Is the survival of teenagers and young adults with cancer associated with the dose and intensity of chemotherapy that they receive? (ODR1819_148)

University of Leeds requires access to NHS England data for the purpose of the following research project:

Is the survival of teenagers and young adults with cancer associated with the dose and intensity of chemotherapy that they receive?

The following is a summary of the aims of the research project provided by University of Leeds:

This is a study to investigate whether the dose intensity of systemic anticancer agents (chemotherapy) received by Teenagers and Young Adults (TYA) with cancer impacts on their survival. It will also determine whether any factors exist which influence a patient’s ability to receive the ideal amount of chemotherapy.

This study will use data from NCRAS to determine whether the amount of chemotherapy received by TYA cancer patients affects their length of life. The specific objectives are to:

1. To obtain detailed chemotherapy treatment history for all patients aged 12-29 years old treated with chemotherapy for chemo-sensitive cancers in the UK using existing linkage between the Systemic Anti-Cancer Therapy (SACT) dataset and the National Cancer Registry.

2. Analyse this data to investigate whether the dose and intensity of chemotherapy administered to patients affect one-year and three-year survival.

3. To investigate patient factors which act as barriers to receiving optimal treatment delivery. Variables include; gender, age, ethnicity, the distance that the patient lives from the treatment centre, stage at diagnosis, tumour site, socioeconomic background and treatment centre (i.e. whether specialist TYA unit or paediatric or adult unit).

4. To explore the SACT dataset for data relating to treatment toxicity, for example, dose modification and dose time delay, and determine whether the level of toxicity experienced has an impact on the total dose of chemotherapy received and patient outcome (in terms of one and three-year survival).

The following NHS England data will be accessed:

• Cancer Registration

• Systemic Anti-Cancer Therapy Data Set (SACT)

The level of the data will be pseudonymised.

The data will be minimised as follows:

• Limited to data between April 1st 2014 – 2020. For each individual patient, data will only be provided from patient ages between 12 to 29 years old at diagnosis.

• Limited to conditions relevant to the study identified by specific ICD or OPCS codes;

o ICD10 codes C00 – C97, D32-D33

• Limited to the following geographic area(s): England

The University of Leeds 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 the findings are important to TYA cancer patients and have the potential to impact survival rates and the quality of survivorship. In addition, emerging findings from this research outline ways in which this data could be improved, which would be of benefit to the public.

The funding is provided by the National Institute for Health and Care Research (NIHR). The funding is specifically for the study described. Funding is in place until 31/12/2023.

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.

Microsoft Azure (LASER) provides IT hosting services to University of Leeds and will store the data as contracted by the University of Leeds.

Data will be accessed by a PhD student employed by University of Leeds and a clinical trainee working under honorary contract. The individuals have completed mandatory data protection and confidentiality training and is subject to University of Leeds’s policies on data protection and confidentiality. The individuals accessing the data will do so under the supervision of a substantive employee of University of Leeds. University of Leeds would be responsible and liable for any work carried out by the study team. The study team would only work on the data for the purposes described in this Agreement.

The data controller engages members of the public and participants through the presentations of the study results. Feedback from families and cancer survivors have shown that they are hugely grateful for the Register and research carried out on their behalf. Those attending these presentations felt that they had been sufficiently informed about the research and are comfortable and supportive of the need to collect and process this data without informed consent. The study team have carried out local and national PPI workshops which have enabled the study team to ensure that the research questions are important and relevant to patients and their families/ carers.

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 provided the relevant records from the Cancer Registration and SACT datasets to the University of Leeds. The data contained no direct identifying data items but contained 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 not be transferred to any other location.

All data is held on a secure, encrypted Microsoft Azure cloud platform (LASER) at the University of Leeds, (see https://lida-data-analytics-team.github.io/laserdocs/docs/laser_info/laser.html).

In 2023/2024 there is a planned migration from Microsoft Azure cloud platform (LASER) at the University of Leeds to AIMES trusted research environment (TRE) an encrypted private cloud service. At this point the following physical precautions will be in place to protect the data and the University of Leeds will submit an amendment to NHS England to reflect the transfer of data processor.

