Evaluating the age extension of the NHS Breast Screening Programme (AgeX Trial) (ODR_2014_367)

The University of Oxford requires National Disease Registration Service (NDRS) data for the purposes of the following research project: Evaluating the age extension of the NHS Breast Screening Programme (known as the AgeX Trial). This request was previously managed by Public Health England (PHE), prior to their dissolution in October 2021, under the reference ODR_2014_367.

The NHS Breast Screening Programme (NHSBSP) routinely invites women aged 50-70 years to come for a three-yearly screening. Because of uncertainty about the effects of screening outside this age range, an England-wide cluster-randomised trial is underway to assess the risks and benefits of additional invitations for screening at ages 47 to 49 and, separately, after age 71 (currently 71-73).

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

• Amass and analyse sufficient evidence that will enable the final reports to provide definitive unequivocal evidence on an issue that has been the subject of controversy for over 15 years – specifically whether the harms of breast screening outweigh the benefits.

• Assess the risks of screening (in particular, the chances of being diagnosed and treated for non-life-threatening cancer) and benefits (in particular, the chances of saving a life) for women undergoing additional screening at ages 47-49, and 71-73.

The findings will help the UK government decide whether to widen the age range for routine breast screening.

The University of Oxford requires continued access to the following NDRS data previously disseminated by PHE:

• NDRS Cancer Registration Data (01/01/1995-31/12/2018)

In addition, this request covers the dissemination of:

• NDRS Cancer Registration data (01/01/2019 – latest available).

• Systemic Anti-Cancer Therapy (SACT) dataset (01/04/2012- latest Available)

• Radiotherapy Data Set (RTDS) (01/04/2009-latest available)

Data will be disseminated annually until the end of this Data Sharing Agreement (DSA).

NDRS Cancer Registration Data provides the study with information on tumour characteristics of incident cancers (including histology, size, stage, grade, nodal involvement, and receptor profile); and treatment information. Additional information from the SACT dataset and the RTDS provide information on the subsequent treatment of incident cancers. These data can be used to better understand the health outcomes of women included in the trial.

The level of the data held and disseminated will be identifiable. Identifiable data is required to permit the linkage of the data being disseminated under this Agreement with the Civil Registration (Deaths), Demographics, Cancer Registrations and Hospital Episode Statistics (HES) Admitted Patient Care (APC) disseminated under DARS-NIC-147931-DT25Y; and NHS Screening records (previously provided by PHE, but now provided by NHS England). However, it should be noted that only pseudonymised data is processed for the purpose of analysis. All identifiers will be stored separately from the pseudonymised data used for analysis, with access restricted to the senior systems analyst. The identifiers need to be stored in the event any participant withdraws from the trial so the study team can identify and delete their data from further analysis

The data requested has been limited to the minimum amount necessary to achieve the purposes outlined within this DSA, and will be minimised as follows:

• The data will be limited to a cohort of ~4.5 million women that have been included in the AgeX trial in England. This includes all women aged 47-49 or 71-73 who have been randomised into or randomised out of receiving additional breast screenings.

• The request is limited to data between 01/01/1995-Latest Available, it is necessary to have data over such a long period because firstly, the screening programme currently offers women 7 screenings between the ages of 50 and 70 and the trial is investigating the effect of adding just one screen to the existing 7 routinely offered. Therefore, the screening period is already more than 20 years and the effects of screening are likely to become visible at least 10 years after the first screening. Secondly, it is essential for the trial design to have information on morbidity prior to randomization.

In addition, the AgeX trial team have undertaken extensive work with the NDRS Analysts to ensure compliance with the General Data Protection Regulation (GDPR) Principle of Data Minimisation.

The University of Oxford is the research sponsor and controller who determines the purpose and means of processing the requested data and is the organisation responsible for ensuring that the data will only be processed for the abovementioned purpose. Only the University of Oxford is permitted to process the data disseminated under this DSA.

The lawful basis for processing personal data under the UK General Data Protection Regulation (GDPR) is as follows: 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 as follows: 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.

The processing has been deemed to be in the public interest as the research has the potential to determine future policy on National Breast Screening.

The funding is provided by the Department for Health and Social Care, Cancer Research UK and the Medical Research Council. The funding is specifically for the study described. Funding is currently in place until April 2024 with applications in train for future funding. No funder will be given access to the data disseminated under this Agreement or plays a role in determining the purpose and means of processing nor have the ability to suppress or otherwise limit the publication of findings.

Members of the public who are representative of women in the trial have worked in collaboration with the AgeX investigators to ensure that the public voice is represented and included in decision making at all stages of the trial. These members of the public currently include two lay members of the Trial Management Group, and Women members of three public advisory groups: Oxford Biomedical Research Centre PPI Advisory Group; the Oxford Cancer Patient and Public Advisory Group; and Independent Cancer Patients’ Voice. The scope of involvement of the lay members of the Trial Management Group has included providing a public’s perspective on the ongoing progress and conduct of the trial including adherence to the protocol, the need for changes to the protocol, considering recommendations of the data monitoring and ethics committee, and publicly available lay information. The members of the three public advisory groups have provided further input to publicly available lay information. Other PPI activities include, but are not limited to, developing the participant facing information during randomisation, reviewing the content on the AgeX website which has recently been updated (https://www.ceu.ox.ac.uk/research/agex-trial), commenting on the lay summary for a recent grant application. When study results are available, they will be further consulted to provide input to draft manuscripts and grey literature reports, as well as the co-creation of press releases, lay summaries, infographics, and multimedia content such as podcasts and short videos to maximise opportunities for dissemination”.

