Observational study of Age, test THreshold and frequency on English NAtional Mammography screening outcomes

University of Warwick requires access to NHS England data for the purpose of the following research project: Observational study of Age, test THreshold and frequency on English NAtional Mammography screening outcomes (ATHENA-M).

The following is a summary of the aims of the research project.

1. To understand how age of eligibility, screening interval, and recall threshold for breast cancer screening affect benefits and harms including false positive recalls, overdiagnosis and mortality.

2. To inform revision of the quality assurance guidelines for breast screening centres based on maximising benefit and minimising harm from breast screening.

These aims are being addressed through the following objectives, across three work packages:

Work Package 1: Database development and access

Objective 1: To assemble, clean and assess the quality of the combined datasets

a. To obtain approvals to re-use the observational dataset of 13 million women offered breast screening

b. To clean data and describe data quality

Work Package 2: Causal links between age of eligibility, screening interval, recall threshold and health outcomes

Objective 2: To analyse the causal effect of age of eligibility, screening interval, and recall threshold on intermediate outcomes (numbers of breast cancers detected at screening by cancer type, interval cancers, false positive recalls) and health outcomes (mortality, morbidity, overdiagnosis).

Work Package 3: Pathway to impact

Objective 3: To apply findings to inform changes to practice, including changes to the NHS Breast Screening Programme consolidated standards.

As outlined in the original data request form, University of Warwick require continued access to the dataset that was disseminated previously, with no new data flows. The current data products are:

NDRS Cancer Registrations,

NDRS Systemic Anti-Cancer Therapy Dataset (SACT),

NDRS National Radiotherapy Dataset (RTDS),

NDRS-linked HES Admitted Patient Care,

The level of data currently being held is:

• Pseudonymised

The Data was minimised by the following inclusion criteria (limiting by date range of the appointment and the age of women).

Inclusion criteria:

Women invited to routine population breast cancer screening in England from screening programme inception, where DATEOFFIRSTOFFEREDAPPOINTMENT is 01/01/1988 to 31/03/2018, who:

• Were aged 47 – 73 years at their routine screening invitation; and

• Have at least one demographics record (Table 1), required for linking

The University of Warwick is the research sponsor and the 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, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care.

The funding comes from multiple sources. Current and previous funders include:

• NIHR Career Development Fellowship (the POSTBOx study, CDF-2016-09-018) - funding until 31 October 2022

• NIHR’s Health and Social Care Delivery (HS&DR) Research Programme ATHENA-M project (NIHR130107) funding in place until 31 December 2024

• NIHR Research Professorship (NIHR302434) – funding in place until 30 November 2027

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

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

The University of Birmingham is a processor acting under the instructions of the University of Warwick, with associated collaboration agreement and data processing agreements in place. The University of Birmingham is leading on the test threshold analysis and their involvement is limited to this data analysis.

The University of Bristol is a processor acting under the instructions of the University of Warwick, with associated collaboration agreement and data processing agreements in place. The University of Bristol is leading on the age extension and screening interval analyses and their involvement is limited to this data analysis.

Kings College London are a listed as a co-signatory in the collaboration agreement for this project, due to a co-investigator based at this organisation. They have no access to the data but are acting in an advisory capacity.

The data may be accessed by:

• PhD students affiliated with University of Warwick. Any student working with the Data held under this Data Sharing Agreement (DSA) must have completed relevant data protection and confidentiality training and are subject to the University of Warwick’s policies on data protection and confidentiality. We would also ensure that any student accessing the data would first sign up to the project SLSP (system level security plan), which outlines the security measures that must be adhered to. Any students accessing the Data will do so under the supervision of a substantive employee of the University of Warwick. The University of Warwick 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 DSA.

In developing the funding proposal, a Patient and Public Involvement (PPI) team was established. This PPI team helped refine the purpose of the research and supported the collection of the data for the purposes described above.

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 section 251(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 Data Sharing Agreement (DSA).

NHS England provided the relevant records from the above datasets to the University of Warwick previously. University of Warwick require no new data flow out of NHS England.

The Data contains no direct identifying data items. The Data is pseudonymised and individuals cannot be reidentified through linkage with other data in the possession of the recipient.

As outlined in the attached SLSP, the University of Warwick securely transferred the data to the University of Bristol and University of Birmingham.

The data is being securely stored on servers at the University of Warwick, the University of Birmingham and the University of Bristol.

The data will not be backed-up at another location.

The encrypted datasets are stored on the ‘M: drive’ which is the Departmental file store used by the University of Warwick Medical School. This file store is accessed via the virtual Windows server LEELA and is stored on the HP 3PAR Storage array. The data, including the server, is mirrored across HP 3PAR storage arrays in both University House data centre and Argent Court data centre for resiliency. Both data centres are on the University of Warwick Campus in Coventry. The data centres, servers, storage, and backup systems are all managed by specialist teams within the central Information and Digital Group (IDG).

The data will be securely downloaded via ODR approved Secure Electronic File Transfer to an already encrypted folder on a University file server (encrypted to AES 256). The server and related data storage equipment is fully managed by the Information & Digital Group and located in a secure data centre. University Data centres have a strictly policed access control system and CCTV surveillance. Occasional visitors/contractors are always escorted by an appropriate member of the Information & Digital Group staff.

The data will only be accessed from University of Warwick managed computers provided by the Information & Digital Group. Desktop computers are secured in offices in the Medical School building on campus. Offices are kept locked whenever unoccupied and the Medical School building also requires University ID card access so only authorised individuals can enter the building. Laptop computers used by study members have full hard disk encryption (AES 256 encryption).

