The Manchester University NHS Foundation Trust (MUFT) Cardiovascular Magnetic Resonance Study

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Objective for processing

[1 paragraph unchanged] The public interest justification for article 9(2)(j) – for public health purposes, is therefore that the University Hospital of South Manchester (UHSM) CMR study aims to investigate the diagnostic and prognostic utility of CMR scanning in a large cohort of unselected patients who are already undergoing CMR scanning for clinical indications. This means the study team are assessing how well CMR is in not only being able to identify heart conditions (diagnosis), but also how specific heart findings impact on people’s life expectancy and quality of life. The study team are currently looking to assess a subset of the patients from the UHSM CMR study. This subset of patients was recruited between 1st June 2016 and 31st May 2018. CMR indices will be related to the presence and severity of cardiovascular disease and other markers of cardiac disease. For example, the study team will measure how much scar tissue the heart contains and whether this impacts on how well the heart is able to pump blood. This study will rely upon UK GDPR articles 9(2)(j) and 6(1)(e). The justification for Article 6(1)(e) processing therefore, as necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller, is that few centres have sufficient patient through-put to provide this information. The Manchester University NHS Foundation Trust (previously University Hospital of South Manchester (UHSM)) CMR Unit is one of the highest volume CMR centres world-wide with capacity for 5000 scans per year. Thus the UHSM CMR centre is well placed to do this study, indeed it has an obligation to carry out this work and provide this information to the community in order to improve patient care, locally and internationally. The public interest justification for UK GDPR article 9(2)(j) – for public health purposes, is therefore that the Manchester University NHS Foundation Trust (MUFT) CMR study aims to investigate the diagnostic and prognostic utility of CMR scanning in a large cohort of unselected patients who are already undergoing CMR scanning for clinical indications. This means the study team are assessing how well CMR is in not only being able to identify heart conditions (diagnosis), but also how specific heart findings impact on people’s life expectancy and quality of life. The study team are currently looking to assess a subset of the patients from the MUFT CMR study. This subset of patients was recruited between 1st June 2016 and 31st May 2018. CMR indices will be related to the presence and severity of cardiovascular disease and other markers of cardiac disease. For example, the study team will measure how much scar tissue the heart contains and whether this impacts on how well the heart is able to pump blood. All patients recruited into the UHSM CMR study provide written informed consent to be enrolled into the study, with specific consent given stating: ‘I understand that the information held and maintained by The Health and Social Care Information Centre and other central UK NHS bodies, audits and registries, and local healthcare bodies and clinical commissioning groups, may be used to help contact me or provide information about my health status.’ The justification for UK GDPR Article 6(1)(e) processing therefore, as necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller, is that few centres have sufficient patient through-put to provide this information. The Manchester University NHS Foundation Trust (previously University Hospital of South Manchester (UHSM)) CMR Unit is one of the highest volume CMR centres world-wide with capacity for 5000 scans per year. Thus the MUFT CMR centre is well placed to do this study, indeed it has an obligation to carry out this work and provide this information to the community in order to improve patient care, locally and internationally. The UHSM CMR study requires follow-up information on the health status of the study cohort. This is limited to three variables (death, cause of death, hospital admission for heart failure). Such data will be used to perform survival analysis and multivariable regression analysis and risk modelling for death (all-cause and/or cardiovascular) and heart failure hospitalisation. All patients recruited into the MUFT CMR study provide written informed consent to be enrolled into the study, with specific consent given stating: ‘I understand that the information held and maintained by The Health and Social Care Information Centre and other central UK NHS bodies, audits and registries, and local healthcare bodies and clinical commissioning groups, may be used to help contact me or provide information about my health status.’ Hospital episode statistics (HES) are an important source of data and can identify patients who have been admitted to hospital for heart failure. Civil Registration Data (CRF) mortality information can provide information relating to patients who have died including the cause of death. For both data sets the period of interest is between 1st June 2016 and 31st May 2018. This is the recruitment period in the cohort of patients the study team are currently assessing. For data minimisation, no data is requested for patients recruited outside of this time window. No demographic filtering will be required. For the HES data set, the only variables that will be requested are hospital admission date and diagnoses, in order to identify if a patient was treated in hospital for heart failure. No other variables will be selected. For the CRD data set, the study team will only require the variables date of death and cause of death. For data minimisation, no other variables will be requested. The MUFT CMR study requires follow-up information on the health status of the study cohort. This is limited to three variables (death, cause of death, hospital admission for heart failure). Such data will be used to perform survival analysis and multivariable regression analysis and risk modelling for death (all-cause and/or cardiovascular) and heart failure hospitalisation. Identifying data will only be used to confirm the health status of the individuals who have provided written consent to be included in the study and for this information to be obtained by the research team. Information will be kept for a period of 5 years in case of a data challenge to the published findings. The alternative method for obtaining such outcome data is to contact each patient individually (which they have consented to), however this is more intrusive to patients and less practical to given the large cohort size (approximately 4000). Hospital episode statistics (HES) are an important source of data and can identify patients who have been admitted to hospital for heart failure. Civil Registration Data (CRD) mortality information can provide information relating to patients who have died including the cause of death. For both data sets the period of interest is between 1st June 2016 and 31st May 2018. This is the recruitment period in the cohort of patients the study team are currently assessing. For data minimisation, no data is requested for patients recruited outside of this time window. No demographic filtering will be required. For the HES data set, the only variables that will be requested are hospital admission date and diagnoses, in order to identify if a patient was treated in hospital for heart failure. No other variables will be selected. For the CRD data set, the study team will only require the variables date of death and cause of death. For data minimisation, no other variables will be requested. Manchester University NHS Foundation NHS Trust are the sole data controller and data processor for the UHSM CMR study. The study is funded by the National Institute for Health Research Identifying data will only be used to confirm the health status of the individuals who have provided written consent to be included in the study and for this information to be obtained by the research team. Information will be kept for a period of 5 years after the final report in case of a data challenge to the published findings. The alternative method for obtaining such outcome data is to contact each patient individually (which they have consented to), however this is more intrusive to patients and less practical to given the large cohort size (3,844). The full CMR study cohort size is 10,005. The existing agreement pertains to a subset of these patients recruited between June 2016 and May 2018. This cohort comprises 3,844 eligible patients. MUFT are the sole data controller and data processor for the CMR study. The study is funded by the National Institute for Health Research and has been confirmed to cover the study until completion as necessary. Bayer provided start-up funding to support the set-up of the study. Bayer had no role in the study design, data collection, data analysis, data interpretation, or production of any study associated outputs.

