UK Longitudinal Linkage Collaboration (UK LLC) - Consent

The University of Bristol requires access to NHS England data for the purposes of the UK Longitudinal Linkage Collaboration (UK LLC).

The UK LLC is a ‘Trusted Research Environment’ designed to link study data from major inter-disciplinary Longitudinal Population Studies (LPS) participants, to a wide range of participants’ health and non-health records and other sources.

The UK LLC aims to provide a data linkage resource to its partner studies and to provide a simple one-application process to ONS accredited UK based (researchers employed by UK research organisations) applying to access linked longitudinal data.

This unique resource enables cross-sector research and supporting research responses to immediate situations and future policy needs.

The greater availability of large scale, diverse linked data will help provide improved representation, reduce bias and greater statistical power for researchers to study rarer outcomes and seldom reached populations

This Data Sharing Agreement (DSA) sets out the process that the University of Bristol will follow to determine that inclusion in the UK LLC satisfies the common law duty of confidentiality for each person in each cohort prior to requesting their data from NHS England and prior to processing their data in accordance with this DSA. See Part 2: Inclusion Criteria.

This DSA then sets out the process by which a researcher may apply for approval and be granted access to the linked data. See Part 3: Access Controls.

Part 1: Background

The University of Bristol established the UK LLC with its scope initially restricted to research relating to COVID-19. Under a separate DSA (reference: DARS-NIC-420168-K4N1F), the University of Bristol received health data from NHS England for cohorts from 21 LPS using Regulation 3 of the Control of Patient Information (COPI) Regulations 2002 as a legal basis for processing confidential patient information.

From the outset. the University of Bristol’s intention was that the UK LLC would transition to a general-purpose research databank supporting the UK’s LPS. To enable that objective, it is necessary for the legal basis to transition from COPI Regulation 3 to either participant consent or COPI Regulation 5 (hereafter ‘Section 251’).

This DSA (reference: DARS-NIC-748729-Z8B3M) supports the University of Bristol’s aims to facilitate research using data in the UK LLC using consent as a legal basis.

A parallel DSA (reference: DARS-NIC-420229-G9H9S) covers the data of participants using section 251 support.

DSA reference DARS-NIC-420168-K4N1F will continue but only including LPS not yet able to transition to either consent or section 251. Where consent or section 251 support provide a legal basis for the continuing retention and processing of the relevant Data, the applicable DSA will supersede DSA reference DARS-NIC-420168-K4N1F as the contractual controls for that Data.

Part 2: Inclusion Criteria

The University of Bristol has developed a framework for the evaluation of LPS’ consent to inform whether LPS’ cohorts can be included in the UK LLC on the basis of participant consent.

The framework is summarised as follows:

i. An LPS interested in joining the UK LLC completes a templated checklist (filename: DOC-OPE-096_TEMPLATE_UKLLC_ConfidentialityDueDilligence_Checklist_v2.3), provided by the UK LLC, assessing the consent against mandatory inclusion criteria and submits the checklist with supporting evidence (e.g. copies of the consent materials) to the UK LLC for review.

ii. UK LLC representatives review the assessment and supporting evidence provided.

iii. UK LLC representatives conducts an Onboarding Risk Assessment.

iv. UK LLC representatives prepare an application summary including the completed assessments and consent materials and submit these as part of a briefing pack to the UK LLC Legal Basis Due Diligence Panel.

v. The UK LLC Legal Basis Due Diligence Panel meets bi-annually to review the briefing packs and advise on the risks and mitigations and ultimately on whether the LPS meets the criteria for inclusion in the UK LLC on the basis of participant consent. The Panel will act in accordance with its Terms of Reference as documented in ‘DOC-OPE-097_UKLLC_ConfidentailityDueDiligencePanel_TOR_v1.3’.

NHS England is not responsible for assuring consent for individual LPS, the LPS host institution holds this responsibility. The University of Bristol is authorised to determine whether an LPS meets the inclusion criteria for onboarding to the UK LLC in accordance with the agreed process as documented in ‘DOC-OPE-095 _UKLLC_ConfidentialityDueDiligence_FrameworkFlow_v3.3’.

NHS England may review the assessment of consent for individual LPS when auditing compliance with this DSA.

Each year, the University of Bristol will have the opportunity to add new cohort members to LPS already in scope of this DSA and to add new LPS to the scope of this DSA where consent has been established.

The University of Bristol may only request data for consented participants of LPS named in this DSA. To add new LPS, this DSA must be amended.

The following LPS are within the scope of this DSA:

