Epidemiology of Cancer after solid Organ Transplantation - EPCOT study ( ODR_2014_244 )

University Hospitals Birmingham NHS Foundation Trust (UHB) requires access to NHS England data for the purpose of the following research project: Epidemiology of Cancer After Solid Organ Transplant (EpCOT) study.

The following is a summary of the aims of the research project provided by UHB.

Cancer is a major cause of morbidity and has become the leading cause of death after solid organ transplantation.

There is a shortage of research exploring cancer epidemiology after solid organ transplantation in the UK. As a result, there are no guidelines to advise transplant clinicians about post-transplantation cancer and this may impact upon clinical care. This is especially important as outcomes of cancer post-transplantation may differ from the

general population.

Data regarding transplantation, cancer, hospital episodes and death is currently routinely collected as part of mandatory data collection for different registries, but these records are not linked to each other. This means it is impossible to get an integrated insight into cancer epidemiology after solid organ transplantation. Clinicians therefore do not know why post- transplant cancer risk is different for different recipients, what morbidity is associated with posttransplant cancer, how outcomes differ for post-transplant cancer versus the general population.

The main objective for the EpCOT project is to link data sets which already exist in isolation to create an integrated data set that can explore post- transplant cancer epidemiology and help answer some of these questions.

The following NHS England data will be accessed:

- Hospital Episode Statistics (HES) (requested in application DARS-NIC-77142)

- Admitted Patient Care (APC)

- Outpatients (OP)

- Civil Registration Mortality (requested in application DARS-NIC-77142)

- NDRS Cancer Registry (requested in application DARS-NIC-656749)

- NDRS Radiotherapy dataset (RTDS) (requested in application DARS-NIC-656749)

- NDRS Systemic Anti-Cancer Therapy Dataset (SACT) (requested in application DARS-NIC-656749)

The data requested are required for the analysis to obtain the outcomes for the aims of the study, including; comparing of observed and expected risks of specific causes of death, comparing of observed and expected risks of specific cancer types post-transplantation and estimating risk of morbidity requiring hospitalisation both generally and that associated with the development of post-transplantation cancer.

The level of the data will be pseudonymised.

The data will be minimised as follows:

- Limited to data for a study cohort of approximately 85,000 transplant patients. Identified from the UK Transplant Registry (UKTR) who met the inclusion criteria (individuals who have received a solid organ transplant (e.g. kidney, liver, heart, lung, pancreas, small bowel) between 01/01/1985 and 31/12/2015) which UKTR provided to NHS England in the previous iteration of this agreement.

- Limited to data between 1997/98 (where available) and 2018/19 for HES data and latest available (expected 2023) for Civil Registration Mortality.

University Hospitals Birmingham NHS Foundation Trust (UHB) is the data controller and is the organisation responsible for ensuring that the data will only be processed for the purpose described above.

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller.

The lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research and aims to produce generalisable and publicly available information to inform future decisions over patients treatments or care.

The funding is provided by the Wellcome Institutional Strategic Support Fund through the University of Birmingham. The funding is specifically for the study described. Funding is in place with no time limit.

University of Birmingham (UoB) is the data processor acting under the instructions of University Hospitals Birmingham NHS Foundation Trust. UoB's role is limited to processing the data on behalf of the Trust.

The funders will have no ability to suppress or otherwise limit the publication of findings.

Data may be accessed by Postgraduate students affiliated with UoB. Any student working with the data held under this Agreement must have completed mandatory data protection and confidentiality training and are subject to UoB's policies on data protection and confidentiality. Any students accessing the data will do so under the supervision of an employee of UoB with authorised access to data. UoB would be responsible and liable for any

work carried out by students. These students would only work on the data for the purposes described in this Agreement. Any education benefit gained from carrying out this work would be an associated benefit and would not be the primary reason for the research being conducted nor the primary reason for their involvement.

A Public and Patient Information and engagement group was consulted regarding the collection of the data for the purposes described above. The EpCOT project was originally discussed with Patient Advisory Boards within NHS Blood & Transplant and with the UHB PPI group which included transplant patients.

No data will flow to NHS England for the purposes of this Agreement.

In a previous iteration of this agreement, UKTR and Public Health England (NCRAS - this service is now managed by NHS England) transferred data to NHS England. The data consisted of identifying details (specifically NHS Number, Date of Birth, Postcode, Gender and a unique person ID).

