes and complications to support work to improve and standardise treatment selection choices. ACS is the leading cause of death in the developed world, causing more than twice as many deaths as stroke. However, mortality data underestimates the burden of stroke. Stroke is the main cause of neurological disability in the developed world, and a common cause of dementia, depression, epilepsy, falls and fractures. The incidence, case fatality, longer term sequelae of stroke and ACS have never been measured in the same population at the same time. Comparison of OCSP (Oxford Community Stroke Project) and OXMIS (Oxford Myocardial Infarction Study) which took place in the early 1980s suggests that mortality due to stroke is lower than that due to ACS, but overall incidence is similar, and the total clinical instance of stroke may be greater. There are no data from the UK on recent time trends in age and sex specific incidence or disability rates for stroke and ACS. However, there have been major changes over the last 20 years in the life-style, primary and secondary prevention treatments and particularly in population demographics. A formal comparison would provide a firm basis on which local and national policy decisions about allocation of limited NHS funding for clinical services and limited governmental funding for medical research could be made. ACS is the leading cause of death in the developed world, causing more than twice as many deaths as stroke. However, mortality data underestimates the burden of stroke. Stroke is the main cause of neurological disability in the developed world, and a common cause of dementia, depression, epilepsy, falls and fractures. The incidence, case fatality, longer term sequelae of stroke and ACS have never been measured in the same population at the same time. Comparison of OCSP (Oxford Community Stroke Project) and OXMIX (oxysterol mixture) suggests that mortality due to stroke is lower than that due to ACS, but overall incidence is similar, and the total clinical burden of stroke may be greater. A formal comparison would provide a firm basis on which local and national policy decisions about allocation of limited NHS funding for clinical services and limited governmental funding for medical research could be made. NHS Clinical Initiatives also tend to give a higher to MI (myocardial) than to stroke. OxVasc is one of a number of cohort studies funded by the National Institute for Health and Care Research (NIHR) to identify simple low cost interventions and to inform the development of clinical trials to improve the treatment outcomes of vascular disease in the short and long term. By recruiting all eligible participants from a defined population and following them up over a long period of time, OxVasc reduces recruitment bias so the results are more generalizable to the population as a whole and can identify whether the benefits of any intervention are maintained (e.g. sustained blood pressure monitoring and treatment, carotid surgery). Since 2008, mortality and demographic data were supplied to the University of Oxford by ONS and subsequently the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of this research study. The overall aims of the study have not changed since 2002 and the benefits of a cohort study of this length and detail will continue to improve the public’s health through disease prevention, earlier disease diagnosis and better disease management. The study to date has had significant impacts (as described below) and it is expected that further measurable benefits will be outputs that underpin NICE and other Department of Health strategies for detection, management and treatment of vascular disease. The GDPR legal bases for processing the data held under this Agreement are 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) and Article 9(2)(j) (processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes). This research into the health outcomes for people who have suffered from stroke or other vascular events is a task in the public interest under General Data Protection Regulation (GDPR) as it aims to improve care for all patients considering undergoing this type of process – informing clinicians and commissioners of variation and outcomes and complications to support work to improve and standardise treatment selection choices. The protocol has had appropriate ethics committee approval and CAG support (all documentary evidence is included in this application. The University of Oxford does not consider there to be any moral or ethical issues raised by the use of data from NHS Digital or any risk of potential harm to the data subjects. All outputs report numbers at an aggregated level with small numbers suppressed. Since 2008, mortality and demographic data were supplied to the University of Oxford by ONS and subsequently the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of this research study. The overall aims of the study have not changed since 2002 and the benefits of a cohort study of this length and detail will continue to improve the public’s health through disease prevention, earlier disease diagnosis and better disease management. The study to date has had significant impacts (as described in the benefits section) and it is expected that further measurable benefits will be outputs that underpin NICE and other Department of Health strategies for detection, management and treatment of vascular disease. The data subjects are patients registered in one of eight GP practices in Oxfordshire. Since 2002, participants have been recruited from hospital, outpatients’ clinics or home following referral from a collaborating GP and interviewed by a researcher following written consent. Clinical information is gathered from participants about their health, medical history, family history and current treatment. With consent from study participants, the study team extract information about their vascular event and related conditions from health records for the duration of the study in order to follow up on participants health status. Regular face-to-face or telephone contact is maintained with participants and their GPs over the first two years and they are contacted again at five and ten years after entering the study. However, over this period participants may move out of Oxfordshire or register with a different GP. In order to achieve these aims accurate information on the date and cause of death of everyone in the cohort to evaluate long term morbidity and mortality for the study population is required. The minimal information is requested under this agreement to meet the aims of the study and ensure integrity of study outputs, specifically: The earliest participants were recruited while the study was in a pilot phase and they were all asked to re-consent to participate in the full study when version 2 of the consent form (dated 28/12/2006) came into use. Under this Agreement, the University of Oxford is permitted to share with NHS Digital details of participants who gave consent using version 2 of the consent form or any subsequent version. This Agreement does not permit the processing of data relating to any participant who was recruited using an earlier version - which did not include a declaration of consent for "information held by the NHS and records maintained by the General Register Office" to be used to maintain contact and follow up their health status - did not re-consent using version 2 or a subsequent version. Date of death-survival after vascular event to evaluate treatment interventions, natural history of disease and to stop further contact for follow up visits. Mortality due to stroke and ACS has fallen in most countries over the past four decades. However, the