Our Future Health Outcomes TRE Data Linkage Application with Sublicensing

Our Future Health was formed as part of the UK Life Sciences Industrial Strategy. It is designed to be the UK’s largest ever health research programme with the goal to recruit up to 5 million adult participants from across the UK to create a detailed picture that reflects the whole of the population.

Our Future Health is a company limited by guarantee registered in England and Wales (Number 12212468) and a charity registered with the Charity Commission for England and Wales (charity number 1189681) and OSCR, Scottish Charity Regulator (charity number SC050917). It is designed to help people live healthier lives for longer through better prevention, earlier detection, and improved treatment of diseases.

Our Future Health was initially discussed in 2016, when several medical research charities, the Medical Research Council, and leading public health practitioners and academics started exploring the rationale. The concept was outlined in the 2017 Life Sciences Industrial Strategy. An Ethics and Feedback Advisory Group was established in Sept 2019 to provide strategic advice on the development of ethical guidelines and principles for Our Future Health, and to develop an Ethics and Governance Framework to guide its operations. Building on that work, an Ethics Advisory Board has been established as part of the long-term governance of the cohort and is responsible for monitoring the implementation of the Ethics and Governance Framework, and for reviewing and updating it as appropriate.

The specific aims of the programme are:

> Specific Aim 1: Build a resource linking multiple sources of health and health-relevant information, including genetic data, on five million people in the UK, to facilitate basic discovery research by academic and commercial researchers on early indicators of disease.

> Specific Aim 2: Analyse the data in the resource to estimate personal disease risk information for participants, based on genetic and non-genetic information, and offer this estimated personal health information to participants who wish to receive it.

> Specific Aim 3: Re-contact sub-groups of participants generally for additional samples, non-routine data and secondary studies over time.

> Specific Aim 4: Re-contact participants on a risk-stratified basis (i.e. recall-by-genotype/phenotype or sociodemographic characteristics) over time specifically to enable secondary studies by academic and commercial researchers that is greatly enhanced by being able to identify highly enriched sub-populations/sub-cohorts of participants.

In this Data Sharing Agreement (DSA) Our Future Health wishes to:

a) Obtain identifiable personal record-level Data linked to a cohort of consenting participants held by Our Future Health. Linkage to health records is a central component of the Our Future Health programme, forming part of the core cohort dataset. To enable the high priority data linkages that will include secondary care, cancer Data, and death Data.

b) sub-licence the linked Data with the global research community within the Our Future Health Trusted Research Environment (hereinafter referred to as the 'TRE').

Our Future Health aims to be a world-leading resource for health research and will provide two key resources for health research:

> A prospective observational dataset with the ability to analyse the stored blood samples, for basic science/epidemiological, discovery and aetiological research e.g., on the causes and early signs of disease; and

> A cohort of people who can be re-contacted based on their characteristics including future risk of disease. They could be invited to take part in further data collection (including repeat blood samples), interventional and large-scale implementation research to develop and test cutting-edge diagnostic technologies, prevention strategies and treatments.

The combination of its scale, population diversity, and risk-based recall of participants will set it aside from other programmes. Building this resource will facilitate a new generation of discovery and translational research that will advance the development and testing of early diagnostic technologies and preventive interventions. The programme aims to achieve proportional representation from England, Wales, Scotland, and Northern Ireland. It aims to be reflective of geographic areas within the home nations and socio-economic groups especially those groups with traditionally low levels of participation in health research. To date, in 12 months, the programme has recruited more participants from traditionally underrepresented groups than any other large cohort, including over 28,500 from Black and Asian ethnicities (9% of full participants recruited via NHS Digitrials), 66,000 non-British white ethnicity and 180,000 from the three most deprived deciles.

The main mode of recruitment is via direct invitation through the NHS DigiTrials service, but Our Future Health are investing significant effort in assessing various other routes to invite participants to join the programme. These include collaboration via Primary Care – sending invitations via SMS text message from registered GP services via IPLATO; collaborations with well-known high street names – invitations by e-mail in partnership with Boots; and collaboration with other NHS organisations – such as their collaboration with NHS Blood and Transplant, a scaled up version of which was launched in June 2023. Recruitment is open to all adults living in the UK (age 18 years or over), whether they have received a direct invitation to join or not.

Our Future Health have recruited more real terms numbers of participants from traditionally underrepresented groups than any other large cohort study. For example, in 9 months, Our Future Health has over 50,000 people of non-British white ethnicity signed up - compared to 34,000 in UK Biobank after 3.5 years. Similarly, over 140,000 people from the three most deprived deciles signed up, compared to 80,000 in UK Biobank.

Participants will be asked to provide information about their health and lifestyles and a small sample of their blood. With their informed consent, Our Future Health will combine this with existing information about them, including their health-related records held by NHS England and other organisations within the UK. Participants provide consent to Our Future Health storing and sharing identifiable information, such as their name and date of birth, with those organisations which hold wider health records, to allow secure and accurate data linkage. Participants will be able to withdraw at any point, with an option to leave existing data in the programme or opt for all data not already used or in active use as part of a study to be destroyed.

Our Future Health has an Access Procedure and Access Board Procedures. A detailed Access Process Standard Operating Procedure (SOP) is available to the public from late summer 2024. The Access Board’s objective is to enable access to Our Future Health resources for research studies, while ensuring we meet our commitments to participants and to the wider public interest. It will also make sure that projects are in line with the Our Future Health protocol, Ethics and Governance Framework and Our Future Health ethical approval from the Health Research Authority. This provides enhanced access to appropriate data to support research and accelerate the discovery and development of innovative diagnostics and treatments for researchers from around the world such as those from charities, academia, government, the NHS and industry.

Researchers are able to apply for approval to study the information and samples to make new discoveries about health and disease. It is hoped that discoveries made through Our Future Health will lead to new ways to predict, prevent, and detect diseases earlier in life when they can be treated more easily, including diseases such as dementia, cancer, diabetes, heart disease and stroke.

CONTROLLERS AND PROCESSORS

> Our Future Health is the controller as the organisation responsible for ensuring that the data will only be processed for the purpose described above.

