Investigating the association between X-ray guided endovascular aortic aneurysm repair and incidence of cancer

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

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Datasets: + NDRS Cancer Registrations

Objective for processing

This application from King’s College London is to study the potential association between X-ray guided endovascular aortic aneurysm repairs (EVAR), which expose patients to radiation both during the procedure and follow-up CT scans, and future incidence of cancer. It is hoped that defining the risk of cancer after EVAR will contribute to the process of informed consent and decision making between open aneurysm repair and EVAR. Kings College London (KCL) requires access to NHS England data for the purpose of the following research project: Investigating the association between X-ray guided endovascular aortic aneurysm repair (EVAR) and incidence of cancer. Primary objective: There are two objectives to the study: To define the relative risk of developing cancer after EVAR versus after open repair for aortic aneurysms. Primary objectives: To define the relative risk of developing cancer after EVAR versus after open repair for aortic aneurysms thereby giving patients more information while they make decisions for their treatment options. [1 paragraph unchanged] To identify the types of cancers that develop in patients after EVAR. To determine the median intervals between radiation exposure during EVAR and development of cancer. To determine the median intervals between radiation exposure during EVAR and development of cancer. The reason for data access is to compare the incidence of radiation-related cancer for patients who underwent endovascular aneurysm repair (EVAR) versus open aneurysm repair. Lawful basis: The following NHS England data will be accessed: King’s College London’s justification for processing is GDPR Article 6 (1) (e): The processing necessary to perform this task is in the public interest and the task has a clear basis in law. The results of this study will provide information about the risks of radiation-cancer associated with EVAR. Given that an alternative is available, these results could inform decisions about which treatment should be offered to patients in future. KCL are a public authority (university) carrying out a research project. - Hospital Episode Statistics Admitted Patient Care (HES APC): To identify patients who underwent endovascular aneurysm repair and open aneurysm repair from January 2000 to December 2018. Relevant demographic and medical information are required to account for cofounding factors. This dataset will also be used to create the cohort for the National Disease Registration Service (NDRS) Cancer Registry dataset. GDPR Article 9 (2)(j): processing is necessary for scientific research purposes and shall be proportionate to the aim pursued, respect 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 is a scientific research project. - NDRS Cancer Registry Data: To compare the incidence of cancer between two groups of patients following their respective procedures. Timeline of cancer diagnosis and cancer morphology is key to understand their relation to radiation exposure. Ethical considerations: The level of the data will be pseudonymised. The dissemination of the aggregated results of this study pose minimal risk to the public. The two datasets mentioned above should be linked by NHS England and all identifiable details are pseudonymised prior to data release. Only data that is relevant to the purpose of this study is requested. Potential ethical considerations are that patients in the HES registry and NCRAS did not actively give consent for their data to be used for this study, and seeking consent is not feasible due to the number of patients involved and the fact that many of these patients will already be deceased. The study team have gained authorisation to use this data under s251 approval. Potential data breaches are another ethical consideration. The study team (at KCL) will be minimising this by requesting only pseudonymised data from NHS Digital and NCRAS and only the necessary data for the analysis to be transferred to KCL. However, there will be a need for one transfer of data owed a duty of confidence (NHS number and DOB) between NHS digital and Public Health England in order to facilitate data linking. Both NHS Digital and Public Health England will then send pseudonymised data to the research team at Kings College London. The data linkage between the NHS D data and the NCRAS data will occur based on the pseudo-IDs. The pseudonymised data received by KCL will be stored on 2 encrypted password protected computers. HES APC The study team have discussed the feasibility of the proposal with NHS digital and Public Health England, who hold and manage the HES and NCRAS databases, respectively. Both of these organisations will be named as sources of the data on any ensuing publications. Publications resulting