Un-CoV-er: Understanding the impact of SARS- CoV-2 infection in patients with blood cancer. (ODR1718__301)

The Clatterbridge Cancer Centre NHS Foundation Trust requires access to NHS England data for the purpose of the following research project: Un-CoV-er: Understanding the impact of SARS- CoV-2 infection in patients with blood cancer.

The following is a summary of the aims of the research project provided by The Clatterbridge Cancer Centre NHS Foundation Trust:

The overall aim of this study is to establish an evidence base that will lead to a more stratified approach to protecting people with blood cancer from COVID-19 during the chronic phase of the pandemic. The study has been designed as a population-based, observational, retrospective cohort study and will involve the analysis of England-wide data obtained from the National Cancer Registration and Analysis Service (NCRAS) and NHS England. It will be performed in two parts.

Part 1: Incidence and severity of SARS-CoV-2 infection

This part of the study will document the incidence and severity of SARS-CoV-2 infection in people with blood cancer compared to a control cohort representative of the general population. It will also elucidate risk factors for acquiring SARS-CoV-2 infection and experiencing severe or fatal COVID-19 outcomes. Key research questions are:

What was the rate of SARS-CoV-2 infection in people with blood cancer during the different phases of the pandemic, and how does this compare with the general population?

What were the risk factors for acquiring SARS-CoV-2 infection in people with blood cancer?

What was the rate of severe or fatal COVID-19 in people with blood cancer who were infected with SARS-CoV-2, and how does this compare with the general population?

What were the risk factors for developing severe or fatal COVID-19 in people with blood cancer who were infected with SARS-CoV-2?

Part 2: Impact of COVID-19 on cancer diagnosis, management and outcomes

A range of COVID-19 mitigation strategies were implemented at the start of the pandemic aiming to reduce the risk of viral exposure, minimise iatrogenic immunosuppression and free up capacity in secondary care to deal with the COVID surge. However, the extent to which these measures were implemented and their effect on cancer diagnosis, treatment and outcomes is unclear. Part 2 of the study will capture this information, not only to shed light on the overall uptake and impact of COVID-19 mitigation strategies, but also as a retrospective evaluation of specific treatments. Key research questions are:

How did the diagnosis and management of different types of blood cancer change as a result of the pandemic?

Were specific changes in the diagnosis and management of blood cancer uniformly distributed, or were some patient groups affected more than others?

What was the clinical effectiveness, toxicity and cost effectiveness of novel or variant treatment approaches applied during the course of the study?

The following NHS England data will be accessed and disseminated annually:

• Linked NDRS Cancer Registration is the cohort-defining dataset alongside linked Rapid Cancer Registrar Dataset (RCRD) and Systemic Anti-Cancer Treatment (SACT) and will help identify the different types of blood cancers. Furthermore, it will provide the necessary information related to when the diagnosis was made, length of diagnosis and its relation to patient demographics.

• NDRS Hospital Episode Statistics Admitted Patient Care (HESAPC), NDRS Hospital Episode Statistics Accident & Emergency (HESAE), NDRS Hospital Episode Statistics Outpatients (HESOP). These datasets are necessary as it will help understand the emergency, inpatient and outpatient admissions related to therapy that the patient has received. Furthermore, it will enable correlation with patient demographics to understand if particular patients are at risk of complications such as treatment side effects as well as COVID infections. HES data will also enable health economics analyses.

• NDRS Cancer Waiting Times (Treatment only) (CWT) dataset is necessary as it will help to understand the differences in cancer waiting times pre- and post-COVID.

• NDRS Diagnostic Imaging Dataset (DID) dataset is necessary as it will help to understand the route to diagnosis and any geographic variation in access to diagnostic imaging. Furthermore, it will help in health economics analysis.

• NDRS National Radiotherapy Dataset (RTDS) is the dataset that will help provide information about radiotherapy treatment received and enable correlation with patient demographics. Furthermore, health economic analysis will be performed using this dataset.

• NDRS Systemic Anti-Cancer Therapy (SACT) dataset is crucial in providing information about anti-cancer therapy received pre- and post-COVID and how this relates to demographics, geography, markers of social deprivation and patient outcomes.

• NDRS Rapid Cancer Registration Dataset (RCRD) dataset is required to complement the cancer registration data and provide more concurrent cases of cancer diagnosis.

The level of the data will be pseudonymised.

The data will be minimised as follows:

For all datasets:

• Limited to data from January 2014 to the most recent available data.

• Pseudonymised data will be obtained for data minimisation purposes.