>Microsoft Azure is a processor acting under the instructions of Our Future Health and their role is limited to provision of cloud storage, support to the system and the processing infrastructure for Our Future Health under two separate tenancies:

>>Tenancy one receives identifiable personal data on the Our Future Health Participants from a range of sources and Our Future Health applies reversible pseudonymisation to the data.

>>Tenancy two hosts TRE software functionality provided by DNA Nexus (see below). De-identified data from Tenancy one is imported into the TRE.

Microsoft Azure are not permitted to process the data for any other purposes. Microsoft Azure will store NHS England data only in UK data centres for both Tenancy one and two. Microsoft Azure has been reviewed and approved by NHS England's cyber security team.

> DNAnexus is a processor acting under the instructions of Our Future Health and their role is limited to supplying IT support for the TRE software functionality which uses DNANexus software. This sits upon the Microsoft Azure cloud storage and processing Tenancy two. DNAnexus are not permitted to process the data for any other purposes. DNANexus has been reviewed and approved by NHS England's cyber security team.

The record-level de-identified data are then made available via the TRE (which uses DNAnexus' software) to registered researchers employed by or affiliated with a research organisation. The research organisation, who is acting in a capacity of sole controllership, is entering into a Data Access Agreement along with Our Future Health. In addition, registered researchers must agree to a set of terms and conditions governing access to record-level de-identified data in the TRE prior to being granted access to this data, following a successful application through the Access Process. As part of the Data Access Agreement the registered researchers acknowledge that the UK GDPR 2020 and the Data Protection Act 2018 continue to apply to the record-level de-identified data which the registered researchers are granted access to via the TRE. Processing of data into the TRE, and administration of access to the data within the TRE by approved researchers is managed entirely by Our Future Health.

NHS Blood and Transplant and Boots UK Limited have ONLY been involved as recruitment partners. They have liaised in the design and implementation of a recruitment channel but have NOT been involved in the development of the project purpose, methodology or use of data. Neither Boots nor NHS Blood and Transplant will have access to record level Data from NHS England other than via an access agreement through the TRE access board process, as applies to all researcher applicants.

FUNDERS AND COMMISSIONERS

Our Future Health received initial funding of £79 million from UK Research and Innovation (UKRI) Life Sciences Industrial Strategy, which is being used to set up and begin to deliver the programme.

With this commitment is also £150 million funding from life sciences companies. For more information on the role of Our Future Health’s industrial partners, please see the YouTube video <https://m.youtube.com/watch?v=OdQd9w-0bNk>

Our Future Health also has a programme of Founding Members, which includes charities and pharmaceutical and diagnostic companies, who will contribute funding to the programme in return for becoming a Founding Member. The Founding Members will contribute a fixed sum each and have a seat on the Founders Board. None of the founding members will view or process NHS England data unless via the formal Access Board process and signing of a sub-licence agreement. They do not make any decisions about the way Our Future Health is conducted or how the data is used.

PATIENT AND PUBLIC INVOLVEMENT AND ENGAGEMENT (PPIE)

Patient and public involvement is at the heart of the conception, design, and delivery of Our Future Health. Extensive focus group and user involvement has shaped the progress to date and continues to underpin all aspects of the programme approach.

Involving the public in the design of Our Future Health is important to its success. Our Future Health has built a governance structure that has public involvement and engagement embedded throughout and has already demonstrated a clear commitment to involving and engaging the public in the development, build and operational activities.

In 2020, Our Future Health involved members of the public in the design and development of the public-facing materials as well as in other aspects of the project design. The design of the participant information sheet and consent form has included:

> 18 focus groups with 82 members of the public;

> 4 meetings with a co-design group comprised of 8 members of the public; and

> 21 user testing interviews with members of the public.

During 2021 Our Future Health worked with Claremont creative agency to conduct a programme of patient and public involvement work. Over 120 members of the public were involved during 2020-2021 including:

> 4 focus groups, 2 co-design meetings, 21 interviews with the public to develop the scientific protocol

> 12 interviews with a variety of stakeholders from charities and existing cohort studies

> 2 focus groups with 11 NHS primary care staff

>18 focus groups, 10 co-design meetings, 21 interviews with the public to co-develop the participant information sheet, consent form and other public-facing videos and materials

>21 interviews to understand the role of industry in health research

>4 focus groups to explore insights around recruitment methods

>3 focus groups to explore public motivators and feedback preferences

>1 member of the public attended the REC approval meeting with a member of Our Future Health

As it was qualitative research, not quantitative, the outputs of the work are summarised as follows:

> Co-designed and REC approved PIS and Consent form

> 4 co-designed explainer videos for Our Future Health (YouTube)

> Public Engagement Strategy (Claremont 2021)

> Engaging Black Audiences Report (written by an external consultant)

Thirty members of the public were invited to join the Our Future Health Public Advisory Board, and 14 accepted. Six are affiliate members of the Secondary Care Working Group, Ethics Advisory Board and Technology Advisory Board (with 2 PPIE representatives on each). The Access Board will have equal representation of expert and public/participant members.

Outputs of these groups since 2021:

> Agreed Terms of Reference, working principles, PPIE training pack and evaluation matrix

>3 meetings held in 2021 and 1 ad-hoc consultation.

>Topics for consultation and input/approval have included the Founding Industry Member Policy, TRE, amendments to the PIS and consent form

In 2020-2022, Our Future Health involved over 3,600 members of the public in the design and development of the major public-facing materials, as well as in other aspects of the programme design. All projects involved members of the public and included representation from the following segments: early adopters (health), early adopters (civic minded), early majority, sceptics, lower income, South Asian ethnic background and Black ethnic background.

In addition, Our Future Health have successfully appointed and trained 22 members of the public to join their advisory boards and working groups (Public Advisory Board, Secondary Care Working Group, Primary Care Working Group, Ethics Advisory Board, Technology Advisory Board, and Access Board), with a further list of over 40 volunteers Our Future Health can consult for future user testing and PPIE activities. To support members of the public in taking on these roles Our Future Health have developed a PPIE training package for new public representatives.

This work has been essential to ensuring that Our Future Health developed:

• a co-designed and REC approved PIS and consent form (one member of the public attended the REC meeting alongside a member of Our Future Health Staff),

• co-designed explainer videos for Our Future Health (YouTube), and

• a Public Engagement Strategy (Claremont 2021)

An example of the work undertaken on user experience was a survey to gauge public attitudes to Our Future Health. 2,767 people completed the survey which confirmed that the general public have a high interest in receiving personalised genetic information: 77% of participants wished to receive risk information of disease which is preventable or treatable, 65% wanted non-treatable risk information and 77% would want ancestry information.