1. The National Study of Health and Development (NSHD aka “The 1946 Birth Cohort”)

2. Avon Longitudinal Study of Parents and Children (ALSPAC aka “Children of the 90s”)

3. Genetic Links to Anxiety and Depression Study (GLAD)

4. English Longitudinal Study of Ageing (ELSA)

5. National Child Development Study (NCDS aka “The 1958 Birth Cohort”)

6. British Cohort Study (BCS aka “The 1970 Birth Cohort”);

7. Next Steps

8. The Millennium Cohort Study (MCS)

9. Track-COVID (which is a subset of INTERVAL, COMPARE and STRIDES bioresource)

10. NIHR (National Institute for Health Research) BioResouce

11. Extended Cohort for E-health, environment, and DNA (EXCEED)

12. UK Household Longitudinal Study (aka “Understanding Society”)

13. Born in Bradford

14. Twins early Development Study (TEDS)

15. TwinsUK

16. STRategies to Improve Donor ExperienceS (STRIDES)

17. COMPARE

18. INTERVAL

19. AIRWAVE

20. UK REACH

21. National Institute for Health and Care Research (NIHR) Bioresource

22. Covid Symptom Study (CSS) Biobank

23. The Early Life Feasibility Study

24. EPIC Oxford

25. Million Women Study

26. ADVANCE (The Armed Services Trauma and Rehabilitation Outcome)

27. COSMOS (Cohort Study of Mobile Phone use and Health)

Part 3: Access Controls

The University of Bristol will only grant access to researchers for projects approved following the rules, processes and procedures defined in the document ‘UK LLC Data Access and Acceptable Use Policy Version POL-ISM-003v2.1’, published online at the following web address: https://ukllc.ac.uk/governance

The University of Bristol must notify NHS England of any changes to this document and receive written authorisation from NHS England before implementing any changes to the rules, processes and procedures used.

Only UK-based bona fide ONS accredited researchers are eligible to apply for access to data. This includes PhD students and Master Students, on condition that appropriate supervision is in place from a co-applicant who is a senior researcher.

Data access will only be approved for research projects for public good as determined during the application process.

Data access to approved researchers will be minimised as follows:

• Only the datasets relevant to the research question are accessible to the researcher(s);

• Only records relating to participants from approved LPS are accessible to the researcher(s);

• Individual LPS own restrictions on data reuse will be respected and consequently data from specific LPS may be withheld from certain users and/or for certain types of research purposes;

• Each research group has its own secured project working area (accessible on a need-to-know basis);

• Each research group is provided with data using a project specific participant ID number;

• Participant objections (made to their LPS) are provided to the University of Bristol by each LPS on a quarterly frequency and these are applied at the start of each project to remove participants who have changed permissions and opted-out.

Part 4: Data and Parties Involved

The following NHS England Data will be accessed:

• Demographics – necessary (i) to establish the linked NHS England denominator (i.e. the list of participants who have been linked to a record); (ii) to enable assessments of linkage quality and bias; (iii) to understand entry and exit from the NHS; (iv) because it contains core demographic variables needed in most research investigations; and (v) because it contains Lower Super Output Area (LSOA) of patient register as a mechanism for privacy-preserving linkage of neighbourhood and environmental data to participants within the TRE.

• Civil Registration Mortality – necessary to determine mortality outcomes and underlying causes and to consider the impact of health, socio-economic, environmental and wider behavioural and lifestyle factors on general rates of mortality, specific causes of mortality outcomes.

• Cancer Registrations – necessary to identify cancer diagnosis and outcomes.

• Hospital Episode Statistics Admitted Patient Care, Accident & Emergency, Critical Care and Outpatients, and the Emergency Care Data Set (ECDS) – necessary to understand secondary health care provision, including disease diagnoses. care pathways and specific therapies, disease outcomes.

• Mental Health (MH) datasets (Mental Health Services Data Set and historical versions including Mental Health Minimum Data Set, Mental Health and Learning Difficulties Data Set; and Improved Access to Psychological Therapies, IAPT) – necessary to determine MH status and treatment pathways, to consider changes in mental health outcomes and to define changes in help seeking behaviours and health care interactions and the effectiveness of care and interventions.

• Medicines Dispensed in Primary Care (NHSBSA) – necessary to understand treatments prescribed, rates of medicines dispensed and evaluations of outcomes of specific therapies.

• Maternity Services - necessary to record early life (and some in utero) exposures and outcomes to study developmental effects and later life health and social outcomes.

• Community Services Data Set – necessary to understand changing patterns in help seeking behaviours and health care interactions (e.g., the provision of care within community settings; MH care pathways).

• NDRS Cancer Consolidated Data Set - necessary to receive data on cancer registrations and care pathways. Improved granularity to supplement the Cancer Registry dataset.

For the UK LLC’s continuing COVID-19 research programme, the following additional data are needed:

• COVID-19 General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR)

• COVID-19 Hospitalization in England Surveillance System

• COVID-19 SGSS First Positives (Second Generation Surveillance System)

• Covid-19 UK Non-hospital Antibody Testing Results (Pillar 3)

• COVID-19 UK Non-hospital Antigen Testing Results (Pillar 2)

• COVID-19 Vaccination Adverse Reactions

• COVID-19 Vaccination Status

These datasets are necessary to define Covid-19 caseness, Covid-19 symptoms and outcomes (including ‘long COVID’, wider health outcomes (including mental health, substance use, addiction), COVID-19 testing, patterns in health service interactions, uptake of COVID-19 vaccine and vaccine behaviours in general, to define pre COVID-19 health status, case ascertainment across non COVID-19 outcomes and multi-morbidities and to asses mid- to long-term changes in trends and outcomes and health help-seeking and provision patterns following the COVID-19 pandemic. All will be used to understand the effectiveness of the COVID-19 response and to prepare for future pandemics and crisis situations. Vaccine data will also be used for broader research to understand changing patterns in vaccine uptake in the population

The University of Bristol will request all available data from all of the above datasets for all LPS participants whose identifying details the University of Bristol provides to NHS England. There will be no variations in the datasets or the periods of data supplied per individual participant accounting for variations in their consent.