The study has support under section 251 of the NHS Act 2006 to enable the common law duty of confidentiality to be temporarily lifted so that confidential patient information can be processed without consent, in line with the s251 approvals obtained by this study the national data opt-out applies.

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). Further details on the NDRS opt out can be found here - https://digital.nhs.uk/ndrs/patients/opting-out

To support future dissemination the University of Oxford will transfer data to NHS England. The data will consist of identifying details: NHS Number, Date of Birth and AgeX ID (StudyID).

NDRS Data Production will provide the relevant records from NDRS Cancer Registrations, NDRS RTDS and NDRS SACT to the University of Oxford. The data will contain directly identifying data items including NHS Number, Date of Birth and AgeX ID to support linkage with other datasets obtained by the study.

All data received from NHS England is added to the core AgeX database. The data will not be transferred to any other location.

The data will be held on servers exclusively at the Cancer Epidemiology Unit (CEU) within the Nuffield Department of Population Health (NDPH) at the University of Oxford and used solely for the purpose of this project.

Backup storage is in three separate secure rooms within NDPH buildings. Backups should be useable in the event of a disaster at the main site and will be accorded the same physical & electronic protections as live data.

The data will be accessed onsite at the premises of the University of Oxford. Data will also be accessed remotely using laptops provided by the University of Oxford using a secure VPN.

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

Access is restricted to individuals within the Cancer Epidemiology Unit in the Nuffield Department of Population Health at the University of Oxford, who have authorisation from the Principal Investigator. All such individuals are substantive employees of the University of Oxford and have received appropriate training in data protection and confidentiality.

The data will be linked as described above at an individual record level with the following datasets:

• Civil Registration (Deaths) – disseminated under DARS-NIC-147931-DT25Y

• Cancer Registration Data- disseminated under DARS-NIC-147931-DT25Y

• Demographics Data- disseminated under DARS-NIC-147931-DT25Y

• HES APC Data- disseminated under DARS-NIC-147931-DT25Y

• NHS Screening Data – previously disseminated by PHE

The identifying details will be stored in a separate database to the linked dataset used for analysis. All analyses will use a pseudonymised subset of the data provided. When using the pseudonymised data there will be no requirement or attempt to reidentify individuals.

The AgeX trial is ongoing. Results on mortality until 2026 will be reported as soon as they become available (no earlier than 2027), but electronic follow-up could still continue, and longer follow-up will be reported as it becomes available. Results on process indicators will be reported in 2023-24.

These outputs, when available, will be communicated to relevant recipients through the following dissemination channels:

• Submission of academic papers to open-access, high-impact, peer-reviewed journals.

• Public reports developed in collaboration with NHS regulatory bodies to ensure the results are used to help provide evidence for health guidelines and best clinical practice.

• The AgeX Trial website at www.agex.co.uk will provide links to open-access peer-reviewed publications and offer free downloads of lay summaries of key and important findings.

• The Twitter handles at NDPH (@Oxford_NDPH) and Oxford Medical Sciences Division (@OxfordMedSci) with a combined following of over 11,000 will promote all significant findings.

• Presentation of research findings at conferences e.g. the UK Interdisciplinary Breast Cancer Symposium, a biennial conference for all those with an interest in the prevention, early treatment and diagnosis of breast cancer last held in 2022; and the European Breast Cancer Conference, an annual conference for all stakeholders in the breast cancer community

As with any trial, it is necessary to gather evidence incrementally throughout the course of the trial in order to check that the trial itself is not exposing participants to increased risk of harm or, conversely, to check for evidence of benefits. The outputs from the interim analyses will continue to be annual reports to the Data Ethics and Monitoring Committee which may also request additional analyses within the scope of the clinical trials objectives if they identify the need. The Data Ethics and Monitoring Committee must report any concerns about the trial or findings to the trial management group.

Outputs will include any data aggregated with small numbers suppressed in line with the appropriate suppression rules.

The aim of the trial is to assess reliably the risks and benefits of additional NHS invitations for breast screening before age 50 and, separately, after age 70. The results are expected to help determine future NHS policy on age at breast screening, as well as providing a greater understanding of costs and benefits to the NHS and its patients of extending the current breast screening age. The main results are not expected before the mid-2020s but interim results will be reviewed and the trial end date may be brought forward if the evidence is clear before then.

The UK Health Security Agency may use the findings to inform government and influence policy. This may affect breast screening policy in the UK, and influence policy in much of the rest of the world for decades after the results have been published.

While it is not certain whether the results of the study will lead to the extension of the national breast screening age, revisions to national policy based on scientific evidence have the potential to:

• Improve patient outcomes

• Lead to a more informed allocation of funds for screening services

Ultimately benefitting the provision of health and social care.

The benefits of interim analyses are that these will be used to monitor the protection and safety of trial participants in addition to feeding into the wider aims.

The AgeX Trial is ongoing. The first analysis of the data will not be complete until 2027/28, therefore there are no yielded benefits to date.