These insights are being used to support Our Future Health's developing feedback programme.

A full set of the participant-facing materials listed below:

- Baseline Questionnaire

- Consent form

- FAQs

- Invitation letters

- Newsletter

- Participant information sheet

- Pro-forma

- Refer a friend card

- Social postcard

- Thank you, postcard

- Volunteer voices stories

- Walk-in leaflet

With regards to the baseline questionnaire, all questions must have a response entered. The website forces an error response to any areas that are not complete. Participants have an option to select ‘prefer not to say’ or ‘other’ in some areas.

Our Future Health are planning to update the health measurement results proforma to include information about diabetes risk and a link to an online risk calculator (provided by Diabetes UK). This will allow participants to generate a letter to their GP if they are found to be at high risk on their results. Our Future Health will also be providing a link to the British Heart Foundation/NHS website where participants can calculate their ‘heart age’ using the information in the results proforma.

Ongoing PPIE via the Public Attitudes tracker, currently has 2676 respondents and the most recent data, captured in 2023 shows the following in relation to industry involvement and trust, based on the latest cohort of 1192 participants who were asked specifically about industry trust:

Industry Involvement:

* 40.69% (485/1192) would feel comfortable with pharma, diagnostic and health tech companies having access to health information

* 64.85% (773/1192) agree that partnerships with charities and industry will improve Our Future health

* 20.72% (247/1192) agree that partnerships with charities and industry would make them more likely to take part

* 14.26% (170/1192) agree that partnerships with charities and industry would make them less likely to take part

Measures of trust

* 81.5% (971/1192) generally trust medical researchers in universities

* 79.8% (951/1192) generally trust the NHS

* 62.8% (746/1192) generally trust medical charities

* 25.0% (498/1192) generally trust pharmaceutical companies

* 22.6% (269/1192) generally trust the government

ETHICAL APPROVAL

Our Future Health has received favourable ethical opinion on 29/03/2021, reviewed and issued by the NHS Health Research Authority (HRA) East of England – Cambridge East Research Ethics Committee.

An Ethics and Feedback Advisory Group was established in Sept 2019 to provide strategic advice on the development of ethical guidelines and principles for Our Future Health, and to develop an Ethics and Governance Framework to guide its operations. Building on that work, an Ethics Advisory Board has been established as part of the long-term governance of the cohort and is responsible for monitoring the implementation of the Ethics and Governance Framework, and for reviewing and updating it as appropriate. All proposals must be made by either Academic, Charity, NHS, Government or Industry Researchers, or employees of Founding Industry Members and their Affiliates, or employees of Founding Charity Members and their Affiliates, or organisations engaged in health research; henceforth all referred to as “Registered Researchers”.

Registered Researchers must have successfully completed the Our Future Health researcher registration process and had their identity confirmed, including, where necessary, having had their bona fides, affiliations and qualifications verified. To do this, they submit a completed Researcher Application Form, they sign the Researcher Terms & Conditions and submit evidence of information governance training. All proposals by Registered Researchers will be reviewed by the Our Future Health Access Board to ensure that studies are in line with the research protocol, Ethics and Governance Framework and the ethical approval from the Health Research Authority where applicable.

CONTROL AND COHORT GROUPS

The programme will be conducted throughout the UK and the aim is to recruit a total of 5 million participants, via a number of different recruitment routes*. Our Future Health is inviting people over the age of 18 from all backgrounds and ethnic groups, across the UK, to be part of Our Future Health.

*There is a separate DSA in place with NHS England for recruitment of individuals from England and Wales. (DARS-NIC-414067-K8R6J). The study will be applying for equivalent linked data obtaining the related data from the other devolved nations from the relevant organisations.

Inclusion criteria:

>Reside within UK

NOTE: The overall cohort of participants aims to be reflective of the population across UK geographical locations, age, gender, index of deprivation (IMD) and ethnicity.

>18 years or older

NOTE: Our Future Health is not recruiting children under the age of 18 for the following reasons:

>>In order to facilitate research on common complex conditions such as heart disease and type 2 diabetes, it is necessary to have sufficient events or cases develop in the cohort during the first decades of its existence; including children would mean that there would be too few events for this vital discovery research to be enabled for many decades. This would mean that the benefits of the resource would not be realised and would risk diminished value of the cohort to the scientific and health research community, and to wider society.

>>The aetiology of childhood-onset conditions (such as childhood cancers and rare genetic disorders) differs to those of adult-onset conditions (such as breast cancer and Alzheimer's disease).

>>Our Future Health is using an opt-in model with explicit consent

Reflection of the UK population will be achieved via a cohort selection and invitation process designed to monitor and subsequently over-sample people from under-represented groups, and by targeting areas of the country where people from these groups are resident.

While consent will be electronic and remote in the first instance, consent rates and acceptability of this approach by underrepresented groups will be carefully monitored and explored via conversion rate metrics and analyses, and via public involvement and engagement on this topic; alternative methods will be explored over time to reach those who are digitally excluded.

Following extensive piloting, recruitment commenced in July 2022 and will take place over several years. A variety of recruitment methods will be used so that as many people as possible will have the opportunity to be involved in the programme.

In summer 2022 through partnerships with NHS England and Boots UK Limited, members of the public were invited to join the research programme. Our Future Health is also working in partnership with NHS Blood and Transplant and will offer the opportunity to blood donors to take part. The benefit of working together is the opportunity to build this new research programme simply and efficiently whilst people are already giving blood. These invitations commenced in 2023.

For information, Boots UK Limited and NHS Blood and Transplant have not been involved with the decision process for the project design, purpose or how the data is used and are therefore not considered Controllers in this DSA. Neither Boots UK Limited nor NHS Blood and Transplant will receive, store, process or view NHS England data and are therefore not considered Processors in this DSA.

Members of the public who are interested in taking part in Our Future Health from Summer 2022 can register for news and updates at the dedicated website www.ourfuturehealth.org.uk

People wishing to leave Our Future Health will be able to choose between two options:

>Partial withdrawal means Our Future Health will not contact the participant again, or get any further information from their health records, but they can still analyse the samples and pseudonymised data given before withdrawal. All identifiable data will be deleted.