The University of Bristol has obtained support under section 251 NHS Act 2007 to access the Data of participants of specified LPS who have not provided adequate consent. The Data of those participants will be requested separately to the Data of consented participants under a separate DSA (reference: DARS-NIC-420229-G9H9S). Individual participants’ Data may only be requested under this DSA (refence: DARS-NIC-748729-Z8B3M) if consent has been assured as permitting access to all of the above datasets for all available years and may only be requested under the separate DSA (reference: DARS-NIC-420229-G9H9S) if consent has been assured as not permitting access to any of the above datasets for any of the available years and the LPS is within the scope of the section 251 support. There is no facility for Data of an individual participant to be partially obtained on the basis of consent and partially obtained on the basis of section 251 support in scenarios where consent is assured as permitting access to some but not all datasets or available years.

The University of Bristol must maintain accessible records of which Data is requested and obtained per participant per LPS under which legal basis.

The level of the Data will be:

• Pseudonymised

The Data will be minimised as follows:

• Limited to a study cohort identified by the University of Bristol who consented to participate in an LPS named in this DSA and whose consent has been assured as permitting access to all of the above datasets for all available years.

The University of Bristol is the research sponsor and the controller as the organisation responsible for ensuring that the data will only be processed for the purposes described above.

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller;

The lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

The case for this research being in the public interest is established through balancing the strong policy driver of improved understanding of important health questions with consideration of potential harms to the patients/participants whose records are involved.

The funding for the UK LLC core infrastructure is provided by UK Research & Innovation’s (UKRI) Medical Research Council (MRC) and Economic and Social Research Council (ESRC). Funding to continue the UK LLC research database will be sought on an ongoing basis.

Swansea University is a processor acting under the instructions of the University of Bristol. Swansea University host the UK Secure eResearch Platform (UKSeRP). The UK LLC research database will be built using the UKSeRP. Swansea University’s role is limited to providing data infrastructure and management services to the University of Bristol; maintaining the integrity of UKSeRP; managing the ingest of data into UK LLC’s UKSeRP; and conducting output disclosure assessments for any approved research users wishing to export the results of their analysis outside of UKSeRP.

As part of SeRP, Digital Health and Care Wales (DHCW) act as ‘Trusted Third Party’ for UK LLC. DHCW implement LLC’s data linkage by collating the identifiable information of the participants of each LPS and submitting these to NHS England and other data owners as permissions (set by the LPS) allow. DHCW’s role is limited to processing participant identifiers, consent status for record linkage purposes and to conduct ID management. DHCW do not receive any NHS England Data or any LPS attribute data. DHCW are contracted to never share any identifiers with UK LLC or any other party outside the data linkage agreements.

The UK LLC has staff based at the University of Edinburgh. The University of Edinburgh based UK LLC staff manage the project application review process according to the process determined by University of Bristol. They have no other role in determining how NHS England Data will be processed, nor will they have any access to record level Data. The University of Edinburgh lead on administrative operations, communications, and participant/public engagement.

City St George’s University London (SGUL) and University College London (UCL) provide specific scientific expertise and advice to the UK LLC.

The University of Leicester provides geo-coding and environmental exposure modelling functions but does not access any NHS data.

The UK LLC works collaboratively with staff from each of the UK longitudinal population studies (LPS) – all of whom are formal partners in the UK LLC. UK LLC seeks input from each LPS into decision-making, and guidance in future development and operation. Each LPS maintains and manages relationships with ‘their’ participants, including making critical decisions about data use. Each LPS communicates with ‘their’ participants about the existence and work of the UK LLC. As part of the UK LLC model, a secure operating partition will be created inside the UK LLC UKSeRP for each contributing LPS.

Within these, LPS staff can apply (through the same application process as researchers) to access linked LPS and NHS data, restricted to the participants of that LPS. LPS and ONS accredited staff will use this area to conduct descriptive analysis on their participants (e.g., to provide documentation to describe the data asset, to inform bias assessments) and to assess feasibility of projects (e.g., to determine whether there are sufficient cases to scientifically justify inclusion in a proposed project) to inform potential users and to conduct study-level due diligence. Each LPS is responsible for sending a file of participant identifiers and permission flags to DHCW for the linkage purposes every quarter. This file may contain identifiers (such and NHS ID or address) provided by other organisations – including NHS England – where the agreements maintained by the LPS and the other organisations permit this. This sharing of identifiers is important to ensure scientific integrity of data and to reduce bias.

UK LLC has a highly active Public Involvement and Engagement group who provide input into UK LLC decision making and design at all levels of the organisation. Specifically, this includes a public panel who provide advice as to whether applications provide potential public benefit and whether applicants lay summaries are clear. These public contributors have no access to the data or TRE.

The UK LLC model was developed following considerable LPS-level Patient/Participant Involvement and Engagement (PPIE), which included a long track record of participant committees across multiple studies and qualitative research involving participants in interviews about study methodologies. The model itself drew heavily on the PPIE conducted by the Avon Longitudinal Study of Parents and Children (ALSPAC) LPS and on a public dialogue commissioned by the Economic and Social Research Council. UK LLC conducted early PPIE consultations with the Health Data Research UK public panel.

UK LLC has subsequently established a detailed PPIE strategy with a dedicated budget and an experienced Communications PPIE Team.

