Yorkshire Lung Screening Trial (s251)

The University of Leeds requires access to NHS England data for the purpose of the following clinical trial:

Yorkshire Lung Screening Trial (YLST)

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

The Yorkshire Lung Screening Trial (YLST) is a randomised controlled trial to evaluate invitation to community-based low dose computed tomography (LDCT) screening for lung cancer versus usual care in a targeted population at risk. The main aim of YLST is to assess what impact a national screening programme might have on lung cancer outcomes in the UK.

The study uses a Zelen’s design where age 55–80 smokers or ex-smokers are randomised to intervention or usual care groups before approach. Study setup commenced August 2017 with randomisation commencing August 2018. The intervention group were invited to assessment for a Lung Health Check (including LDCT screening for high-risk people) framed as a pilot health service.

Individuals in the intervention arm and control arm were initially identified by participating GPs in the Leeds area. In March 2018, the YLST study received support from the HRA Confidentiality Advisory Group (CAG) to access confidential patient information for the purposes of identifying individuals at participating GPs; randomisation into intervention/control cohorts; and, inviting individuals from the intervention arm to book a telephone appointment for LDCT eligibility screening. The CAG acknowledged that access to confidential patient information was required in order to establish the cohort of patients who were eligible to participate. It was agreed that seeking consent from the wider proportion of patients who would form the control group was not feasible due to the sample size. The legal basis for YLST accessing confidential patient information for these purposes is the Health and Social Care Act 2012, Section 251.

This Data Sharing Agreement (DSA) is one of two required for the purposes of the YLST study to enable technical application of National Data Opt-Outs (NDOO) for individuals within the cohorts who have not consented to participate in the study:

• DARS-NIC-732228-T8Q0V: NDOO's not upheld – Consists of 9,046 individuals from the intervention arm who consented to participate in the study.

• DARS-NIC-788403-Y9M1G: NDOO's upheld – Total ~81,000 individuals consisting of ~45,000 individuals in the control arm, plus ~36,000 individuals in the intervention arm who did not respond to screening invitation, or were not invited to LDCT screening following pre-screening telephone consultation.

By comparing outcomes with a control population, the study team will be able to assess the true benefits (of reducing number of late stage cancers, and therefore lives saved) and possible harms (of overdiagnosis) of introducing screening in the UK. The study team will use Cancer Registration data from NHS England to report stage distribution and actual numbers of late-stage cancers (stage III/IV) in the intervention and control groups as a whole.

In the absence of a UK national lung screening programme at the time of study design in 2017; an objective of the study was to provide evidence to identify optimal strategies for defining a high-risk population for screening in the UK to aid any subsequent roll-out of a national screening programme. In June 2023, the Secretary of State for Health in England announced the planned roll-out of CT screening for lung cancer to occur over a 5-year period. The decision followed the UK National Screening Committee recommending a lung cancer screening programme, informed in part by participation data from the YLST.

YLST study objectives:

• Measure participation rates of a community-based lung cancer screening programme.

• Assess the clinical outcomes of targeted community-based LDCT screening for lung cancer versus usual care.

• Determine the effect of invitation to the screening programme on smoking rates, comparing intervention and usual care arms at the end of the study.

• Undertake a health economic evaluation of community-based LDCT screening for lung cancer, specifically comparing the health economic impact with selection criteria for the following:

- US Preventative Services Task Force (USPSTF)

- Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)

- Liverpool Lung Project (LLP)

• Evaluate the performance of the screening programme, including:

- Attendance rates

- False positive rates

- False negative rates

- Rates of investigation of benign disease

- Benign resection rate

The following NHS England Data will be accessed:

• Civil Registrations of Death- necessary to enable the study team to compare outcomes with a control population, and assess the true benefits (of reducing number of late stage cancers, and therefore lives saved) and possible harms (of overdiagnosis) of introducing screening in the UK. Lung cancer-specific mortality and all-cause mortality are important secondary end points of the study.

• NDRS Cancer Consolidated Data Set - necessary to report stage distribution and actual numbers of late-stage cancers (stage III/IV) in the intervention and control groups as a whole.

The level of the Data will be:

• Identifiable - necessary to enable linkage of the Data with study data collected by the University of Leeds.