relative contributions of changes in incidence and case fatality are uncertain. There is no data from the UK on recent time trends in age and sex specific incidence or disability rates for stroke and ACS. However, there have been major changes over the last 20 years in the life-style, primary and secondary prevention treatments and particularly in population demographics. Reliable data on the current and projected future burdens of stroke and ACS will allow future clinical and research funds to be targeted appropriately. Place of normal residence and place of death-health economic analyses of recovery and use of assisted living/institutional care. Little is known about the differences between risk factors for stroke and ACS. There are some differences in the effects of blood pressure and cholesterol, and it has been identified differences in haematological risk factors and similarities in markers of stability of atherosclerotic plaques. However, more data are required. A better understanding of differences in risk factors would allow preventative strategies to be targeted effectively depending on the predominant pathology, would help refine individual risk protection models, and would help develop joint prevention strategies. Cause of death (including ICD10 codes and free text) to establish underlying and contributing factors to death. Studies have shown that the risk of strokes after transient ischemic attack (TIA) or minor stroke is very high during the first few days, and that absolute benefits from preventative treatments fall rapidly with time after the initial event. Clinical characteristics and risk factors associated with the highest risk of early stroke and reasons for delays in presentation to medical services, assessments and investigation need to be determined. The University of Oxford previously flowed identifying information to NHS Digital for the purpose of list cleaning. The University of Oxford used the list cleaning service to provide a newsletter to participants. Upon receipt of the Demographics data, University of Oxford will destroy this data and provide a data destruction certificate to NHS Digital as it will no longer be required. The University of Oxford is the sole data controller and the only organisation processing the data supplied by NHS Digital under this Agreement. Funding for OxVASC is provided by the Wellcome Trust and the NIHR Oxford Biomedical Research Centre. Past funding has been provided by the Stroke Association which is still acknowledged on some of the study outputs. The funders expect the department to undertake research such as this but neither body can access data nor has a role in analysis or interpretation. No attempt is made to contact families after the death of a participant notified to the study team through this process. The analyses are determined by the Principal Investigator (PI) and the study statistician and performed by the University of Oxford research team to support the aims and objectives of the study. Ethical approval and grant funding from the Wellcome Trust and the NIHR Oxford Biomedical Research Centre have been granted for the study, for the same purposes as described in this Agreement. The progress is evaluated annually and new analyses are added or completed based on findings to date and the length of time required to collect outcomes (cause of death) to determine the prognosis of different presentations of vascular disease and/or achieve statistical power to answer the research question. For example, mortality data is required to determine the outcome (disability or death) and time course of bleeding requiring medical attention in patients taking long-term antiplatelet treatment after acute vascular events. This is then used to estimate the age-specific numbers needed to treat to prevent upper gastrointestinal bleeding with routine proton-pump inhibitor co-prescription. Not all of the work of the Oxford Vascular Study involve use of data on mortality obtained from NHS Digital but use of the data will be important in some analyses in order to determine firstly the impact of any treatment on survival and secondly the health economic value of any intervention e.g. prevention of recurrent stroke and subsequent health resource use. The data subjects are patients registered in one of eight GP practices in Oxfordshire who have had a stroke, transient ischaemic attack (TIA), Acute Coronary Syndrome (ACS) or acute peripheral vascular events. These are the same practices (and associated demographic characteristics of the previous studies-OCSP/OXMIS) allowing valid comparisons over time. Since 2002, participants have been recruited from hospital, outpatients’ clinics or home following referral from a collaborating GP and interviewed by a researcher following written consent. Clinical information is gathered from participants about their health, medical history, family history and current treatment. The study team extract information about their vascular event and related conditions from health records for the duration of the study in order to follow up on participants health status. Regular face-to-face or telephone contact is maintained with participants and their GPs over the first two years and they are contacted again at five and ten years after entering the study. However, over this period participants may move out of Oxfordshire or register with a different GP. In order to achieve the study aims, accurate information on the date and cause of death of participants in the cohort to evaluate long term morbidity and mortality for the study population is required. For this reason, national data is required. Data will need to be shared at a record level as agreed between the University of Oxford and NHS Digital to flag and receive date and cause of death for each individual cohort member and in order to produce accurate matching. There is no alternative way to obtain all cause mortality data sufficiently robust to achieve the aims of the study. All results will be presented as aggregated data. The earliest participants were recruited while the study was in a pilot phase and they were all asked to re-consent to participate in the full study when version 2 of the consent form (dated 28/12/2006) came into use. Under a separate Agreement, DARS-NIC-653950-W8D4Z, the University of Oxford is permitted to share with NHS Digital details of participants who gave consent using version 2 of the consent form or any subsequent version. The DARS-NIC-653950-W8D4Z Agreement does not permit the processing of data relating to any participant who was recruited using an earlier version - which did not include a declaration of consent for "information held by the NHS and records maintained by the General Register Office" to be used to maintain contact and follow up their health status - and did not re-consent using version 2 or a subsequent version. However, processing of data relating to participants recruited using an earlier version is permitted under this Agreement using section 251 support granted from CAG to meet the Common Law Duty of Confidentiality. The University of Oxford is the sole data controller who also process the data supplied by NHS Digital under this Agreement. No other organisation determines the purpose for data processing or has any access to the data. Funding for OxVasc is provided by the Wellcome Trust and the NIHR Oxford Biomedical Research Centre. Past funding has been provided by the Stroke Association which is still acknowledged on some of the study outputs. The funders expect the Nuffield Department of Clinical Neurosciences to undertake research such as this but the funding body can not access data nor has a role in analysis or interpretation.