UK LLC involve public contributors in the following ways:

• UK LLC Strategic Advisory Committee: where three public contributors sit on our independent SAC with a remit to provide strategic guidance, evaluation and advice at a high level

• UK LLC Public Advisory Group: where five public contributors meet regularly to co-produce PPIE strategy, to be closely involved in the development of communication materials/resources, to provide advice on design decisions.

• UK LLC Data Access Committee: where five public contributors meet to review UK LLC project applications, and to provide advice on whether these are likely to generate public goods, whether the lay summary is accessible and sufficient to meet UK LLC transparency objectives and to advice whether project-specific PPIE is necessary

• UK LLC Involvement Network - a wider group of 20-25 public contributors who provide input on an ad-hoc basis on major design and governance decisions, on participant focused policy decisions and where rapid responses are needed.

• UK LLC Confidentiality Due Diligence Panel – a pool of 5 public contributors along with the University of Bristol legal and governance leads including the DPO and a Chair independent of UK LLC.

This package builds on substantial existing and established relationships between LPS and participants which include public/participants in the co-design of UK LLC related mechanisms (e.g., study information materials sent to their participants) and to engage and effectively communicate UK LLC findings more widely with the public (e.g., advising LPS on scientific dissemination strategies and the appropriate and inclusive use of language and reasonable adjustments to standard materials).

UK LLC raised funding to convene a pilot Citizen Panel to work with the existing data access approval process and which will provide (i) input and feedback to improve the process; (ii) a larger and more diverse membership; and (iii) providing a way to gauge changes in public feeling and public perceptions around research data use. The Citizen Panel model was initially suggested by the National Patient Data Guardian, and UK LLC is the first databank to adopt this best practice model.

PROCESSING ACTIVITIES FOR MAINTAINING THE RESEARCH DATABASE:

Each LPS contributing data into UK LLC transfers files of participant identifiers and permission flags to NHS Digital Health Care Wales (DHCW). The permission flags will be set and maintained over time to ensure that participants’ objections are respected.

DHCW will convert these data into the NHS England specified format, apply permission filters, and then transfer data to NHS England. The data will consist of identifying details (specifically NHS Number (where known), Date of Birth, Address, Postcode, Gender, Family Name (Surname), Given Name (Forename), Other Given Name, and a unique person ID) for the Longitudinal Population Study (LPS) cohorts to be linked with NHS England Data.

NHS England will provide the relevant records from the datasets to Swansea University (UKSeRP). The Data will contain no direct identifying data items but will contain a unique person ID which can be used to link the data with other record level data already held by the recipient.

UK LLC is specifically designed to link LPS participant reported data to a wide range of health, socio-economic and environmental data at a pan-UK level. UK LLC offers a wide range of linkage services, but not all LPS will choose to establish each linkage at a study level. The linkages established will depend on the basis established between the study and its participants.

The NHS England Data will be linked at person record level with dataset(s) obtained from each individual LPS. The type of information collected by each LPS include data about almost all conceivable topics. This includes, but is not limited to: self-reported survey data on health symptoms and outcomes including mental and sexual health; socio-economic status and outcomes (e.g., education levels, occupation data); demographic characteristics; health lifestyle factors (e.g., diet) and risky behaviours (e.g., smoking), attitudes and aspirations; family dynamics; life events and traumas (e.g., bereavement, loss of job). The data will also include information derived from biological samples the participant provided, this will include (but is not limited to): genomic data; ‘Omic data relating to wider biological expression and functioning; and, information on hormones and pollutant exposure.

UK LLC will link to equivalent health data from the UK’s devolved nations (Scotland, Wales and Northern Ireland). It may also, over time, link to privately held health records (e.g., dentist and optician records).

UK LLC is working with the Office for National Statistics to link to participants HM Revenue and Customs records (information on employment, employer, pay and some benefits) and Department for Work and Pensions records (information on benefits). This will also extend to linking to the National Pupil Database in England and associated records for further and higher education and for ‘Children Looked After’ and those deemed ‘Children in Need’. Where applicable, UK LLC will also seek to link devolved equivalents.

Participants’ address data will be converted to geo-coordinates which will enable linkage of environmental exposure data (e.g., climate records), pollutant exposure data (e.g., air pollution, noise pollution), and data on the world in which people live (e.g., the amount of greenspace around a participant's house, neighbourhood characteristics) and also about properties (e.g., whether someone lives in a detached or terraced house, or a flat).

The data will be stored on servers at Swansea University.

The Data will be accessed onsite at the premises of Swansea University by UKSeRP system administrators and by authorised personnel via remote access (including UK LLC data staff and approved research users and LPS data managers).

The University of Bristol 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).

Data will be accessed only by substantive employees of University of Bristol or Swansea University (under University of Bristol direction).

• University of Bristol employees are the only individuals who can access all data across all studies and sources in their ‘raw’ and processed forms for the purpose of data processing.

• University of Bristol employees are the only individuals with operational control and access for management of pseudonymised data within the UK LLC TRE, including provision of data to approved users.

• Swansea University employees manage the UKSeRP infrastructure and for this purpose have access to implement data ingest and for technical functionality purposes (e.g., security firewalls, software patching, backups).

• Swansea University maintain a specifically trained group of staff who conduct disclosure checks of research results which users have asked to export from the TRE system. These checks ensure all outputs are anonymous.

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

There will be no requirement and no attempt by any employee or sub-licensee to reidentify individuals when using the data.

