The United Kingdom Aneurysm Growth Study

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

Objective for processing

The University of Leicester wishes is to obtain clinical outcomes (hospital admissions or deaths) for a prospective cohort study, the UK Aneurysm Growth Study. (UKAGS) The University of Leicester requires access to the NHS England data for the purpose of the following research project: The UKAGS is a prospective cohort study of men attending the NHS aneurysm screening programmes in the UK. Between 2010 and 2019 men were recruited into the study after they had been screened for abdominal aortic aneurysm (AAA). These men were directly consented for all study activities by the study team at the University of Leicester. The men in the cohort have been followed up for up to 5 years by annual postal questionnaires. The aim of the processing activity proposed in this Data Sharing Agreement is twofold. Firstly, during the phase of the study when annual questionnaires were being sent it was necessary to identify research participants who had died during study follow-up period so that further questionnaires were not sent to deceased individuals. Secondly, and for the purposes of long-term cohort follow-up now that postal questionnaires are no longer being used to collect data, it is necessary to record healthcare events including date and cause of death as study outcomes. The United Kingdom Aneurysm Growth Study (UKAGS) Men were consented to participate in the study using a postal consent model. Men were invited to join the study at AAA screening clinics by screening staff, or sent a postal invitation by their national AAA screening programme. Men were asked to contact the research team at the University of Leicester if they were interested in participating in the study. These men were sent study information materials including details of how their personal information, including NHS number, would be used to obtain data from NHS Digital. The UKAGS is a prospective cohort study of men attending the NHS aneurysm screening programmes in the UK. Between 2010 and 2019 men were recruited into the study after they had been screened for abdominal aortic aneurysm (AAA). These men were directly consented for all study activities by the study team at the University of Leicester. The men in the cohort have been followed up for up to 5 years by annual postal questionnaires. During the phase of the study when annual questionnaires were being sent it was necessary to identify research participants who had died during study follow-up period so that further questionnaires were not sent to deceased individuals. For the purposes of long-term cohort follow-up now that postal questionnaires are no longer being used to collect data, it is necessary to record healthcare events including date and cause of death as study outcomes. The study only includes men because it is a study of men who have attended for abdominal aortic aneurysm (AAA) screening. The UK NHS AAA screening programmes only invite men for screening so only men have been recruited. Women are not screened for AAA because it is neither clinically nor economically effective. The following is a summary of the aims of the research project provided by / on behalf of the University of Leicester: The University of Leicester is the sole data controller and no other organisations are involved in the data processing. Only the University of Leicester will have access to record level data supplied by NHS Digital. • Identify clinical and biological factors influencing AAA progression to develop clinical interventions aimed at reducing the risk of fatal AAA rupture and surgery needs. The overall aims of the UK Aneurysm Growth Study are to: • Use these factors to design interventions to slow AAA progression, reduce risks of fatal rupture, and prevent surgery in men with AAA. 1) Identify clinical and biological factors associated with the progression of AAA. This information will be used to design clinical interventions to slow the progression of AAA, reduce the risks of fatal AAA rupture and prevent the need for surgery in men with AAA. • Assess whether AAA screening programs can improve overall health in men, beyond just the diagnosis and treatment of AAA. 2) Determine if AAA screening programmes are an opportunity to improve the overall health of men, irrespective of the diagnosis or management of AAA. • Use Hospital Episode Statistics (HES) data to track aneurysm repair, cardiovascular events, and non-cardiovascular outcomes, helping to assess competing health risks and improve care strategies. Long-term clinical outcomes are the key indicators of clinical performance of screening programmes. HES data will provide information on relevant clinical events such as aneurysm repair and other cardiovascular morbidity. HES data for non-AAA and non-cardiovascular outcomes is required to assess competing risks. Mortality data provides information on AAA-related, cardiovascular and non-cardiovascular mortality. • Evaluate competing health risks and mortality data, both AAA-related and non-AAA-related. The activity is compliant with the principles of GDPR. Based on guidance, as this is for University research, the lawful basis for processing data is GDPR 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’. Also referred to as ‘Public Task’. As the research involves health data, which is included in the definition of special categories of personal data, it requires an additional condition for processing. Based on guidance, for health research this is GDPR article 9(2)(j), which details that processing is necessary for scientific and research purposes, subject to appropriate safeguards. This task is in the public interest since it aims to improve the care and health of men diagnosed with abdominal aortic aneurysm and determine if additional health benefits can be derived from aneurysm screening programmes for all men invited for screening (all men in the year of their 65th birthday). Improving the healthcare benefits derived from population screening programmes is of wider public interest as it improves healthcare resource use. • Improve healthcare benefits from population screening programs by deriving additional health benefits for men invited for AAA screening. Background to the study: The following NHS England Data will be accessed: In the UK men are invited for AAA screening in the year of their 65th birthday. Men older than 65 can self-refer if they have not been screened before. Men who are found to have an AAA are offered regular (at least yearly) ultrasound scans to monitor the size of their AAA. This monitoring is undertaken by the AAA screening programmes. • Civil Registrations of Death – necessary to obtain long-term follow up for the cohort and add to the data already available. Men were recruited into the UK Aneurysm Growth Study between 2010 and 2019 from the AAA screening programmes in England, Wales and Scotland. Men provided written consent for their personal information to be used for the purposes of obtaining clinical outcomes (hospital episodes and mortality). • Hospital Episode Statistics Admitted Patient Care (HES APC) – necessary to analyse the clinical events in the cohort and assessing the factors leading to the occurrence of such events. For the purposes of AAA progression, the events of interest are AAA rupture, AAA repair or AAA related mortality. Since AAA screening represents an opportunity to improve the health of men outside of the simple management of AAA, events of interest relate to those where preventative medicine could be deployed. There