Processing activities

Under this Agreement, the data may be securely stored but not otherwise processed. No new data will be provided by NHS Digital under this Agreement. [2 paragraphs unchanged] Identifying details of participants have previously been supplied to ONS and subsequently [13 words unchanged] could be reported to the study. The University of Oxford will flow identifying information identifiers (Surname, First name, NHS number, date of birth, study ID) to NHS Digital for to update the purpose of list cleaning. The University of Oxford will use the list cleaning service cohort to provide a newsletter to participants. The newsletter will be pre-reviewed by NHS Digital prior to publication. flag participants recruited after 2018. The study database contains information collected directly from participants (e.g. family history, lifestyle) and from other sources including hospital and GP surgery notes (e.g. scan results, blood test results, blood pressure measurements). These are entered and coded within the database so they can be downloaded for analysis at a later date. The study database contains identifying data on each participant in order to keep up to date contact details for them so they can be contacted for follow up, but the database is encrypted so any data extracted for analysis does not have identifying details (names, addresses, etc.). The data disseminated under this Agreement will only cover participants where section 251 support has been granted to meet the Common Law Duty of Confidentiality. Data of participants recruited via consent is disseminated under a separate Agreement for this study: DARS-NIC-653950-W8D4Z. The data provided under DARS-NIC-148369-8PPWK and DARS-NIC-653950-W8D4Z will be combined and analysed as one study. Other than the linkages described above, the data will not be linked with any other data. The following datasets are processed by the study: No attempt is made to contact families after the death of a participant is confirmed through this process. i. Civil Registration Mortality data – details of participants’ deaths including date and cause; Data supplied by NHS Digital will be used only for the approved Medical Research Project MR1086-The Oxford Vascular Study. No data will be shared with any individuals or agencies outside of the study team. All study staff are employees of the University of Oxford. ii. Demographics – details of embarkations or lost to follow up The analyses are determined by the Principal Investigator (PI) and the study statistician and performed by the research team to support the aims and objectives of the study as outlined in the application for ethical approval and grant funding from the Wellcome Trust and the NIHR Oxford BRC. Data received from NHS Digital will be linked to unique study ID using date of birth and NHS number to ensure a perfect match to each participant’s date of vascular event to calculate outcomes (Kaplan-Meier survival analyses). All data supplied by NHS Digital will be used only for the approved Medical Research Project MR1086-The Oxford Vascular Study. No data will be shared with any individuals or agencies outside of the study team and all study staff are substantive employees of the University of Oxford. The progress is evaluated annually and new analyses are added or completed based on findings to date and the length of time required to collect outcomes (cause of death) to determine the prognosis of different presentations of vascular disease and/or achieve statistical power to answer the research question. For example, mortality data is required to determine the outcome (disability or death) and time course of bleeding requiring medical attention in patients taking long-term antiplatelet treatment after acute vascular events. This is then used to estimate the age-specific numbers needed to treat to prevent upper gastrointestinal bleeding with routine proton-pump inhibitor co-prescription. The data is stored in an access-controlled server room within the University of Oxford Medical Sciences Division, situated on the Old Road Campus and connected to the main University network, located behind a firewall. Physical access is limited to Computer Services Department staff. Data will be encrypted using industry standard techniques meeting the Information Governance Toolkit standard (RBQ). Not all of the work of the Oxford Vascular Study involve use of data on mortality obtained from NHS Digital but use of the data will be important in some analyses in order to determine firstly the impact of any treatment on survival and secondly the health economic value of any intervention e.g. prevention of recurrent stroke and subsequent health resource use. The data is held in an access-controlled server room and connected to the main University network, located behind a firewall. Physical access is limited to Computer Services Department staff. Data will be encrypted using industry standard techniques meeting the Information Governance Toolkit standard (RBQ).