The University of Bristol will:

1) Undertake data curation to manage, store, describe and quality assess the data in the UK LLC. This will involve: transforming the data into new forms (e.g., database loading), ensuring linkage to wider records held in UK LLC, creating immutable copies for disaster recovery (within TRE), conducting quality checks of the record linkage and data content of each variable (e.g., checking for valid/non-valid data items). The data and its processing will be described in metadata (e.g., population level anonymous descriptive statistics) and narrative documentation. These processes will support applied research undertaken and improve the understanding of outcomes.

2) Undertake data disclosure risk assessments and implement risk mitigation controls. Assessing incoming data for risky variables (i.e., checking that de-identification at source has been implemented); controlling for occurrences where the data should be further protected using UK LLC’s disclosure policies. These measures protect participant confidentiality.

3) Use linked NHS data to inform descriptive documentary analysis of the UK LLC dataset, aiming to describe the combined LPS population; assess,document linkage,data quality (and assess bias) and availability (i.e., aggregate and anonymous counts); clarify and characterise the LLC denominator, including how this sub-set relates to the wider population (comparison with aggregated populations statistics). It will help research users and policy makers to draw inferences and allow users to understand what data the UK LLC holds.

4) Undertake data derivations, harmonisation and outcome adjudication (i.e., creating derived variables indicating whether an individual has a health condition) of key exposures, outcomes and confounders common to research.; utilise study and linked data to address missing data and data error/bias. These will be made available through the UK LLC application and data provision process and only accessible within the UK LLC TRE. This will improve research efficiency, reduce research costs and improve research agility.

5) Conduct feasibility assessments to determine viability of proposed projects. UK LLC staff will query the UK LLC integrated dataset (LPS data and linked NHS Records) to determine if UK LLC has sufficient case numbers to inform a query. This enhances ethical and governance position, since data will not be shared where they cannot meaningfully inform, it also ensures the efficient use of research funding and resources.

6) Process the data to make sub-sets available for sub-licensees.

The University of Bristol employees will:

1) Carry out validation of the NHS England Data received; will clean the data by removing or transforming non-valid entries; will combine this with other data as described above, and will document all data quality and transformations;

2) Process the linked data to assess and minimise the risk of disclosure;

3) Conduct descriptive and documentary analysis of the UK LLC dataset to produce documentation and methodological papers on the quality and content of the data and to summarise the characteristics of the UK LLC pooled LPS sample.

4) Create derived variables of commonly used exposures, outcomes and treatment factors (e.g., care treatment pathways, outcome adjudication across multiple datasets) using both NHS and wider data sources.

5) Conduct feasibility assessments to determine whether proposed research projects have sufficient data and sample size to be viable.

6) Process the data to make sub-sets available for sub-licensees.

Swansea University employees will:

1) Ingest data received from NHS England into the UK LLC UKSeRP and transform it into structures capable of being loaded into a database;

2) Conduct participant ID management and encryption of geographical variables to meet UK LLC’s strict disclosure policies;

3) Conduct backups of the UK LLC database(s);

4) Conduct disclosure reviews of project results to confirm they are anonymous aggregate statistics.

PROCESSING ACTIVITIES FOR SUB-LICENSING:

For LPS employees:

A secure operating partition will be created for each contributing LPS. The NHS England Data, restricted to the participants of the specific LPS, will be made available to approved LPS study staff by the University of Bristol. The study staff will use this area to conduct descriptive analysis on their participants (e.g., to provide documentation to describe the data asset, to inform bias assessments) and to assess feasibility of projects (e.g., to determine whether there are sufficient cases to scientifically justify inclusion in a proposed project) to inform potential users and to conduct study-level due diligence.

For research users:

Secure operating partitions will be created for each UK LLC approved project. The UK LLC approved users for these projects will have access to their folder and database views which will contain a sub-set of data relevant to that study where onward sharing conditions of data providers are met. The UK LLC research users will control any data processing and analysis for their approved project. Once the research user has completed their analysis, they will be required to submit their research results (e.g., tables and graphs of statistical findings) for disclosure review checks undertaken by Swansea University.

Research users are permitted to use diverse statistical approaches, including AI approaches, where scientifically appropriate and considered safe from a disclosure risk and data Controllership/Ownership perspective. All projects using AI methods need specific ethical approval. UK LLC will not accept any AI methods which either involve moving AI model data into the TRE or involve exporting any AI model out of the TRE. I.e., only methods which can be accepted are where (a) the model is built from scratch inside the TRE and (b) the only outputs from the TRE are anonymous statistical findings.

Remote processing will be from secure locations within the UK. The data will not leave Wales at any time.

The primary output of the processing will be a database to be utilised as a resource for health research which contributes to UK Government policy to build a standing responsive and ongoing research capability. Reflecting this, the UK’s Chief Medical Officer added UK LLC to his list of strategic scientific infrastructure (see https://www.gov.uk/government/publications/chief-medical-officers-annual-report-2023-health-in-an-ageing-society). Use of the research database by sub-licensees is expected to give rise to:

• summaries - all projects will be required to summarise their project findings and make the summary available in accessible lay language via the UK LLC data use register (https://ukllc.ac.uk/data-use-register).

• Submissions to peer reviewed scientific journals (it is anticipated that all approved projects should generate at least one journal article reporting their methods, results and conclusions).

All publications arising form the resource are available here:

https://ukllc.ac.uk/publication-data.