The Data will be accessed by authorised personnel via remote access:

- Remote access will only be from secure locations situated within the territory of use stated within the DSA;

- Access controls granting users the minimum level of access required are in place;

- Remote access is only via VPN to protect data;

- Multifactor authentication (MFA) is required for remote access;

- Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access;

- All remote access is undertaken within the scope of the project SLSP and complies with the University of Warwick’s remote access policy.

The above applies in addition to any condition set out elsewhere within the DSA (e.g. who may carry out processing, and for what purpose).

The Data will not leave the UK at any time.

Access is restricted to employees of the University of Warwick, the University of Birmingham and the University of Bristol and to PhD students enrolled with the University of Warwick. All such individuals will require pre-authorisation from the Principal Investigator.

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

The dataset was linked within Public Health England (PHE) before being shared with the University of Warwick, however the Data will not be linked with any other data outside of this DSA.

All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset.

All individual data will be combined to develop the models so no individual data will be reported.

Researchers from the University of Warwick will analyse the Data for the purposes described above.

In addition, researchers from the University of Birmingham will analyse the Data for the specific research questions as outlined above (the analysis on test threshold) and researchers from the University of Bristol will analyse the data as outlined above (the analysis on age and screening interval).

The expected outputs of the processing will be:

• Submissions to peer reviewed journals – we have already submitted one paper and anticipate four more papers

• Presentations to key policy makers

• Presentations at appropriate national and international conferences

• A report summarising the findings to the NIHR (as funder of the ATHENA-M project)

Since the data provided is pseudonymized no patient identifiable data is available. In addition, the outputs 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:

• Peer reviewed scientific journals

• Workshops involving key policy colleagues

• Reports to the funder of the research (NIHR)

• Conference presentation and abstracts at national and international conferences

In addition, a series of meetings with policy-makers will be held throughout the project to collaboratively consider how findings may influence policy and the best way to disseminate these findings.

An article in the British Journal of Radiology was published in August 2023 describing development of the ATHENA-M dataset and describing key data quality aspects of the data.

University of Warwick anticipate publishing 4 further journal articles, presenting the main results from the analysis of screening age (anticipated submission date: May 2024), the main results of the analysis on screening interval (anticipated submission date: July 2024) and the main analysis on the analysis on test threshold and the sub analysis on test threshold (focusing on the analysis on number of readers, anticipated submission date: June 2024).

University of Warwick anticipate presenting the work at a number of national and international conferences from the summer 2024 onwards.

University of Warwick plan to hold a dissemination event in summer/Autumn 2024, to include their policy and practice advisory group members and further national champions and stakeholders.

University of Warwick will use the findings to inform the UK National Screening Committee and revision of the English quality assurance guidelines for breast cancer screening. This will depend on results, but could for example include revising the targets for proportion of women recalled, of DCIS detection rates, or level of flexibility in the screening interval target. The aim is that future screening policy decisions are based on the available evidence.

It is hoped that this research will improve future breast screening design and answer the question of how best to organise screening; such as how often should women be screened, at what age and how many should be recalled for further tests. This should indicate how to best maximise benefits for women and minimise the harms of screening.

It is hoped that through communicating our findings to the UK National Screening Committee and feeding into the process of redrafting the English quality assurance guidelines for breast cancer screening University of Warwick will ensure that future screening policy decisions are based on the evidence arising from the processing of this data.

University of Warwick will explore the implications of the results with their co-applicants and discuss them further at a dissemination event in Autumn 2024, to include their policy and practice advisory group members and further national champions and stakeholders, and this will be the start of their engagement with NHS England to influence English quality assurance guidelines for breast cancer screening.

Bimonthly co-applicant group meetings have helped shape the analysis and have ensured early conversations around how to best disseminate emerging results. This group includes clinicians, policy makers, analysts and patient and public involvement leads.

University of Warwick already have links with various breast cancer charities such as IPCV and Breast Cancer Now and will work closely with them on how they can best share their results.

Finally, the researchers will work closely with the University of Warwick Press Office to advertise the findings to a wider audience should the findings warrant such attention.

Analysis of this dataset has been conducted to develop an understanding of how changes in the breast screening programme (age of eligibility, screening interval, number of readers and recall threshold) affect the benefits and harms of breast cancer screening. Examples include:

> Initial results have been presented to the Breast screening programme board and a special meeting was requested to discuss these further.

> University of Warwick expect the results to impact on breast screening policy, to help ensure that future screening policy decisions are based on the available evidence - by feeding into the process of redrafting the English quality assurance guidelines for breast cancer screening.

Update April 29th 2024:

Analysis of this dataset is being conducted to develop an understanding of how changes in the breast screening programme (the age of eligibility, screening interval, number of readers and recall threshold) affect the benefits and harms of breast cancer screening. The study team is looking to understand which version of screening offers the most benefit with the least harm, and these findings will be used to advise the UK National Screening Committee and suggest how to change the English quality assurance guidelines for breast cancer screening.

The study team has carried out data cleaning and published a paper on the data quality aspects of this dataset and the analyses outlined above are well underway. Results from the analyses on number of readers and age of eligibility will be ready for dissemination in the next couple of months and analysis of screening intervals and reader thresholds will be complete by May.

Following this there is a programme of dissemination planned with various research papers,

attendance at conferences and policy meetings. This is all on target with revised plans, having had a 12-month no-cost extension approved in 2023.

Initial results have been presented to the Breast screening programme board and a special

meeting was requested to discuss these further, to be held in spring 2024. The study team

expects the results from this research to impact on breast screening policy, to help ensure that future screening policy decisions are based on the available evidence - by feeding into the process of redrafting the English quality assurance guidelines for breast cancer screening.