Expected output

This Agreement permits the secure retention of the data only and no other processing. The study overall has produced over 250 peer reviewed publications on incidence of disease, risk factor management, prognosis and outcomes. Peer-reviewed manuscripts on original research arising from the study are subject to the Wellcome Trust open access policy and are available to all free of charge on publication. A statement on data used and data sharing is provided in line with the individual publisher guidelines and the NIHR. The data received under this Agreement will continue to be used in the same way as previously outlined and is important for use in analyses of the effects of new/extended uses of primary and secondary prevention of vascular disease over a long period of time. No new outputs will be produced under this Data Sharing Agreement. Research aims and findings from the Oxford Vascular Study are summarised on the study website (www.ndcn.ox.ac.uk/research/oxvasc) and presented at open days organised by the NIHR Oxford Biomedical Research Centre (BRC), Nuffield Department of Clinical Neurosciences and public involvement and engagement groups. Talks on OxVasc and related topics (e.g., high blood pressure, vascular dementia) are also available on YouTube (https://oxfordbrc.nihr.ac.uk/research-themes-overview/stroke-and-vascular-dementia/videos-stroke-and-vascular-dementia). Selected results of the study have been reported in the local, national and international press. OxVasc is one of a number of cohort studies funded by the NIHR to identify simple low cost interventions and to inform the development of clinical trials to improve the treatment outcomes of vascular disease in the short and long term. By recruiting all eligible participants from a defined population and following them up over a long period of time, OxVasc reduces recruitment bias so the results are more generalizable to the population as a whole and can identify whether the benefits of any intervention are maintained (e.g. sustained blood pressure monitoring and treatment, carotid surgery). The study overall has produced over 200 publications of incidence of disease, risk factor management, prognosis and outcomes, including: - Change in incidence, mortality and risk factors for stroke from 1981 to 2004. (Lancet, 2004) showing the fall in incidence over the past 20 years is association with increased use of preventive treatments. -Reported incidence, case fatality, burden and cost of all acute vascular events in a defined population. (Lancet, 2005)- - Reported incidence and outcome of acute aortic dissection and Ischemic Peripheral Arterial Events from 2002-2012. (Circulation, 2013, 2015) showing uncontrolled high blood pressure remains the most significant treatable risk factor for acute aortic dissection and focussed use of existing treatments would be beneficial. Yearly reports on the progress of the researchhave been given to the funders with all outputs and impacts for the previous year. The study also benefits the individual participants by providing: 1. Rapid assessment and treatment following TIA and minor stroke in order to identify the cause and provide treatment. 2. Ongoing assessment of vascular risk factors (BP, cholesterol), health care advice (smoking cessation, lifestyle advice) at follow up, enabling participants and the collaborating GP to improved secondary prevention of vascular disease. Research findings from the Oxford Vascular Study are summarised on the study website (www.ndcn.ox.ac.uk/research/oxvasc) and presented at open days organised by the NIHR Oxford BRC. Talks on OxVasc and related topics (e.g. high blood pressure, vascular dementia) are also available on YouTube. Results of the study have been reported in the local, national and international press. [1 paragraph unchanged] Peer-reviewed manuscripts on original research arising from the study are subject to the Wellcome Trust open access policy and are available to all free of charge on publication. A statement on data used and data sharing is provided in line with the individual publisher guidelines and the NIHR. No data, even anonymised, from NHS Digital will be shared. Yearly reports on the progress of this research have been given to the funders with all outputs and impacts for the previous year. Many of the outputs arising from the Oxford Vascular Study include data on mortality obtained from NHS Digital, often to corroborate information reported by hospitals, GPs and/or relatives of participants on cause of death. Data from NHS Digital provides the collated ICD10 codes, and these data continue to be important in some analyses together with the detailed clinical information collected from participants as part of the study. A statement regarding sharing of data collected from and about participants is available on the study website. All outputs (presentations, posters, peer reviewed publications and oral presentations at conferences) report numbers at an aggregated level, with small numbers suppressed.