is a strong link between aortic diameter at screening and future cardiovascular health. These data will be used to assess opportunities for cardiovascular risk reduction in both the case and control groups. Men recruited into the cohort have been classified as those with AAA (cases) and those without (controls). Both groups are followed up. The level of the Data will be: During the cohort recruitment phase (2010 to 2019) data obtained from NHS Digital was used solely to flag men who have died who should not be sent further study materials. The study has now finished recruiting new participants and the study is now in its follow-up phase. • Identifiable – necessary to link to the data already gathered for the cohort. Future follow up of cohort members in England and Wales will be through NHS Digital. The data obtained from NHS Digital will be used to define clinical events such as AAA repair or even death from AAA rupture. These clinical events will be the study endpoints used to study factors associated with AAA growth and opportunities for health improvement. HES data will be supplied for England only and Mortality data for England and Wales. The Data will be minimised as follows: Clinical event data from NHS Digital enhances the quality of the UK Aneurysm Growth Study. These data are those from both HES and mortality datasets that enable the analysis of AAA-related events during follow-up (AAA repair, AAA rupture, AAA mortality) and those that can identify additional opportunities to improve the health of men with AAA (cardiovascular morbidity and mortality). Non-AAA and non-cardiovascular events are also important to gather to allow comparison of the incidence of such events with AAA/cardiovascular events. At present AAA growth in the UK Aneurysm Growth Study is measured using the serial ultrasound measurements for men in the cohort. Limited to a study cohort recruited into the UK Aneurysm Growth Study from 2010 to 2019. Men were recruited into the UK Aneurysm Growth Study between 2010 and 2019 from the AAA screening programmes in England, Wales and Scotland. Men provided written consent for their personal information to be used for the purposes of obtaining clinical outcomes (hospital episodes and mortality). Men recruited into the cohort have been classified as those with AAA (cases) and those without (controls). Both groups are followed up. The study cohort was recruited from across England, Wales and Scotland. Data is requested for all cohort members in England and Wales. Ultrasound measurement of AAA growth is subject to significant measurement variability. The alternative method to measure disease progression in AAA is to measure the time between diagnosis and any adverse clinical events including death from AAA rupture or surgical repair. These data are not systematically collected by AAA screening programmes. Data from NHS Digital addresses this deficiency. The University of Leicester 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. Data required: The lawful basis for processing personal data under the UK GDPR is: Hospital episode statistics and civil registration (mortality) data. Data from the HES Admitted Patient Care dataset other than ‘maternity’ category data and mortality data (date of death, cause of death, death in an NHS establishment). Data is required from the start of the UKAGS study (2010) to date. 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. Justification: The lawful basis for processing special category data under the UK GDPR is: These datasets are required to enable the analysis of clinical events in the cohort. This will enable the analysis of factors leading to the occurrence of such event. For the purposes of AAA progression, the events of interest are AAA rupture, AAA repair or AAA related mortality. Since AAA screening represents an opportunity to improve the health of men outside of the simple management of AAA, events of interest relate to those where preventative medicine could be deployed. There is a strong link between aortic diameter at screening and future cardiovascular health. These data will be used to assess opportunities for cardiovascular risk reduction in both the case and control groups. 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. Identifiable individual participant level data is required to link to the data already gathered for the cohort. Personal identifiers were collected from the research participants with their consent at the time of recruitment. No additional personal identifying information was requested from NHS Digital other than that supplied by the study team. The data received back from NHS Digital was linked with the overall study dataset by study ID number. The funding is provided by the British Heart Foundation. The funding is specifically for the UK Aneurysm Growth Study Men were recruited into the UK Aneurysm Growth Study from 2010 to 2019, using the process described above. Men were classified according to their outcome at AAA screening as cases (those with AAA, aortic diameter >29mm) or controls (those without AAA, aortic diameter <30mm). These two groups are considered separately for the purposes of the study and each group had different consent materials used for recruitment. Both groups provided written informed consent to participate in the study. The wider project includes other organisations providing data for the cohort; these are the UK AAA screening programmes and their IT providers, and the NHS Central Register (Scotland). Each of the UK AAA screening programmes (in England, Wales, Scotland and Northern Ireland) are provided with identifiable data for their screening cohorts on an annual basis by their country's central NHS registry. For example, in England, NHS England provide the NHS AAA Screening Programme details of their screening cohort under Section 251 approval. The UK Aneurysm Growth Study has been funded by the Circulation Foundation in the past (2010 to 2014) and has since been funded by the British Heart Foundation through two separate funding awards (2014 to 2019 and 2019 to 2023). The study cohort was recruited from across England, Wales and Scotland. Data is requested for all cohort members in England and Wales. University of Leicester are the sole Data Controller and the sole organisation that processes the data. The wider project includes other organisations providing data for the cohort; these are the UK AAA screening programmes and their IT providers, and the NHS Central Register (Scotland). Each of the UK AAA screening programmes (in England, Wales, Scotland and Northern Ireland) are provided with identifiable data for their screening cohorts on an annual basis by their country's central NHS registry. For example, in England, NHS Digital provide the NHS AAA Screening Programme details of their screening cohort under Section 251 approval. The screening programmes use these data to invite men for screening. Men who attend for screening give consent for screening and, optionally, for their data to be retained so that they can be informed of research opportunities by the programmes. It was via this pathway that each of the programmes invited men who had provided such consent to join the UK Aneurysm Growth Study. The first invitation to men to join the study was from the screening programmes. Men were asked to contact the research team at the University of Leicester if they were interested. This contact then triggered the research team to send study information materials to the men. Any information provided by men who subsequently did not consent to join the study was deleted.