>Full withdrawal means Our Future Health will not contact the participant again and will destroy all identifiable and pseudonymised data and samples they collected, besides from an audit record to say that they were once part of the project. However, it will not be possible to remove their de-identified data from any research that is extant at the date of withdrawal or was completed prior to withdrawal.

NHS ENGLAND DATASETS REQUESTED AND JUSTIFICATION

The following NHS England Data will be accessed:

> Demographics. Necessary to:

1) perform linkage to below datasets;

2) for transfer to Our Future Health to facilitate future linkage activities. Data on GP are requested to track if someone changed GP and reasons for removal to investigate reasons for loss of follow-up.

> Hospital Episode Statistics (HES): including Admitted Patient Care (APC), Critical Care (CC), Outpatients (OP) and Accident and Emergency (A&E). Necessary because Secondary care Data provide detailed records of hospital outpatient and inpatient visits, surgeries, and procedures that are an essential component of understanding a participant’s health status, diagnoses, and progression/regression of disease.

> Emergency Care Data Set (ECDS). Necessary because this dataset replaced the HES Accident and Emergency Data Set in April 2019+ and provides crucial information on urgent and emergency care.

>Civil Registrations (Deaths) Data. Necessary to obtain vital status, date of death, underlying cause of death, and contributory causes of death which are essential data for any study within the Our Future Health programme, and are also required so that Our Future Health do not contact participants who have since died.

>National Diabetes Audit. Type 2 Diabetes (T2D) is a major cause of morbidity and mortality in the UK. Many people pass through a pre-diabetic phase before a T2D diagnosis. This is usually determined by the levels of Haemoglobin A1c (HbA1c) in the blood. Both the transition from pre-diabetes to T2D and the complications of T2D can be reduced by lifestyle changes and/or medications. Risk calculators have been developed that use characteristics such as age, family history of diabetes, and body mass index to calculate risk of developing T2D. These can now be supplemented with a polygenic risk score for T2D calculated from the genome array Our Future Health will run on participants.

At enrolment participants in Our Future Health agree to be re-contacted and are told they will receive personal health information – if they wish. Our Future Health propose to offer participants who do not already know they have T2D their risk based on a calculator currently hosted by Diabetes UK that has been used online by over 3 million people. This will be supplemented with unique information from the Polygenic Risk Score*.

* The Polygenic Risk Score is a simple calculator which is owned and managed by Diabetes UK.

In order to assess the impact of providing this information, Our Future Health will follow-up with a subset of participants to assess their psychological responses to the information and whether they use it to contact their GP practice. Our Future Health will monitor, through primary health care records, what actions are taken based on the information and how many new diagnoses of pre-diabetes or T2D are made and what clinical actions are taken. This will inform NHS practice, particularly whether the polygenic risk score adds meaningfully to the numbers of new diagnoses. These data will also be needed for health economic evaluation of this polygenic risk score.

Since GP level Data around this topic is not available currently, Our Future Health have requested the National Diabetes Audit Dataset in order to help achieve the aims of the proposal regarding Type 2 Diabetes incidence and management in the UK.

>National Disease Registration Service (NDRS) Cancer Registration Data, including:

>> Cancer Registry,

>> Cancer Registration (pre-1995),

>> Cancer Pathway,

>> Systemic Anti-Cancer Therapy Dataset (SACT),

>> National Radiotherapy Data Set (RTDS), and

> Annual drops of Somatic Molecular Dataset.

Necessary because the NDRS Cancer registration Data sets above provide almost complete capture of cancer diagnoses in the UK. These Datasets provide patient and tumour level information including pathology reports, molecular testing results, treatment records, and hospital activity records.

The identifiable data (e.g., name, date of birth, full postcode, and NHS number) will not be included in the data viewable on the OFH TRE to registered researchers working on approved studies. The registered researcher will only ever be provided with a study-specific, unique identification number for each participant. This is designed to prevent registered researchers who have been granted access to the Our Future Health TRE from identifying participants.

DATA MINIMISATION

To maximise the societal benefits of the resource, Our Future Health seeks all available (historical) data available for participants across their lifetime within the above datasets.

For the cohort to have the most benefit to society, it needs to be reflective of the whole population. Hence, this Data Sharing Agreement (DSA) is for linkage to healthcare data from the whole of England. Separate DSA applications will be made for Wales, Scotland, and Northern Ireland.

It is not practical to collect the depth of healthcare data Our Future Health seeks directly from the participants themselves. Participants are being asked to complete a health-related questionnaire, which primarily focuses on elements not covered in the datasets being requested for linkage (e.g., family medical history, drug history). It would not be possible to collect this data from 5 million people, nor to do so in a way that would provide levels of consistency that would be considered scientifically valuable. Even if it were possible to include all the variables of interest in a questionnaire, it would be unduly burdensome to expect participants to remember all relevant information and update it on a quarterly basis.

Our Future Health takes the protection of data, and the individual, seriously.  Recognising the increased risks of re-identification associated with linking health data to genomic data, Our Future Health consulted the ICO and incorporated their advice into their de-identification policy, established to ensure the risk of unintentional re-identification is minimised. Our Future Health took part in an ICO SANDBOX exercise. As part of this, Our Future Health informed the ICO that it had concluded that the personal data in the TRE will be pseudonymous. Our Future Health also stated that it is not possible to anonymise genetic information whilst retaining its utility for research. The ICO agreed with the assessment that it is likely that the personal data Our Future Health enters into the TRE will be pseudonymous (and not anonymous). Furthermore, Our Future Health is of the opinion that regardless of whether genetic data can be regarded as directly or indirectly identifiable, they are applying the same protections to genetic data, both when processed directly by Our Future Health and when accessible by third party researchers, as if it were directly identifiable data. Our Future Health will seek to strike the balance between restricting access (for minimisation purposes) and ensuring the full research potential of the programme, as anticipated by the participants who consent, is achieved by supporting hitherto unknown patterns and causal relationships to be identified.