Expected measurable benefits

This Agreement permits the secure retention of the data only and no other processing. The overall aims of the Oxford Vascular Study are to improve the public’s health through disease prevention, earlier disease diagnosis and better management of known risk factors. Results from the study to date have been used to underpin NICE guidelines and other Department of Health strategies (some of these benefits are described in yielded benefits to date) by providing evidence for ways to improve diagnosis of disease and how to effectively treat common risk factors such as high blood pressure. The overall aims of the Oxford Vascular Study are to improve the public’s health through disease prevention, earlier disease diagnosis and better management of known risk factors. Results from the study to date have been used to underpin NICE guidelines and other Department of Health strategies by firstly providing evidence for ways to improving diagnosis of disease and secondly how to effectively treat common risk factors such as high blood pressure. The Oxford Vascular Study has ongoing funding from the Wellcome Trust and the NIHR to continue recruitment and complete follow up of the 25 year cohort. This will allow the study to continue providing new evidence to inform stroke prevention and vascular disease generally for the benefit of the population at large, with the continuing recruitment and long term follow up of OxVasc participants. These benefits fulfil the requirements necessary for data processing outlined in Article 6(1)(e). Most outputs arising from the Oxford Vascular Study include data on mortality obtained from NHS Digital and these data continue to be important in some analyses together with the detailed clinical information collected from participants as part of the study. The study also benefits the individual participants by providing: 1. Rapid assessment and treatment following TIA and minor stroke in order to identify the cause and provide treatment. 2. Ongoing assessment of vascular risk factors (BP, cholesterol), health care advice (smoking cessation, lifestyle advice) at follow up, enabling participants and the collaborating GP to improved secondary prevention of vascular disease. Mortality data from NHS Digital also potentially reduces distress to participant’s relatives by attempting to contact them for follow up/information about circumstances of death. The OxVasc study has been running for over 20 years, during which time many improvements in assessment/diagnosis and treatment of TIA, stroke and ischaemic heart diseases have been made. Analysis of morbidity and mortality over this time period is expected to provide additional insights into how further gains can be made in stroke prevention and care. An example of how long term cohort studies like OxVasc can direct further research is in stoke incidence in younger age groups, which appears to be increasing. A new study to better understand the role of treatable risk factors in young stroke patients which could potentially be informative for future clinical guidelines is now underway. (https://www.medicalresearchfoundation.org.uk/projects/contribution-of-the-presence-susceptibility-to-and-control-of-modifiable-vascular-risk-factor-in-young-stroke-and-tia-a-prospective-cohort-and-nested-case-control-study). This study is separate from the OxVasc study and does not use that data held under this Agreement, however, the new study builds on OxVasc research to improve treatment for young stroke victims.