• Journals (UK LLC has published about how it operates to widen the reach of it's processes). UK LLC team publications are here: https://ukllc.ac.uk/publication-data

• Presentations to research funders (a standard condition of most research funding)

• Presentations to NHS staff, charities and other ‘third sector’ organisations working to tackle specific health conditions or working with specific patient groups (this is a common outcome of most research projects).

• Presentations at specific scientific, charity and government conferences related to health conditions or more general policy audiences (this is a common outcome of most research projects).

• Reports via briefings, infographics or other summary formats to policy makers and politicians and associated policy groups (e.g., think tanks). For UK LPS, the CLOSER LPS consortium works with the Parliamentary Office of Science and Technology and synthesises findings into policy impact briefings (e.g., https://closer.ac.uk/wp-content/uploads/CLOSER-Active-Travel-Briefing-Note-June-2023.pdf) and in response to consultations (e.g., https://closer.ac.uk/wp-content/uploads/CLOSER-written-evidence-Social-and-economic-impact-of-the-gambling-industry.pdf). The new UK Research and Innovation funded Population Research UK programme has an ambition to support this work across a broader range of LPS (https://www.infraportal.org.uk/infrastructure/population-research-uk).

•UK LLC will work with researchers to bring case studies to the public using mixed media, including animations (e.g., https://www.youtube.com/watch?v=e7pHbY6Avn4), infographics (e.g., explaining data processing, research outcomes) and blog articles (e.g., UK Data Service).

In collaboration with the Health & Safety Executive, UK LLC have been working with occupational health experts to enhance the resource through harmonising job-role and other work-based study data to support a breadth of occupational research and to inform Health & Safety Executive’s 10-year strategy to reduce work-based mental ill-health.

Findings from the Longitudinal Health and Wellbeing National Core Study have led to Cabinet office and NHS England 'teach in' sessions, a national GP alert, an NHS enhanced service specification (guidelines and mechanisms to improve services), rapid reports for SAGE, and they have provided key evidence to guide the NICE Long COVID guidelines.

• Policy makers have been provided with information on Long COVID burden of disease, risk factors, definition and long-term outcomes via Cabinet briefing reports and SAGE reports to inform future policy.

• Low levels of Long COVID GP coding were reported. This led to an NHS enhanced service specification, directed at GPs to drive an increase in Long COVID coding

• NICE used Long COVID findings in its evidence to review risk factors.

The outputs generated from research conducted in the UK LLC research database 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.

All ‘meta’ products of the UK LLC research (such as code list definitions, syntax, workings for derived variables) will be made available for reuse and interrogation/replication.

UK LLC have provided methodological and governance expertise to wide groups. This will provide benefits to the UK's data infrastructure landscape in terms of best practice exemplars and knowledge exchange.

The research database will be advertised to potential researchers through the following channels:

• Workshops (UK LLC host quarterly LPS data manager workshops to co-develop the resource; hold regular data user workshops to provide support; hold focus groups and other workshops on research methods and approaches)

• Blogs and Webinars (hosted on the UK LLC website (https://ukllc.ac.uk/) and Social media (UK LLC has an active social media channels to promote the resource; including YouTube - https://www.youtube.com/@ukllcollab; and LinkedIN https://www.linkedin.com/company/ukllc/posts/?feedView=all)

• Researcher Roadshows and conference sponsorship (e.g., attendance and sponsorship and promotional stands at the Administrative Data Research UK, Health Data Research UK, SocSoc Med conferences. With many additional talks hosted in Universities and centres of excellence.

• Open-source frameworks (UK LLC share its own code and materials via GitHub which also hosts research users reusable products - https://github.com/UKLLC)

• Scientific Presentations and Posters at many scientific conferences (e.g., Administrative Data Research UK, Health data Research UK International Population Data Linkage Network, European Social Research Association, Society of Longitudinal and Lifecourse Studies).

• UK LLC will work with Population Research UK to co-host events on data management and use (UK-LLC led PRUK hosted metadata standards workshop, September 2025).

• Press/media engagement by UK LLC communications staff, and via consortia such as CLOSER and Population Research UK and with LPS, eg, https://www.bristol.ac.uk/alspac/news/2023/ukllc-funding-announcement.html)

The research database will be advertised to the public through the following channels:

• UK LLC website (which contains specific details for the public including animations, infographics, blogs and news items and a fair processing privacy notice).

LPS participant newsletters (each contributing study will be provided with case study materials to use in participant newsletters to report on UK LLC findings and supported by materials such as infographics and animations etc).

As a generic research databank, UK LLC anticipates a period of steady generic use which will grow as research grant support based on UK LLC activity is secured and as awareness of both UK LLC as a resource and the methods needed to use UK LLC grow. Training and capacity building and promotion via PRUK will support this growth. UK LLC will lead a PRUK-led funded programme in 2026-2028 to develop and pilot a synthetic training platform. By 2027-28 financial year UK LLC are targeting up to 200 users. Early indications (based on expressions of interest, and UK LLC’s support to researchers submitting research grant proposals) support this strong projected use.

The findings of research conducted using this research database are expected to contribute to evidence-based decision-making for policy-makers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of health care users. As a generic research databank, the benefits are expected to be broad and relevant across a wide range of subject matters.