• Limited to conditions relevant to the study identified by specific ICD or OPCS codes; ICD-O-3/ICD-10

o ICD-10: C44, C81-C96.

o ICD-O-3: 9590/3, 9591/3, 9596/3, 9597/3, 9650/3, 9651/3, 9652/3, 9653/3, 9654/3, 9655/3, 9659/3, 9661/3, 9662/3, 9663/3, 9664/3, 9665/3, 9667/3, 9670/3, 9671/3, 9673/3, 9675/3, 9678/3, 9679/3, 9680/3, 9684/3, 9687/3, 9688/3, 9689/3, 9690/3, 9691/3, 9695/3, 9698/3, 9699/3, 9700/3, 9701/3, 9702/3, 9705/3, 9708/3, 9709/3, 9712/3, 9714/3, 9716/3, 9717/3, 9718/1, 9718/3, 9719/3, 9724/3, 9725/3, 9726/3, 9727/3, 9728/3, 9729/3, 9731/3, 9732/3, 9733/3, 9734/3, 9735/3, 9737/3, 9738/3, 9740/1, 9740/3, 9741/3, 9742/3, 9750/3, 9751/3, 9752/1, 9753/1, 9754/3, 9755/3, 9756/3, 9757/3, 9758/3, 9759/3, 9760/3, 9761/3, 9762/3, 9764/3, 9765/1, 9766/1, 9767/1, 9768/1, 9769/1, 9800/3, 9801/3, 9805/3, 9806/3, 9807/3, 9808/3, 9809/3, 9811/3, 9812/3, 9813/3, 9814/3, 9815/3, 9816/3, 9817/3, 9818/3, 9820/3, 9823/3, 9826/3, 9827/3, 9831/3, 9832/3, 9833/3, 9834/3, 9835/3, 9836/3, 9837/3, 9840/3, 9860/3, 9861/3, 9863/3, 9865/3, 9866/3, 9867/3, 9869/3, 9870/3, 9871/3, 9872/3, 9873/3, 9874/3, 9875/3, 9876/3, 9891/3, 9895/3, 9896/3, 9897/3, 9898/1, 9898/3, 9910/3, 9911/3, 9920/3, 9930/3, 9931/3, 9940/3, 9945/3, 9946/3, 9948/3, 9950/3, 9960/3, 9961/3, 9962/3, 9963/3, 9964/3, 9965/3, 9966/3, 9967/3, 9970/1, 9971/1, 9971/3, 9975/3, 9980/3, 9982/3, 9983/3, 9984/3, 9985/3, 9986/3, 9987/3, 9989/3, 9991/3, 9992/3.

The Clatterbridge Cancer Centre NHS Foundation Trust is the controller as 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 will identify patient variables which may correlate with the severity of COVID and treatment outcomes. The analyses will identify patients who may be at particular risk of worse outcomes and help inform policy and strategy to improve patient care for the most disadvantaged patients. Furthermore, it will enable the identification of the best clinical treatment algorithms for patients with cancer in the post-COVID era.

The funding comes from multiple sources. Current funders include:

• Isle of Man Anti-Cancer Association – Funding is in place until 31/07/2023.

• Gilead Sciences Ltd – Funding is in place for 12 months from payment of the first instalment of the grant.

• The Clatterbridge Cancer Centre NHS Foundation Trust – The date for funding is to be decided as a no-cost extension has been applied for, but it is likely to be another 1 year.

• Blood Cancer UK – Funding is in place for 36 months.

• University of Liverpool – Funding is in place until 14 July 2023.

Funding to continue the work described will be sought on an ongoing basis.

The funder(s) will have no ability to suppress or otherwise limit the publication of findings.

The University of Liverpool are processors acting under the instructions of The Clatterbridge Cancer Centre NHS Foundation Trust. University of Liverpool’s role is limited to processing and storing the data.

1) Data will be accessed by undergraduate, Masters or PhD students affiliated with University of Liverpool. Any student working with the data held under this Agreement must have completed relevant data protection and confidentiality training and are subject to University of Liverpool’s policies on data protection and confidentiality. Any students accessing the data will do so under the supervision of a substantive employee of University of Liverpool. University of Liverpool 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.

2) An individual with an honorary contract with the University of Liverpool . The individual has completed mandatory data protection and confidentiality training and is subject to University of Liverpool’s policies on data protection and confidentiality. The individual accessing the data is a substantive employee of AIMES Management Service. University of Liverpool would be responsible and liable for any work carried out by the individual. The individual would only work on the data for the purposes described in this Agreement. AIMES Management Service are required as they specialise in data integration, curation and cleaning and this is something which was not available at the University of Liverpool at the time. Furthermore, the sponsor had worked with the organisation and approved its funding. There is a contract in place to specify the scope of the work.

A patient representative has been already approached to be part of the study team. The patient representative is strongly supportive of the overall aim of the study as well as its specific objectives and will contribute to the refinement and prioritisation of specific research questions. The patient representative is also willing to play an active role in disseminating the findings to service users.

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 (11) of the National Health Service Act 2006.

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 data will flow to NHS England for the purposes of this Agreement.

NHS England data will provide the relevant records from the HESAPC, HESAE, HESOP, CWT, DID, Cancer Registrations, Rapid Cancer Registrations, RTDS, SACT, NCDA, CPES datasets to the University of Liverpool. The data will contain no direct identifying data items but will contain a unique person ID which can be used to link the data with other record level data already held by the recipient.

The data will be stored on servers at the University of Liverpool. University of Liverpool uses offsite back-up services provided by the IT services at the University.

The data will be accessed onsite at the premises of University of Liverpool who will use the relevant subset of data to undertake the socio-economic analysis described above and this will be accessed onsite at the University of Liverpool.

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 students of University of Liverpool who have authorisation from Principal Investigator. Access will be restricted and granted by the respective University’s IT support centre .

The Clatterbridge Cancer Centre NHS Foundation Trust is not permitted to access the data. All personnel accessing the data have been appropriately trained in data protection and confidentiality.

The data will not be linked with any other data outside of the scope of the agreement and

there will be no requirement and no attempt to reidentify individuals when using the data.

The study team will analyse the data for the purposes described above.

The expected outputs of the processing will be:

• Submissions to peer reviewed journals

• Presentations at national and international conferences

The data will include summary of patients and descriptive statistics. It will not contain patient level information.

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

• Journals

• Posters displayed at American Society of Haematology (ASH), European Haematology Association (EHA), British Society of Haematology (BSH) amongst other haematology conference.

It is expected that the first publication to submit in a peer reviewed journal is to be ready in about 9 months, after this, there should be quick succession of publications every 4-6 months (or less), as the data analyses process becomes more efficient. Prior to these publications, it may be aimed to present these findings as oral/poster presentations at ASH/EHA/BSH conferences.

The project is of national interest and has become recognised project as part of the NCRI haemato-oncology portfolio of projects. The results will further understanding of blood cancers as a whole. The results may add to a body of evidence available to policymakers that they can use to better inform and optimise the provision of health and social care.

Particularly, the project will identify patients at risk of COVID infections and worse outcomes. This will enable risk stratification of these patients. Furthermore, analyses will guide healthcare workers towards which treatments are effective in particular groups of patients (based on clinical/demographics) and how to manage them effectively. Specifically, the project will look at novel agents in blood cancers and understand their toxicity profile which will complement data from clinical trials. This will help to understand the true burden of side effects in the patient cohort so that they could be risk-managed appropriately.

The research findings will be shared with stakeholders and policymakers, including national policy steering groups such as NCRI haemato-oncology groups, patient groups, associations, and publications. The analyses conducted will focus on both clinical and patient-centric perspectives, aiming to generate maximum public benefit through the study's outputs. By analysing this extensive dataset, it is aimed to bridge the knowledge gap regarding patient outcomes in real-world settings. This analysis will provide insights into the true burden of the disease and the impact of various factors, such as baseline patient characteristics and treatment received, in the context of the COVID-19 pandemic. The results obtained from clinically relevant research questions will guide the development of optimal treatment strategies and inform national BSH guidelines on treatment algorithms. Ultimately, the overarching objective is to enhance patient care by utilising real-world data to shape future medical practices.

A group of patients from prominent patient organisations such as Lymphoma Action and Chronic Lymphocytic Leukaemia (CLL) support association have been engaged. They are an integral part of the UnCoVer project and help develop and prioritise the research clinical questions. Furthermore, the Clatterbridge Cancer Centre NHS Foundation Trust are in dialogue with Blood Cancer UK regarding the output of the analysis guiding the Blood Cancer Action Plan. The outputs from the research will be disseminated to patients and presented at their meetings, local and international meetings. The project has been widely advertised to national experts in blood cancers through the NCRI Lymphoma and Haemato-oncology Groups and has received positive feedback already. Furthermore, the Clatterbridge Cancer Centre NHS Foundation Trust aim to present the findings at large international conferences and publish in high-impact journal to ensure that the findings of the project are advertised to a wider audience.

The Clatterbridge Cancer Centre NHS Foundation Trust envisage multiple high-impact publications from this. This organisation have successfully applied for multiple funding based on this project and hope to deliver this with a multitude of oral presentations and publications.

Although the project has not yet reached a point where the data can be analysed, it has already yielded a number of benefits:

• Focal point for the creation of a fully inclusive health data research community within the UK that spans the whole of blood cancer

• Increased awareness of NCRAS and its work within the UK blood cancer health data research community

• Improved linkage between the UK blood cancer health data research community and NCRAS

• Strong involvement/engagement of patients and national patient advocacy groups such as Lymphoma Action and CLL Support Association

• Strong ECR involvement (6 involved so far)

• >£400K of research funding leveraged