Benefits reported

Some examples of the yielded benefits of data collated in the Oxford Vascular Study (OxVasc) to date include: are outlined below. Emergency prevention of “threatened” stroke "threatened" stroke. Major strokes are sometimes preceded by minor events – so called transient ischaemic attacks (TIA) or minor strokes. It was thought for many years that these events were relatively benign and that investigations were done on a non-urgent basis over weeks or months. Analyses of OxVasc outcomes showed that the risk of major stroke in the first few hours and days after these warning events was, in fact, very high (BMJ 2004), such that they were re-branded as a medical emergency in all international guidelines. A validated and refined simple risk scores (ABCD system) to triage high-risk individuals (Lancet 2005; Lancet 2007) and showed that delays to treatment substantially undermined benefits and showed that urgent use of existing treatments (aspirin, other antiplatelet drugs, blood pressure lowering drugs and statins) reduced the 90-day risk of major stroke by 80% (Lancet 2007; Lancet Neurol 2009. Stroke is a devastating disease for patients and their families, and is estimated to cost the NHS around £3billion per year, with additional cost to the economy of £4billion in lost productivity, disability and informal care (NHS, 2017). Research resulting from the Oxford Vascular Study (OXVASC), which is partly funded by the NIHR, has had significant impact on stroke prevention and the way minor strokes and transient ischaemic attacks (TIAs, or ‘mini strokes’) are managed, by informing clinical guidelines. This simple, cheap but highly effective strategy was rolled out across the UK in the Department of Health’s National Stroke Strategy and NICE guidelines, is estimated to prevent 10,000 strokes per year in the UK alone, saving £200 million in NHS costs, and is now the standard of care worldwide. The first phase of the OxVasc study showed that the risk of stroke after a TIA is greater than originally considered, that there is a narrow time-window for prevention, and that individuals who are at highest risk of having a stroke can be identified with a simple clinical score – the ABCD. It also showed that the requirement for appointments could lead to a delay in referrals for patients with a suspected TIA or minor stroke. Further work has shown that most of the 80% reduction in the early risk of major stroke seen in OxVasc was due purely to aspirin, which also substantially reduces the severity of recurrent strokes. This new observation has major implications for public education - immediate self-administration of aspirin after possible TIA or minor stroke symptoms has the potential to prevent many millions of strokes worldwide at virtually no cost (Lancet, 2016). Based on learning from phase 1, the second phase of the research led to impacts on emergency treatment of TIA and minor stroke in primary care. In this second phase, primary-care physicians were asked to send the patients immediately to the clinic, without any appointment, where treatment was initiated immediately if the diagnosis was confirmed. This led to an 80 per cent decrease in the 90-day risk of recurrent stroke in patients referred to the phase 2 clinic compared with those referred to the phase 1 clinic. In addition, clinic hospital admissions for recurrent stroke were lower when the requirement for appointments was removed, which translated to cost reductions of £624 per patient. The Early use of eXisting PREventive Strategies for Stroke (EXPRESS) study, nested within OXVASC, determined the effect of more rapid treatment after a TIA and minor stroke in patients who are not admitted directly to hospital. Screening for aortic aneursysms These findings have had an impact on service provision and professional education about TIA and minor stroke. This is demonstrated by the changes the research has produced in clinical guidelines. Findings from the EXPRESS study have informed the 2007 National Stroke Strategy; the 2008 National Institute for Health and Care Excellence guidelines Stroke: National Clinical Guideline for Diagnosis and Initial Management of Acute Stroke and Transient Ischemic Attack (TIA); and the 2012 Royal College of Physicians Intercollegiate Stroke Working Party’s National Clinical Guideline for Stroke. The recommendations in these documents reflect the findings from the EXPRESS study that there is a need for identification of patients at high risk of subsequent stroke and early specialist intervention, including commencement of appropriate secondary prevention treatments. Based on the estimations from the EXPRESS study, it was calculated that emergency treatment of TIA and minor stroke in primary care could prevent about 10,000 strokes per year, adding up to cost reductions of up to £200 million annually in acute care costs alone in the NHS. The schedule for abdominal aortic aneurysm (AAA) screening in men age 65 might have limited impact on overall AAA death rates if incidence of acute events is moving to older ages. Data form OxVasc showed two thirds of acute AAA occurred at ≥75 years of age, indicating screening older age groups should be considered. In addition, 25% of acute events were in women and the screening of nonsmokers at age 65 is likely to have very little impact on AAA event rates (Br J Surg. 2015, J Am Heart Assoc. 2015). Follow up of the EXPRESS cohort in OxVasc has shown urgent assessment and treatment of patients with transient ischemic attack or minor stroke resulted in a long-term reduction in recurrent strokes and improved outcomes, with little atrophy of the early benefit over time, representing good value for money even with a 10-year time horizon (reported in 2021). This suggest that other effective acute treatments in transient ischemic attack/minor stroke in the short-term will also have the potential to have long-term benefit. Evaluation of screening for aortic aneurysms The schedule for abdominal aortic aneurysm (AAA) screening in men age 65 might have limited impact on overall AAA death rates if incidence of acute events is moving to older ages. Data form OxVasc showed two thirds of acute AAA occurred at ≥75 years of age, indicating screening older age groups should be considered. In addition, 25% of acute events were in women and the screening of non-smokers at age 65 is likely to have very little impact on AAA event rates (2015). This was based on the first twelve years of the study, by increasing the number of OxVasc participants further analyses of what other factors may be important in disease progression and outcome, especially as primary prevention of vascular disease over the time of the study has improved. [1 paragraph unchanged] Outcome in stroke trials is often based on an assessment of 3-month [10 words unchanged] outcomes will depend on late recovery, delayed stroke-related deaths, recurrent strokes, and nonstroke non-stroke deaths. Data from OxVasc reaffirmed the use of outcome at 3 months [50 words unchanged] non-stroke-related deaths. Further work is underway to document the time course of long‐term quality‐adjusted long-term quality-adjusted life expectancy and healthcare costs in relation to early disability scores. (J Am Heart Assoc. 