The Epidemiology of Cancer after solid Organ Transplantation (EPCOT) study is a data linkage project to analyse cancer epidemiology after solid organ transplantation. This is a major cause of morbidity and mortality with little empirical research to guide clinical management and patient counselling.

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

Data controllers: + UNIVERSITY OF BIRMINGHAM · − UNIVERSITY HOSPITALS BIRMINGHAM NHS FOUNDATION TRUST

Datasets: + HES-ID to MPS-ID HES Admitted Patient Care; + HES-ID to MPS-ID HES Outpatients; + NDRS Cancer Registrations; + NDRS Cancer registration (pre-1995); + NDRS National Radiotherapy Dataset (RTDS); + NDRS Systemic Anti-Cancer Therapy Dataset (SACT)

Objective for processing

University Hospitals of Birmingham NHS Foundation Trust (UHB) (UoB) requires access to NHS England data for the purpose of the following research project: [1 paragraph unchanged] The following is a summary of the aims of the research project provided by UHB: UoB: [8 paragraphs unchanged] • NDRS Cancer Registrations • NDRS National Radiotherapy Dataset (RTDS) • NDRS Systemic Anti-Cancer Therapy Dataset (SACT) [3 paragraphs unchanged] • Limited to data for a study cohort of approximately 85,000 115,000 transplant patients. Identified from the UK Transplant Registry (UKTR) who met the [9 words unchanged] transplant (e.g. kidney, liver, heart, lung, pancreas, small bowel) between 01/01/1985 and 31/12/2015) 31/12/2024) which UKTR provided provides to NHS England in the previous iteration of this agreement. England. • Limited to data between 1997/98 (where available) and 2018/19 for HES data and - to latest available (expected 2023) for Civil Registration Mortality. available. 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. • NDRS- 1985/86 - to latest available. University of Birmingham are the data controller and is the organisation responsible for ensuring that the data will only be processed for the purpose described above. [6 paragraphs unchanged] 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. [2 paragraphs unchanged]

Processing activities

[1 paragraph unchanged] In a previous iteration of this agreement, UKTR and Public Health England (NCRAS – this service is now managed by NHS England) transferred UK Transplant Registry (UKTR) will transfer data to NHS England. The data consisted consist of identifying details (specifically NHS Number, Date of Birth, Postcode, Gender and a unique person ID). ID (CPID) for the cohort to be linked with NHS England data. NHS England applied national data opt-outs to the supplied cohorts and then 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 patients sent from UKTR (NHS Blood Transplant patients) to HES, CRD and NDRS datasets. NHS England will then provide the relevant records from the datasets to University of Birmingham. The Data will contain no direct identifying data items but will contain a unique person ID (CPID) which can be used to link the Data with other record level data already held by the recipient NHS England will then 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. Separately UK Transplant Registry (UKTR) will supply University of Birmingham data containing NHS Blood Transplant patients. The Data will contain no direct identifying data items but will contain the unique person ID (CPID) which can be used to link to the Data received by NHS England. [5 paragraphs unchanged] 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. Investigator. [1 paragraph unchanged] The data will be linked at person record level with NHBST and NCRAS datasets which contain a Study ID (CPID) obtained from NHS England. unique person ID. [2 paragraphs unchanged]

Benefits reported

No yielded benefits have been produced as yet, due to insufficient information being obtained for the purpose of the study and is the reason for this amendment. Since obtaining our study data in 2024, we have been working hard to clean, curate and prepare our data for analysis. We have been able to produce a significant amount of work already which has been presented this year. For example, we present our preliminary work exploring incidence and mortality of cancer after solid oran transplantation versus the general population at the European Society for Organ Transplantation congress in London (June 2025, London, UK) and the World Transplant Congress (August 2025, San Francisco, USA). Citations for these publications are; De Novo Cancer Incidence After Solid Organ Transplantation in England: The EpCOT Study. Stephens, C. et al. American Journal of Transplantation, Volume 25, Issue 8, S239; Cancer-Related Mortality After Solid Organ Transplantation in England: The EpCOT Study. Stephens, C. et al. American Journal of Transplantation, Volume 25, Issue 8, S511. Both these abstracts have now been submitted as manuscripts for consideration to The Lancet. Abstracts prepared for submission to scientific conferences next year so far include; 1. Post-transplant cancer risk and survival after liver transplantation: the EpCOT Study 2. Post transplant lymphoproliferative disease after solid organ transplantation in England: The EpCOT study On 15th July 2025, a patient webinar was organised for the UK Organ Donation & Transplantation Research Network to discuss the aims, ambitions and scope of the EpCOT project with various solid organ transplant patients. This project needs to be combined with data from DARS-NIC-656749 (which is the cancer data and we would like a cancer data update too) as it is one project. I would appreciate a discussion of how we can merge these two into one project. I would also be keen to obtain more up to date data from NHSBT so that we have solid organ transplant recipients from 2016-2025 added to this dataset. This extra data would allow greater power to explore some of our important research questions for the next 3 years.