Processing activities

The UHSM CMR study data is stored in a database on an NHS computer, [40 words unchanged] in a locked office, in order to contact the participants if required. The flow of data into NHS Digital England is limited to personal identifying information required for data linkage and verification, including study ID, NHS number, date of birth, and gender. Data files can be sent via secure nhs.net email account with associated [SECURE] encryption application. All participants provided written informed consent to take part in the study, including for access to their health records and information held and maintained by NHS Digital formally known as The Health and Social Care Information Centre. England. [2 paragraphs unchanged] Outcome data supplied by NHS England will be processed and included in the UHSM CMR Study database to allow for subsequent ethically approved analysis. Outcome data will be linked to the participant record contained within the database. The UHSM MUFT CMR Study database is then pseudonymised. Dates of events, including date of death and date of hospital admission, are required to calculate time periods for subsequent survival analysis. All data processing is performed onsite within an NHS trust. Database access is limited to qualified research staff associated with the study. Manchester University NHS Foundation Trust is the sole data controller for this study. All research staff working with the data are substantive employees at the host site. MUFT. Data will not be shared with any third parties who are not affiliated with the study. Heart failure and heart disease has a very high incidence in the United Kingdom, therefore it is considered highly unlikely that re-identification will occur. No further linkage is permitted in this Agreement,