Any release of genomic data into the TRE will be reviewed by an internal group, prior to release, to assess the specific risks of re-identification presented, and agree mitigations required.  While Our future Health acknowledges that genomic data is, by definition, identifiable, it requires a reference data set to confirm identity.  By implementing strong and careful de-identification of other data Our Future Health wi

Our Future Health will be a long-term cohort, designed to support a wide range of potential studies into disease development, identification, and treatment. It will provide a resource and facilitate both basic and translational research across the UK, on a very large, national scale. In line with the objectives and aims described in 5a, with most cases, Our Future Health will not be generating the outputs. Rather, these will be generated by the researchers who have approval from the Our Future Health Access Board to use the Our Future Health resource. Outputs will include peer-reviewed journal articles as well as presentations at conferences.

Outputs produced from the Our Future Health dataset will be presented in aggregate form only with suppression of small numbers in line with Office for National Statistics guidance and the HES analysis guide to avoid inadvertent identification. In cases where founding members have indicated preference for the release of non-identifiable but person-level data, this form of outputs may be made available (but will not be publicly available). These conditions will be detailed in a governance policy describing the statistical non-disclosure policies (please refer to above mentioned Access process description).

Our Future Health has dedicated communications and partnerships teams that will ensure substantial reach and awareness across the research community. This includes regular and in-depth engagement with numerous organisations and networks across the life sciences industry, academia, public sector, research charities and patient groups. Networking and presentations at conferences are envisioned to be a significant part of work to disseminate findings. Newsletters, bulletins and updates on digital platforms and social media will be provided to aim for regular and ongoing dissemination across the wider research community.

Submission of research to peer-reviewed journals will be another stream of dissemination for research and insight to gather traction and exposure to the research that is being carried out by approved researchers. Unless there is a justifiable reason for not doing so which has been agreed with the Access Board, researchers who use Our Future Health will be required to disseminate the results of their research as rapidly and widely as possible, subject to ethics and confidentiality considerations. They will be encouraged to discuss their research findings with other scientists and the public, and to share relevant materials as openly as possible. This means that Our Future Health will constantly grow in breadth and depth, to the benefit of other researchers in future.

In addition to publishing their work, Researchers are required to provide a plain language summary of their research at the point of application. This will be made publicly available at the point of approval.

Researchers will also be required to provide Our Future Health with a copy of all of results data of their research based on the Our Future Health data and samples (including any negative results data and relevant supporting data) for incorporation into a central database, upon completion of the research.

The abovementioned plans for dissemination of research outputs will be allocated to all registered research partners of Our Future Health who access and produce outputs from the programme. Our Future Health plans to provide infrastructure to third party researchers and facilitate dissemination of results through peer-reviewed publications, conferences, newsletters and ongoing updates and communications.

Registered Researchers will agree to publicise their results to promote the Our Future Health Resource and maximise its usage, whilst making knowledge advancements available to other scientists and researchers to maximise the output.

Our Future Health expects the first research outputs from the cohort to be published in late 2024.

The Initial Data Sharing Agreement was signed in December 2023 so the time for generation of Yielded Benefits is limited, however:

Our Future Health has now established an accredited TRE with 1 million participants who have questionnaire data. 330k of those participants also have genetic data available in the TRE.

By September 2024, it is forecast that there will be up to 1.12 million participants in the TRE, who will have their NHS England Data linked to demographic and questionnaire data collected by Our Future Health. NHS England Data will also be linked to genetic data collected by Our Future Health where available.

This is already a valuable sample with respect to the scale and diversity of the participants for research use, with the numbers of participants only set to increase.

6 studies' applications have been received up to May 2024, including applications to access the NHS England Data. These cover a wide range of health topics as follows (summarised to protect confidentiality prior to approval of any study):

 1st study – common diseases.

 2nd study – autoimmune, diabetes, genetic disorders, infectious diseases, immune system, rare diseases, mental health, neurology.

 3rd study – cancer, cardiovascular, infectious diseases, immune system, neurology, respiratory.

 4th study – general epidemiology.

 5th study – cancer, mental health, gastrointestinal.

 6th study – rare diseases.

The applications include requests for access from a range of international locations as follows:

 1st study – EEA

 2nd study – EEA

 3rd study – UK

 4th study – EEA

 5th study – UK

 6th study – USA (subject to appropriate permissions)

The applications are being reviewed, and if approved, will represent the start of delivering on the vision of enabling research with valuable public benefit.

The Our Future Health gateway on the Health Data Research UK (HDR UK) website is now live. This can be found at https://www.healthdatagateway.org and navigating to ‘Explore’ > ‘Data Uses’ and filtering the Data Custodian to ‘Our Future Health’. The gateway will provide an up-to-date summary of all study applications that have been approved by Our Future Health.

Our Future Health was formed as part of the UK Life Sciences Industrial Strategy. It is designed to be the UK’s largest ever health research programme with the goal to recruit up to 5 million adult participants from across the UK to create a detailed picture that reflects the whole of the population.

Our Future Health is a company limited by guarantee registered in England and Wales (Number 12212468) and a charity registered with the Charity Commission for England and Wales (charity number 1189681) and OSCR, Scottish Charity Regulator (charity number SC050917). It is designed to help people live healthier lives for longer through better prevention, earlier detection, and improved treatment of diseases.

Our Future Health was initially discussed in 2016, when several medical research charities, the Medical Research Council, and leading public health practitioners and academics started exploring the rationale. The concept was outlined in the 2017 Life Sciences Industrial Strategy. An Ethics and Feedback Advisory Group was established in Sept 2019 to provide strategic advice on the development of ethical guidelines and principles for Our Future Health, and to develop an Ethics and Governance Framework to guide its operations. Building on that work, an Ethics Advisory Board has been established as part of the long-term governance of the cohort and is responsible for monitoring the implementation of the Ethics and Governance Framework, and for reviewing and updating it as appropriate.

The specific aims of the programme are:

> Specific Aim 1: Build a resource linking multiple sources of health and health-relevant information, including genetic data, on five million people in the UK, to facilitate basic discovery research by academic and commercial researchers on early indicators of disease.

> Specific Aim 2: Analyse the data in the resource to estimate personal disease risk information for participants, based on genetic and non-genetic information, and offer this estimated personal health information to participants who wish to receive it.

> Specific Aim 3: Re-contact sub-groups of participants generally for additional samples, non-routine data and secondary studies over time.