Unchanged: Expected output, Expected measurable benefits.

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

Datasets: + Civil Registrations of Death

Objective for processing

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 the aetiology, pathophysiology and outcomes of cancer post-transplantation may differ from the general population. University Hospitals Birmingham NHS Foundation Trust (UHB) requires access to NHS England data for the purpose of the following research project: The current level of evidence for post-transplant cancer has several limitations. Firstly, the bulk of published evidence comes from transplant cohorts in the United States but this data may not be directly translatable to the United Kingdom. Differences in demographics, immunosuppression regimens and post-transplant practise means transplant outcomes are completely different between the two countries. Previous work has shown cancer epidemiology data is not translatable between kidney transplant cohorts between England and New York State (Jackson-Spence et al. Cancer Medicine 2018). Only two publications have reported cancer epidemiology in the United Kingdom (Collette et al. Am J Transplant 2010; Farrugia et al. Kidney Int 2014). However, both are now outdated in line with significant evolution of delivery of post-transplant care over the last 10-15 years and both fail to integrate multiple registries to obtain a more complete and more integrated pathway of the patient journey. Epidemiology of Cancer After Solid Organ Transplant (EpCOT) study. 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. We therefore do not know why post-transplant cancer risk is different for different recipients, what morbidity is associated with post-transplant cancer, how outcomes differ for post-transplant cancer versus the general population among many other unanswered questions. This study is called the Epidemiology of Cancer After Solid Organ Transplantation (EpCOT) study. 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. This integrated data set will not be used for any research other than that stated in this Purpose Section. The following is a summary of the aims of the research project provided by UHB: University Hospitals Birmingham NHS Foundation Trust (UHB) wants to study an anonymised extract of data from University of Birmingham derived from a cohort of transplant patients provided by NHS Blood and Transplant (NHSBT) (all people included in the register as having had a transplant between 1985 and 2015 - circa 85,000 patients) and a cohort of individuals on the National Cancer Registration and Analysis Service (NCRAS) provided by PHE, linked to pseudonymised data from NHS Digital under this DSA to examine cancer incidence, management, and mortality, along with the resource implications. UHB is acting as the sole Data Controller, while the University of Birmingham is the sole Data Processor. “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. Public Health England and NHS Blood and Transplant (NHSBT) are involved in the wider project as collaborators but are not processing data in any way. They will be providing the cancer and transplant-specific data to NHS Digital for record linkage and will provided the anonymised data to the University of Birmingham with the unique study identifier for the Data Processor to link. 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. We therefore do not know why post- transplant cancer risk is different for different recipients, what morbidity is associated with post-transplant cancer, how outcomes differ for post-transplant cancer versus the general population. This application is not linked to any other wider project and is the first and only project of its type in the United Kingdom. This project will be using an English cohort of 85,410 patients who have received a solid organ transplant (e.g. kidney, liver, heart, lung, pancreas, small bowel) between 01/01/1985 and 31/12/2015 and who have data stored with the UK Transplant Registry (UKTR) by mandatory requirement cross-referenced with individuals on the National Cancer Registration and Analysis Service (NCRAS) held by PHE. After record linkage with the appropriate national population-based data registries, the EpCOT researchers will be able to distinguish solid organ transplant recipients with a diagnosis of post-transplant cancer versus solid organ transplant recipients who do not develop post-transplant cancer. 