Processing activities

Historically, the University of Leicester sent lists of study participants, who have consented in the study, to NHS Digital (via secure upload) for flagging. Details of new recruits were submitted periodically. The lists contained NHS number, date of birth, name and address. At the University of Leicester all study data gathered directly from participants is pseudonymised and held separately to any identifiable data. Furthermore, NHS Digital data is held in a separate secure folder. The University of Leicester will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number, Date of Birth, Name and Postcode) for the cohort to be linked with NHS England data. The following data/samples have been collected by the research team to date: NHS England will provide the relevant records from the Hospital Episode Statistics Admitted Patient Care (HES APC) and Civil Registrations of Death datasets to The University of Leicester. -Baseline health data obtained directly from study participants by postal questionnaire. The Data will contain directly identifying data items including Names, NHS Number, Date of Birth and Postcode which are required to link the Data at record level with data already held by the University of Leicester. -Annual updates on health status obtained directly from study participants by postal questionnaire. The Data will not be transferred to any other location -Blood, urine and/or saliva samples. These were collected by the participant’s general practitioner or local hospital unit and sent to the research team by post. The Data will be stored on servers at the University of Leicester -Outcomes of AAA screening including follow-up scan data for men with AAA in surveillance programmes. These data have been obtained from the relevant national AAA screening programme or their IT provider. The Data will be accessed by authorised personnel via remote access. During the recruitment phase civil registration data (mortality) was obtained from NHS Digital for the purposes of identifying men who had died who should not be sent further study materials. That data has subsequently been destroyed and is no longer held by the University of Leicester, but up to date mortality data will again be provided under this data sharing agreement. 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. The University of Leicester are requesting additional data from NHS Digital to obtain long-term follow up for the cohort and add to the data already available above. For remote access: The study data, including data previously provided by NHS Digital are held at the University of Leicester. All study data is stored in pseudonymised form. All identifiable data is held in a separate database to the study data. Access to study databases is restricted to University of Leicester substantive employees who have been trained in information security. - 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; The University of Leicester will send lists of study participants, who have consented in the study, to NHS Digital (via secure upload) for flagging. The lists contain study identifier, NHS number, date of birth, name and address. - Access controls granting users the minimum level of access required are in place; NHS Digital will match the study participants and return a pseudonymised dataset containing hospital episode statistics and mortality data (HES Admitted Patient Care and mortality data) to the University of Leicester who will link the data to the overall pseudonymised study dataset. Only the pseudonymised dataset will be made available to the wider research team (all substantive employees, University of Leicester) for the purposes of research analysis. - Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data; Mortality data was originally used to avoid writing out to participants who were deceased, but this will no longer be the case as there will be no further postal contact with participants. - Multifactor authentication (MFA) is required for remote access; All outputs for dissemination will be aggregated outputs with small numbers suppressed in line with the HES Analysis Guide. No other data will be shared with third parties. The Data will only be used for the purposes described in this Agreement. - Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access; All organisations party to this Agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract i.e.: employees, agents and contractors of the Data Recipient who may have access to that data). - All remote access is undertaken within the scope of the organisation’s DSPT (or other security arrangements as per this DSA) 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). The Data will not leave England/Wales Access is restricted to employees of the University of Leicester who have the authorisation from the Principal Investigator. All personnel accessing the Data have been appropriately trained in data protection and confidentiality. 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.

