Investigating the association between X-ray guided endovascular aortic aneurysm repair and incidence of cancer (v2)

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.

Primary objective:

To define the relative risk of developing cancer after EVAR versus after open repair for aortic aneurysms.

Secondary objectives:

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.

Lawful basis:

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.

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.

Ethical considerations:

The dissemination of the aggregated results of this study pose minimal risk to the public.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The number of years requested is based on the following power calculation.

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.

Recommended sample size = 39,000 patients (13,000 EVAR, 26,000 open)

+ 3% for attrition of data = 40,170 (13,390 EVAR, 26,780 open)

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.

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.

Data Flow

The steps involved in this are as follows:

1) King’s College London provides inclusion criteria to NHS Digital

2) NHS Digital identifies patients from HES according to ICD-10 and OPCS-4 codes

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 (THIS AGREEMENT)

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

5) Public Health England extracts cancer data relevant to these patients from NCRAS

6) Public Health England sends cancer data and pseudo IDs to King’s College London

7) Linking of demographic, surgical and cancer data at King’s College London (via pseudo study ID)

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.

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.

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 PHE********

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)”.

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.

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.

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.

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 (THIS AGREEMENT)

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:

ICD-10 Diagnostic codes – 1714, 1719

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

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.

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.

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 DARS-NIC-264102.

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.

******This application is for the flow of data to PHE.********

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.

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.

The raw data will be deleted at the end of the study. The target date for completion of the study is October 2023.

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.

******This application is for the flow of data to PHE.********

It is anticipated the data will inform on the risk of radiation-related cancer after endovascular aneurysm repairs and be beneficial when informing and consenting patients for operations and help them decide, with the clinical team, which procedure is most appropriate for them. It is anticipated the information will also inform the vascular community about the long-term risks of these procedures and contribute 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 knowledge base upon which treatment decisions are taken.

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.

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.

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 PHE.********

Yielded Benefits is not a requirement for new applications.