> Specific Aim 4: Re-contact participants on a risk-stratified basis (i.e. recall-by-genotype/phenotype or sociodemographic characteristics) over time specifically to enable secondary studies by academic and commercial researchers that is greatly enhanced by being able to identify highly enriched sub-populations/sub-cohorts of participants.

In this Data Sharing Agreement (DSA) Our Future Health wishes to:

a) Obtain identifiable personal record-level Data linked to a cohort of consenting participants held by Our Future Health. Linkage to health records is a central component of the Our Future Health programme, forming part of the core cohort dataset. To enable the high priority data linkages that will include secondary care, cancer Data, and death Data.

b) sub-licence the linked Data with the global research community within the Our Future Health Trusted Research Environment (hereinafter referred to as the 'TRE').

Our Future Health aims to be a world-leading resource for health research and will provide two key resources for health research:

> A prospective observational dataset with the ability to analyse the stored blood samples, for basic science/epidemiological, discovery and aetiological research e.g., on the causes and early signs of disease; and

> A cohort of people who can be re-contacted based on their characteristics including future risk of disease. They could be invited to take part in further data collection (including repeat blood samples), interventional and large-scale implementation research to develop and test cutting-edge diagnostic technologies, prevention strategies and treatments.

The combination of its scale, population diversity, and risk-based recall of participants will set it aside from other programmes. Building this resource will facilitate a new generation of discovery and translational research that will advance the development and testing of early diagnostic technologies and preventive interventions. The programme aims to achieve proportional representation from England, Wales, Scotland, and Northern Ireland. It aims to be reflective of geographic areas within the home nations and socio-economic groups especially those groups with traditionally low levels of participation in health research. To date, in 9 months, the programme has recruited more participants from traditionally underrepresented groups than any other large cohort, including over 28.5k from Black and Asian ethnicities (9% of full participants recruited via NHS Digitrials), 50,000 non-British white ethnicity and 140,000 from the three most deprived deciles.

The main mode of recruitment is via direct invitation through the NHS DigiTrials service, but Our Future Health are investing significant effort in assessing various other routes to invite participants to join the programme. These include collaboration via Primary Care – sending invitations via SMS text message from registered GP services via IPLATO; collaborations with well-known high street names – invitations by e-mail in partnership with Boots; and collaboration with other NHS organisations – such as their collaboration with NHS Blood and Transplant, a scaled up version of which was launched in June 2023. Recruitment is open to all adults living in the UK (age 18 years or over), whether they have received a direct invitation to join or not.

So far, of those who book an appointment with Our Future Health, 77% are known to have joined using a URL or QR code from an NHS DigiTrials invitation letter. This is likely an underestimate of the true number of people who have joined after receiving an NHS DigiTrials letter. Our Future Health have recruited more real terms numbers of participants from traditionally underrepresented groups than any other large cohort study. For example, in 9 months, Our Future Health has over 50,000 people of non-British white ethnicity signed up - compared to 34,000 in UK Biobank after 3.5 years. Similarly, there are over 140,000 people from the three most deprived deciles, compared to 80,000 in UK Biobank.

Participants will be asked to provide information about their health and lifestyles and a small sample of their blood. With their informed consent, Our Future Health will combine this with existing information about them, including their health-related records held by NHS England and other organisations within the UK. Participants provide consent to Our Future Health storing and sharing identifiable information, such as their name and date of birth, with those organisations which hold wider health records, to allow secure and accurate data linkage. Participants will be able to withdraw at any point, with an option to leave existing data in the programme or opt for all data not already used or in active use as part of a study to be destroyed.

Our Future Health has an Access Procedure and Access Board Procedures. A detailed Access Process Standard Operating Procedure (SOP) was reviewed by a sub-group of the Access Board and is due for final sign off the OFH Access Board on 18 July 2023. The Access Board’s objective is to enable access to Our Future Health resources for research studies, while ensuring we meet our commitments to participants and to the wider public interest. It will will also make sure that projects are in line with the Our Future Health protocol, Ethics and Governance Framework and Our Future Health ethical approval from the Health Research Authority. This provides enhanced access to appropriate data to support research and accelerate the discovery and development of innovative diagnostics and treatments for researchers from around the world such as those from charities, academia, government, the NHS and industry.

Researchers are able to apply for approval to study the information and samples to make new discoveries about health and disease. It is hoped that discoveries made through Our Future Health will lead to new ways to predict, prevent, and detect diseases earlier in life when they can be treated more easily, including diseases such as dementia, cancer, diabetes, heart disease and stroke.

CONTROLLERS AND PROCESSORS

> Our Future Health is the controller as the organisation responsible for ensuring that the data will only be processed for the purpose described above.

>Microsoft Azure is a processor acting under the instructions of Our Future Health and their role is limited to provision of cloud storage, support to the system and the processing infrastructure for Our Future Health under two separate tenancies:

>>Tenancy one receives identifiable personal data on the Our Future Health Participants from a range of sources and Our Future Health applies reversible pseudonymisation to the data.

>>Tenancy two hosts TRE software functionality provided by DNA Nexus (see below). De-identified data from Tenancy one is imported into the TRE.

Microsoft Azure are not permitted to process the data for any other purposes. Microsoft Azure will store NHS England data only in UK data centres for both Tenancy one and two. Microsoft Azure has been reviewed and approved by NHS England's cyber security team.

> DNAnexus is a processor acting under the instructions of Our Future Health and their role is limited to supplying IT support for the TRE software functionality which uses DNANexus software. This sits upon the Microsoft Azure cloud storage and processing Tenancy two. DNAnexus are not permitted to process the data for any other purposes. DNANexus has been reviewed and approved by NHS England's cyber security team.

The record-level de-identified data are then made available via the TRE (which uses DNAnexus' software) to registered researchers employed by or affiliated with a research organisation. The research organisation, who is acting in a capacity of sole controllership, is entering into a Data Access Agreement along with Our Future Health. In addition, registered researchers must agree to a set of terms and conditions governing access to record-level de-identified data in the TRE prior to being granted access to this data, following a successful application through the Access Process. As part of the Data Access Agreement the registered researchers acknowledge that the UK GDPR 2020 and the Data Protection Act 2018 continue to apply to the record-level de-identified data which the registered researchers are granted access to via the TRE. Processing of data into the TRE, and administration of access to the data within the TRE by approved researchers is managed entirely by Our Future Health.