Expected output

[3 paragraphs unchanged] None of the outputs to date have utilised data obtained from NHS Digital England in their analyses as mortality data received by UKAGS was used to [7 words unchanged] not be sent further study materials, rather than to inform research analysis. [7 paragraphs unchanged]

Expected measurable benefits

The main benefit that may be derived from the addition of NHS Digital England data will be in precision medicine. The combined UK Aneurysm Growth Study [98 words unchanged] AAA screening) and the assessment of non-AAA and non-cardiovascular events for comparison. [6 paragraphs unchanged]

Benefits reported

Data received from NHS Digital England has not been used in the generation of research outputs to date. The data is being currently being used for research, with publications pending. Data previously received to date has ensured that deceased study participants did not receive study materials during the recruitment and direct postal follow up phase of the UK Aneurysm Growth Study.

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

Datasets: + Hospital Episode Statistics Admitted Patient Care (HES APC) · − MRIS - Cause of Death Report; − MRIS - Cohort Event Notification Report; − MRIS - Flagging Current Status Report; − MRIS - Members and Postings Report

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 University of Leicester 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). The University of Leicester wishes is to obtain clinical outcomes (hospital admissions or deaths) for a prospective cohort study, the UK Aneurysm Growth Study. (UKAGS) The following provides background information on the purpose of the original study: The UKAGS is a prospective cohort study of men attending the NHS aneurysm screening programmes in the UK. Between 2010 and 2019 men were recruited into the study after they had been screened for abdominal aortic aneurysm (AAA). These men were directly consented for all study activities by the study team at the University of Leicester. The men in the cohort have been followed up for up to 5 years by annual postal questionnaires. The aim of the processing activity proposed in this Data Sharing Agreement is twofold. Firstly, during the phase of the study when annual questionnaires were being sent it was necessary to identify research participants who had died during study follow-up period so that further questionnaires were not sent to deceased individuals. Secondly, and for the purposes of long-term cohort follow-up now that postal questionnaires are no longer being used to collect data, it is necessary to record healthcare events including date and cause of death as study outcomes. The UKAGS is a prospective cohort study of men attending the NHS aneurysm screening programmes in the UK. Men are recruited into the study after they have been screened for abdominal aortic aneurysm (AAA) and are directly consented for all study activities by the study team at the University of Leicester. Men are followed up for up to 5 years by annual postal questionnaires. The aim of this processing activity was twofold. Firstly, it is necessary to identify research participants who had died during study follow-up period so that further questionnaires are not sent to deceased individuals. Secondly, it is necessary to establish date and cause of death as study outcomes. University of Leicester is sole data controller and no other organisations are involved in the data processing. Only the University of Leicester will have access to record level data supplied by NHS Digital. Men were consented to participate in the study using a postal consent model. Men were invited to join the study at AAA screening clinics by screening staff, or sent a postal invitation by their national AAA screening programme. Men were asked to contact the research team at the University of Leicester if they were interested in participating in the study. These men were sent study information materials including details of how their personal information, including NHS number, would be used to obtain data from NHS Digital. The aim of this work is to establish a resource for the study of outcomes related to AAA screening. The study only includes men because it is a study of men who have attended for abdominal aortic aneurysm (AAA) screening. The UK NHS AAA screening programmes only invite men for screening so only men have been recruited. Women are not screened for AAA because it is neither clinically nor economically effective. During the cohort recruitment phase (2011 to 2018) data obtained from NHS Digital was used solely to flag men who have died who should not be sent further study materials. The study has now finished recruiting new participants and the study is now in it’s follow-up phase. The University of Leicester is the sole data controller and no other organisations are involved in the data processing. Only the University of Leicester will have access to record level data supplied by NHS Digital. Under a subsequent Agreement, the University of Leicester will require mortality data for the extended follow-up of the cohort. UKAGS is focused on AAA. Most outcomes of interest related to AAA only occur many years after screening (e.g. a 3cm AAA takes on average 7 years to grow to 5.5cm when the risk of AAA rupture then becomes significant). It is therefore necessary to continue follow-up of the cohort over a long period of time. The overall aims of the UK Aneurysm Growth Study are to: To recruit an adequate number of men with AAA into the UKAGS it has been essential to recruit on a national basis. Aortic screening is focused on the prevention of aneurysm-related mortality but all-cause mortality is an important outcome to assess in the long-term. There is currently considerable interest in the academic community regarding the possibility of using aortic screening as the basis of a general health check. Without access to all mortality data in the longer term, important academic analyses will not be possible and this will devalue the study. 1) Identify clinical and biological factors associated with the progression of AAA. This information will be used to design clinical interventions to slow the progression of AAA, reduce the risks of fatal AAA rupture and prevent the need for surgery in men with AAA. Personal identifiers were collected from the research participants with their consent at the time of recruitment. No additional personal identifying information was requested from NHS Digital other than that supplied by the study team. The data received back from NHS Digital was linked with the overall study dataset by study ID number. 2) Determine if AAA screening programmes are an opportunity to improve the overall health of men, irrespective of the diagnosis or management of AAA. AAA screening was phased in between 2009 and 2013. Aimed at reducing mortality from AAA, the screening process involves inviting men in the year of their 65th birthday for a focused ultrasound scan of the abdomen to measure the diameter of the abdominal aorta. Men with diameters over 29mm are diagnosed with an AAA. Men with diameters under 30mm are discharged. Some AAAs progress rapidly to a point where surgery is required to repair the AAA and some do not. Little is known about why these differences between men exist. For men without AAAs it is thought that the data gathered at AAA screening may be useful as a predictor of general health, and particularly as a predictor of cardiovascular risk. Long-term clinical outcomes are the key indicators of clinical performance of screening programmes. HES data will provide information on relevant clinical events such as aneurysm repair and other cardiovascular morbidity. HES data for non-AAA and non-cardiovascular outcomes is required to assess competing risks. Mortality data provides information on AAA-related, cardiovascular and non-cardiovascular mortality. The University of Leicester applied for and secured funding from the Circulation Foundation and the British Heart Foundation to undertake this work. The UKAGS was set up to develop a comprehensive resource of clinical data and biological samples from men screened for AAA who had been followed up over time. The activity is compliant with the principles of GDPR. Based on guidance, as