2017). scores, informing assessment of outcomes used in clinical trials evaluating new treatments for acute stroke. The following is an extract from the publication ‘The National Institute for Health Research at 10 Years | An impact synthesis: 100 Impact Case Studies’ (see: https://www.rand.org/pubs/research_reports/RR1574.html): Costs arising from the treatment of stroke and costs incurred due to productivity loss of the UK population have been calculated to amount to approximately £8.9 billion a year [1]. Stroke treatment costs represent about 5 per cent of total UK NHS costs [1]. Research resulting from the Oxford Vascular Study (OXVASC), which is partly funded by the NIHR, has had significant impact on stroke prevention and the way minor strokes and transient ischaemic attacks (TIAs, or ‘mini strokes’) are managed, by informing clinical guidelines. The OXVASC study started in 2002 and provides data on the incidence and outcome of all acute vascular events occurring in the population in Oxfordshire [2]. The NIHR has contributed to the research in different ways, such as: funding specific research on cost savings arising from early detection of TIA and stroke, in phase 2 of the OXVASC study, and providing an NIHR Senior Investigator Award to one of the principal investigators [3]. The first phase of the OXVASC study showed that the risk of stroke after a TIA is greater than originally considered, that there is a narrow time-window for prevention, and that individuals who are at highest risk of having a stroke can be identified with a simple clinical score – the ABCD [2]. It also showed that the requirement for appointments could lead to a delay in referrals for patients with a suspected TIA or minor stroke. Based on learning from phase 1, the second phase of the research led to impacts on emergency treatment of TIA and minor stroke in primary care [2]. In this second phase, primary-care physicians were asked to send the patients immediately to the clinic, without any appointment, where treatment was initiated immediately if the diagnosis was confirmed. This led to an 80 per cent decrease in the 90-day risk of recurrent stroke in patients referred to the phase 2 clinic compared with those referred to the phase 1 clinic. In addition, clinic hospital admissions for recurrent stroke were lower when the requirement for appointments was removed, which translated to a savings of £624 per patient [4]. The Early use of eXisting PREventive Strategies for Stroke (EXPRESS) study, nested within OXVASC, determined the effect of more rapid treatment after a TIA and minor stroke in patients who are not admitted directly to hospital [4][5]. These findings have had an impact on service provision and professional education about TIA and minor stroke. This is demonstrated by the changes the research has produced in clinical guidelines. Findings from the EXPRESS study have informed the 2007 National Stroke Strategy; the 2008 National Institute for Health and Care Excellence guidelines Stroke: National Clinical Guideline for Diagnosis and Initial Management of Acute Stroke and Transient Ischemic Attack (TIA); and the 2012 Royal College of Physicians Intercollegiate Stroke Working Party’s National Clinical Guideline for Stroke [3]. The recommendations in these documents reflect the findings from the EXPRESS study that there is a need for identification of patients at high risk of subsequent stroke and early specialist intervention, including commencement of appropriate secondary prevention treatments. Based on the estimations from the EXPRESS study, it was calculated that emergency treatment of TIA and minor stroke in primary care would prevent about 10,000 strokes per year, adding up to savings of up to £200 million annually in acute care costs alone in the NHS [3]. Overall, the health and care system has benefited from improved stroke prevention as a result of determining the resource costs, health outcomes and cost-effectiveness in stroke care using evidence from the Oxford Vascular Study. Evidence 1] Saka Ö, McGuire A, Wolfe C. 2009. Cost of stroke in the United Kingdom. Age and Ageing 38 (1): 27-32. doi:10.1093/ageing/afn281 Study reporting the annual cost of stroke to the UK economy using a combination of direct and indirect cost measures. [2] National Institute for Health Research. 2016. Improving stroke prevention in routine clinical practice: Phase 2 of the Oxford Vascular Study (OXVASC) programme. As of 2 May 2016: http://www.nihr.ac.uk/funding/funded-research/funded-research.htm?postid=2164 Link to a project page on the National Institute for Health Research website, describing the OXVASC Study programme. [3] Research Excellence Framework. 2014. Reduction of stroke risk by risk stratification and urgent intervention after a transient ischaemic attack (TIA) or minor stroke. [Case study 14720.] As of 2 May 2016: http://impact.ref.ac.uk/CaseStudies/CaseStudy.aspx?Id=14720 The case study summarises the achievements of the team from the Stroke Prevention Research Unit in Oxford from early 2000 to 2013. [4] Luengo-Fernandez R, Gray AM, Rothwell PM. 2009. Effect of urgent treatment for transient ischaemic attack and minor stroke on disability and hospital costs (EXPRESS study): A prospective population-based sequential comparison. The Lancet. Neurology. 8: 235-43. doi: 10.1016/S1474- 4422(09)70019-5 This paper summarises the findings on the cost-effectiveness of the phase 2 intervention. It concludes that urgent assessment and treatment of patients with a TIA or minor stroke who were referred to a specialist outpatient clinic reduced subsequent hospital bed-days, acute costs and six-month disability. [5] Health Economics Research Centre. 2016. Resource costs, health outcomes and cost-effectiveness in stroke care: Evidence from the Oxford Vascular Study. Nuffield Department of Population Health. As of 2 May 2016: http://herc.medsci.ox.ac.uk/research/disease-cost-studies/studies-4/resource-costs-healthoutcomes-and-cost-effectiveness-in-stroke-care-evidence-from-the-oxford-vascular-study The page offers a comprehensive account of this part of the research of the Oxford Vascular Study, including the publications resulting from it. This project aimed to: 1) estimate the size and predictors of immediate and long-term (i.e. five years after the event) National Health Service resource use and healthcare costs of stroke and transient ischaemic attacks; 2) estimate the size and predictors of immediate and long-term health outcomes, including five-year life expectancy, patient disability, quality of life, and quality-adjusted life expectancy; and 3) assess if urgent clinical assessment and treatment of nonhospitalised patients with a minor stroke or TIA was cost effective.