NHS Blood and Transplant and Boots UK Limited have ONLY been involved as recruitment partners. They have liaised in the design and implementation of a recruitment channel but have NOT been involved in the development of the project purpose, methodology or use of data. Neither Boots nor NHS Blood and Transplant will have access to record level Data from NHS England other than via an access agreement through the TRE access board process, as applies to all researcher applicants.

FUNDERS AND COMMISSIONERS

Our Future Health received initial funding of £79 million from UK Research and Innovation (UKRI) Life Sciences Industrial Strategy, which is being used to set up and begin to deliver the programme.

With this commitment is also £150 million funding from life sciences companies. For more information on the role of Our Future Health’s industrial partners, please see the YouTube video <https://m.youtube.com/watch?v=OdQd9w-0bNk>

Our Future Health also has a programme of Founding Members, which includes charities and pharmaceutical and diagnostic companies, who will contribute funding to the programme in return for becoming a Founding Member. The Founding Members will contribute a fixed sum each and have a seat on the Founders Board. None of the founding members will view or process NHS England data unless via the formal Access Board process and signing of a sub-licence agreement. They do not make any decisions about the way Our Future Health is conducted or how the data is used.

PATIENT AND PUBLIC INVOLVEMENT AND ENGAGEMENT (PPIE)

Patient and public involvement is at the heart of the conception, design, and delivery of Our Future Health. Extensive focus group and user involvement has shaped the progress to date and continues to underpin all aspects of the programme approach.

Involving the public in the design of Our Future Health is important to its success. Our Future Health has built a governance structure that has public involvement and engagement embedded throughout and has already demonstrated a clear commitment to involving and engaging the public in the development, build and operational activities.

In 2020, Our Future Health involved members of the public in the design and development of the public-facing materials as well as in other aspects of the project design. The design of the participant information sheet and consent form has included:

> 18 focus groups with 82 members of the public;

> 4 meetings with a co-design group comprised of 8 members of the public; and

> 21 user testing interviews with members of the public.

During 2021 Our Future Health worked with Claremont creative agency to conduct a programme of patient and public involvement work. Over 120 members of the public were involved during 2020-2021 including:

> 4 focus groups, 2 co-design meetings, 21 interviews with the public to develop the scientific protocol

> 12 interviews with a variety of stakeholders from charities and existing cohort studies

> 2 focus groups with 11 NHS primary care staff

>18 focus groups, 10 co-design meetings, 21 interviews with the public to co-develop the participant information sheet, consent form and other public-facing videos and materials

>21 interviews to understand the role of industry in health research

>4 focus groups to explore insights around recruitment methods

>3 focus groups to explore public motivators and feedback preferences

>1 member of the public attended the REC approval meeting with a member of Our Future Health

As it was qualitative research, not quantitative, the outputs of the work are summarised as follows:

> Co-designed and REC approved PIS and Consent form

> 4 co-designed explainer videos for Our Future Health (YouTube)

> Public Engagement Strategy (Claremont 2021)

> Engaging Black Audiences Report (written by an external consultant)

Thirty members of the public were invited to join the Our Future Health Public Advisory Board, and 14 accepted. Six are affiliate members of the Secondary Care Working Group, Ethics Advisory Board and Technology Advisory Board (with 2 PPIE representatives on each). The Access Board will have equal representation of expert and public/participant members.

Outputs of these groups since 2021:

> Agreed Terms of Reference, working principles, PPIE training pack and evaluation matrix

>3 meetings held in 2021 and 1 ad-hoc consultation.

>Topics for consultation and input/approval have included the Founding Industry Member Policy, TRE, amendments to the PIS and consent form

In 2020-2022, Our Future Health involved over 3,600 members of the public in the design and development of the major public-facing materials, as well as in other aspects of the programme design. All projects involved members of the public and included representation from the following segments: early adopters (health), early adopters (civic minded), early majority, sceptics, lower income, South Asian ethnic background and Black ethnic background.

In addition, Our Future Health have successfully appointed and trained 22 members of the public to join their advisory boards and working groups (Public Advisory Board, Secondary Care Working Group, Primary Care Working Group, Ethics Advisory Board, Technology Advisory Board, and Access Board), with a further list of over 40 volunteers Our Future Health can consult for future user testing and PPIE activities. To support members of the public in taking on these roles Our Future Health have developed a PPIE training package for new public representatives.

This work has been essential to ensuring that Our Future Health developed:

• a co-designed and REC approved PIS and consent form (one member of the public attended the REC meeting alongside a member of Our Future Health Staff),

• co-designed explainer videos for Our Future Health (YouTube), and

• a Public Engagement Strategy (Claremont 2021)

An example of the work undertaken on user experience was a survey to gauge public attitudes to Our Future Health. 2,767 people completed the survey which confirmed that the general public have a high interest in receiving personalised genetic information: 77% of participants wished to receive risk information of disease which is preventable or treatable, 65% wanted non-treatable risk information and 77% would want ancestry information.

These insights are being used to support Our Future Health's developing feedback programme.

A full set of the participant-facing materials listed below::

- Baseline Questionnaire

- Consent form

- FAQs

- Invitation letters

- Newsletter

- Participant information sheet

- Pro-forma

- Refer a friend card

- Social postcard

- Thank you, postcard

- Volunteer voices stories

- Walk-in leaflet

With regards to the baseline questionnaire, all questions must have a response entered. The website forces an error response to any areas that are not complete. Participants have an option to select ‘prefer not to say’ or ‘other’ in some areas.

Our Future Health are planning to update the health measurement results proforma to include information about diabetes risk and a link to an online risk calculator (provided by Diabetes UK). This will allow participants to generate a letter to their GP based if they are found to be at high risk on their results. Our Future Health will also be providing a link to the British Heart Foundation/NHS website where participants can calculate their ‘heart age’ using the information in the results proforma.