The use of LPS data have – across many decades – delivered tens of thousands of research findings, some of which have led to transformational breakthroughs and policy impact. While longitudinal data can deliver almost any research outcome, the Expressions of interest, applications and projects in progress this year represent a range of impactful outcomes summarised below.

UK LLC will be well suited to using self-reported data to understand:

(1) Improved understanding of medicines:

• Response and side effects of medications for example psychiatric medications

• Safety of medicines during pregnancy.

• Associations between trauma and eating disorders

(2) How behaviours and life events impact on health-care seeking behaviours and adherence to treatments and improved provision/access to therapies and services:

• Understanding health trajectories and service utilisation around individuals with special educational needs

• Understanding the effectiveness and differential outcomes from those utilising Talking Therapies (IAPT) services

(3) Predicting clinical, social and psychological trajectories

• In depression

• In dementia

(4) sub-clinical events which occur prior to NHS care seeking and/or are under-reported to the NHS (e.g., mental health and mental ill-health related behaviours such as self-harm and eating disorders);

• how behaviours and life events impact on health-care seeking behaviours and adherence to treatments;

• other associations of healthy and/or risky behaviours and health outcomes (e.g., Vaping as a new potential health risk; factors which ameliorate occupational stress as a trigger for mental ill-health);

(5) Interactions between genomic and other ‘Omic expression and health outcomes;

(6) complex health-socio-economic-environmental associations (e.g., the increasing health risks associated with climate change, ingrained health inequalities, the association between environmental factors such as air pollution and mould in houses and health outcomes).

(7) Ongoing impact of COVID-19 virus as a risk factor for wider health outcomes and the health, socio-economic and wellbeing impacts of the pandemic (e.g., lockdown) on the wider populations:

• whether COVID-19 viral outcomes change the population risk profiles for CVD and wider disease;

• whether existing clinical tools - such as risk profiling algorithms - need updating to account for COVID-19 infection outcomes;

• changes in vaccine behaviours and uptake;

• whether poorer mental health status during COVID-19 impacted on adverse product consumption (e.g., increasing alcohol or junk food purchasing)

All these examples draw on the benefits of being able to link self-reported information which contains details not recorded in routine records, with genetic and other assayed biological data, and objective records on health outcomes and care patterns. As demonstrated in the COVID-19 research programme, this provides a unique insight for the Health and Social Care System not available via analysis of health records alone.

As such, the UK LLC generic research databank could provide benefits across a range of outcomes:

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

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

• advance understanding of regional and national trends in health and social care needs.

• advance understanding of the need for, or effectiveness of, preventative health and care measures for particular populations, those in particular occupations and for conditions such as respiratory, cancer, cardiovascular and mental health and understanding of those with multimorbidity.

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

• inform decisions on how to effectively allocate and evaluate funding according to health needs.

• support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work), such as improved understanding of the quality of routine health records through comparison to self-reported data, and improved longitudinal methods.

• To investigate the accuracy and effectiveness of algorithms (e.g., those used to predict risks of health outcomes), to inform improvements and mitigations against bias.

UK LLC is a service designed to support primarily observational epidemiological and social science research. As an observational form of research, the participant is not likely to directly benefit from the research outcomes, rather, the outcomes are intended to benefit society through improved understanding and improved service provision and delivery.

In addition to improved services, UK LLC should support the longitudinal research community build an improved societal understanding of how life-course events and personal behaviours and aspirations impact on health outcomes. Strong examples of this already exist relating to the negative health consequences of smoking, and the ‘back to sleep' campaign for parents to place babies to sleep on their backs as a means to reduce rates of sudden infant death syndrome.

Through publication of findings in appropriate media, it is hoped that the findings of research from this database will add to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients.

UK LLC has a specific objective to promote the resource to a wide range of charities and audiences. Roadshow events have already been held at policy research groups and contacts made with condition specific charities (e.g., MQ mental health charity, Department for Health and Social Care). A systematic briefings and road show plan will be undertaken once all approvals are in place for our generic research databank. PRUK has a further objective to support improved advocacy channels for UK LLC and other LPS infrastructure to policy makers, charities and wider audiences.

Research users are expected to demonstrate broad dissemination plans which involve charities and wider audiences where relevant.

Further publications form researchers accessing the TRE can be found at:

https://ukllc.ac.uk/publication-data

Case study examples of outputs already generated by UK LLC database users include:

1. Understanding the impacts of healthcare disruption on avoidable hospitalisation (Lead Investigator: Green; UK LLC Project https://ukllc.ac.uk/data-use-register/llc_0009/)

The pandemic resulted in healthcare disruption on a scale never seen before. It was expected that the disruption would increase hospital admission but national GP data analysed in OpenSAFELY showed (BMJ Open, https://bmjopen.bmj.com/content/14/1/e077948) falls in absolute numbers and reduced headline levels of social inequalities in avoidable hospitalisations.

The same author then sought to investigate the same topic in UK LLC to test if the richer data provided by study participants provided a different perspective. Using UK LLC’s linked LPS and hospital admission records, Green and colleagues found that individuals’ reporting greater levels of care disruption were more likely to be admitted to hospital, suggesting pandemic disruptions adversely influenced care management (BMJ,

https://doi.org/10.1136/bmj-2023-075133).

These findings were presented to National Institute for Health and Care Excellence (NICE) and the Scientific Advisory Group for Emergencies (SAGE) and used in health service planning considerations. This project demonstrates the key advantage of having LPS self-reported study measures of disruption (information that is not captured in health care records), and that since hospital admission is relatively rare, both UK LLC’s linked data and pooled sample size were needed to inform this research.

2. Comparing the burden of Long COVID in the community as measured by self-report and Electronic Healthcare Records (Lead Investigator: Williams; UK LLC Project: https://ukllc.ac.uk/data-use-register/llc_0006/). Publication: Knuppel, Anika et al. The Lancet, 2024; 403, Issue 10440,1981:1982

UK LLC enabled researchers to directly compare LPS self-reported long COVID and NHS interactions with UK LLC’s linked healthcare diagnoses and referral codes which identified the proportion of LPS participants with long COVID who had sought GP care and coded as needing further treatment. These findings and wider research to understand long COVID by the NIHR CONVALESENCE team have led to improvements in GP coding and changes designed to improve coding patterns for long COVID, such as the implementation of GP system ‘pop-ups’, to improve care. The new research additionally shows the strengths of LPS and UK LLC linked health data to inform exploration of under-reported or under-coded conditions and determine sub-group effects.

Longitudinal Health & Wellbeing researchers compared OpenSAFELY national data on Long-COVID rates with the findings of the ONS COVID Infection Survey. This suggested large disparities between estimated Long-COVID rates in the population (as collected by the ONS) and individuals recorded with Long COVID in GP health records. This potential under recording of Long-COVID would complicate research using health records and service planning.

Using UK LLC, they directly compared LPS self-reported Long-COVID symptoms and these participants GP records linked in UK LLC (ie, their GP diagnoses and treatment referral codes). Using eight UK LLC studies, we identified ~800 participants self-reporting Long-COVID by spring 2021, <1.5% received a Long COVID diagnosis or referral code after over 1 year of follow-up (see https://doi.org/10.1101/2023.02.10.23285717 for initial findings, subject to peer review). We reported these findings to NICE who developed improved GP coding guidance and improvements to coding practices. It also was highlighted to the UK Chief Medical Officer in an LPS briefing.

This project demonstrates the ability of LPS and UK LLC to inform analysis of under-reported or under-coded conditions and assess sub-group effects. Through this, UK LLC can provide unique insights into population health and service/system requirements and insights into how to target upstream interventions and care.

(3) Gittins M, et al

COVID-19 risk by work-related factors: pooled analysis of individual linked data from 14 cohorts Occupational and Environmental Medicine 2024;81:564-573

Multi-Longitudinal Cohort Study into occupational factors and COVID Risk as part of PROTECT National Core Study (Lead Investigator: Gittins; UK LLC Project: https://ukllc.ac.uk/data-use-register/llc_0007/ )

Assessed infection risks across job-role and work-related characteristics (e.g., if someone was a COVID ‘key worker’) using self-reported employment status data from 14 LPS linked to NHS England health records, including COVID-19 diagnostic testing. SARS-CoV-2 infection and COVID-19 infection risk was greater in key-workers vs not; among non-home working or some home working vs all home working; while part-time workers vs full-time; and furlough vs not had reduced risk (see https://doi.org/10.1101/2023.12.19.23298502 for initial findings subject to peer review). This research was conducted with the PROTECT National Core Study which was led by the Health & Safety Executive and tasked with developing policies to minimise work-place COVID-19 transmission risk. The findings informed Health & Safety Executive policy and can help assessments of whether COVID-19 control measures were effective or not.

This project demonstrates the near unique opportunities for researchers to investigate occupational health risk factors in the UK – given that job role is not recorded in any health or non-health routine system (outside of the national census programme). For this reason, with its national coverage, large and diverse sample size, and linkages to non-health records, UK LLC is emerging as a national resource for occupational health research.

In collaboration with the Health & Safety Executive, UK LLC have been working with occupational health experts to enhance the resource through harmonising job-role and other work-based study data to support a breadth of occupational research and to inform Health & Safety Executive’s 10-year strategy to reduce work-based mental ill-health.

Findings from the Longitudinal Health and Wellbeing National Core Study have led to Cabinet office and NHS England 'teach in' sessions, a national GP alert, an NHS enhanced service specification (guidelines and mechanisms to improve services), rapid reports for SAGE, and they have provided key evidence to guide the NICE Long COVID guidelines.

(4) Shaw R, et al., Associations between different measures of SARS-CoV-2 infection status and subsequent economic inactivity: A pooled analysis of five longitudinal surveys linked to healthcare records, PLOSOne, 2025.

https://doi.org/10.1371/journal.pone.0321201

From a methodological and infrastructure perspective:

(1) UK LLC is intended as a new way of working providing increased data security and transparency for study participants, easier routes to safe data access for research users and it is efficient for data owners (e.g., the NHS and wider government departments) and research funding agencies. UK LLC removes duplication of effort which drives efficiency and savings and enables prioritisation of limited funding to core functionality such as security and governance measures and improved user functionality. Increasing numbers of studies are joining UK LLC which in turn drives this efficiency for UK government.

(2) UK LLC have provided methodological and governance expertise to wide groups including: Other strategic investments (e.g., UK Biobank, Our Future Health), Gambling Commission, UK Chief Scientific Advisor, National Data Library (Cabinet Office), House of Commons Library, Met Office. This has provide knowledge exchange and insights to these programmes based on the investment and innovations at UK LLC.