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Datasets: − Demographics

Objective for processing

This Data Sharing Agreement permits the retention of the data provided under previous iterations of this Agreement for an interim period. This is a pragmatic approach to provide an active Agreement whilst enabling The University of Oxford to complete the necessary actions to enable a subsequent application to extend the Agreement meeting all applicable data sharing standards as published in NHS Digital’s website (see: https://digital.nhs.uk/services/data-access-request-service-dars/dars-guidance). This Agreement will additionally permit the University of Oxford to flow the identifying information of study participants to NHS Digital so that NHS Digital can provide updated details of participants’ vital status and current status of registration with the NHS and latest known addresses (if alive and currently registered with an NHS GP). The University of Oxford is permitted to use this information to send out patient notifications to living participants to provide additional information about their ongoing participation in this study to ensure that participants are fully informed. No other processing of the data is permitted. For clarity, this restriction on the purpose for processing applies to any data supplied under any versions of the Agreement it supersedes, including copies of that data which have been incorporated into a larger dataset. [13 paragraphs unchanged]

Processing activities

Under this Agreement, the data already provided under previous iterations of this Agreement may be securely stored but not otherwise processed. No new data will be provided by NHS Digital under this Agreement. The University of Oxford is permitted to supply a file containing identifying details of study participants to NHS Digital. NHS Digital will supply details of participants' current vital status, current status of registration with an NHS GP and latest known addresses for living participants registered with an NHS GP. The University of Oxford will use this information to determine which study participants should appropriately be sent a patient notification by post. [1 paragraph unchanged] The study data, including data provided by NHS Digital under previous versions [43 words unchanged] connected to the main University of Oxford’s network. At no time will sole employees of John Radcliffe Hospital have access to the data held on the server for University of Oxford. [9 paragraphs unchanged]

Expected output

This Agreement permits the secure retention of the data only and no other processing. [2 paragraphs unchanged] The study overall has produced over 100 200 publications of incidence of disease, risk factor management, prognosis and outcomes, including: [10 paragraphs unchanged]

Expected measurable benefits

This Agreement permits the secure retention of the data only and no other processing. [2 paragraphs unchanged]

Unchanged: Benefits reported.