Ongoing PPIE via the Public Attitudes tracker, currently has 2676 respondents and the most recent data shows the following in relation to industry involvement and trust:

Industry Involvement:

* 40.69% (485/1192) would feel comfortable with pharma, diagnostic and health tech companies having access to health information

* 64.85% (773/1192) agree that partnerships with charities and industry will improve Our Future health

* 20.72% (247/1192) agree that partnerships with charities and industry would make them more likely to take part

* 14.26% (170/1192) agree that partnerships with charities and industry would make them less likely to take part

Measures of trust

* 81.5% (971/1192) generally trust medical researchers in universities

* 79.8% (951/1192) generally trust the NHS

* 62.8% (746/1192) generally trust medical charities

* 25.0% (498/1192) generally trust pharmaceutical companies

* 22.6% (269/1192) generally trust the government

ETHICAL APPROVAL

Our Future Health has received favourable ethical opinion on 29/03/2021, reviewed and issued by the NHS Health Research Authority (HRA) East of England – Cambridge East Research Ethics Committee.

An Ethics and Feedback Advisory Group was established in Sept 2019 to provide strategic advice on the development of ethical guidelines and principles for Our Future Health, and to develop an Ethics and Governance Framework to guide its operations. Building on that work, an Ethics Advisory Board has been established as part of the long-term governance of the cohort and is responsible for monitoring the implementation of the Ethics and Governance Framework, and for reviewing and updating it as appropriate. All proposals must be made by Registered Researchers. Registered Researchers are defined as a researcher who has successfully completed the Our Future Health researcher registration process and had their identity confirmed, including, where necessary, having had their bona fides, affiliations and qualifications verified. To do this, they submit a completed Researcher Application Form, they sign the Researcher Terms & Conditions and submit evidence of information governance training. All proposals by Registered Researchers will be reviewed by the Our Future Health Access Board to ensure that studies are in line with the research protocol, Ethics and Governance Framework and the ethical approval from the Health Research Authority.

CONTROL AND COHORT GROUPS

The programme will be conducted throughout the UK and the aim is to recruit a total of 5 million participants, via a number of different recruitment routes*. Our Future Health is inviting people over the age of 18 from all backgrounds and ethnic groups, across the UK, to be part of Our Future Health.

*There is a separate DSA in place with NHS England for recruitment of individuals from England and Wales. (DARS-NIC-414067-K8R6J). The study will be applying for equivalent linked data obtaining the related data from the other devolved nations from the relevant organisations.

Inclusion criteria:

>Reside within UK

NOTE: The overall cohort of participant aims to be reflective of the population across UK geographical locations, age, gender, index of deprivation (IMD) and ethnicity.

>18 years or older

NOTE: Our Future Health is not recruiting children under the age of 18 for the following reasons:

>>In order to facilitate research on common complex conditions such as heart disease and type 2 diabetes, it is necessary to have sufficient events or cases develop in the cohort during the first decades of its existence; including children would mean that there would be too few events for this vital discovery research to be enabled for many decades. This would mean that the benefits of the resource would not be realised and would risk diminished value of the cohort to the scientific and health research community, and to wider society.

>>The aetiology of childhood-onset conditions (such as childhood cancers and rare genetic disorders) differs to those of adult-onset conditions (such as breast cancer and Alzheimer's disease).

>>Our Future Health is using an opt-in model with explicit consent

Reflection of the UK population will be achieved via a cohort selection and invitation process designed to monitor and subsequently over-sample people from under-represented groups, and by targeting areas of the country where people from these groups are resident.

While consent will be electronic and remote in the first instance, consent rates and acceptability of this approach by underrepresented groups will be carefully monitored and explored via conversion rate metrics and analyses, and via public involvement and engagement on this topic; alternative methods will be explored over time to reach those who are digitally excluded.

Following extensive piloting, recruitment commenced in July 2022 and will take place over several years. A variety of recruitment methods will be used so that as many people as possible will have the opportunity to be involved in the programme.

In summer 2022 through partnerships with NHS England and Boots UK Limited, members of the public were invited to join the research programme. Our Future Health is also working in partnership with NHS Blood and Transplant and will offer the opportunity to blood donors to take part. The benefit of working together is the opportunity to build this new research programme simply and efficiently whilst people are already giving blood. These invitations will commence in 2023.

For information, Boots UK Limited and NHS Blood and Transplant have not been involved with the decision process for the project design, purpose or how the data is used and are therefore not considered Controllers in this DSA. Neither Boots UK Limited nor NHS Blood and Transplant will receive, store, process or view NHS England data and are therefore not considered Processors in this DSA.

Members of the public who are interested in taking part in Our Future Health from Summer 2022 can register for news and updates at the dedicated website www.ourfuturehealth.org.uk

People wishing to leave Our Future Health will be able to choose between two options:

>Partial withdrawal means Our Future Health will not contact the participant again, or get any further information from their health records, but they can still analyse the samples and pseudonymised data given before withdrawal. All identifiable data will be deleted.

>Full withdrawal means Our Future Health will not contact the participant again and will destroy all identifiable and pseudonymised data and samples they collected, besides from an audit record to say that they were once part of the project. However, it will not be possible to remove their de-identified data from any research that is extant at the date of withdrawal or was completed prior to withdrawal.

NHS ENGLAND DATASETS REQUESTED AND JUSTIFICATION

The following NHS England Data will be accessed:

> Demographics. Necessary to:

1) perform linkage to below datasets;

2) for transfer to Our Future Health to facilitate future linkage activities. Data on GP are requested to track if someone changed GP and reasons for removal to investigate reasons for loss of follow-up.

> Hospital Episode Statistics (HES): including Admitted Patient Care (APC), Critical Care (CC), Outpatients (OP) and Accident and Emergency (A&E). Necessary because Secondary care Data provide detailed records of hospital outpatient and inpatient visits, surgeries, and procedures that are an essential component of understanding a participant’s health status, diagnoses, and progression/regression of disease.

> Emergency Care Data Set (ECDS). Necessary because this dataset replaced the HES Accident and Emergency Data Set in April 2019+ and provides crucial information on urgent and emergency care.

>Civil Registrations (Deaths) Data. Necessary to obtain vital status, date of death, underlying cause of death, and contributory causes of death are essential data for any study within the Our Future Health programme, and are also required so that Our Future Health do not contact participants who have since deceased.

>National Diabetes Audit. Necessary to obtain Type 2 Diabetes (T2D) is a major cause of morbidity and mortality in the UK. Many people pass through a pre-diabetic phase before a T2D diagnosis. This is usually determined by the levels of Haemoglobin A1c (HbA1c) in the blood. