UK Lung Cancer Screening Trial Lung Cancer Registry and Mortality data for consented individuals

In term In term in the September 2026 edition: the latest version runs to 31 May 2027.

Reference: DARS-NIC-19237-R3T6S
Current version: v9.6
Term of current version: 15 May 2026 to 31 May 2027
Start date: Before 1 June 2019
Data controller: Sole Data Controller
Commercial purposes: No
Sublicensing: No
Files released to date: 37

Why the data was released

Objective for processing

The Data will be used for the purpose of a research project: UK Lung Cancer Screening Trial Lung Cancer Registry and Mortality

The United Kingdom Lung Cancer Screening (UKLS) trial is a study of lung cancer screening in the UK. The overall aim of the trial was to provide the information required for an informed decision about the introduction of population screening for lung cancer. This involved establishing the impact of screening on lung cancer mortality, determining the best screening strategy and assessing the physical and psychological consequences and the health implications of screening. An additional objective was to create a resource for future improvements to screening strategies.

The UKLS started with a Health Technology Assessment (HTA) funded randomised control trial of low-dose CT (initial recruitment and baseline CT scan completed September 2011 to October 2012), which is now in long-term follow-up to assess the impact in terms of lung cancer detection and mortality. Research continues to be funded from a variety of sources with the aim of analysing the contribution of lifestyle, medical history, nodule characteristics and molecular biomarkers on the ability to improve early detection of lung cancer.

It was initially anticipated that the pilot study would be followed by a more in-depth extended trial with a larger cohort of people if funding was available. The HTA was approached to provide funding for this but by 2013 further funding was not available at the level required - essentially due to the high cost of the extended trial and lack of available funds for such a trial at that time. The data is therefore limited to the pilot study with a cohort of 4,061 participants, of which recruitment has now ended. As a more economic alternative to the extended trial, to increase the statistical power of the trial's findings, it was planned that the findings would be combined and assessed along with the findings from a similar study in the Netherlands, NELSON.

Under this Agreement, NHS England will provide longitudinal, observational follow-up data for the UKLS lung cancer screening study, which aims to provide evidence to improve early detection of lung cancer. Hence it is a task in the public interest, leading to improved understanding of disease and opportunities for improved treatment resulting in lives saved and improved health.

The University of Liverpool require NHS England data to inform the current status (alive/dead) and dates and causes of death; this data specifically informs the prime question of the study, helping to identify both lung cancer mortality (within causes of death) and the time from recruitment or treatment until death (all-cause mortality, an important measure of health status and outcome). This data needs to be provided for specific individuals (by linkage through NHS number with verification by month/year of birth) to allow appropriate data for personal level risk model development and evaluation. For the long-term follow-up of the study, it is important to follow as many subjects as possible until death, so the UKLS requires data on all available years (including retention of data already provided and incremental updates). Although the study was based on residence in Merseyside and Cambridgeshire, recruited individuals may have moved subsequent to recruitment, therefore all UK data relating to this cohort is requested. Alternative methods of assessing mortality status (e.g. re-contacting individuals) would be either more intrusive (likely to cause harm/distress), less informative or incomplete.

NHS England will also provide cancer registry data, identifying all cancer diagnosis, with dates (where available). The justification for this is broadly the same as for cause of death, but this data provides additional information on timing and specific diagnosis of lung cancers (a primary outcome measure of the study) and other cancers (which may be significant confounding factors that must be taken into account during analysis). Again, this must be at the individual level, for all dates available and all geographical areas to provide the best dataset of personalised prognostic prediction. Alternative methods (e.g. case-note review) are likely more intrusive, less efficient and incomplete.

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

Processing activities

The University of Liverpool will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number, Name, Date of Birth, Postcode, Gender and a unique person ID) for the cohort to be linked with NHS England data.

NHS England will provide the relevant records from the cancer, deaths and demographics datasets to the University of Liverpool. The Data will contain directly identifying data items including Names, NHS Number, Date of Birth, Postcode and Gender which are required to ensure quality assurance of linkage.

The Data will not be transferred to any other location.

The Data will be stored on servers at the University of Liverpool.

The Data will be accessed by authorised personnel on-site at the University of Liverpool and via remote access.

The Controller(s) 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 be linked at person record level with data in the UKLS clinical database, including subject data held by UKLS that has been provided by the participants as part of the trial. For those randomised to the CT screening arm, details of CT scan results are held and diagnostic tests or any treatment received as part of the trial. This linkage will be done using the subject specific MPI number only. The data within this database are pseudonymised as much as practically possible and include health data and event dates. Event dates are required for calculation of time periods in relation to other events both within the data provided by NHS England and to events collected by other means, e.g. directly from the subject or by review of hospital records.

Researchers within the University of Liverpool have access to the pseudonymised data for analysis only, which is imported into statistical software, usually SAS, STATA, or Excel. In most cases the data is combined with new data produced from biological or biochemical assays (in associated samples provided from the UKLS biobank), from algorithms based on risk data provided by subjects via questionnaire or from CT data on detected nodules and cancers. Having combined the data an assessment is made as to whether the new data allows the researchers to predict specific health outcomes (e.g. diagnosis, specific disease sub-type related, disease severity or outcome) – providing a risk score or diagnostic algorithm that may help guide future diagnosis or treatment (e.g. to better managed indeterminate nodules detected at CT scan). Additionally correlations are made between data that help the researchers understand the biology of lung cancer, which provides new opportunities for alternative treatments.

This processing activity (of data stripped of identifiers) is not considered to constitute a risk of re-identification, because of the significant ambiguity of the data being combined, the lack of specific time points or geographical locations and the common nature of lung cancer. Furthermore, contractual and governance controls are in place to restrict data use for re-identification; no attempt will be made to link data to other publicly available sources.

Given the high incidence of lung cancer and associated co-morbidities, it is considered incredibly unlikely that any re-identification could occur, even with access to other data.

Subsets of data from the clinical database including information derived from the data under this Agreement may be extracted and shared with collaborative organisations specified in the protocol for the purpose specified in this Agreement. The derived data will be shared in combination with data from other sources (e.g. pathology records, electronic patient records, questionnaires) but this data will not contain identifying information or any information which would result in any shared data being identifiable as originating or deriving from the data from NHS England or possible to reverse-engineer such that it can be so identified. Any data that is shared with these collaborative organisations will be pseudonymised with a unique study ID which does not allow the collaborative organisations to link data to identifiable individuals (but which does allow the UKLS to link results of analysis back to the individuals if required). Dates are removed (replaced by ages or time periods, e.g. time form diagnosis to death) or limited (e.g. year or month + year); health events are curated (e.g. classed as lifetime events rather than time dependent events) or recoded to remove granularity (e.g. grouping into less specific terms such as “lung disease”). The combined data will conform to the specification shared with NHS England (filename ‘UoL Lung projects Data sharing MD209180218’) which NHS England has approved.

The derived variables which may shared are limited to the following:

i. An indicator for whether a patient has died or not (1 = Dead; 0 = Alive);

ii. The Cause of death simplified (‘Died from Lung Cancer’, ‘Died from other Malignant disease’, ‘Died from other cause’ or ‘Cause of death unknown’)

iii. Age at death (calculated from date of death minus date of birth divided by 365.25)*

iv. Time to death in days or months from date of diagnosis**

*Date of birth will not be included in any dataset with the variables above.

**Date of diagnosis will not be included in any dataset with the variables above.

Any data shared with collaborators must be subject to the conditions that the collaborating organisation:

i. must not combine it with other datasets which could potentially increase the risk of reidentification for individuals in the dataset;

ii. must not attempt to re-identify individuals in the dataset;

iii. must not onwardly share the dataset;

iv. must use the dataset for a defined purpose in support of the UKLS’s aims defined within this Agreement, and

v. must not publish the data.

Under the terms of this Agreement, the University of Liverpool is responsible for ensuring compliance with the above conditions and for confirming destruction of the data by any collaborating organisation once the data is no longer required for the purpose for which it was shared.

Although the database includes NHS numbers, only pseudonymised data will be made available to researchers within the University of Liverpool for the purpose of the UKLS. Subjects will be identified using a pseudonymised unique identifier in any extracted data.

Expected output

The expected outputs of the processing will be:

• Submissions to internationally renowned oncology, epidemiology and public health journals. Journals for consideration will include: Thorax, Journal of Thoracic Oncology, Lung Cancer, British Journal of Cancer, Cancer epidemiology, biomarkers & prevention, Scientific Reports, Oncology Letters, Nature Genetics, Nature Communications, Lancet and Lancet Oncology. The initial findings/conclusions of the trial data were published in the BMJ-Thorax Online First. This included methods, trial design, recruitment, randomisation, nodule management, number of cancers, treatment, cost effectiveness modelling. The full report of these aspects of the UKLS trial has also been published by the funder, National Institute for Health Research, Health Technology Assessment Programme (NIHR HTA). Both of these are available as open access publications.

• A report to the UK National Screening Committee on the cost effectiveness and mortality benefit of introducing a lung cancer screening programme into the UK

• International Conference and Meeting presentations (both oral and poster). Further such presentations are anticipated. Conferences are expected to include: World Conference on Lung Cancer, American Association for Cancer Research Annual Meeting and National Cancer Research Institute Annual Meeting

• Currently proposed risk models are based on the ability to predict risk of lung cancer (either within the general population or within those with nodules detected during CT imaging), these rely of lung cancer outcomes provided separately through Public Health England. In the future it may prove informative to define models for risk of early death from lung cancer (identifying those with aggressive life-threatening disease from those with indolent disease unlikely to be the cause of premature death). In this case mortality data (time to death and cause of death) will be important for discovery and validation of such models, but the UKLS study itself is not large enough to both generate and validate such models. This need to combine data to provide more powerful and meaningful outcomes of clinical importance is one of the drivers for the University of Liverpool's desire to share anonymised, individual level data including data derived from NHS Digital data under this Agreement with collaborating researchers in future. It is expected that any risk models produced will be utilised in the public interest and made freely available (open access). Whilst their generation will, in part, be dependent on exploitation of data provided by NHS Digital and this will be acknowledged in any publications, the data itself will not be used by the final model, which will be an algorithm based on a larger cohort of data from multiple sources.

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:

• Journals

• Conferences

• Reports

• Papers will be accompanied by web-page updates and press releases at the time of publication, to provide information to both scientific and non-scientific audiences

Expected measurable benefits

The dissemination of mortality data for individuals participating in the UKLS study provides an important benefit in helping discern the value of early detection for lung cancer through risk prediction and low-dose CT. Proof of value on mortality is a key indicator for such screening trials, to demonstrate that the University of Liverpool are benefiting patients by intervening at an earlier stage (as opposed to knowing about the cancer earlier but being unable to significantly impact on life expectancy). It is therefore clearly a legitimate public interest to address this issue and in particular in the UK, given that this is the largest randomised trial of its sort, carried out within the NHS.

Dissemination of data will be limited to the research team within the University of Liverpool. Greater benefit will accumulate from plans to combine UKLS data (including data derived from NHS England data) with other large international trials. Dissemination of benefits will be broader. Publication of results in the scientific and medical literature, or through presentations at meetings, will inform others undertaking similar studies (in the UK and globally) and contribute to the evidence considered by policy makers weighing up the introduction of larger scale early detection or screening. In particular the UK National Screening Committee (UKNSC) will refer to the data when deciding about lung cancer screening in the NHS.

The types of benefits that are likely from early detection of lung cancer (based on evidence already accrued from UKLS and other studies), include:

• earlier detection of lung cancer at a stage when surgical intervention is possible, resulting in longer survival and better quality of life

• reduced treatment costs (as earlier stage disease treatable by surgery and avoids or delays some chemotherapy & radiotherapy and associated additional imaging).

Mortality and Cancer Registry Data have been received on a quarterly basis since 2012. This was vital information during the conduct of the trial as any deceased participants, or those diagnosed with lung cancer, were annotated on the database and marked as "Off Study" so that the UKLS project team would not contact them again to arrange repeat scans or complete follow up questionnaires.

The trial has now finished but the follow up data on deaths and lung cancer diagnosis is still required. Once the outcome data is available, the success of the screening can be evaluated. This analysis will be provided in aggregated form to the UK National Screening Committee (UKNSC) to help inform decision-making as to whether a lung cancer screening programme should be implemented in the UK. The UKNSC will not be using only the UKLS analysis, but will also receive analysis from a larger lung cancer screening trial run in the Netherlands (NELSON - European Nederlands-Leuvens Screening Onderzoek). The NELSON Trial Trial has provided further evidence that LD-CT intervention reduces lung cancer mortality (de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial. N Engl J Med 2020; 382(6): 503-13), so that we should now seriously consider implementation of lung cancer CT screening in Europe and the rest of the world (Oudkerk M, Liu S, Heuvelmans MA, Walter JE, Field JK. Lung cancer LDCT screening and mortality reduction — evidence, pitfalls and future perspectives. Nat Rev Clin Oncol 2021; 18: 135-151)

The UKLS trial sample size is too small to give adequate statistical power to calculate the mortality benefit and cost effectiveness. The UKLS trial design was based on a larger lung cancer screening trial run in the Netherlands (NELSON). The NELSON trail has now reported and has been included in a meta-analysis of all LDCT randomised control trials, a alongside publication of UKLS mortality data (Field JK, Vulkan D, Davies MPA, Baldwin DR, Brain KE, Devaraj A, et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. The Lancet Regional Health - Europe. 2021;10(100179):100179-). The data from these trials and from UK LDCT implementation studies has been used to provide the information to the UKNSC as to whether or not to implement a lung cancer CT screening programme in the UK. (currently under review).

Further benefit will be derived by linking the data collected as part of the trial (risk questionnaire data and low-dose CT imaging data) with the outcome data received from both Civil Registry mortality and cancer registration (lung cancer incidence) for: (i) generation of improved risk models for identifying those at greatest risk of lung cancer; (ii) improving clinical management the nodules identified during CT scans; and (iii) risk models for lung cancer mortality. Furthermore, use of this combined dataset in conjunction with biomarker analysis performed on samples collected as part of the UKLS study will be incredibly valuable to help define new molecular biomarkers for early detection and incorporate these into lung cancer risk and nodule management tools.

By collecting biosamples under tightly controlled conditions and collating data relating to both lung cancers and other types of cancer, UKLS is a very valuable resource for studies of early detection for multiple cancer types and for multi-cancer early detection. Future benefits are therefore expected beyond lung cancer. Furthermore, under the appropriate conditions samples and data might (in aggregate form) contribute toward regulatory approval for new diagnostic or predictive biomarkers.

The magnitude of the impact for improved early detection is considered to be great, as lung cancer is the biggest cause of cancer mortality and this is largely because of detection at late stage when treatments are less effective. Screening by low dose CT has already been proved to be of benefit and has been adopted in the USA; UKLS is the only randomised control trial that addresses this in the UK NHS setting and has been informative for the introduction of further low dose CT early detection pilots (which also utilise the LLP risk model developed by our group and used in UKLS for patient selection). One of the benefits of using a risk-based approach is in cost-saving by improved targeting of screening to those most likely to benefit; such studies need to consider both cancer detection and overall mortality when assessing outcomes. The LLP risk model is currently being used in the NHS Targeted Lung Health Check programme, which aims to screen 600,000 people over 4 years and is expected to lead to the early detection of approximately 3,400 lung cancers; unlike current diagnosis, most of these will be early stage disease for which curative surgery is possible, leading to significantly improved outcomes.

Biomarkers that allow early detection (e.g. from blood samples) or improve screening results (by stratifying risk for those with small potentially pre-cancerous lesions) are also likely to provide a large benefit in terms of numbers of individuals benefiting and efficiency savings (e.g. reducing the need for follow-up scans). These benefits are likely to take longer to achieve as whilst UKLS samples will be very valuable for initial retrospective validation, prospective clinical trials will need to be performed before implementation.

It is considered that this research will contribute to benefits to the general population, through improved health and lower mortality as it provides evidence demonstrating the feasibility of earlier lung cancer detection. Early lung cancer detection would also benefit the NHS - e.g. by providing lower costs of treatment. Research Funders are primarily non-profit, but may benefit from royalties paid if any intellectual property is developed and exploited. Those funders that are commercial enterprises aim to benefit by generation or exploitation of intellectual property (e.g. biomarkers and drugs); although it should be noted that the University of Liverpool and other funders have protected intellectual property in order to share these benefits. Given that UKLS researchers plan to publish their research findings it is possible that third parties will benefit, although to do so they will have to extend the work.

iii. Yielded Benefits :

The UKLS statistician has developed a risk model to predict lung cancer utilising nodule data from the UKLS study. This has now been published in Thorax (Probability of cancer in lung nodules using sequential volumetric screening up to 12 months: the UKLS trial. Michael W Marcus, Stephen W Duffy, Anand Devaraj, Beverley A Green, Matthijs Oudkerk, David Baldwin, John Field. doi: 10.1136/thoraxjnl-2018-212263).

The LLPv2 lung cancer risk model used in UKLS has been validated and update of the LLP lung cancer risk model (to LLPv3) with a more accurate estimation of absolute risk, as published in Thorax (Field JK, Vulkan D, Davies MPA, Duffy SW, Gabe R. Liverpool Lung Project lung cancer risk stratification model: calibration and prospective validation. THORAX. 2021;76(2):161-8). This will allow more efficient selection of at risk groups in future LDCT screening and other early-detection scenarios.

UoL have published lung cancer incidence data and mortality data in relation to the UKLS lung cancer screening trial (including as part of a meta-analysis of all related randomised control trials) in The Lancet Regional Health - Europe (Field JK, Vulkan D, Davies MPA, Baldwin DR, Brain KE, Devaraj A, et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. The Lancet Regional Health - Europe. 2021;10(100179):100179-). This data completes the world-wide randomised control trial assessment of LD-CT screening and provides evidence for the benefits of LDCT early lung cancer detection.

The UKLS data is particularly informative for UK implementation of LD-CT, supporting both the NHS Targeted Lung Health Check programme (which is currently underway) and being central to the current considerations of the UK National Screening Committee.

Lives have already been saved as part of UKLS and more lives will be saved by the further implementation of LD-CT that is supported by the UKLS results, with efficiency savings from the demonstrated utility and validation of the LLP lung cancer risk score.

The UKLS data continues to be used for analysis in major international research project (e.g. the NIH-funded INTEGRAL project looking to improve risk-based early detection and lung nodule management, which has been extended by 5 years) and for publications (e.g. Moez, E., et al.2023 Circulating Proteome for Pulmonary Nodule Malignancy. Journal of the National Cancer Institute, doi:10.1093/jnci/djad122; Davies et al. 2024 Impact of single round of low dose CT lung cancer screening on cause of mortality in different socio-economic groups: a post-hoc analysis of long-term follow-up of the UKLS trial. Lancet Regional Health Europe doi: 10.1016/j.lanepe.2024.100936). As an invaluable resource for early detection biomarker studies, being the UK’s oldest establish repository of biosamples taken at the time of low-dose CT screening, with the longest follow-up, the UKLS study will continue to yield significant benefits going forward.

The UKLS trial radiology dataset, including anonymised LDCT images, original radiology reports and consensus reads and outcome data, are now recognised as a major resource, including for validation of recent advances in artificial intelligence for aiding diagnosis from LDCT scans and tackling the potential manpower issues posed by rolling out lung cancer screening. In collaboration with iDNA and associated academic groups, we have published a number of papers (having first presented results at major international conferences).

In collaboration with iDNA and associated academic groups, a number of papers have been published (having first presented results at major international conferences).

Benefits reported so far

The LLPv2 lung cancer risk model used in UKLS has been validated and update of the LLP lung cancer risk model (to LLPv3) with a more accurate estimation of absolute risk, as published in Thorax (Liverpool Lung Project lung cancer risk stratification model: calibration and prospective validation). This will allow more efficient selection of at risk groups in future LDCT screening and other early-detection scenarios.

UoL have published lung cancer incidence data and mortality data in relation to the UKLS lung cancer screening trial (including as part of a meta-analysis of all related randomised control trials) in The Lancet Regional Health - Europe (Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis). This data completes the world-wide randomised control trial assessment of LD-CT screening and provides evidence for the benefits of LDCT early lung cancer detection.

Datasets on the current version

Legal basis for provision: Health and Social Care Act 2012 – s261(2)(c)

Datasets approved under DARS-NIC-19237-R3T6S-v9.6
Dataset	Type of data	Sensitivity	Frequency	Confidential data
Cancer Registration Data	Identifiable	Sensitive	Ongoing	Consent (Reasonable Expectation)
Civil Registrations of Death	Identifiable	Sensitive	Ongoing	Consent (Reasonable Expectation)
Demographics	Identifiable	Sensitive	Ongoing	Consent (Reasonable Expectation)
MRIS - Cause of Death Report	Identifiable	Sensitive	Ongoing	Consent (Reasonable Expectation)
MRIS - Cohort Event Notification Report	Identifiable	Sensitive	Ongoing	Consent (Reasonable Expectation)
MRIS - Flagging Current Status Report	Identifiable	Sensitive	One-Off	Consent (Reasonable Expectation)
MRIS - Members and Postings Report	Identifiable	Sensitive	One-Off	Consent (Reasonable Expectation)

Files released

Files released counts only files released externally by DARS. Access granted in NHS England's own systems, such as its Secure Data Environment, is not included.

Patient opt-outs were not applied to any of the 37 files released under this agreement, across every version. About opt-outs

No files recorded as released under the current version. 37 were released under earlier versions, shown in the version history.

Version history

The register lists each renewal of this agreement as a separate row. This site has 5 versions — earlier versions existed before this site's records begin.

DARS-NIC-19237-R3T6S-v9.6 15 May 2026 to 31 May 2027

Title: UK Lung Cancer Screening Trial Lung Cancer Registry and Mortality data for consented individuals
Commercial: No
Sublicensing: No
Datasets: 7
Files released: 0

Datasets: Cancer Registration Data; Civil Registrations of Death; Demographics; MRIS - Cause of Death Report; MRIS - Cohort Event Notification Report; MRIS - Flagging Current Status Report; MRIS - Members and Postings Report

What changed from DARS-NIC-19237-R3T6S-v8.2

Text removed is ~~struck through~~; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Fields changed from DARS-NIC-19237-R3T6S-v8.2
Field	Was	Became
Start date	~~2025-02-07~~	2026-05-15
End date	~~2026-05-31~~	2027-05-31

Objective for processing

The Data will be used for the purpose of a research project: UK Lung Cancer Screening Trial Lung Cancer Registry and Mortality [3 paragraphs unchanged] As a University using health data for research purposes, “task in the public interest” is the legal basis for processing personal and sensitive information under the General Data Protection Regulations [Article 6 (1) (e)]. As the study is for scientific research purposes, the University also rely on Article 9 (2) (j) of the General Data Protection Regulation. The cohort consists of lung cancer free individuals recruited by postal invite from Merseyside and Cambridgeshire, following a selection process based on a questionnaire using the Liverpool Lung Project Risk Model (version2) to identify those at greatest risk of lung cancer. The final participant list was limited by cost to 4,061, of whom half were randomised to receive low dose CT detection for lung cancer and the remainder the current standard of care (follow-up only). For the interventional trial the test group received CT and the control group did not, but in the observational follow-up and follow-up risk model discovery/refinement/validation studies, both groups contribute to lung cancer risk modelling, whilst the CT group additionally contributes to work on CT-detected nodule management. [1 paragraph unchanged] The University of Liverpool (UoL) is the sole Data Controller and also processes the data for this study. No other organisations process the data for this purpose. Only individuals based at the University of Liverpool - specifically the Chief Investigator and two other individuals involved in post-trial analysis - will make decisions on how and/or why the data under this Agreement are processed. The Royal Liverpool and Broadgreen University Hospitals NHS Trust was originally a co-sponsor due to intervention aspects of the project but, after reviewing their ongoing role, in 2018, they withdrew sponsorship from the study and consequently asked to be removed as a named co-sponsor in the Study Protocol. This request was approved by North West - Liverpool Central Research Ethics Committee. As co-sponsors they did not have any control over how the NHS England data was used or the purpose for which the data will be used. The Royal Liverpool and Broadgreen University Hospitals NHS Trust is no longer involved in any decision-making in respect of any data received from NHS England. This organisation is not involved in the follow-up study utilising cancer registry or mortality data and no data is shared with them. An individual from Barts and the London School of Medicine has the role of Lead Statistician/Trial Design. This individual is not involved in any decision-making over 'how' or 'why' personal data are processed. His role in 'trial design' is advisory – for example, the Investigators at the University of Liverpool will share with him the details of proposed analyses and, as a subject matter expert, the Lead Statistician will advise on the merits or flaws in the proposed method. The University of Liverpool is not obliged to secure this individual’s approval prior to processing the data but obviously takes into account his advice based on his specialist expertise. This individual only receives derived data which has been manipulated to the extent that it is not considered personal data. He will receive derived data (i.e. the outputs of the analyses) to review and advise whether the analyses were undertaken correctly. Other individuals from other organisations named in the study Protocol were previously part of the UKLS Trial Team put in place to manage and to undertake the trial during its lifetime. The trial is now complete, as far as recruitment and clinical intervention are concerned, the main findings have been published and the current analysis are part of the follow-up studies (which concern statistical analysis of outcomes and biomarker research). Therefore, these individuals have no ongoing role in determining the purposes for collection and processing of the mortality and cancer data from NHS England [2 paragraphs unchanged] Data requirements have been limited to those health-related events that directly impact the aims of the study and address the public interest justification, along with significant confounding factors, such as occurrence of other cancers and other causes of death. The research project is part of a wider international effort to address the critical issue of earlier detection of lung cancer, required to address the single largest cause of cancer-related mortality. The data will be recorded on the United Kingdom Lung Cancer Screening Trial (UKLS) database and pseudonymised data given to researchers - all of whom are substantive employees of the University of Liverpool - in order to ascertain any mortality advantage to screening and inform the UK National Screening committee. 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 provided by NHS England covered by this Agreement will be shared with any third parties.~~ The study investigators are unaware of any risk of potential harm to the public by the dissemination. The potential for harm has been assessed by University of Liverpool (Data Protection and Study Sponsor) and by NRES ethical approval. Safeguards are in place that protect the interests of the data subjects. These have been judged as proportional to the substantial public interest (together with informed consent) and also support the common law duty of confidentiality. Safeguards include physical and operational barriers protecting privacy and allowing processing of personal identifiers and sensitive data only by staff contractually obliged to fulfil the requirements set out by the University of Liverpool Data Protection Policy, compliant with all laws and approvals. Processing activity and storage of personal and sensitive (special category) data is limited according to best practice (both in terms of scope and timing), but recognising that longitudinal follow-up data for prospective studies require long-term data linkage and that research studies require anonymised and pseudonymised data to be available for a significant amount of time. These issues have been explained to participants during informed consent and are covered in a publicly accessible Privacy Notice. Collection and analysis of outcome data, in terms of mortality, is planned for 10 years from recruitment. Cumulative data will be assessed after each download but interim statistical analysis of mortality will only be undertaken when a significant number of events has been reached (as judged by the University of Liverpool research team with advice from the UKLS Statistical Lead, based on aggregate data). Further mortality analysis will be undertaken based on this preliminary analysis and also on the full 10-year data. Meanwhile, biomarker analysis relating to cancer incidence will be undertaken using the next available data download (providing >5 years follow-up on all participants) and revisited at a later date, as guided by initial results. The research project is part of a wider international effort to address the critical issue of earlier detection of lung cancer, required to address the single largest cause of cancer-related mortality. As such, the University of Liverpool intends to share data which has been derived from processing the data under this Agreement with other research groups in future, but will do so in a controlled way, bound by conditions in the Data Sharing Agreement that confer the same level of adherence to protecting the rights of individuals involved in research and specifically covered by informed consent of subjects. All such data shared is either aggregate (as in publication) or pseudonymised data containing no NHS England data but containing variables derived from NHS England. The data is provided at an appropriate level such that additional data provided by the collaboration can be added to the sum of knowledge about subjects within the UKLS but without allowing others to link data and/or risk re-identification – this includes measures to suppress rare events. The record level data (including derived variables) being shared is irreversibly pseudonymised person-level data containing indicators of prior diagnosis of various high-level conditions (e.g. lung cancer, COPD, etc.) and containing no directly identifying information nor any combination of details which could result in a person’s re-identification. The work undertaken by the University of Liverpool in regards to UKLS is funded by multiple organisations (research charities and government agencies, including international bodies). Their role is to provide funding for the research to the University of Liverpool (and collaborating research centres); they also support and encourage adherence to the highest standards of governance, public dissemination of results and scientific rigour.

Processing activities

An updated cohort Excel file (containing details of participants who have given informed consent) has been sent to NHS England by UKLS Project Manager. The flow of data into NHS England is limited to personal identifiers required for linkage (NHS number) and for verification of that linkage: unique cohort MPI No. (Master Patient Index), Name, Date Of Birth, Gender, NHS Number and Postcode. The updated cohort file is as a result of removal of those participants who have died (as informed by previous data received from NHS England. No special categories of data, such as health data will be provided to NHS England The University of Liverpool will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number, Name, Date of Birth, Postcode, Gender and a unique person ID) for the cohort to be linked with NHS England data. The flow of data out of NHS England consists of a download of data files containing the data initially supplied, plus matching fields from NHS England and the requested health care and outcome data, the majority of which can be considered as special category data: specifically race/ethnic origin and health data. As previously, identifying data other than the minimum required for basic data linkage (via MPI), are provided to ensure quality assurance of linkage (i.e. latest name, gender, Date of Birth, postcode). NHS England will provide the relevant records from the cancer, deaths and demographics datasets to the University of Liverpool. The Data will contain directly identifying data items including Names, NHS Number, Date of Birth, Postcode and Gender which are required to ensure quality assurance of linkage. NHS England will upload linked dataset file onto their secure portal and notify UKLS Lung Cancer IT technician. The file will be downloaded and saved as a password protected document into a folder. The data files are transferred to an encrypted drive on a dedicated University of Liverpool virtual server. NHS England data, prior to processing and transfer to the UKLS clinical database, is only accessed on University of Liverpool premises across a secure data network (password protected) from a BitLocker) encrypted virtual server (by approved UKLS study staff); the secure server is firewall protected and accessible only from 3 designated PCs (with unique IP addresses). The Data will not be transferred to any other location. This data is held by the University of Liverpool and, in accordance with the common law duty of confidentiality, is only provided for those who have given informed consent for taking part in the study, including for access to their health records. The Data will be stored on servers at the University of Liverpool. Data processing is performed within a University of Liverpool managed environment (password protected) and limited to specific folders accessible only to qualified staff associated with the UKLS study. In addition the UKLS database on which the trial data (including personal identifiers) resides is on a separately managed server with additional controls on staff access. The Data will be accessed by authorised personnel on-site at the University of Liverpool and via remote access. Previously, the UKLS Project Manager updated the UKLS database with deaths and cancers notified to ensure no further contact with those individuals is attempted. As the trial is now closed, and no further contact is planned, the database will not be updated and all linkage will be with research data already extracted from the UKLS database, after removing personal identifiers (linkage via unique UKLS patient identifiers). The Controller(s) 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. Data supplied by NHS England is processed for inclusion into the UKLS clinical database, to enable its use for the approved purpose. The data is linked at patient level with data in the UKLS clinical database using the subject specific MPI number only. The data within this database are pseudonymised as much as practically possible, but include health data and event dates Event dates are required for calculation of time periods in relation to other events both within the data provided by NHS England and to events collected by other means, e.g. directly from the subject or by review of hospital records. For remote access: ~~The data will only be accessed by researchers employed by the University of Liverpool and not shared with any third parties.~~ - 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; ~~Only substantive employees of the University of Liverpool will process the data and only for the purpose as defined in this Agreement.~~ - Access controls granting users the minimum level of access required are in place; After processing, data is stored in files located on a secure data network at the University of Liverpool; this network is only accessible to staff and is password protected. Data is located in folders that are limited to named staff. All hardware is in secure environments: servers within the Computer Services Department and PCs within research building with swipe-access control. Procedural control ensures that PCs are never left accessible. All data is stored on servers (rather than individual PCs) and is backed-up routinely with the same level of protection (i.e. the encrypted server has an encrypted back-up). - Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data; The Lung Cancer IT Technician will write/run queries to extract selected data from the UKLS Mortality/Cancer Registry data. The output will include the pseudonymised unique patient identifier (UKLS MPI) in order that it can be linked to other subject data held by UKLS. Subject data is data that has been provided by the participants as part of the trial. For those randomised to the CT screening arm, details of CT scan results are held and diagnostic tests or any treatment received as part of the trial. - 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 be linked at person record level with data in the UKLS clinical database, including subject data held by UKLS that has been provided by the participants as part of the trial. For those randomised to the CT screening arm, details of CT scan results are held and diagnostic tests or any treatment received as part of the trial. This linkage will be done using the subject specific MPI number only. The data within this database are pseudonymised as much as practically possible and include health data and event dates. Event dates are required for calculation of time periods in relation to other events both within the data provided by NHS England and to events collected by other means, e.g. directly from the subject or by review of hospital records. [18 paragraphs unchanged] The processing of data leads to findings in publications made publicly available for the benefit of the wider research community. Special care is taken to ensure confidentiality is maintained and re-identification is not possible; e.g. data is always presented in aggregate form in publications. Although the database includes NHS numbers, only pseudonymised data will be made available to researchers within the University of Liverpool for the purpose of the UKLS. Subjects will be identified using a pseudonymised unique identifier in any extracted data. The clinical database used within the UKLS has data for 4,061 subjects. All data is held securely (with additional password protection) and accessed only by the named users, in compliance with The University of Liverpool Data Policies. Although the database includes NHS numbers, only pseudonymised data will be made available to researchers within the University of Liverpool for the purpose of the UKLS. Subjects will be identified using a pseudonymised unique identifier in any extracted data.

Expected output

The initial findings/conclusions of the trial data were published in the BMJ-Thorax Online First. This included methods, trial design, recruitment, randomisation, nodule management, number of cancers, treatment, cost effectiveness modelling. The full report of these aspects of the UKLS trial has also been published by the funder, National Institute for Health Research, Health Technology Assessment Programme (NIHR HTA). Both of these are available as open access publications. The expected outputs of the processing will be: One specific output from the ongoing processing of data for the UKLS will be a report to the UK National Screening Committee on the cost effectiveness and mortality benefit of introducing a lung cancer screening programme into the UK. Prior to this report it will be necessary for the statistician to analyse the data on causes of death and lung cancer diagnoses target date for this was 2020-2021 which has now been completed. UoL have published lung cancer incidence data and mortality data in relation to the UKLS lung cancer screening trial (including as part of a meta-analysis of all related randomised control trials) in The Lancet Regional Health - Europe (Field JK, Vulkan D, Davies MPA, Baldwin DR, Brain KE, Devaraj A, et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. The Lancet Regional Health - Europe. 2021;10(100179):100179-) and presented this work at the 2021 World Conference on Lung Cancer and elsewhere, with associated press releases. • Submissions to internationally renowned oncology, epidemiology and public health journals. Journals for consideration will include: Thorax, Journal of Thoracic Oncology, Lung Cancer, British Journal of Cancer, Cancer epidemiology, biomarkers & prevention, Scientific Reports, Oncology Letters, Nature Genetics, Nature Communications, Lancet and Lancet Oncology. The initial findings/conclusions of the trial data were published in the BMJ-Thorax Online First. This included methods, trial design, recruitment, randomisation, nodule management, number of cancers, treatment, cost effectiveness modelling. The full report of these aspects of the UKLS trial has also been published by the funder, National Institute for Health Research, Health Technology Assessment Programme (NIHR HTA). Both of these are available as open access publications. UoL have also published the validation and update of the LLP lung cancer risk model, based on UKLS data, in Thorax (Field JK, Vulkan D, Davies MPA, Duffy SW, Gabe R. Liverpool Lung Project lung cancer risk stratification model: calibration and prospective validation. THORAX. 2021;76(2):161-8.) During 2022 UoL have presented UKLS cancer incidence and mortality data as part of posters at 2 major international scientific meeting (British Thoracic Oncology Group meeting, Dublin January 2022; World Conference on Lung Cancer, August 2022). • A report to the UK National Screening Committee on the cost effectiveness and mortality benefit of introducing a lung cancer screening programme into the UK ~~It is anticipated that the analysis from this study will continue to be included in internationally renowned oncology, epidemiology and public health journals. Journals for consideration will include:~~ • International Conference and Meeting presentations (both oral and poster). Further such presentations are anticipated. Conferences are expected to include: World Conference on Lung Cancer, American Association for Cancer Research Annual Meeting and National Cancer Research Institute Annual Meeting ~~- Thorax~~ • Currently proposed risk models are based on the ability to predict risk of lung cancer (either within the general population or within those with nodules detected during CT imaging), these rely of lung cancer outcomes provided separately through Public Health England. In the future it may prove informative to define models for risk of early death from lung cancer (identifying those with aggressive life-threatening disease from those with indolent disease unlikely to be the cause of premature death). In this case mortality data (time to death and cause of death) will be important for discovery and validation of such models, but the UKLS study itself is not large enough to both generate and validate such models. This need to combine data to provide more powerful and meaningful outcomes of clinical importance is one of the drivers for the University of Liverpool's desire to share anonymised, individual level data including data derived from NHS Digital data under this Agreement with collaborating researchers in future. It is expected that any risk models produced will be utilised in the public interest and made freely available (open access). Whilst their generation will, in part, be dependent on exploitation of data provided by NHS Digital and this will be acknowledged in any publications, the data itself will not be used by the final model, which will be an algorithm based on a larger cohort of data from multiple sources. ~~- Journal of Thoracic Oncology~~ 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. ~~- Lung Cancer~~ The outputs will be communicated to relevant recipients through the following dissemination channels: ~~- British Journal of Cancer~~ • Journals ~~- Cancer epidemiology, biomarkers & prevention~~ • Conferences ~~- Scientific~~ • Reports ~~- Oncology Letters~~ • Papers will be accompanied by web-page updates and press releases at the time of publication, to provide information to both scientific and non-scientific audiences ~~- Nature Genetics~~ ~~- Nature Communications~~ ~~- Lancet~~ ~~- Lancet Oncology~~ In addition, this high profile study has been subject to numerous international Conference and Meeting presentations (both oral and poster). Further such presentations are anticipated. Conferences are expected to include: ~~- World Conference on Lung Cancer~~ ~~- American Association for Cancer Research Annual Meeting~~ ~~- National Cancer Research Institute Annual Meeting~~ The University of Liverpool have published lung cancer incidence data and mortality data in relation to the UKLS lung cancer screening trial (including as part of a meta-analysis of all related randomised control trials) in The Lancet Regional Health - Europe (Field JK, Vulkan D, Davies MPA, Baldwin DR, Brain KE, Devaraj A, et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. The Lancet Regional Health - Europe. 2021;10(100179):100179-) and presented this work at the 2021 World Conference on Lung Cancer and elsewhere, with associated press releases. The University of Liverpool have also published the validation and update of the LLP lung cancer risk model, based on UKLS data, in Thorax (Field JK, Vulkan D, Davies MPA, Duffy SW, Gabe R. Liverpool Lung Project lung cancer risk stratification model: calibration and prospective validation. THORAX. 2021;76(2):161-8.) During 2022 The University of Liverpool have presented UKLS cancer incidence and mortality data as part of posters at 2 major international scientific meeting (British Thoracic Oncology Group meeting, Dublin January 2022; World Conference on Lung Cancer, August 2022). ~~Papers will be accompanied by web-page updates and press releases at the time of publication, to provide information to both scientific and non-scientific audiences.~~ ~~Outputs will contain only data that is aggregated with small numbers suppressed in line with relevant guidance.~~ Currently proposed risk models are based on the ability to predict risk of lung cancer (either within the general population or within those with nodules detected during CT imaging), these rely of lung cancer outcomes provided separately through Public Health England. In the future it may prove informative to define models for risk of early death from lung cancer (identifying those with aggressive life-threatening disease from those with indolent disease unlikely to be the cause of premature death). In this case mortality data (time to death and cause of death) will important for discovery and validation of such models, but the UKLS study itself is not large enough to both generate and validate such models. This need to combine data to provide more powerful and meaningful outcomes of clinical importance is one of the drivers for the University of Liverpool's desire to share anonymised, individual level data including data derived from NHS Digital data under this Agreement with collaborating researchers in future. It is expected that any risk models produced will be utilised in the public interest and made freely available (open access). Whilst their generation will, in part, be dependent on exploitation of data provided by NHS Digital and this will be acknowledged in any publications, the data itself will not be used by the final model, which will be an algorithm based on a larger cohort of data from multiple sources.

Expected measurable benefits

[8 paragraphs unchanged] The UKLS Trial has been published in the journal Thorax (Field JK, Duffy SW, Baldwin DR, et al. UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening. Thorax 2016; 71(2): 161-70) and also as a Full HTA report (Field JK, Duffy SW, Baldwin DR, et al. The UK Lung Cancer Screening Trial: a pilot randomised controlled trial of low-dose computed tomography screening for the early detection of lung cancer. Health Technol Assess 2016; 20(40): 1-146), in addition there have been a number of other supporting publications on the UKLS trial. [1 paragraph unchanged] By collecting biosamples under tightly controlled conditions and collating data relating to both lung cancers and other types of cancer, UKLS is a very valuable resource for studies of early detection for multiple cancer types and for multi-cancer early detection. Future benefits are therefore expected beyond lung cancer. Furthermore, under the appropriate conditions samples and data might (in aggregate form) contribute toward regulatory approval for new diagnostic or predictive biomarkers. [3 paragraphs unchanged] iii. Yielded Benefits : The UKLS statistician has developed a risk model to predict lung cancer utilising nodule data from the UKLS study. This has now been published in Thorax (Probability of cancer in lung nodules using sequential volumetric screening up to 12 months: the UKLS trial. Michael W Marcus, Stephen W Duffy, Anand Devaraj, Beverley A Green, Matthijs Oudkerk, David Baldwin, John Field. doi: 10.1136/thoraxjnl-2018-212263). The LLPv2 lung cancer risk model used in UKLS has been validated and update of the LLP lung cancer risk model (to LLPv3) with a more accurate estimation of absolute risk, as published in Thorax (Field JK, Vulkan D, Davies MPA, Duffy SW, Gabe R. Liverpool Lung Project lung cancer risk stratification model: calibration and prospective validation. THORAX. 2021;76(2):161-8). This will allow more efficient selection of at risk groups in future LDCT screening and other early-detection scenarios. UoL have published lung cancer incidence data and mortality data in relation to the UKLS lung cancer screening trial (including as part of a meta-analysis of all related randomised control trials) in The Lancet Regional Health - Europe (Field JK, Vulkan D, Davies MPA, Baldwin DR, Brain KE, Devaraj A, et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. The Lancet Regional Health - Europe. 2021;10(100179):100179-). This data completes the world-wide randomised control trial assessment of LD-CT screening and provides evidence for the benefits of LDCT early lung cancer detection. The UKLS data is particularly informative for UK implementation of LD-CT, supporting both the NHS Targeted Lung Health Check programme (which is currently underway) and being central to the current considerations of the UK National Screening Committee. Lives have already been saved as part of UKLS and more lives will be saved by the further implementation of LD-CT that is supported by the UKLS results, with efficiency savings from the demonstrated utility and validation of the LLP lung cancer risk score. The UKLS data continues to be used for analysis in major international research project (e.g. the NIH-funded INTEGRAL project looking to improve risk-based early detection and lung nodule management, which has been extended by 5 years) and for publications (e.g. Moez, E., et al.2023 Circulating Proteome for Pulmonary Nodule Malignancy. Journal of the National Cancer Institute, doi:10.1093/jnci/djad122; Davies et al. 2024 Impact of single round of low dose CT lung cancer screening on cause of mortality in different socio-economic groups: a post-hoc analysis of long-term follow-up of the UKLS trial. Lancet Regional Health Europe doi: 10.1016/j.lanepe.2024.100936). As an invaluable resource for early detection biomarker studies, being the UK’s oldest establish repository of biosamples taken at the time of low-dose CT screening, with the longest follow-up, the UKLS study will continue to yield significant benefits going forward. The UKLS trial radiology dataset, including anonymised LDCT images, original radiology reports and consensus reads and outcome data, are now recognised as a major resource, including for validation of recent advances in artificial intelligence for aiding diagnosis from LDCT scans and tackling the potential manpower issues posed by rolling out lung cancer screening. In collaboration with iDNA and associated academic groups, we have published a number of papers (having first presented results at major international conferences). In collaboration with iDNA and associated academic groups, a number of papers have been published (having first presented results at major international conferences).

Benefits reported

The UKLS statistician has developed a risk model to predict lung cancer [18 words unchanged] lung nodules using sequential volumetric screening up to 12 months: the UKLS ~~trial. Michael W Marcus, Stephen W Duffy, Anand Devaraj, Beverley A Green, Matthijs Oudkerk, David Baldwin, John Field. doi: 10.1136/thoraxjnl-2018-212263).~~ trial). The LLPv2 lung cancer risk model used in UKLS has been validated [11 words unchanged] with a more accurate estimation of absolute risk, as published in Thorax ~~(Field JK, Vulkan D, Davies MPA, Duffy SW, Gabe R. Liverpool~~ (Liverpool Lung Project lung cancer risk stratification model: calibration and prospective ~~validation. THORAX. 2021;76(2):161-8).~~ validation). This will allow more efficient selection of at risk groups in future LDCT screening and other early-detection scenarios. UoL have published lung cancer incidence data and mortality data in relation [14 words unchanged] all related randomised control trials) in The Lancet Regional Health - Europe ~~(Field JK, Vulkan D, Davies MPA, Baldwin DR, Brain KE, Devaraj A, et al. Lung~~ (Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international ~~meta-analysis. The Lancet Regional Health - Europe. 2021;10(100179):100179-).~~ meta-analysis). This data completes the world-wide randomised control trial assessment of LD-CT screening and provides evidence for the benefits of LDCT early lung cancer detection. [2 paragraphs unchanged] The UKLS data continues to be used for analysis in major international [14 words unchanged] lung nodule management, which has been extended by 5 years) and for publications (e.g. Moez, E., et al.2023 Circulating Proteome for Pulmonary Nodule Malignancy. Journal of the National Cancer Institute, doi:10.1093/jnci/djad122; Davies et al. 2024 Impact of single round of low dose CT lung cancer screening on cause of mortality in different socio-economic groups: a post-hoc analysis of long-term follow-up of the UKLS trial. Lancer Regional Health Europe doi: 10.1016/j.lanepe.2024.100936). publications. As an invaluable resource for early detection biomarker studies, being the UK’s [16 words unchanged] follow-up, the UKLS study will continue to yield significant benefits going forward. The UKLS trial radiology dataset, including anonymised LDCT images, original radiology reports and consensus reads and outcome data, are now recognised as a major resource, including for validation of recent advances in artificial intelligence for aiding diagnosis from LDCT scans and tackling the potential manpower issues posed by rolling out lung cancer screening.

DARS-NIC-19237-R3T6S-v8.2 7 February 2025 to 31 May 2026

Title: UK Lung Cancer Screening Trial Lung Cancer Registry and Mortality data for consented individuals
Commercial: No
Sublicensing: No
Datasets: 7
Files released: 0

What changed from DARS-NIC-19237-R3T6S-v7.3

Text removed is ~~struck through~~; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Fields changed from DARS-NIC-19237-R3T6S-v7.3
Field	Was	Became
Title	~~MR1298: UK Lung Cancer Screening Trial Lung Cancer Registry and Mortality data for consented individuals~~	UK Lung Cancer Screening Trial Lung Cancer Registry and Mortality data for consented individuals
Start date	~~2022-09-06~~	2025-02-07
End date	~~2025-05-31~~	2026-05-31

Objective for processing

[5 paragraphs unchanged] Under this Agreement, NHS ~~Digital~~ England will provide longitudinal, observational follow-up data for the UKLS lung cancer screening [28 words unchanged] and opportunities for improved treatment resulting in lives saved and improved health. [1 paragraph unchanged] The Royal Liverpool and Broadgreen University Hospitals NHS Trust was originally a [49 words unchanged] As co-sponsors they did not have any control over how the NHS ~~Digital~~ England data was used or the purpose for which the data will be [13 words unchanged] involved in any decision-making in respect of any data received from NHS ~~Digital.~~ England. This organisation is not involved in the follow-up study utilising cancer registry or mortality data and no data is shared with them. [1 paragraph unchanged] Other individuals from other organisations named in the study Protocol were previously [69 words unchanged] for collection and processing of the mortality and cancer data from NHS ~~Digital.~~ England The University of Liverpool require NHS ~~Digital~~ England data to inform the current status (alive/dead) and dates and causes of [149 words unchanged] be either more intrusive (likely to cause harm/distress), less informative or incomplete. NHS ~~Digital~~ England will also provide cancer registry data, identifying all cancer diagnosis, with dates [79 words unchanged] methods (e.g. case-note review) are likely more intrusive, less efficient and incomplete. [2 paragraphs unchanged] No data provided by NHS ~~Digital~~ England covered by this Agreement will be shared with any third parties. [4 paragraphs unchanged] The research project is part of a wider international effort to address [90 words unchanged] is either aggregate (as in publication) or pseudonymised data containing no NHS ~~Digital~~ England data but containing variables derived from NHS ~~Digital.~~ England. The data is provided at an appropriate level such that additional data [69 words unchanged] nor any combination of details which could result in a person’s re-identification. [1 paragraph unchanged]

Processing activities

An updated cohort Excel file (containing details of participants who have given informed consent) has been sent to NHS ~~Digital~~ England by UKLS Project Manager. The flow of data into NHS ~~Digital~~ England is limited to personal identifiers required for linkage (NHS number) and for [32 words unchanged] participants who have died (as informed by previous data received from NHS ~~Digital).~~ England. No special categories of data, such as health data will be provided to NHS ~~Digital.~~ England The flow of data out of NHS ~~Digital~~ England consists of a download of data files containing the data initially supplied, plus matching fields from NHS ~~Digital~~ England and the requested health care and outcome data, the majority of which [32 words unchanged] quality assurance of linkage (i.e. latest name, gender, Date of Birth, postcode). NHS ~~Digital~~ England will upload linked dataset file onto their secure portal and notify UKLS [25 words unchanged] an encrypted drive on a dedicated University of Liverpool virtual server. NHS ~~Digital~~ England data, prior to processing and transfer to the UKLS clinical database, is [30 words unchanged] protected and accessible only from 3 designated PCs (with unique IP addresses). [3 paragraphs unchanged] Data supplied by NHS ~~Digital~~ England is processed for inclusion into the UKLS clinical database, to enable its [54 words unchanged] in relation to other events both within the data provided by NHS ~~Digital~~ England and to events collected by other means, e.g. directly from the subject or by review of hospital records. [7 paragraphs unchanged] Subsets of data from the clinical database including information derived from the [60 words unchanged] data being identifiable as originating or deriving from the data from NHS ~~Digital~~ England or possible to reverse-engineer such that it can be so identified. Any [97 words unchanged] disease”). The combined data will conform to the specification shared with NHS ~~Digital~~ England (filename ‘UoL Lung projects Data sharing MD209180218’) which NHS ~~Digital~~ England has approved. [16 paragraphs unchanged]

Expected output

~~August 2022 (v7) rewrite:~~ [22 paragraphs unchanged] ~~The University of Liverpool plan to submit this work for publication in a scientific journal (e.g. Lancet Respiratory Medicine) during 2022.~~ ~~A paper is planned on improved targeting of individuals for recruitment into lung cancer screening (winter 2022).~~ The University of Liverpool also plan to submit several papers on lung cancer biomarkers related to improved diagnosis of lung cancer from our work on plasma protein biomarkers (Autumn 2022) and genome wide association studies (spring/summer 2023) and radiobiological . This work will also form the basis of reports to the funding body and renewal of the funding for a further 5 years. [3 paragraphs unchanged]

Expected measurable benefits

[1 paragraph unchanged] Dissemination of data will be limited to the research team within the [6 words unchanged] accumulate from plans to combine UKLS data (including data derived from NHS ~~Digital~~ England data) with other large international trials. Dissemination of benefits will be broader. [55 words unchanged] to the data when deciding about lung cancer screening in the NHS. [11 paragraphs unchanged]

Benefits reported

[5 paragraphs unchanged] The UKLS data continues to be used for analysis in major international research project (e.g. the NIH-funded INTEGRAL project looking to improve risk-based early detection and lung nodule management, which has been extended by 5 years) and for publications (e.g. Moez, E., et al.2023 Circulating Proteome for Pulmonary Nodule Malignancy. Journal of the National Cancer Institute, doi:10.1093/jnci/djad122; Davies et al. 2024 Impact of single round of low dose CT lung cancer screening on cause of mortality in different socio-economic groups: a post-hoc analysis of long-term follow-up of the UKLS trial. Lancer Regional Health Europe doi: 10.1016/j.lanepe.2024.100936). As an invaluable resource for early detection biomarker studies, being the UK’s oldest establish repository of biosamples taken at the time of low-dose CT screening, with the longest follow-up, the UKLS study will continue to yield significant benefits going forward.

Objective for processing

As a University using health data for research purposes, “task in the public interest” is the legal basis for processing personal and sensitive information under the General Data Protection Regulations [Article 6 (1) (e)]. As the study is for scientific research purposes, the University also rely on Article 9 (2) (j) of the General Data Protection Regulation.

The cohort consists of lung cancer free individuals recruited by postal invite from Merseyside and Cambridgeshire, following a selection process based on a questionnaire using the Liverpool Lung Project Risk Model (version2) to identify those at greatest risk of lung cancer. The final participant list was limited by cost to 4,061, of whom half were randomised to receive low dose CT detection for lung cancer and the remainder the current standard of care (follow-up only). For the interventional trial the test group received CT and the control group did not, but in the observational follow-up and follow-up risk model discovery/refinement/validation studies, both groups contribute to lung cancer risk modelling, whilst the CT group additionally contributes to work on CT-detected nodule management.

The University of Liverpool (UoL) is the sole Data Controller and also processes the data for this study. No other organisations process the data for this purpose. Only individuals based at the University of Liverpool - specifically the Chief Investigator and two other individuals involved in post-trial analysis - will make decisions on how and/or why the data under this Agreement are processed.

The Royal Liverpool and Broadgreen University Hospitals NHS Trust was originally a co-sponsor due to intervention aspects of the project but, after reviewing their ongoing role, in 2018, they withdrew sponsorship from the study and consequently asked to be removed as a named co-sponsor in the Study Protocol. This request was approved by North West - Liverpool Central Research Ethics Committee. As co-sponsors they did not have any control over how the NHS England data was used or the purpose for which the data will be used. The Royal Liverpool and Broadgreen University Hospitals NHS Trust is no longer involved in any decision-making in respect of any data received from NHS England. This organisation is not involved in the follow-up study utilising cancer registry or mortality data and no data is shared with them.

An individual from Barts and the London School of Medicine has the role of Lead Statistician/Trial Design. This individual is not involved in any decision-making over 'how' or 'why' personal data are processed. His role in 'trial design' is advisory – for example, the Investigators at the University of Liverpool will share with him the details of proposed analyses and, as a subject matter expert, the Lead Statistician will advise on the merits or flaws in the proposed method. The University of Liverpool is not obliged to secure this individual’s approval prior to processing the data but obviously takes into account his advice based on his specialist expertise. This individual only receives derived data which has been manipulated to the extent that it is not considered personal data. He will receive derived data (i.e. the outputs of the analyses) to review and advise whether the analyses were undertaken correctly.

Other individuals from other organisations named in the study Protocol were previously part of the UKLS Trial Team put in place to manage and to undertake the trial during its lifetime. The trial is now complete, as far as recruitment and clinical intervention are concerned, the main findings have been published and the current analysis are part of the follow-up studies (which concern statistical analysis of outcomes and biomarker research). Therefore, these individuals have no ongoing role in determining the purposes for collection and processing of the mortality and cancer data from NHS England

Data requirements have been limited to those health-related events that directly impact the aims of the study and address the public interest justification, along with significant confounding factors, such as occurrence of other cancers and other causes of death.

The data will be recorded on the United Kingdom Lung Cancer Screening Trial (UKLS) database and pseudonymised data given to researchers - all of whom are substantive employees of the University of Liverpool - in order to ascertain any mortality advantage to screening and inform the UK National Screening committee.

No data provided by NHS England covered by this Agreement will be shared with any third parties.

The study investigators are unaware of any risk of potential harm to the public by the dissemination. The potential for harm has been assessed by University of Liverpool (Data Protection and Study Sponsor) and by NRES ethical approval.

Safeguards are in place that protect the interests of the data subjects. These have been judged as proportional to the substantial public interest (together with informed consent) and also support the common law duty of confidentiality. Safeguards include physical and operational barriers protecting privacy and allowing processing of personal identifiers and sensitive data only by staff contractually obliged to fulfil the requirements set out by the University of Liverpool Data Protection Policy, compliant with all laws and approvals.

Processing activity and storage of personal and sensitive (special category) data is limited according to best practice (both in terms of scope and timing), but recognising that longitudinal follow-up data for prospective studies require long-term data linkage and that research studies require anonymised and pseudonymised data to be available for a significant amount of time. These issues have been explained to participants during informed consent and are covered in a publicly accessible Privacy Notice.

Collection and analysis of outcome data, in terms of mortality, is planned for 10 years from recruitment. Cumulative data will be assessed after each download but interim statistical analysis of mortality will only be undertaken when a significant number of events has been reached (as judged by the University of Liverpool research team with advice from the UKLS Statistical Lead, based on aggregate data). Further mortality analysis will be undertaken based on this preliminary analysis and also on the full 10-year data. Meanwhile, biomarker analysis relating to cancer incidence will be undertaken using the next available data download (providing >5 years follow-up on all participants) and revisited at a later date, as guided by initial results.

The research project is part of a wider international effort to address the critical issue of earlier detection of lung cancer, required to address the single largest cause of cancer-related mortality. As such, the University of Liverpool intends to share data which has been derived from processing the data under this Agreement with other research groups in future, but will do so in a controlled way, bound by conditions in the Data Sharing Agreement that confer the same level of adherence to protecting the rights of individuals involved in research and specifically covered by informed consent of subjects. All such data shared is either aggregate (as in publication) or pseudonymised data containing no NHS England data but containing variables derived from NHS England. The data is provided at an appropriate level such that additional data provided by the collaboration can be added to the sum of knowledge about subjects within the UKLS but without allowing others to link data and/or risk re-identification – this includes measures to suppress rare events. The record level data (including derived variables) being shared is irreversibly pseudonymised person-level data containing indicators of prior diagnosis of various high-level conditions (e.g. lung cancer, COPD, etc.) and containing no directly identifying information nor any combination of details which could result in a person’s re-identification.

The work undertaken by the University of Liverpool in regards to UKLS is funded by multiple organisations (research charities and government agencies, including international bodies). Their role is to provide funding for the research to the University of Liverpool (and collaborating research centres); they also support and encourage adherence to the highest standards of governance, public dissemination of results and scientific rigour.

Expected output

One specific output from the ongoing processing of data for the UKLS will be a report to the UK National Screening Committee on the cost effectiveness and mortality benefit of introducing a lung cancer screening programme into the UK. Prior to this report it will be necessary for the statistician to analyse the data on causes of death and lung cancer diagnoses target date for this was 2020-2021 which has now been completed. UoL have published lung cancer incidence data and mortality data in relation to the UKLS lung cancer screening trial (including as part of a meta-analysis of all related randomised control trials) in The Lancet Regional Health - Europe (Field JK, Vulkan D, Davies MPA, Baldwin DR, Brain KE, Devaraj A, et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. The Lancet Regional Health - Europe. 2021;10(100179):100179-) and presented this work at the 2021 World Conference on Lung Cancer and elsewhere, with associated press releases.

UoL have also published the validation and update of the LLP lung cancer risk model, based on UKLS data, in Thorax (Field JK, Vulkan D, Davies MPA, Duffy SW, Gabe R. Liverpool Lung Project lung cancer risk stratification model: calibration and prospective validation. THORAX. 2021;76(2):161-8.) During 2022 UoL have presented UKLS cancer incidence and mortality data as part of posters at 2 major international scientific meeting (British Thoracic Oncology Group meeting, Dublin January 2022; World Conference on Lung Cancer, August 2022).

It is anticipated that the analysis from this study will continue to be included in internationally renowned oncology, epidemiology and public health journals. Journals for consideration will include:

- Thorax

- Journal of Thoracic Oncology

- Lung Cancer

- British Journal of Cancer

- Cancer epidemiology, biomarkers & prevention

- Scientific Reports

- Oncology Letters

- Nature Genetics

- Nature Communications

- Lancet

- Lancet Oncology

In addition, this high profile study has been subject to numerous international Conference and Meeting presentations (both oral and poster). Further such presentations are anticipated. Conferences are expected to include:

- World Conference on Lung Cancer

- American Association for Cancer Research Annual Meeting

- National Cancer Research Institute Annual Meeting

The University of Liverpool have published lung cancer incidence data and mortality data in relation to the UKLS lung cancer screening trial (including as part of a meta-analysis of all related randomised control trials) in The Lancet Regional Health - Europe (Field JK, Vulkan D, Davies MPA, Baldwin DR, Brain KE, Devaraj A, et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. The Lancet Regional Health - Europe. 2021;10(100179):100179-) and presented this work at the 2021 World Conference on Lung Cancer and elsewhere, with associated press releases.

The University of Liverpool have also published the validation and update of the LLP lung cancer risk model, based on UKLS data, in Thorax (Field JK, Vulkan D, Davies MPA, Duffy SW, Gabe R. Liverpool Lung Project lung cancer risk stratification model: calibration and prospective validation. THORAX. 2021;76(2):161-8.)

During 2022 The University of Liverpool have presented UKLS cancer incidence and mortality data as part of posters at 2 major international scientific meeting (British Thoracic Oncology Group meeting, Dublin January 2022; World Conference on Lung Cancer, August 2022).

Papers will be accompanied by web-page updates and press releases at the time of publication, to provide information to both scientific and non-scientific audiences.

Outputs will contain only data that is aggregated with small numbers suppressed in line with relevant guidance.

Currently proposed risk models are based on the ability to predict risk of lung cancer (either within the general population or within those with nodules detected during CT imaging), these rely of lung cancer outcomes provided separately through Public Health England. In the future it may prove informative to define models for risk of early death from lung cancer (identifying those with aggressive life-threatening disease from those with indolent disease unlikely to be the cause of premature death). In this case mortality data (time to death and cause of death) will important for discovery and validation of such models, but the UKLS study itself is not large enough to both generate and validate such models. This need to combine data to provide more powerful and meaningful outcomes of clinical importance is one of the drivers for the University of Liverpool's desire to share anonymised, individual level data including data derived from NHS Digital data under this Agreement with collaborating researchers in future. It is expected that any risk models produced will be utilised in the public interest and made freely available (open access). Whilst their generation will, in part, be dependent on exploitation of data provided by NHS Digital and this will be acknowledged in any publications, the data itself will not be used by the final model, which will be an algorithm based on a larger cohort of data from multiple sources.

Benefits reported

The UKLS data continues to be used for analysis in major international research project (e.g. the NIH-funded INTEGRAL project looking to improve risk-based early detection and lung nodule management, which has been extended by 5 years) and for publications (e.g. Moez, E., et al.2023 Circulating Proteome for Pulmonary Nodule Malignancy. Journal of the National Cancer Institute, doi:10.1093/jnci/djad122; Davies et al. 2024 Impact of single round of low dose CT lung cancer screening on cause of mortality in different socio-economic groups: a post-hoc analysis of long-term follow-up of the UKLS trial. Lancer Regional Health Europe doi: 10.1016/j.lanepe.2024.100936). As an invaluable resource for early detection biomarker studies, being the UK’s oldest establish repository of biosamples taken at the time of low-dose CT screening, with the longest follow-up, the UKLS study will continue to yield significant benefits going forward.

DARS-NIC-19237-R3T6S-v7.3 6 September 2022 to 31 May 2025

Title: MR1298: UK Lung Cancer Screening Trial Lung Cancer Registry and Mortality data for consented individuals
Commercial: No
Sublicensing: No
Datasets: 7
Files released: 9

What changed from DARS-NIC-19237-R3T6S-v6.2

Text removed is ~~struck through~~; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Fields changed from DARS-NIC-19237-R3T6S-v6.2
Field	Was	Became
Start date	~~2020-05-21~~	2022-09-06
End date	~~2022-05-31~~	2025-05-31

Objective for processing

[1 paragraph unchanged] The UKLS started with a Health Technology Assessment (HTA) funded randomised control trial of low-dose CT (initial recruitment and baseline CT [49 words unchanged] molecular biomarkers on the ability to improve early detection of lung cancer. [1 paragraph unchanged] As a University using health data for research purposes, “task in the public interest” is the legal basis for processing personal and sensitive information under the General Data Protection Regulations [Article 6 (1) (e)]. As the study is for scientific research purposes, the University also rely on Article 9 (2) (j) of the General Data Protection Regulation. [2 paragraphs unchanged] The University of Liverpool (UoL) is the sole Data Controller and also processes the data for this [34 words unchanged] decisions on how and/or why the data under this Agreement are processed. [4 paragraphs unchanged] NHS Digital will also provide cancer registry data, identifying all cancer diagnosis, with dates (where ~~available through Public Health England).~~ available). The justification for this is broadly the same as for cause of [65 words unchanged] methods (e.g. case-note review) are likely more intrusive, less efficient and incomplete. [3 paragraphs unchanged] The study investigators are not aware of any moral or ethical issues raised by the proposed dissemination of NHS Digital data to the University of Liverpool, nor the dissemination of the aggregated study results to the wider public. The study investigators are unaware of any risk of potential harm to [14 words unchanged] of Liverpool (Data Protection and Study Sponsor) and by NRES ethical approval. [5 paragraphs unchanged]

Expected output

August 2022 (v7) rewrite: [1 paragraph unchanged] One specific output from the ongoing processing of data for the UKLS [37 words unchanged] statistician to analyse the data on causes of death and lung cancer ~~diagnoses. [Target~~ diagnoses target date ~~2020-2021]~~ for this was 2020-2021 which has now been completed. UoL have published lung cancer incidence data and mortality data in relation to the UKLS lung cancer screening trial (including as part of a meta-analysis of all related randomised control trials) in The Lancet Regional Health - Europe (Field JK, Vulkan D, Davies MPA, Baldwin DR, Brain KE, Devaraj A, et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. The Lancet Regional Health - Europe. 2021;10(100179):100179-) and presented this work at the 2021 World Conference on Lung Cancer and elsewhere, with associated press releases. ~~It is anticipated that the analysis from this study will be included in internationally renowned oncology, epidemiology and public health journals. Journals for consideration will include:~~ UoL have also published the validation and update of the LLP lung cancer risk model, based on UKLS data, in Thorax (Field JK, Vulkan D, Davies MPA, Duffy SW, Gabe R. Liverpool Lung Project lung cancer risk stratification model: calibration and prospective validation. THORAX. 2021;76(2):161-8.) During 2022 UoL have presented UKLS cancer incidence and mortality data as part of posters at 2 major international scientific meeting (British Thoracic Oncology Group meeting, Dublin January 2022; World Conference on Lung Cancer, August 2022). It is anticipated that the analysis from this study will continue to be included in internationally renowned oncology, epidemiology and public health journals. Journals for consideration will include: [15 paragraphs unchanged] The UKLS statistician is also designing a risk model to predict lung cancer utilising nodule data from the UKLS study and, if successful, this will be submitted for publication. The most appropriate publication will be identified when the analysis is complete. This may include Epidemiological or Radiological publications, such as BMJ-Thorax. Submission to a publication does not guarantee acceptance so it may be submitted to more than one publication before being accepted. The University of Liverpool have published lung cancer incidence data and mortality data in relation to the UKLS lung cancer screening trial (including as part of a meta-analysis of all related randomised control trials) in The Lancet Regional Health - Europe (Field JK, Vulkan D, Davies MPA, Baldwin DR, Brain KE, Devaraj A, et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. The Lancet Regional Health - Europe. 2021;10(100179):100179-) and presented this work at the 2021 World Conference on Lung Cancer and elsewhere, with associated press releases. ~~Outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.~~ The University of Liverpool have also published the validation and update of the LLP lung cancer risk model, based on UKLS data, in Thorax (Field JK, Vulkan D, Davies MPA, Duffy SW, Gabe R. Liverpool Lung Project lung cancer risk stratification model: calibration and prospective validation. THORAX. 2021;76(2):161-8.) During 2022 The University of Liverpool have presented UKLS cancer incidence and mortality data as part of posters at 2 major international scientific meeting (British Thoracic Oncology Group meeting, Dublin January 2022; World Conference on Lung Cancer, August 2022). The University of Liverpool plan to submit this work for publication in a scientific journal (e.g. Lancet Respiratory Medicine) during 2022. A paper is planned on improved targeting of individuals for recruitment into lung cancer screening (winter 2022). The University of Liverpool also plan to submit several papers on lung cancer biomarkers related to improved diagnosis of lung cancer from our work on plasma protein biomarkers (Autumn 2022) and genome wide association studies (spring/summer 2023) and radiobiological . This work will also form the basis of reports to the funding body and renewal of the funding for a further 5 years. Papers will be accompanied by web-page updates and press releases at the time of publication, to provide information to both scientific and non-scientific audiences. Outputs will contain only data that is aggregated with small numbers suppressed in line with relevant guidance. [1 paragraph unchanged]

Expected measurable benefits

[6 paragraphs unchanged] The trial has now finished but the follow up data on deaths [77 words unchanged] in the Netherlands (NELSON - European Nederlands-Leuvens Screening Onderzoek). The NELSON Trial ~~is estimated to report during 2019.~~ Trial has provided further evidence that LD-CT intervention reduces lung cancer mortality (de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial. N Engl J Med 2020; 382(6): 503-13), so that we should now seriously consider implementation of lung cancer CT screening in Europe and the rest of the world (Oudkerk M, Liu S, Heuvelmans MA, Walter JE, Field JK. Lung cancer LDCT screening and mortality reduction — evidence, pitfalls and future perspectives. Nat Rev Clin Oncol 2021; 18: 135-151) The UKLS trial sample size is too small to give adequate statistical [17 words unchanged] larger lung cancer screening trial run in the Netherlands (NELSON). The NELSON ~~is due to report 2019~~ trail has now reported and ~~the intention is to pool~~ has been included in a meta-analysis of all LDCT randomised control trials, a alongside publication of UKLS mortality data (Field JK, Vulkan D, Davies MPA, Baldwin DR, Brain KE, Devaraj A, et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. The Lancet Regional Health - Europe. 2021;10(100179):100179-). The data from ~~both~~ these trials and from UK LDCT implementation studies has been used to provide the information to the UKNSC as to whether or not to implement a lung cancer CT screening programme in the UK. (currently under review). The UKLS Trial has been published in the journal Thorax (Field JK, Duffy SW, Baldwin DR, et al. UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening. Thorax 2016; 71(2): 161-70) and also as a Full HTA ~~report,~~ report (Field JK, Duffy SW, Baldwin DR, et al. The UK Lung Cancer Screening Trial: a pilot randomised controlled trial of low-dose computed tomography screening for the early detection of lung cancer. Health Technol Assess 2016; 20(40): 1-146), in addition there have been a number of other supporting publications on the UKLS trial. [1 paragraph unchanged] The magnitude of the impact for improved early detection is considered to [120 words unchanged] need to consider both cancer detection and overall mortality when assessing outcomes. The LLP risk model is currently being used in the NHS Targeted Lung Health Check programme, which aims to screen 600,000 people over 4 years and is expected to lead to the early detection of approximately 3,400 lung cancers; unlike current diagnosis, most of these will be early stage disease for which curative surgery is possible, leading to significantly improved outcomes. [2 paragraphs unchanged]

Benefits reported

[1 paragraph unchanged] Some preliminary analysis has been undertaken utilising the NHS Digital data, to ascertain the numbers of UKLS patients with lung cancer and those who have died, however this analysis is ongoing. The current data from NHS Digital data has not been published/released or reported upon as the data has not matured sufficiently yet. The LLPv2 lung cancer risk model used in UKLS has been validated and update of the LLP lung cancer risk model (to LLPv3) with a more accurate estimation of absolute risk, as published in Thorax (Field JK, Vulkan D, Davies MPA, Duffy SW, Gabe R. Liverpool Lung Project lung cancer risk stratification model: calibration and prospective validation. THORAX. 2021;76(2):161-8). This will allow more efficient selection of at risk groups in future LDCT screening and other early-detection scenarios. ~~Data received to date has been utilised to update the UKLS database to ensure University of Liverpool did not contact deceased individuals.~~ UoL have published lung cancer incidence data and mortality data in relation to the UKLS lung cancer screening trial (including as part of a meta-analysis of all related randomised control trials) in The Lancet Regional Health - Europe (Field JK, Vulkan D, Davies MPA, Baldwin DR, Brain KE, Devaraj A, et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. The Lancet Regional Health - Europe. 2021;10(100179):100179-). This data completes the world-wide randomised control trial assessment of LD-CT screening and provides evidence for the benefits of LDCT early lung cancer detection. The UKLS data is particularly informative for UK implementation of LD-CT, supporting both the NHS Targeted Lung Health Check programme (which is currently underway) and being central to the current considerations of the UK National Screening Committee. Lives have already been saved as part of UKLS and more lives will be saved by the further implementation of LD-CT that is supported by the UKLS results, with efficiency savings from the demonstrated utility and validation of the LLP lung cancer risk score.

Unchanged: Processing activities.

Objective for processing

Under this Agreement, NHS Digital will provide longitudinal, observational follow-up data for the UKLS lung cancer screening study, which aims to provide evidence to improve early detection of lung cancer. Hence it is a task in the public interest, leading to improved understanding of disease and opportunities for improved treatment resulting in lives saved and improved health.

The Royal Liverpool and Broadgreen University Hospitals NHS Trust was originally a co-sponsor due to intervention aspects of the project but, after reviewing their ongoing role, in 2018, they withdrew sponsorship from the study and consequently asked to be removed as a named co-sponsor in the Study Protocol. This request was approved by North West - Liverpool Central Research Ethics Committee. As co-sponsors they did not have any control over how the NHS Digital data was used or the purpose for which the data will be used. The Royal Liverpool and Broadgreen University Hospitals NHS Trust is no longer involved in any decision-making in respect of any data received from NHS Digital. This organisation is not involved in the follow-up study utilising cancer registry or mortality data and no data is shared with them.

The University of Liverpool require NHS Digital data to inform the current status (alive/dead) and dates and causes of death; this data specifically informs the prime question of the study, helping to identify both lung cancer mortality (within causes of death) and the time from recruitment or treatment until death (all-cause mortality, an important measure of health status and outcome). This data needs to be provided for specific individuals (by linkage through NHS number with verification by month/year of birth) to allow appropriate data for personal level risk model development and evaluation. For the long-term follow-up of the study, it is important to follow as many subjects as possible until death, so the UKLS requires data on all available years (including retention of data already provided and incremental updates). Although the study was based on residence in Merseyside and Cambridgeshire, recruited individuals may have moved subsequent to recruitment, therefore all UK data relating to this cohort is requested. Alternative methods of assessing mortality status (e.g. re-contacting individuals) would be either more intrusive (likely to cause harm/distress), less informative or incomplete.

NHS Digital will also provide cancer registry data, identifying all cancer diagnosis, with dates (where available). The justification for this is broadly the same as for cause of death, but this data provides additional information on timing and specific diagnosis of lung cancers (a primary outcome measure of the study) and other cancers (which may be significant confounding factors that must be taken into account during analysis). Again, this must be at the individual level, for all dates available and all geographical areas to provide the best dataset of personalised prognostic prediction. Alternative methods (e.g. case-note review) are likely more intrusive, less efficient and incomplete.

No data provided by NHS Digital covered by this Agreement will be shared with any third parties.