from this data will be readily available to healthcare professionals, patients, and the public. • Limited to data between 01 January 2000 to 31 December 2018, Where possible, the study team have sought to seek the opinions of relevant patient groups and the public on this research. The study team recently held an event at the Academic Department of Vascular Surgery attended by vascular and cardiology patient groups, as well as donors and staff from the British Heart Foundation. This study proposal was presented and discussed during a session on the effects of ionizing radiation in vascular surgery. The study has also been discussed with the local Patient and Public Involvement group for their input. • Limited to the following geographic areas England, It is hoped that the data requested will allow an assessment of the relative risk of cancer after EVAR compared to open aneurysm repair. It will also inform on the most likely types of cancer. • Limited to patients above the age of 50, The request is part of a PhD based at the Academic Department of Vascular Surgery (King’s College London), a British Heart Foundation centre of excellence. The PhD student is substantively employed at King’s College London as a Clinical Research Fellow. The wider project commenced in October 2018 and is investigating the effects of radiation in vascular surgery, both on patients and surgeons. • Limited to conditions relevant to the study identified by specific ICD or OPCS codes; The data requested here will be used for the described segment of the project only and will have no use in any other segment of the wider project. However, the wider project, as above, commenced in October 2018 and is investigating the effects of radiation in vascular surgery, both on patients and surgeons. This mainly involves basic laboratory research and is a collaboration between the team at King’s College London and the Centre for Health Effects of Radiological and Chemical Agents (Brunel University) and the Centre for Radiation, Chemical and Environmental Hazards (Public Health England). The requested data will be used for the arm of the study investigating the long-term effects of radiation from EVAR on patients. The PhD consists of several parts - one of which depends on the requested data from NHS Digital and PHE. - ICD-10 codes, I714, I719, The subjects in this study are all patients over 50 years old who have undergone aortic aneurysm repairs. The study arm will be made up of those who underwent an endovascular aneurysm repair (EVAR), which involves radiation, whereas the control arm is made up of patients who underwent an open aneurysm repair. Within the EVAR group, the patients can be further subdivided into simple and complex EVAR for subgroup analysis. - OPCS-4 codes, L184, L185, L186, L188, L189, L194, L195, L196, L198, L199, L231, L236, L238, L239, L254, L258, L259, L271, L275, L276, L278, L279, L281, L285, L286, L289. The purpose of this project is to investigate the association, if any, of radiation exposure during endovascular aneurysm repair (EVAR) with future development of cancer. For this the study team will be comparing a cohort of patients undergoing EVAR with a control cohort undergoing open aneurysm repair. Cancer Registry Patient identifiers (DOB and NHS numbers) will be required in order to facilitate linking of HES data with the National Cancer Registration and Analysis Service (NCRAS) database. Patient demographics, age, past medical history and social history are also required to account for confounding factors during statistical analysis. • Limited to data between 01 January 2000 to latest available, Once the initial transfer from NHS digital to PHE (NCRAS) is complete, patient identifiers will be removed, and the research group will receive pseudonymised HES data. • Limited to the following geographic areas England, The number of years requested is based on the following power calculation. • Limited to conditions relevant to the study identified by specific ICD or OPCS codes; To achieve 95% confidence, 80% power assuming proportion of deaths caused by any cancer of 20.9% (EVAR) and 19.7% (open) – these figures are taken from the currently available literature. - ICD-10 codes: C00-C97 for malignant disease, Recommended sample size = 39,000 patients (13,000 EVAR, 26,000 open) - ICD-10 codes: D00 – D48 for benign disease for benign disease. + 3% for attrition of data = 40,170 (13,390 EVAR, 26,780 open) Kings College London 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. UK Health Security Agency a joint data processor with Kings College London. Based on approximate number of patients undergoing EVAR and open aneurysm repairs in England each year, 18 years of data will be required to achieve these number. The lawful basis for processing personal data under the UK GDPR is: Only data that will be required from statistical analysis to answer the study question has been requested. Patient identifiers will be required for data linkage with NCRAS so once the HES data has been extracted by NHS Digital based on ICD-10 and OPCS-4 codes, the relevant identifiers (NHS Number, DOB) and pseudonymised data (Date of Surgery and Study ID) will be passed to PHE. However, beyond the first transfer of data from NHS digital to PHE, patient identifiers will not be used, and the resultant HES data will be pseudonymised before being sent to the research team at KCL. 