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.” Responding to the need for research into post-transplantation cancer, the aim of the study is to improve delivery of care to solid organ transplant patients in the UK who are at risk or currently living with cancer. The following research questions will be investigated: The following NHS England data will be accessed: 1. Compare observed and expected risks of specific causes of deaths, in particular cancer-related death, by linking the UKTR with the national death registry to obtain underlying causes of death and determine factors related to increased risk of specific causes of death post-transplantation. General population mortality rates will be used to calculate expected number of deaths from specific causes and identify subgroups of post-transplant patients (e.g. age, sex, transplant centre, organ type, etc.) at excess risk compared with expected. • Hospital Episode Statistics (HES) 2. Investigate survival and causes of death after cancer in post-transplant patients versus individuals from the general population who develop similar new onset cancer of the same age, sex, and calendar year of diagnosis. - Admitted Patient Care (APC) 3. Compare observed and expected risks of specific cancer types post-transplantation by linking the UKTR with the national cancer registry to obtain observed numbers of cancers and determine factors related to increased risk of specific types of cancer. General population cancer incidence rates will be used to calculate expected numbers of cancers of specific type and identify subgroups of post-transplant patients at excess risk of specific cancers compared with expected. - Outpatients (OP) 4. Estimate risk of morbidity requiring hospitalisation both generally and that associated with development of post-transplantation cancer by linking the UKTR with Hospital Episode Statistics (HES). Risk of hospital admissions and procedures (e.g. surgery) for specific morbidities will be investigated. We will calculate expected risks for specific conditions requiring hospitalisation, enabling identification of specific subgroups of post-transplant patients at excess risk compared with expected. • Civil Registration Mortality DATA REQUESTED 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 general hospitalisation, compared to the risk of morbidity requiring hospitalisation specifically associated with the development of post-transplantation cancer. This project will require linkage between four data sets: The level of the data will be pseudonymised. 1) UK Transplant Registry (UKTR) contains transplant-specific data provided by NHS Blood and Transplant (NHSTB); The data will be minimised as follows: 2) the National Cancer Registry (from the National Cancer Registration and Analysis Service (NCRAS) provided by Public Health England (PHE)); • 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. 3) HES APC and OP data for secondary care episodes and procedures (NHS Digital) and • Limited to data between 1997/98 (where available) and 2018/19 for HES data and latest available (expected 2023) for Civil Registration Mortality. 4) Civil Registrations - Deaths data (also NHS Digital). (only a flag indicating that death has occurred and the months from transplantation to death, and cause of death to determine death-specific mortalities). 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. This data is already in existence for audit, governance and approved research perspectives within individual registries. However, to obtain a complete picture of the transplant patients journey with a diagnosis of cancer, it is important to link up these data sets to ensure all captured information is available. Only patients who match in both UK Transplant Registry and National Cancer Registry will have their data transferred to the Data Processor. The lawful basis for processing personal data under the UK GDPR is: No patient identifiable data is being requested. Data requested is to allow analysis of important epidemiological outcomes only. UHB is requesting the minimum required data to ensure the study outcomes are achieved. UHB has asked for a reduced set of HES data to minimise the amount of information used for the project. They have requested information on mortality but would like only a flag indicating that death has occurred and the months from transplantation to death, and cause of death to determine death-specific mortalities. 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. This study is funded by a grant from the Wellcome Institutional Strategic Support Fund through the University of Birmingham. The funder has no role in the conduct of this study and is therefore not a Data 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. 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.