this is for University research, the lawful basis for processing data is GDPR 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’. Also referred to as ‘Public Task’. As the research involves health data, which is included in the definition of special categories of personal data, it requires an additional condition for processing. Based on guidance, for health research this is GDPR article 9(2)(j), which details that processing is necessary for scientific and research purposes, subject to appropriate safeguards. This task is in the public interest since it aims to improve the care and health of men diagnosed with abdominal aortic aneurysm and determine if additional health benefits can be derived from aneurysm screening programmes for all men invited for screening (all men in the year of their 65th birthday). Improving the healthcare benefits derived from population screening programmes is of wider public interest as it improves healthcare resource use. The combined UKAGS dataset (including cause of death) and bio resource will enable the examination of clinical and biological data taken at the time of AAA screening as predictors of future health in men. Background to the study: UKAGS has been running since 2011.. The majority of data is collected directly from the participants but this is supplemented by mortality data provided by NHS Digital. In the UK men are invited for AAA screening in the year of their 65th birthday. Men older than 65 can self-refer if they have not been screened before. Men who are found to have an AAA are offered regular (at least yearly) ultrasound scans to monitor the size of their AAA. This monitoring is undertaken by the AAA screening programmes. There have been no changes to the objectives of the study to date. Mortality data has been provided under versions of this Agreement since 21/06/2012. Men were recruited into the UK Aneurysm Growth Study between 2010 and 2019 from the AAA screening programmes in England, Wales and Scotland. Men provided written consent for their personal information to be used for the purposes of obtaining clinical outcomes (hospital episodes and mortality). 1. Data from NHS Digital will be required to identify study participants who have died during follow-up. This prevents study materials being sent to these individuals in the event of their death. The purpose of this isto avoid the distress of bereaved relatives in dealing with these communications. Only fact of death (conveyed through the date of death) is required for this purpose. Men recruited into the cohort have been classified as those with AAA (cases) and those without (controls). Both groups are followed up. 2. Data is required as a study outcome. Cause and date of death is a key outcome for the study since AAA screening is aimed at reducing deaths from AAA. During the cohort recruitment phase (2010 to 2019) data obtained from NHS Digital was used solely to flag men who have died who should not be sent further study materials. The study has now finished recruiting new participants and the study is now in its follow-up phase. . Future follow up of cohort members in England and Wales will be through NHS Digital. The data obtained from NHS Digital will be used to define clinical events such as AAA repair or even death from AAA rupture. These clinical events will be the study endpoints used to study factors associated with AAA growth and opportunities for health improvement. HES data will be supplied for England only and Mortality data for England and Wales. Clinical event data from NHS Digital enhances the quality of the UK Aneurysm Growth Study. These data are those from both HES and mortality datasets that enable the analysis of AAA-related events during follow-up (AAA repair, AAA rupture, AAA mortality) and those that can identify additional opportunities to improve the health of men with AAA (cardiovascular morbidity and mortality). Non-AAA and non-cardiovascular events are also important to gather to allow comparison of the incidence of such events with AAA/cardiovascular events. At present AAA growth in the UK Aneurysm Growth Study is measured using the serial ultrasound measurements for men in the cohort. Ultrasound measurement of AAA growth is subject to significant measurement variability. The alternative method to measure disease progression in AAA is to measure the time between diagnosis and any adverse clinical events including death from AAA rupture or surgical repair. These data are not systematically collected by AAA screening programmes. Data from NHS Digital addresses this deficiency. Data required: Hospital episode statistics and civil registration (mortality) data. Data from the HES Admitted Patient Care dataset other than ‘maternity’ category data and mortality data (date of death, cause of death, death in an NHS establishment). Data is required from the start of the UKAGS study (2010) to date. Justification: These datasets are required to enable the analysis of clinical events in the cohort. This will enable the analysis of factors leading to the occurrence of such event. For the purposes of AAA progression, the events of interest are AAA rupture, AAA repair or AAA related mortality. Since AAA screening represents an opportunity to improve the health of men outside of the simple management of AAA, events of interest relate to those where preventative medicine could be deployed. There is a strong link between aortic diameter at screening and future cardiovascular health. These data will be used to assess opportunities for cardiovascular risk reduction in both the case and control groups. Identifiable individual participant level data is required to link to the data already gathered for the cohort. Personal identifiers were collected from the research participants with their consent at the time of recruitment. No additional personal identifying information was requested from NHS Digital other than that supplied by the study team. The data received back from NHS Digital was linked with the overall study dataset by study ID number. Men were recruited into the UK Aneurysm Growth Study from 2010 to 2019, using the process described above. Men were classified according to their outcome at AAA screening as cases (those with AAA, aortic diameter >29mm) or controls (those without AAA, aortic diameter <30mm). These two groups are considered separately for the purposes of the study and each group had different consent materials used for recruitment. Both groups provided written informed consent to participate in the study. The UK Aneurysm Growth Study has been funded by the Circulation Foundation in the past (2010 to 2014) and has since been funded by the British Heart Foundation through two separate funding awards (2014 to 2019 and 2019 to 2023). The study cohort was recruited from across England, Wales and Scotland. Data is requested for all cohort members in England and Wales. University of Leicester are the sole Data Controller and the sole organisation that processes the data. The wider project includes other organisations providing data for the cohort; these are the UK AAA screening programmes and their IT providers, and the NHS Central Register (Scotland). Each of the UK AAA screening programmes (in England, Wales, Scotland and Northern Ireland) are provided with identifiable data for their screening cohorts on an annual basis by their country's central NHS registry. For example, in England, NHS Digital provide the NHS AAA Screening Programme details of their screening cohort under Section 251 approval. The screening programmes use these data to invite men for screening. Men who attend for screening give consent for screening and, optionally, for their data to be retained so that they can be informed of research opportunities by the programmes. It was via this pathway that each of the programmes invited men who had provided such consent to join the UK Aneurysm Growth Study. The first invitation to men to join the study was from the screening programmes. Men were asked to contact the research team at the University of Leicester if they were interested. This contact then triggered the research team to send study information materials to the men. Any information provided by men who subsequently did not consent to join the study was deleted.

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. Historically, the University of Leicester sent lists of study participants, who have consented in the study, to NHS Digital (via secure upload) for flagging. Details of new recruits were submitted periodically. The lists contained NHS number, date of birth, name and address. At the University of Leicester all study data gathered directly from participants is pseudonymised and held separately to any identifiable data. Furthermore, NHS Digital data is held in a separate secure folder. The study data, including data provided by NHS Digital under previous agreements, are currently held by University of Leicester. The following data/samples have been collected by the research team to date: The following provides background on the processing activities undertaken prior to this Agreement: -Baseline health data obtained directly from study participants by postal questionnaire. Data for all study participants has been collected with consent. -Annual updates on health status obtained directly from study participants by postal questionnaire. No new data will be provided by NHS Digital under this Agreement. -Blood, urine and/or saliva samples. These were collected by the participant’s general practitioner or local hospital unit and sent to the research team by post. The University of Leicester sent lists of study participants, who have consented in the study, to NHS Digital (via secure upload) for flagging. Details of new recruits were submitted periodically. The lists contained NHS number, date of birth, name and address. All pseudonymised study data is held separately to any identifiable data. Furthermore, NHS Digital data is held in a separate secure folder. -Outcomes of AAA screening including follow-up scan data for men with AAA in surveillance programmes. These data have been obtained from the relevant national AAA screening programme or their IT provider. It is intended that the future Data Sharing Agreement will be amended to include linkage to Hospital Episode Statistics. This Agreement, however, relates to mortality data only. During the recruitment phase civil registration data (mortality) was obtained from NHS Digital for the purposes of identifying men who had died who should not be sent further study materials. That data has subsequently been destroyed and is no longer held by the University of Leicester, but up to date mortality data will again be provided under this data sharing agreement. The University of Leicester will store downloaded data within the UKAGS database. The data will be linked with the overall study dataset by study ID number. During the cohort recruitment phase (2011 to 2018) data obtained from NHS Digital was used solely to flag men who have died who should not be sent further study materials. The data will not be made available to any third parties. Data will be used for study outputs described in this Agreement. All outputs for dissemination will be aggregated outputs with small numbers suppressed in line with the HES Analysis Guide. The University of Leicester are requesting additional data from NHS Digital to obtain long-term follow up for the cohort and add to the data already available above. The study data, including data previously provided by NHS Digital are held at the University of Leicester. All study data is stored in pseudonymised form. All identifiable data is held in a separate database to the study data. Access to study databases is restricted to University of Leicester substantive employees who have been trained in information security. The University of Leicester will send lists of study participants, who have consented in the study, to NHS Digital (via secure upload) for flagging. The lists contain study identifier, NHS number, date of birth, name and address. NHS Digital will match the study participants and return a pseudonymised dataset containing hospital episode statistics and mortality data (HES Admitted Patient Care and mortality data) to the University of Leicester who will link the data to the overall pseudonymised study dataset. Only the pseudonymised dataset will be made available to the wider research team (all substantive employees, University of Leicester) for the purposes of research analysis. Mortality data was originally used to avoid writing out to participants who were deceased, but this will no longer be the case as there will be no further postal contact with participants. All outputs for dissemination will be aggregated outputs with small numbers suppressed in line with the HES Analysis Guide. No other data will be shared with third parties. The Data will only be used for the purposes described in this Agreement. [1 paragraph unchanged] No data will be shared with 3rd parties. The Data will only be used for the purposes described in this agreement.