The research project is part of a wider international effort to address the critical issue of earlier detection of lung cancer, required to address the single largest cause of cancer-related mortality. As such, the University of Liverpool intends to share data which has been derived from processing the data under this Agreement with other research groups in future, but will do so in a controlled way, bound by conditions in the Data Sharing Agreement that confer the same level of adherence to protecting the rights of individuals involved in research and specifically covered by informed consent of subjects. All such data shared is either aggregate (as in publication) or pseudonymised data containing no NHS Digital data but containing variables derived from NHS Digital. The data is provided at an appropriate level such that additional data provided by the collaboration can be added to the sum of knowledge about subjects within the UKLS but without allowing others to link data and/or risk re-identification – this includes measures to suppress rare events. The record level data (including derived variables) being shared is irreversibly pseudonymised person-level data containing indicators of prior diagnosis of various high-level conditions (e.g. lung cancer, COPD, etc.) and containing no directly identifying information nor any combination of details which could result in a person’s re-identification.

Expected output

August 2022 (v7) rewrite:

- Thorax

- Journal of Thoracic Oncology

- Lung Cancer

- British Journal of Cancer

- Cancer epidemiology, biomarkers & prevention

- Scientific Reports

- Oncology Letters

- Nature Genetics

- Nature Communications

- Lancet

- Lancet Oncology

- World Conference on Lung Cancer

- American Association for Cancer Research Annual Meeting

- National Cancer Research Institute Annual Meeting

The University of Liverpool plan to submit this work for publication in a scientific journal (e.g. Lancet Respiratory Medicine) during 2022.

A paper is planned on improved targeting of individuals for recruitment into lung cancer screening (winter 2022).

The University of Liverpool also plan to submit several papers on lung cancer biomarkers related to improved diagnosis of lung cancer from our work on plasma protein biomarkers (Autumn 2022) and genome wide association studies (spring/summer 2023) and radiobiological . This work will also form the basis of reports to the funding body and renewal of the funding for a further 5 years.

Papers will be accompanied by web-page updates and press releases at the time of publication, to provide information to both scientific and non-scientific audiences.

Outputs will contain only data that is aggregated with small numbers suppressed in line with relevant guidance.

Benefits reported

DARS-NIC-19237-R3T6S-v6.2 21 May 2020 to 31 May 2022

Title: MR1298: UK Lung Cancer Screening Trial Lung Cancer Registry and Mortality data for consented individuals
Commercial: No
Sublicensing: No
Datasets: 7
Files released: 22

What changed from DARS-NIC-19237-R3T6S-v5.3

Text removed is ~~struck through~~; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Fields changed from DARS-NIC-19237-R3T6S-v5.3
Field	Was	Became
Start date	~~2019-06-01~~	2020-05-21

Datasets: + Cancer Registration Data; + Civil Registrations of Death; + Demographics

Unchanged: Objective for processing, Processing activities, Expected output, Expected measurable benefits, Benefits reported.

Objective for processing

The UKLS started with a Health Technology Assessment funded randomised control trial of low-dose CT (initial recruitment and baseline CT scan completed September 2011 to October 2012), which is now in long-term follow-up to assess the impact in terms of lung cancer detection and mortality. Research continues to be funded from a variety of sources with the aim of analysing the contribution of lifestyle, medical history, nodule characteristics and molecular biomarkers on the ability to improve early detection of lung cancer.

The University of Liverpool is the sole Data Controller and also processes the data for this study. No other organisations process the data for this purpose. Only individuals based at the University of Liverpool - specifically the Chief Investigator and two other individuals involved in post-trial analysis - will make decisions on how and/or why the data under this Agreement are processed.

The Royal Liverpool and Broadgreen University Hospitals NHS Trust was originally a co-sponsor due to intervention aspects of the project but, after reviewing their ongoing role, in 2018, they withdrew sponsorship from the study and consequently asked to be removed as a named co-sponsor in the Study Protocol. This request was approved by North West - Liverpool Central Research Ethics Committee. As co-sponsors they did not have any control over how the NHS Digital data was used or the purpose for which the data will be used. The Royal Liverpool and Broadgreen University Hospitals NHS Trust is no longer involved in any decision-making in respect of any data received from NHS Digital. This organisation is not involved in the follow-up study utilising cancer registry or mortality data and no data is shared with them.

NHS Digital will also provide cancer registry data, identifying all cancer diagnosis, with dates (where available through Public Health England). The justification for this is broadly the same as for cause of death, but this data provides additional information on timing and specific diagnosis of lung cancers (a primary outcome measure of the study) and other cancers (which may be significant confounding factors that must be taken into account during analysis). Again, this must be at the individual level, for all dates available and all geographical areas to provide the best dataset of personalised prognostic prediction. Alternative methods (e.g. case-note review) are likely more intrusive, less efficient and incomplete.

No data provided by NHS Digital covered by this Agreement will be shared with any third parties.

The study investigators are not aware of any moral or ethical issues raised by the proposed dissemination of NHS Digital data to the University of Liverpool, nor the dissemination of the aggregated study results to the wider public. The study investigators are unaware of any risk of potential harm to the public by the dissemination. The potential for harm has been assessed by University of Liverpool (Data Protection and Study Sponsor) and by NRES ethical approval.

The research project is part of a wider international effort to address the critical issue of earlier detection of lung cancer, required to address the single largest cause of cancer-related mortality. As such, the University of Liverpool intends to share data which has been derived from processing the data under this Agreement with other research groups in future, but will do so in a controlled way, bound by conditions in the Data Sharing Agreement that confer the same level of adherence to protecting the rights of individuals involved in research and specifically covered by informed consent of subjects. All such data shared is either aggregate (as in publication) or pseudonymised data containing no NHS Digital data but containing variables derived from NHS Digital. The data is provided at an appropriate level such that additional data provided by the collaboration can be added to the sum of knowledge about subjects within the UKLS but without allowing others to link data and/or risk re-identification – this includes measures to suppress rare events. The record level data (including derived variables) being shared is irreversibly pseudonymised person-level data containing indicators of prior diagnosis of various high-level conditions (e.g. lung cancer, COPD, etc.) and containing no directly identifying information nor any combination of details which could result in a person’s re-identification.

Expected output

It is anticipated that the analysis from this study will be included in internationally renowned oncology, epidemiology and public health journals. Journals for consideration will include:

- Thorax

- Journal of Thoracic Oncology

- Lung Cancer

- British Journal of Cancer

- Cancer epidemiology, biomarkers & prevention

- Scientific Reports

- Oncology Letters

- Nature Genetics

- Nature Communications

- Lancet

- Lancet Oncology

- World Conference on Lung Cancer

- American Association for Cancer Research Annual Meeting

- National Cancer Research Institute Annual Meeting

The UKLS statistician is also designing a risk model to predict lung cancer utilising nodule data from the UKLS study and, if successful, this will be submitted for publication. The most appropriate publication will be identified when the analysis is complete. This may include Epidemiological or Radiological publications, such as BMJ-Thorax. Submission to a publication does not guarantee acceptance so it may be submitted to more than one publication before being accepted.

Outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Benefits reported

Some preliminary analysis has been undertaken utilising the NHS Digital data, to ascertain the numbers of UKLS patients with lung cancer and those who have died, however this analysis is ongoing. The current data from NHS Digital data has not been published/released or reported upon as the data has not matured sufficiently yet.

Data received to date has been utilised to update the UKLS database to ensure University of Liverpool did not contact deceased individuals.

DARS-NIC-19237-R3T6S-v5.3 1 June 2019 to 31 May 2022

Title: MR1298: UK Lung Cancer Screening Trial Lung Cancer Registry and Mortality data for consented individuals
Commercial: No
Sublicensing: No
Datasets: 4
Files released: 6

Datasets: MRIS - Cause of Death Report; MRIS - Cohort Event Notification Report; MRIS - Flagging Current Status Report; MRIS - Members and Postings Report

Objective for processing

The Royal Liverpool and Broadgreen University Hospitals NHS Trust was originally a co-sponsor due to intervention aspects of the project but, after reviewing their ongoing role, in 2018, they withdrew sponsorship from the study and consequently asked to be removed as a named co-sponsor in the Study Protocol. This request was approved by North West - Liverpool Central Research Ethics Committee. As co-sponsors they did not have any control over how the NHS Digital data was used or the purpose for which the data will be used. The Royal Liverpool and Broadgreen University Hospitals NHS Trust is no longer involved in any decision-making in respect of any data received from NHS Digital. This organisation is not involved in the follow-up study utilising cancer registry or mortality data and no data is shared with them.

No data provided by NHS Digital covered by this Agreement will be shared with any third parties.

The research project is part of a wider international effort to address the critical issue of earlier detection of lung cancer, required to address the single largest cause of cancer-related mortality. As such, the University of Liverpool intends to share data which has been derived from processing the data under this Agreement with other research groups in future, but will do so in a controlled way, bound by conditions in the Data Sharing Agreement that confer the same level of adherence to protecting the rights of individuals involved in research and specifically covered by informed consent of subjects. All such data shared is either aggregate (as in publication) or pseudonymised data containing no NHS Digital data but containing variables derived from NHS Digital. The data is provided at an appropriate level such that additional data provided by the collaboration can be added to the sum of knowledge about subjects within the UKLS but without allowing others to link data and/or risk re-identification – this includes measures to suppress rare events. The record level data (including derived variables) being shared is irreversibly pseudonymised person-level data containing indicators of prior diagnosis of various high-level conditions (e.g. lung cancer, COPD, etc.) and containing no directly identifying information nor any combination of details which could result in a person’s re-identification.

Expected output

It is anticipated that the analysis from this study will be included in internationally renowned oncology, epidemiology and public health journals. Journals for consideration will include:

- Thorax

- Journal of Thoracic Oncology

- Lung Cancer

- British Journal of Cancer

- Cancer epidemiology, biomarkers & prevention

- Scientific Reports

- Oncology Letters

- Nature Genetics

- Nature Communications

- Lancet

- Lancet Oncology

- World Conference on Lung Cancer

- American Association for Cancer Research Annual Meeting

- National Cancer Research Institute Annual Meeting

Outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

Benefits reported

Data received to date has been utilised to update the UKLS database to ensure University of Liverpool did not contact deceased individuals.

Register history

When this agreement appeared in, or was edited in, each monthly edition of the register. Built by comparing every edition this site holds, the earliest of which is July 2021.

July 2021 — already listed in the earliest edition this site holds, so it may be older.
2 versions: DARS-NIC-19237-R3T6S-v5.3, DARS-NIC-19237-R3T6S-v6.2
October 2022
1 version added: DARS-NIC-19237-R3T6S-v7.3
March 2025
1 version added: DARS-NIC-19237-R3T6S-v8.2
June 2026
1 version added: DARS-NIC-19237-R3T6S-v9.6

Cite this page

NHS England (2026) Data Uses Register, September 2026 edition, agreement DARS-NIC-19237-R3T6S, “UK Lung Cancer Screening Trial Lung Cancer Registry and Mortality data for consented individuals”. Read via NHS Data Access Explorer (unofficial), https://healthdatauses.uk/agreements/dars-nic-19237-r3t6s/ (accessed [date]).

This address stays the same, but the page is rebuilt with each monthly edition, so the citation names the edition it shows. Every edition's data is kept in the facts store.

Source: datausesregister_september2026.xlsx, September 2026 edition of the NHS England Data Uses Register. Search that workbook for DARS-NIC-19237-R3T6S to see the original rows.