Expected output

The study team intends to produce a large high quality database, containing NHS Digital data, populated with clinically relevant disease markers and labels associated with cardiovascular disease. A stated objective for data processing was to establish the prognostic value of information CMR provides and furthermore, to relate CMR indices to the presence and severity of cardiovascular diseases and other markers of cardiac disease. The outputs from this database will include comprehensive descriptive modelling of cardiovascular diseases, predominantly relating to heart failure and cardiomyopathy. Furthermore, specific causes of cardiovascular disease (for example, myocardial fibrosis or ‘heart scarring’) can be interrogated and, with the information from NHS Digital, their impact on outcome assessed. This is important to potentially identify newer ways of treating patients through meaningful disease mechanisms using targeted therapies. Stated outputs that have so far been achieved include: The outputs from the database will include submission of academic papers to peer reviewed journals, commencing in 2020 onwards. The results will be disseminated amongst the medical community via presentations at academic conferences both nationally and internationally. The findings and results will also be presented to patient groups. • The production of a large, high-quality database populated with relevant markers associated with cardiovascular disease The study have a dedicated patient advisory group. This is funded by NIHR. The group comprises 6 patients and is chaired by a representative of a patient-led charity. The group helped confirmed the studies importance for patients. The group has met annually throughout the study to provide input on study progress and management. The study team will discuss the findings with the group and get their input on the interpretation of the findings. The dissemination will include presentation to patient groups, and members of the advisory group will take part in these presentations • Descriptive modelling of patients with, or at risk of, heart failure (a specific cardiovascular disease), to identify factors in these patients that are most associated with adverse outcomes including hospitalisation for heart failure and death This will form the bases for a series of peer reviewed journal articles, commencing in 2020 onwards. • Presentation of novel research findings at national conferences including BSCMR (British Society for Cardiovascular Magnetic Resonance), BSH (British Society for Heart Failure) and BCS (British Cardiovascular Society) Findings from such articles will be disseminated amongst the medical community via presentations at both national and international conferences. Additionally, findings will be communicated to patients via Patient and Public involvement (PPI) including charity foundations (including the Pumping Marvellous Foundation, the largest UK Heart Failure Charity). However, there remain some outstanding outputs, as well as some further outputs in line with the stated objectives that have arisen as a direct result of the planned investigations. Outstanding or previously unstated outputs to be completed include: Furthermore, the UHSM CMR Study provides an annual update to a Patient Advisory Group (PAG), consisting of patients and members of the public. • Assessment of the impact of myocardial fibrosis, or ‘low-level heart scarring’ (a known cause of cardiovascular disease), in the onset of heart failure in patients with prior history of myocardial infarction (also known as ‘heart attacks’) Completion expected 31/07/2024. • Determine predictors of cardiac remodelling in patients with prior history of heart attack, and to determine the relationship between cardiac remodelling and the scale of cardiac damage resulting from heart attacks infarct size. Completion expected 31/07/2024. • Presentation of these outputs at international conferences • Due to the impact of the COVID-19 pandemic, the annual update to a dedicated patient advisory group was suspended indefinitely in 2020. Communication of these outputs to patients and members of the public therefore remains outstanding. The outputs have been presented at conferences, and further presentations may yet be undertaken where appropriate.

Benefits reported

Yielded Benefits is not a requirement for new applications. The benefits achieved as an outcome of the proposed data uses are outlined below: • Demonstrated the importance of myocardial fibrosis quantification, in combination with other clinically relevant disease markers, as a prognostic marker in patients with, or at risk of, heart failure. Excellent risk stratification is now possible in these patient groups thanks to the bespoke risk calculator developed and validated. Work to implement the risk calculator for the purpose of improving patient health outcomes is planned. • The risk calculator developed with the data has informed the design of a programme to investigate the utility of the risk prediction tool in a primary care setting. The developed tool is implemented with the purpose of identifying patients at risk from heart failure earlier in the patient pathway. The improved detection of early heart failure leads to subsequent improvements in the timing and targeting of interventions, in a more cost-effective, and potentially preventative manner. • Development of the database has led to increased understanding of the health of the regional population. As the primary centre for cardiovascular imaging in the North-West, this represents an understanding of the health of the UKs third largest region. • The outputs have contributed to the planning of a subsequent database to more closely interrogate ‘heart failure with preserved ejection fraction’, and improve outcomes within this condition. In part thanks to the database developed, it is becoming clear that the diagnosis of heart failure with preserved ejection fraction includes patients with a range of different underlying heart and blood vessel abnormalities, as well as different underlying conditions which may contribute to their heart failure. A nationwide registry has therefore been commissioned. • Supported knowledge creation and exploratory research, and in turn the innovations and developments that might result from that work Further future potential benefits from the database generated with support from NHS England could include clarification of the disease processes underpinning a range of cardiovascular disorders.

Unchanged: Expected measurable benefits.