Expected output

This Agreement permits the secure retention of the data only and no other processing. The recruitment phase of this study is now complete with the major outputs and benefits directly deriving from this dissemination expected between 2021 and 2024. No new outputs will be produced under this Data Sharing Agreement. Outputs to date: The recruitment phase of this study is now complete with the major outputs and benefits expected five to ten years from now. The following provides a summary of projected outputs and benefits. These may change depending on the results of the analysis. The UK Aneurysm Growth Study dataset has generated several important outputs to date. Most relate to the clinical management of AAA and these have informed both NICE and other clinical practice guidelines. The cohort DNA resource has also contributed to the important international genomic collaboration, the Genome Aggregation Database. The initial output will be the creation of a resource of clinical and biological data relating to abdominal aortic aneurysm through the conduct of a prospective cohort study. Electronic health data, including cause of death are a central component of the resource. This resource will be used by the University of Leicester to examine clinical and biological data taken at the time of AAA screening as predictors of future health in men. None of the outputs to date have utilised data obtained from NHS Digital in their analyses as mortality data received by UKAGS was used to identify men who had died who should not be sent further study materials, rather than to inform research analysis. Academic papers will be published in relevant journals that target clinicians on the growth and development of AAA in the immediate future (before 2020). Papers using cause of death as an outcome are not expected to be published until 5 years after recruitment is complete (2023). The most relevant journal for the publication for such outputs is the British Journal of Surgery, a journal where UKAGS outputs to date have already been published. This dissemination of both mortality and HES data will permit extension of the analyses to include a clinical assessment of AAA progression based on time to clinical event analyses. These analyses will primarily consist of clinical and genomic factors influencing AAA progression. Other potential journals that will be considered are the Journal of Medical Screening and, if outputs have significant interest to the broader health community, the British Medical Journal or The Lancet. Academic papers on the growth and development of AAA will be published in relevant journals that target clinicians. Papers using clinical events as an outcome are not expected to be published until 3-5 years after recruitment (2022-24). Data in outputs: All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide. Dissemination and communication plan: The strategy for future outputs will be to use the same approach as that for existing outputs from the overall study. The main target will be academic publications. Study outputs will also be highlighted on the study website and include a plain English summary via that route. Policymakers will be contacted via the research team’s network of national and international policy committees such as the NHS AAA Screening Programme Research Advisory Committee. [1 paragraph unchanged] All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Expected measurable benefits

This Agreement permits the secure retention of the data only and no other processing. The main benefit that may be derived from the addition of NHS Digital data will be in precision medicine. The combined UK Aneurysm Growth Study dataset (including cause of death) and bioresource may enable the examination of clinical and biological data taken at the time of AAA screening as predictors of future health in men. Whilst primarily focussed on AAA related events (rupture, cardiovascular events/mortality) the potential of such a resource to study overall cardiovascular diseases is also important. HES and mortality data will provide clinical events that can be used to determine AAA related morbidity and mortality (e.g. AAA repair or rupture), cardiovascular morbidity/mortality such as admission for cardiovascular events or interventions (improving cardiovascular health is the main potential secondary utility of AAA screening) and the assessment of non-AAA and non-cardiovascular events for comparison. The main benefit that will be derived from the addition of NHS Digital data as study outputs will be in the field of precision medicine. The combined UKAGS dataset (including cause of death) and bio resource will enable the examination of clinical and biological data taken at the time of AAA screening as predictors of future health in men. Whilst primarily focussed on AAA related events (rupture, cardiovascular events/mortality) the potential of such a resource to study other diseases is also important. It is hoped the benefits of the UK Aneurysm Growth Study will primarily be in the clinical management of men with small AAA. Current knowledge of the best management for such men is poor. There is limited advice that clinicians can provide regarding how to prevent an AAA progressing and the UK Aneurysm Growth Study should provide such information. Beyond the management of AAA, UK Aneurysm Growth Study hopefully aims to identify if there are any high risk markers of future poor health that can be identified at AAA screening. These markers may be used in the future to target primary or secondary preventative strategies at any high-risk groups identified. This resource needs to be established first to achieve this benefit. This work is currently in progress. Then a suitable length of follow-up time will need to be added to the resource (5-10 years). Once established, the resource can be used as the basis for additional funding applications to enhance the resource (e.g. with genomic data) and expand upon future utility of the resource. An example for this is the association between high lipid levels and AAA. It is not known but suspected that the new drugs used to treat hyperlipidaemia will also be of benefit for people with AAA. To prove this the study needs to show that the genetic targets of these new drugs are associated with AAA progression. That is one of the aims of the study. If the study can show this then clinical trials of these drugs to prevent AAA progression can be justified. The expected benefits of the UKAGS will not be made until after the initial recruitment period (after 2018). This was established with the funders of the study (primarily the British Heart Foundation) at the time of application for funding. Whilst immediate benefits are desirable in research, the long-term benefits of cohort studies has long been established. Overall genomics studies are helping to build up a genetic profile of men who suffer from AAA. However, it is critical to have a comprehensive understanding of the manifestation and progression of the disease to be able to interpret the genetic data, and in turn publish high quality academic papers. Studies, based on high quality clinical, as well as genetic, data will be critical for clinicians to be able to develop preventative strategies for AAA treatment. The study expect the benefits of the UKAGS to be primarily in the clinical management of men with small AAA. Current knowledge of the best management for such men is poor. There is limited advice that clinicians can provide regarding how to prevent an AAA progressing and the UKAGS will provide such information. Beyond the management of AAA, UKAGS will identify if there are any high risk markers of future poor health that can be identified at AAA screening. These markers may be used in the future to target primary or secondary preventative strategies at any high-risk groups identified. Each year around 500,000 men are screened for AAA in the UK and around 4000 AAA detected. Men with AAA are expected to benefit from this research and a proportion of all men screened should benefit. Each year around 500,000 men are screened for AAA in the UK and around 4000 AAA detected. Men with AAA will directly benefit from this research and a proportion of all men screened will benefit. The United Kingdom Aneurysm Growth Study (UKAGS) have good links with policy makers and other research groups. For example, the Principal Investigator sits on the NHS AAA Screening Programme Research Advisory Committee and is a member of an international consortium for AAA genomics. This may assist in bringing the findings to the attention of key decision-makers in policy or in direct care. Additional benefit of receiving date of death report will be to enable the researcher not to cause distress /not to write to anyone who have died. UKAGS consider it to be good practice to share research findings with study participants and will do this via the website.

Benefits reported

Not stated in the previous version; added here.

Data received from NHS Digital has not been used in the generation of research outputs to date.

Data received to date has ensured that deceased study participants did not receive study materials during the recruitment and direct postal follow up phase of the UK Aneurysm Growth Study.

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

Datasets: + Civil Registrations of Death; + Demographics

Unchanged: Objective for processing, Processing activities, Expected output, Expected measurable benefits.

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

Objective for processing

This Data Sharing Agreement permits the retention and processing of the data provided under previous iterations of this Agreement for an interim period. This is a practical step pragmatic approach to enable NHS Digital to work with the provide an active Agreement whilst enabling University of Leicester to ensure they have complete the necessary legal requirements. 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). The following information provides background information on the purpose of the original study: [14 paragraphs unchanged]

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. The study data, including data provided by NHS Digital under previous agreements, are currently held by University of Leicester. The following provides background on the processing activities undertaken prior to this Agreement: [7 paragraphs unchanged]

Expected output

This Agreement permits the secure retention of the data only and no other processing. No new outputs will be produced under this Data Sharing Agreement. [6 paragraphs unchanged]

Expected measurable benefits

This Agreement permits the secure retention of the data only and no other processing. [6 paragraphs unchanged]