The Data will be minimised as follows:

• Limited to a study cohort identified by University of Leeds through collaboration with participating GP’s in the Leeds area.

Prior to randomisation, individuals in the intervention arm and control arm were initially identified by Participating GPs:

Inclusion criteria:

• Limited to the Leeds CCG area (YLST confirmed the boundaries of the ICB match those of former CCG’s involved)

• Ages 55-80 years old at time of randomisation (Age checked at time of extraction from GP data)

• Any record of previous tobacco use

Exclusion criteria:

• Patients with diagnosis of lung cancer within the previous 5 years before GP data extraction by PCT

• On Palliative Care Register

• On Dementia Register

• Severe frailty (Electronic Frailty Index >0.36) are excluded

• Patients resident in nursing home

The University of Leeds is the research sponsor and a joint controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above.

Leeds Teaching Hospital NHS Trust (LTH) are a joint controller and the substantive employer of the Chief Investigator.

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 is provided by Yorkshire Cancer Research. The funding is specifically for the trial described. Funding is in place until 30th June 2026.

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

Researchers and Academics from the following organisations acted in an advisory capacity for development of the protocol, but are not involved in controllership or processing activities:

• Nottingham University Hospitals NHS Trust

• Manchester University NHS Foundation Trust

• University of York

• University College London

• York Medical School

• National Institute for Health Research

• Kings College London

• University of Nottingham

• Cardiff University

Data will be accessed by:

• Substantive employees of the University of Leeds who have authorisation from the Chief Investigator.

• Individuals from QMUL holding a Visitor Title under the supervision of a substantive employee of University of Leeds for the purposes described in this DSA only. University of Leeds must maintain records in a single location that cover the following details of each individual given access under a Visitor Title:

- Their substantive employer;

- Their role in respect of the purpose for the processing specified in the DSA;

- The start date and end date of the duration in which the Data will be accessed by the individual under an honorary contract;

- The necessity for the Data to be accessed by the person(s) holding an honorary contract, instead of a substantive employee of an organisation named as controller or a processor in this DSA;

- Confirmation that an appropriate contract is in place which follows the relevant guidance and is countersigned by the substantive employer of the honorary contract holder.

A Public and Patient Involvement and Engagement group helped refine the purpose of the research. The YLST has had substantive PPI input since inception and was reviewed by a PPI forum at two sessions run on 3rd and 6th Nov 2017. The group supported the collection of the data for the purposes described above.

When YLST first identified participants from GP records, the study team widely publicised the study to let people in Leeds know that their data might be used without their consent. Dissent information was published in the Yorkshire Evening Post and displayed on posters in 86 GP surgeries in Leeds and all nearby pharmacies. 98 individuals are excluded from the data request due to personal choice. These include:

• Individuals from the control arm who registered a dissent with the study-team,

• Individuals from the intervention arm who were did not attend a screening appointment, and registered a dissent with the study-team,

• Individuals from the intervention arm who did not consent at LDCT screening appointment.

The University of Leeds will transfer data to NHS England. The data will consist of identifying details, specifically NHS Number, Date of Birth, and a unique person ID, for the cohorts to be linked with NHS England data.

NHS England will provide the relevant records from the NDRS Cancer Consolidated Data Set and Civil Registrations of Death datasets. 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 not be transferred to any other location.

The data will be stored in LASER, a Trusted Research Environment (TRE), also known as a Data Safe Haven, managed and run by Leeds Institute for Data Analytics, University of Leeds. LASER is ISO27001 accredited and NHS Data Security and Protection Toolkit compliant. LASER stores data on the Azure Cloud provided by Microsoft.

The University of Leeds TRE (LASER) stores Data on the Azure Cloud provided by Microsoft. The Microsoft ‘Azure Backup Service’ enables backup and data to be restored from the Azure cloud. The Azure Backup Service is based upon the Microsoft Azure Recovery Services (MARS) agent and uses a Backup Service Vault, connected to Azure storage services. These agents will be utilised within the VRE environment.

The Data will be accessed onsite at the premises of University of Leeds.

The Data will also be accessed by authorised personnel via remote access.