The University of Leeds currently stores data and all daily backups on the Cloud provided by Microsoft Azure servers. Backups are for a 12-month period. The backup retention policy can be found at https://lida-data-analytics-team.github.io/laserdocs/docs/laser_info/backups.html

The data will be accessed by authorised personnel via remote access. The data will remain on the servers at Microsoft data servers at all times (until the migration to AIMES). All users of the Microsoft Azure cloud platform (LASER) system must sign a confidentiality agreement, which includes stipulating that security and confidentiality must be maintained. Certain breaches of security could lead to disciplinary and legal action being taken.

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 University of Leeds and an academic clinical trainee working under an honorary contract who have authorisation from the Principal Investigator. All persons accessing the data will be required to complete the University’s Information Governance training.

Only those essential members of staff who work on the Register and require direct access to the database are granted authorisation from the Principal Investigator.

No NHS Digital data will be transferred outside of the University of Leeds or shared with any third-party individual or organisation.

This data will not be linked to any other data sources outside the scope of this agreement. The data will be analysed as a complete dataset.

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

Researchers from the University of Leeds will analyse the data for the purposes described above. Data will only be used for the purposes described in this Agreement.

The data requested in this agreement is not considered confidential under the Health and Social Care Act 2012 and therefore is not subject to a duty of confidence, as such the national data opt-out is not applied.

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

The expected outputs of the processing will be:

• Three publications dates are estimated and may be subject to slight changes.

- July 2023 - first publication submitted focusing national treatment of germ cell tumours.

- Dec 2023 - second publication submitted focusing on bone tumours.

- January 2024 - third publication focusing on the comparison of what data is available at a national and regional level (comparing data [but not sharing or linking data] from this agreement with a separate dataset held by the research team, the Yorkshire Specialist Register of Cancer in Children and Young People).

• An abstract was presented at the International Data Linkage conference on use of this data in the TYA population in September 2022.

• An abstract was presented at advances in Ewings sarcoma conference in October 2022.

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: research journals, conferences, presentations at relevant organisational meetings, social media (e.g. twitter).

Outputs generated by the data thus far;

Presentation of an abstract at the International Data Linkage conference in Edinburgh in September 2022.

Presentation of an abstract at the International SIOP conference in Barcelona in September 2022. This work was in collaboration with DATA-CAN and the CCLG exploring the views of young people and carers of young people with cancer regarding the use of medical data for research. This work is currently being written up for publication.

In October 2022 presentation of an abstract at the Advances in Ewing Sarcoma Research conference which won a prize for best poster.

There is evidence being gathered that there may be a case for de-escalation trials in some patient groups. This may have potential to reduce effects caused through chemotherapy, reducing the treatment burden on the NHS and improving quality of life for the patients.

The outcome of this project could lead to changes in the recommended management of these patients and improve patient outcomes. The hope is that where dose matters for outcomes, identification of barriers to patients receiving optimal chemotherapy can guide NHS interventions to optimise the treatment that patients receive.

The study team are also able to access whether patients in this age category are achieving optimum doses of chemotherapy within real world NHS care.

This study will also determine how useful this data is for use in the Teenage and Young Adult Cancer population and any improvements that could be made.

The research team work with both local and national Patient and Public Involvement (PPI) groups. These groups ensure that the research questions being asked are important and relevant to the target patient groups and aid dissemination. The study team have carried out national PPI workshops alongside the Teenage and Young Adult (TYAC)/ Children's Cancer and Leukaemia Group (CCLG) charities and organisations such as UseMyData with the aim of improving public confidence in the use of children and young adults cancer data for research purposes, hoping to reduce the number of opt outs. This work has been written up for publication. If the results were felt to warrant attention the study team will disseminate these results via these charities.

In the coming months the study team are working alongside the local Children’s cancer charity Candlelighters at a University open day showcasing the work to the public.

The work will also be disseminated internationally at relevant conferences such as SIOP or the AYA international congress.

Data for this study has previously been shared when the data were controlled and managed by Public Health England (PHE). Due to COVID delays in data dissemination the study team is now just reaching the point of producing outputs from the data and so expect the benefits to be yielded shortly.