NHS England generated a common patient identifier (a random unique large integer) for all individuals in the underlying cohort from UKTR - hereby referred to as CPID. NHS England identified and linked those patients who were common to both cohorts. NHS England returned the identifying details provided, along with the CPID back to NCRAS and UKTR respectively.

NHS England will link the UKTR cohort to the relevant records from HES APC, OP and Mortality datasets, along with the CPID, and provide to UoB. The data will contain no direct identifying data items. The data will be pseudonymised and individuals cannot be reidentified through linkage with other data in the possession of the recipient.

NCRAS at Public Health England linked the UKTR cohort to the relevant records from Cancer Reg, SACT and RTDS datasets, along with the CPID, and provide to UoB. The data contained no direct identifying data items. The data was pseudonymised and individuals cannot be reidentified through linkage with other data in the possession of the recipient.

The data will not be transferred to any other location.

The data will be stored on servers at the University of Birmingham (UoB).

The data will be accessed onsite at the premises of the University of Birmingham (UoB) and the data will also be accessed by authorised personnel via remote access. The data will remain on the servers at UoB at all times.

Personnel are prohibited from downloading or copying data to local devices.

The data will not leave England/Wales at any time.

Access is restricted to employees or agents of the University of Birmingham who have authorisation from the Chief Investigator at University Hospitals Birmingham NHS Trust.

All personnel accessing the data have been appropriately trained in data protection and confidentiality.

NCRAS data sets will be linked to data sets disseminated under BAU DARS-NIC-77142 and NHS Blood and Transplant (NHSBT).

There will be no requirement and no attempt to re-identify individuals when using the data.

Researchers from the University of Birmingham will process the data for the purposes described above.

The expected outputs of the processing will be:

• Submissions to peer reviewed journals (e.g., New England Journal of Medicine, The Lancet, JAMA (Journal of the American Medical Association), JAMA Oncology, The BMJ (British Medical Journal), The BMJ Oncology, American Journal of Transplantation, Transplantation, etc.)

• Presentations to transplant webinars (open to professionals and transplant patients)

• Presentations at both national and international transplant conferences (e.g., British Transplantation Society congress, European Society for Organ Transplantation, American Transplant Congress.)

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 datasets from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Webinars open to transplant professionals and patients.

• Social media

• Co-hosted events with professional societies

The target date for production and dissemination of the outputs is 2025.

The findings of this research study are expected to contribute to evidence-based decision-making for policymakers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of health care users relevant to the subject matter of the study.

The use of the data could:

- help the system to better understand the health and care needs of populations.

- lead to the identification or improvement of treatments or interventions, or health and care system design

to improve health and care outcomes or experience.

- advance understanding of regional and national trends in health and social care needs.

- advance understanding of the need for, or effectiveness of, preventative health and care measures for particular populations or conditions.

- inform planning health services and programmes, for example to improve equity of access, experience and outcomes.

- inform decisions on how to effectively allocate and evaluate funding according to health needs.

- provide a mechanism for checking the quality of care. This could include identifying areas of good practice to learn from, or areas of poorer practice which need to be addressed.

- support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work).

This project has the potential to directly impact upon the care delivered to solid organ transplant recipients in relation to one of the most common and feared immunosuppression-related complications. The dissemination of outcomes for EpCOT may directly influence the development of Standards of Care guidelines to aid transplant clinicians in the delivery of care and may aid counselling for solid organ transplant candidates for their actual risk of post-transplant cancers.

It is hoped that through publication of findings in appropriate media, the findings of this research will add to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients.

The benefits may lead to the development of Standards of Care guidelines to improve the delivery of care for solid organ transplant recipients. This may have an impact upon the approximate 4,000 incident solid organ transplant recipients performed annually in the UK but more importantly upon the approximate 45-50,000 prevalent solid organ transplant recipients alive in the UK at the current moment in time. The immediate benefit of the study may be, improved counselling for solid organ transplant candidates by transplant doctors in advance of their transplant surgery, using the evidence for what the likely risk of posttransplant cancer may be. This may better inform patients prior to transplantation, to help them make an informed decision about risk versus benefit, and also raise awareness for transplant doctors to monitor posttransplant care appropriately. With the development of Standards of Care guidelines, the study aims to bring uniformity and best practice evidence to the UK transplant community in view of the current lack of evidence, to guide clinical management and decision-making.

No yielded benefits have been produced as yet, as none of the previous data disseminated was downloaded or processed, due to insufficient information being provided (Civil Registration of Deaths) within the DARS BAU application. This did not provide the relevant data required to deliver the study outcomes. Updated data was disseminated within the DARS BAU application.