The Controllers must confirm and provide evidence upon audit by NHS England that access via any remote device complies with the data security obligations within this DSA and the Data Sharing Framework Contract.

For remote access:

• Remote access will only be from secure locations situated within the territory of use (as further restricted elsewhere within the DSA if so done) stated within this DSA;

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

• Remote access is only via secure connections (e.g., VPNs or secure protocols) 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 organisation’s DSPT (or other security arrangements as per this DSA) and complies with the organisation’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 England/Wales at any time.

Data will be accessed by individuals from QMUL holding a Visitor Title with University of Leeds. The individuals will act as an agent of University of Leeds at all times under supervision from employees of University of Leeds. Aside from these individuals, access is restricted to employees or agents of University of Leeds who have authorisation from the Chief Investigator.

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

The Data will be linked at person record level with study data collected by University of Leeds.

The identifying details will be stored in a separate database to the linked dataset used for analysis. All analyses will use the pseudonymised dataset.

Researchers from the Leeds Institute for Data Analytics at University of Leeds and Statisticians from Queen Mary University London working under Visitor Titles with University of Leeds, will analyse the Data for the purposes described above.

The expected outputs of the processing will be:

• Submissions to peer reviewed journals – YLST aim to submit the main paper based on these results to a high impact factor journal in early 2026. YLST have already been approached by Nature Medicine who are keen for YLST to submit when papers are finalised.

• YLST aim to coordinate the presentation if possible, with presentation at a key conference (e.g. World Conference on Lung Cancer, Seoul, September 2026)

• A lay-report of the findings will be made available through the study website (www.leedslunghealthcheck.nhs.uk) at the time of journal publication. All participants have been advised that the study findings will be available at study conclusion.

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 the academic community through publication in journals and presentation at national and international conferences as described above.

In addition, a lay summary of trial findings will be made available through the study website. All participants being discharged from the study have been made aware of these plans (and given the study website address). In addition, the funder Yorkshire Cancer Research, has an extensive network of public and patient involvement groups through whom the study findings will be disseminated.

The target date for the first dissemination of outputs is June 2026.

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.

The use of the data could:

• Help the system to better understand the health and care needs of populations.

• Lead to the identification or improvement of treatments or interventions, or health and care system design to improve health and care outcomes or experience.

• Advance understanding of the need for, or effectiveness of, preventative health and care measures for particular populations or conditions such as lung cancer.

• Inform planning health services and programmes, for example to improve equity of access, experience and outcomes.

• Support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work).

• 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.

In June 2023, the Secretary of State for Health in England announced the planned roll-out of CT screening for lung cancer to occur over a 5-year period. The decision followed the UK National Screening Committee recommending a lung cancer screening programme, informed in part by participation data from the YLST.

Lung cancer is much more common in deprived communities, and yet these populations are less likely to participate in both established screening programmes and research studies. The study hopes to answer questions such as how to design services that are convenient and accessible to people from deprived populations who are most at risk; how much extra benefit might be seen with targeted screening of high-risk current or ex-smokers in the UK compared to the US; is overdiagnosis a problem (where screening detects indolent cancers that would not have caused patients harm during their lifetime); and what effect screening has on smoking rates.

The study expects that answering these questions will inform future screening programme design, an increased uptake of screening services by patients in deprived communities, therefore identifying some cancers sooner and improving health outcomes of those patients.

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.

Clients will need to take action based on the information provided to them in order to realise the potential improvement opportunities.

A key issue for the ongoing success of the NHS England Lung Cancer Screening Programme is participation. Nationally this is currently running at 53% uptake and it is know (from YLST data) that those people who decide not to take part are very likely to be more at risk from lung cancer than those who do participate. Thus publicising the benefits of lung cancer screening to the target population is critical to maximising public benefit.

Yorkshire Cancer Research have extensively promoted the study and Lung Cancer Screening generally throughout the region. YLST are keen to publicise the results of the study further when outcome data is available, with the aim of increasing uptake in screening if invited and eligible. YLST are in regular contact with the communications team at the charity and will coordinate a multi-faceted dissemination in due course depending on the eventual results.

Yielded Benefits is not a requirement for new applications.