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. Data Flow The lawful basis for processing special category data under the UK GDPR is: The steps involved in this are as follows: 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. 1) King’s College London provides inclusion criteria to NHS Digital This processing is in the public interest because the results of this study will provide information about the risks of radiation-cancer associated with EVAR. Given that an alternative is available, these results could inform decisions about which treatment should be offered to patients in future. 2) NHS Digital identifies patients from HES according to ICD-10 and OPCS-4 codes The funding comes from Kings College London 3) NHS Digital transfers identifiers of those patients only (NHS number, DOB) along with pseudonymised data (date of surgery, pseudo ID) to Public Health England. This will be done under DARS-NIC-467721 Funding to continue the work described will be sought on an ongoing basis. 4) NHS Digital transfers patient demographic and surgical data and pseudo IDs to King’s College London. This will be done under DARS-NIC-264102 (THIS AGREEMENT) The funders will have no ability to suppress or otherwise limit the publication of findings. 5) Public Health England extracts cancer data relevant to these patients from NCRAS UK Health Security Agency is a joint data processor acting under the instructions of Kings College London. The Radiation Epidemiology Group at UKHSA, as recognised leading experts in epidemiological analysis, will be providing support in the data processing and analysis part of the project. The academic collaboration on radiation-related research between the two units is well-established. The Radiation Epidemiology Group has the experience and expertise in managing the size of the data the study team are expecting and will therefore be able to provide valuable insight. UK Health Security Agency’s role is limited to analysing the data provided in accordance with this application. 6) Public Health England sends cancer data and pseudo IDs to King’s College London Data will be accessed by a PhD student affiliated with Kings College London and the supporting staff. The individual has completed mandatory data protection and confidentiality training and is subject to Kings College London’s policies on data protection and confidentiality. The individual accessing the data will do so under the supervision of a substantive employee of Kings College London. Kings College London would be responsible and liable for any work carried out by the individual. The PhD student would only work on the data for the purposes described in this Agreement. 7) Linking of demographic, surgical and cancer data at King’s College London (via pseudo study ID) Additionally, an individual from UK Health Security Agency will be accessing the data to conduct statistical and epidemiological analysis of the data. The individual has completed mandatory data protection and confidentiality training and is subject to UK Health Security Agency’s policies on data protection and confidentiality. UK Health Security Agency would be responsible and liable for any work carried out by the individual. The sole data controller will be the research team at King’s College London as previously detailed. The other organisation involved is National Cancer Registration and Analysis Service (NCRAS), based at Public Health England (PHE). The team at PHE will provide cancer data from NCRAS pertaining to the patients identified from the HES database. In line with the national data opt-out policy, opt-outs are not applied because the data is not Confidential Patient Information as defined in section 251(10) and section 251(11) of the National Health Service Act 2006. The primary investigator is a substantive employee of King’s College London and has a clinical role at St Thomas Hospital. No other St Thomas Hospital staff will be involved in the project. The PI will lead on the processing of the data and will be responsible for any output from this project. Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out. No other organisations will be involved in accessing or processing this data. The Centre for Health Effects of Radiological and Chemical Agents (Brunel University) is involved in the wider project and their role is specifically in the processing of biological samples. They will not be involved in the processing or decision making regarding NHS Digital data. No funders/commissioners will be involved in the project. ******This application is for the flow of data to KCL.********

Processing activities

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 ie: employees, agents and contractors of the Data Recipient who may have access to that data)”. No data flows into NHS England for the purposes of this Agreement. Patients undergoing aortic aneurysm repair either by an open approach (OAR) or endovascular approach (EVAR) between January 2000 and December 2018 will be identified by NHS Digital from the Hospital Episode Statistics (HES) dataset using OPCS codes. NHS England will derive the cohort for the NDRS Cancer Registry dataset using the BAU HES APC dataset. NHS England will provide the relevant records from the BAU HES APC dataset and the NDRS Cancer Registry datasets to Kings College London. The data will contain no direct identifying data items but will contain a unique person ID. These patients will be over the age of 50, as those under the age of 50 have a different pathology which makes them unsuitable for this study. This should provide approximately 40,000 patients as per the sample size calculation detailed above. NHS England will identify two groups of patients (endovascular and open aneurysm repair) from the BAU HES APC dataset and will link these with the NDRS Cancer Registry datasets to get corresponding information for the two groups. Once the patients have been identified from HES by NHS Digital, the national opt-out will be applied to remove any patients who have requested an opt-out. Patients aged under 50 years at time of operation and patients having their operation outside of England will also be excluded at this stage. There will be no further flows of data to any other location or organisation. A list of the remaining patient NHS numbers, dates of birth and a unique pseudo ID will be transferred to Public Health England (PHE) by secure electronic transfer agreed between NHS Digital and PHE. This will be done under DARS-NIC-467721 The data will be stored on servers at King’s College London. Patients will be identified by ICD-10 diagnostic codes for aortic aneurysm and also by OPCS-4 for various types of aortic aneurysm repair as follows: No data will be stored or backed-up in any other locations other than King's College London. UKHSA will not receive any of the data. ICD-10 Diagnostic codes – 1714, 1719 The data will be accessed by UKHSA via King’s College Londons One Drive with password and authenticator protection. The data will only be accessed via the secured networks of King’s College London and UKHSA. The Data will be accessed by all authorised personnel via remote access meeting the following standards: OPCS-4-Procedural codes – L184, L185, L186, L188, L189, L194, L195, L196,L198, L199, L231, L236, L238, L239, L254, L258, L259, L49, L271, L275, L276, L278, L279, L281, L285, L286, L289 - 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; At PHE, the National Cancer Registration and Analysis Service (NCRAS) will perform a look up on the cancer registry using deterministic matching based on NHS number and date of birth. This process will identify which patients developed cancer after their procedure. Follow-up on NCRAS will continue to December 2020 such that any patients from the original HES dataset who have a diagnosis of a primary tumour as per future NCRAS data releases can be included in the analysis. - Access controls granting users the minimum level of access required are in place; PHE will then send the cancer data including date of diagnosis, type and stage of cancer to King’s College London (KCL) in a pseudonymised format using pseudo IDs. - Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data; NHS digital will also send the demographic (date of birth, sex), clinical details (e.g. smoking status, diabetes, heart disease) and operative details to KCL in a pseudonymised format using the same pseudo IDs. (THIS WILL BE DONE UNDER UNDER DARS-NIC-264102 - THIS AGREEMENT) - Multifactor authentication (MFA) is required for remote access; Linking of pseudonymised data from HES and NCRAS will then be performed at KCL. At this point, dates of surgery will be compared with dates of cancer diagnosis to allow exclusion of patient with pre-existing cancers or previous radiotherapy treatment. An interval period between date of surgery and date of cancer diagnosis will also be applied to account for concurrent diagnoses. - Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access; ******This application is for the flow of data to KCL.******** - 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 data will not leave England/Wales at any time. The use of data provided will solely for the purpose of the study. Access is restricted to employees and students of King's College London and the Radiation Epidemiology Group of UK Health Security Agency who have authorisation from the Principal Investigator. No other organisations are permitted to access the data other than King’s College London and the Radiation Epidemiology Group of UK Health Security Agency. Individuals accessing the data are appropriately trained in data protection and confidentiality and supported by expert epidemiologist. The data will not be linked with any other data outside of the scope of the agreement. Patients’ identifiable details are only used by NHS England to link the two separate datasets, only pseudonymised information will be released upon completion of data extraction. There will be no requirement and no attempt to reidentify individuals when using the data. The incidence of cancer and number of X-ray diagnostic images will be linked to patients who underwent endovascular and open aneurysm repair and compare between two groups. Researchers from Kings College London and the Radiation Epidemiology Group at UK Health Security Agency will process the data for the purposes described above.