Processing activities

NCRAS (part of PHE) and UKTR (part of NHSBT) will supply NHS Digital with a list of identifying details for their respective cohorts [NHS Number, Date of Birth, Postcode, Pseudonymised Study ID] thus allowing NHS Digital to identify and link those patients who are common to both data sets. NHS Digital will then generate a random unique identifier (large integer) for each linked patient and then return the identifying details originally provided, along with this common identifier, back to NCRAS and UKTR respectively. NCRAS and UKTR will then extract the relevant clinical/health data only relating to the target 85,410 solid organ transplant recipients between the stated time period of 1985-2016. All three organisations will then independently send to the Data Processor their agreed respective data set (cancer data (NCRAS), transplant data (UKTR); HES and mortality data (NHS Digital) as pseudo-anonymised data with the common patient identifier provided by NHS Digital to allow record linkage by the Data Processor. No data will flow to NHS England for the purposes of this Agreement. Data linkage will be conducted by the NHS Digital who will facilitate linkage of non-identifiable patient data between various data resources: 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). 1. UK Transplant Registry [provided by NHSBT] will provide a cohort of approximately 85,000 transplant patients. This cohort is static, being made up on patients who underwent transplants between 1985 and 2015. NHS England applied national data opt-outs to the supplied cohorts and then 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. The Information Governance teams at both UHB and UKTR are content there is no need for a DPA in this setting (EpCOT already receive data files from UKTR based on individual requests). NHS England will then 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. 2. National Cancer Registration and Analysis Service (NCRAS) [provided by PHE] The data will not be transferred to any other location. PHE will transfer direct identifiers to NHS Digital [NHSNUMBER, BIRTHDATEBEST, POSTCODE, PATIENTID (project specific pseudo ID)] to enable linkage to data held by the UK Transplant Registry. The data will be stored on servers at the University of Birmingham (UoB). - Cancer site: All cancer sites and morphologies (C00x – C097x and D00 – D48) 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. - Geography: resident in England Personnel are prohibited from downloading or copying data to local devices. - Diagnosis dates: 1 January 1985 through 31 December 2017. The data will not leave England/Wales at any time. - Male and female patients aged 0 – 100 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. - Where there is an unambiguous match, NHS Digital will return a list of pseudonymised patient IDs to PHE. All personnel accessing the data have been appropriately trained in data protection and confidentiality. 3. HES data sets (NHS Digital) The data will be linked at person record level with NHBST and NCRAS datasets which contain a Study ID (CPID) obtained from NHS England. HES APC Annual Refresh between 1997/98 to 2018/19. There will be no requirement and no attempt to reidentify individuals when using the data. HES OP Annual Refresh between start of data set (2003/04) to 2018/19. Researchers from the University of Birmingham will process the data for the purposes described above. 4. Civil Registration - Deaths Secondary Care cut data (NHS Digital) - a flag on the resultant cohort indicating that death (any death) has occurred (month and year of death) and cause of death to determine death-specific mortalities. Start of data set to end of 2018/19. Data linkage methodology - The linkage methodology will involve UK Transplant Registry and NCRAS sending to NHS Digital only a list of identifying details for their respective cohorts. - NHS Digital will link the UK Transplant Registry and NCRAS cohorts and determine which patients are common in both data sets. - NHS Digital would then provide a list of pseudonymous IDs of patients common in both data sets to UK Transplant Registry and NCRAS respectively so that they can extract the clinical/health data from their data sets respectively. - NHS Digital to link cohorts to HES and Civil Registration - Deaths [a flag indicating that death has occurred and the months from transplantation to death, and cause of death to determine death-specific mortality] and extract records. - NHS Digital to supply pseudo-records to University of Birmingham with the common patient identifier to facilitate linkage. There will be no need, requirement or possibility to re-identify individuals after record linkage by the Data Processor. The data sent to the Data Processor will be stored on a separate array of disks and accessed on a mapped drive as part of the University of Birmingham campus network. Access to this mapped drive will be limited to the named University researchers who can only access the University of Birmingham campus network with a personalised username/password combination. The personal computers used to access the data will have additional virus checking/data security software installed (Malwarebytes). The separate array of disks will reside in a controlled environment with access only by accredited University IT staff. The data from this disk array will be backed up under a separate storage policy which once deleted will make the data unavailable for restore. The linkage, processing and analysis of the data from UKTR, NCRAS and NHS Digital will only be carried out the specified researchers within the University of Birmingham as the Data Processor who are appropriately trained in data protection and confidentiality. There will be no attempt made to link any data requested under this application to any held under other Data Sharing Agreements. This database of the pseudonymised data will be accessible only to named personnel within the project and will be kept in auditable documents. In addition, analysts fulfilling database administrator role (who are substantive members of the University of Birmingham) will also have access to the database but undertake no processing. At the end of the project the data will be destroyed in line with strict policies and procedures on the destruction of data. No record level information will leave the Data Processor or aggregated data without small number suppression in line with the NHS Digital HES Analysis Guide.

Expected output

The aim of this project is to produce targeted studies looking at the epidemiology of post-transplantation cancer, and this data will be disseminated through presentations at speciality congresses (e.g. British Transplantation Society Annual Congress, European Society for Organ Transplantation) and submitted for publication in leading medical journals. The aim is also to develop Standards of Care guidelines with the Standards Committee of the British Transplantation Society to provide evidence based clinical evidence for direct patient benefit and we have their support and agreement for this. It is also the aim to plan patient-focused dissemination in plain English through various channels of communication for public consumption. The expected outputs of the processing will be: Outputs will only contain aggregate data with small numbers suppressed in line with the NHS Digital HES Analysis Guide. • 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.) Both NHS Blood and Transplant and Public Health England (who provide the initial data cohorts on this project) have mechanisms for dissemination of information to both professional and general population and the EpCOT Researchers will use these to share the results from EpCOT widely. We also aim to do similar research presentation at Research Open Days at both University Hospitals Birmingham and the University of Birmingham. Summary research findings are actively disseminated via social media channels (e.g. @AdnanSharif1979; @UHBResearch; @ImmunologyUoB) and also for the respective partners(@NHSBT_RD; @PHE_uk). We are also planning to work on evidence-based guidelines with the British Transplantation Society and these will be made freely available to the community at their website (https://bts.org.uk/guidelines-standards/). The plan is to produce significant research output for presentation as free communications and submission of manuscripts for peer-reviewed publication consideration. • Presentations to transplant webinars (open to professionals and transplant patients) The investigator team has a proven track record of presenting scientific abstract work at meetings and congresses, invited lectures and high-impact peer-reviewed publications to ensure the communication of our research output is provided to the largest, and most diverse, audience possible. This will be undertaken both professionally but also locally (UHB and University of Birmingham) and national organisations (NHS Blood and Transplant, Public Health England, British Transplantation Society) with stakeholder interest in this project. • Presentations at both national and international transplant conferences (e.g., British Transplantation Society congress, European Society for Organ Transplantation, American Transplant Congress.) The data will not be shared with any organisation outside the Data Processor so there will be no exploitation of outputs for development of treatment algorithms. The results and output will be used to guide the development of Standards of Care guidelines for transplant clinicians to utilise through working with the Standards Committee of the British Transplantation Society. 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. These dissemination roles will be facilitated by the Data Controller and Data Processor, with the research team in charge of research facilitation. Project partners will be encouraged to disseminate their involvement through social media channels. The dissemination of the Standards of Care guidelines that will be developed will be facilitated through the British Transplantation Society. The outputs will be communicated to relevant recipients through the following dissemination channels: The aim is for dissemination of data in congresses in 2020 and 2021, with submission of manuscripts for peer-reviewed publications planned for 2020. Development of Standards of Care guidelines will occur from 2021 once the preliminary epidemiological studies have been undertaken and presented. Social media dissemination at various important stages of the project will be undertaken by the lead applicant (@AdnanSharif1979) with relevant organisation and partners tagged. • 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 the end of 2025.

Expected measurable benefits

Despite cancer being a major complication after solid organ transplantation, there are no standards of care to guide clinical decision making and this impacts upon the care given to solid organ transplant recipients with or without cancer (as all are at risk due to the need for lifelong immunosuppression). Solid organ transplantation is frequently in the public arena for discussion and will be more so with the move to opt-out organ donation in England and Scotland during 2020. It is important that the advantages of solid organ transplantation for individuals with end-stage organ failure are balanced by increased awareness and education regarding the immunosuppression-related complications of solid organ transplantation. The findings of this research study are expected to contribute to evidence-based decision-making for policy-makers, 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. Cancer is a major cause of morbidity and has become the leading cause of death after solid organ transplantation. It is cited as one of the leading concerns for solid organ transplant recipients themselves. Unfortunately, there is a shortage of research exploring cancer epidemiology after solid organ transplantation in the UK. Much of what we know about cancer management for transplant patients is simply translated from the general population, but this may not be the best model of care for solid organ transplant recipients who have altered risk for cancer due to immunosuppression. The bulk of available data relating to transplant cohorts comes from the United States or Australia/New Zealand and this data may not be translatable to the UK due to different demographics, disease burdens, immunosuppression protocols etc. Therefore, our output will provide clinical evidence for a UK-specific cohort and guide transplant clinicians with better prevention and management techniques. The use of the data could: 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 data for EpCOT will directly influence the development of Standards of Care guidelines to aid transplant clinicians in the delivery of care and aid counselling for solid organ transplant candidates for their actual risk of post-transplant cancers. • help the system to better understand the health and care needs of populations. Targeted EpCOT epidemiological studies will aim to understand some of the following unanswered questions related to the epidemiology of cancer after solid organ transplantation that will have direct impact on care for solid organ transplant recipients: • lead to the identification or improvement of treatments or interventions, or health and care system design to improve health and care outcomes or experience. a) Cancer incidence post-transplantation (target 2020) • advance understanding of regional and national trends in health and social care needs. • How many solid organ transplant patients are living with cancer? • advance understanding of the need for, or effectiveness of, preventative health and care measures for particular populations or conditions. • How do cancer cases differ between different solid organ transplant recipients? • inform planning health services and programmes, for example to improve equity of access, experience and outcomes. • How do cancer cases differ between transplant and non-transplant patients? Is cancer more aggressive at diagnosis in the context of transplantation? • inform decisions on how to effectively allocate and evaluate funding according to health needs. • What are the risk factors for cancer post-transplantation and are some solid organ transplant recipients at greater risk than others? What is the influence of selected immunosuppresant agents on cancer occurrence? • 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. • Does cancer occurrence differ between national transplant centres (a reflection of differing immunosuppression regimens across transplant centres)? • support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work). • What is the risk for cancer occurrence post-transplantation for patients with previous history of cancer? Does that risk differ dependent upon type of cancer? 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. b) Cancer management post-transplantation (target 2020) 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. • Does cancer progress faster in transplant recipients versus a matched cohort of non-transplant cancer 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 post-transplant 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 post-transplant 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. • Is management of cancer post-transplantation different in comparison to non-transplant setting? • What is the impact of cancer on solid organ transplant recipients? How does cancer impact upon morbidity post-transplantation such as hospitalisations, complications, procedures etc? • What is the influence of selected immunosuppresant agents on cancer progression? c) Cancer mortality post-transplantation (target 2020) • Is higher cancer-related mortality post-transplantation due to higher incidence, faster progression or both? • Which solid organ transplant recipients are at greater risk for death after a diagnosis of cancer? • How does cancer mortality differ among recipients of different solid organs? d) Resource implications for cancer post-transplantation (target 2020-2021) • What transplant-specific screening strategies may be effective to prevent certain types of cancers? For example, longer periods of dialysis pre-kidney transplantation have been identified as a potential risk factor for post-transplantation renal cell cancer – how long is too long on dialysis pre-transplantation before routine screening may be beneficial? Does risk differ between different dialysis modalities pre-transplantation? • Where should investment be directed to help improve outcomes? • Is there any variation across the country with treatment and outcomes (patient, allograft and cancer-related)? Dissemination of these findings will be done professionally (at congresses, invited lectures and high-impact peer-reviewed publications) and through distribution channels through both local (UBH and University of Birmingham) and national organisations (NHS Blood and Transplant, Public Health England, British Transplantation Society) with stakeholder interest in this project. The benefits will lead to development of Standards of Care guidelines to improve delivery of care for solid organ transplant recipients. This will 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 our study will be improved counselling for solid organ transplant candidates by transplant doctors in advance of their transplant surgery using our evidence for what the likely risk of post-transplant cancer will be. This will 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 post-transplant care appropriately. With development of Standards of Care guidelines, we aim to bring uniformity and best practise evidence to the UK transplant community in view of the current paucity of evidence to guide clinical management and decision making.

Benefits reported

Yielded Benefits is not a requirement for new applications. No yielded benefits have been produced as yet, due to insufficient information being obtained for the purpose of the study and is the reason for this amendment.