Expected output

The data will be analysed by the research team at King's College London and its conclusions will be published in the medical literature in adherence to local publication policies. The outputs of this project will also contribute to a PhD thesis. All outputs will be aggregated with small numbers suppressed in line with the HES analysis guide. NHS digital and PHE will be named as sources of the data on any resulting publications. The conclusions of the study will also be disseminated by way of presentations at vascular surgery conferences such as the Vascular Society of Great Britain and Ireland, Charing Cross Symposium, and the European Society of Vascular Surgeons. As a result of participation at these conferences, the headline messages from the project may be shared on social media platforms. The expected outputs of the processing will be: By these means of publicly available medical journal publications and conference presentations, the key message of the relative risk of radiation-related cancer after endovascular aneurysm repairs will be disseminated. This information will be beneficial when clinicians are informing and consenting patients for operations and help them decide, with the clinical team, which procedure is most appropriate for them. Furthermore, these conclusions will add to the current knowledge base and better inform patients with abdominal aortic aneurysms about their options and the risks involved. • Submissions to peer reviewed journals at the end of the study, The raw data will be deleted at the end of the study. The target date for completion of the study is October 2023. • Submission to Kings College London to complete PhD studies, One member of the research team who will be involved in data analysis is currently undertaking a PhD and is a substantive employee of King's College London. The outputs of this project will contribute to his PhD studies. • Presentations at appropriate conferences such as: British Society Endovascular Therapy (BSET), European Society for Vascular Surgery (ESVS) Annual Meeting. ******This application is for the flow of data to KCL.******** The outputs will not contain NHS England data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived. The outputs will be communicated to relevant recipients through the following dissemination channels: • Industry newsletter, • Journals, • Posters displayed at conferences, • Patient Information leaflets available at hospitals. Target date of the project completion is 01 October 2025. It is envisaged that the data analysis would be completed, and the PhD thesis would be submitted by this date.

Expected measurable benefits

It is anticipated the data will inform on the risk of radiation-related cancer after endovascular aneurysm repairs and This information may be beneficial when clinicians are informing and consenting patients for operations and will help them decide, with the clinical team, which procedure is most appropriate for them. It is anticipated the information patient. These conclusions will also inform the vascular community about the long-term risks of these procedures and contribute add to the debate about the cost effectiveness of endovascular aneurysm repairs. The dissemination of the results will be in the public interest as it will provide transparency around the current knowledge base upon which treatment decisions are taken. and better inform patients with abdominal aortic aneurysms about their options and the risks involved. Ultimately, patients will be reliably informed of their risk of developing cancer after endovascular aneurysm repairs. They will be able to use this information in deciding whether to accept that risk or opt for an open surgical repair, or indeed to decline surgery altogether. The outputs of the research are hoped to ascertain the radiation-related risk of EVAR thereby helping both clinicians and patients make decisions on treatment options for abdominal aortic aneurysm. The journals and the conferences will allow clinicians to be more informed about the risks and will let them decide the appropriate treatment for the patient and the information will assist the clinicians when informing the patient on their treatments. It is hoped the outputs will provide a calculation of the relative risk of developing cancer after having an endovascular aneurysm repair versus and open aneurysm repair. After accounting for confounding factors, a comparison will be made between the two procedures, thus achieving the stated purpose. The conclusions of the research will be disseminated by way of presentations at appropriate vascular surgery conferences. As a result of participation at these conferences, the headline messages from the project may be shared on social media platforms. It is hoped that the benefits of this project will be to add to the current knowledge base and better inform patients with abdominal aortic aneurysms about their options and the risks involved. The research team are clinicians in vascular surgery and therefore will be able to directly use the outputs of this project to inform their patients. Hopefully, dissemination of data will allow other clinicians to do the same. ******This application is for the flow of data to KCL.********

Benefits reported

Stated in the previous version and removed here.

Yielded Benefits is not a requirement for new applications.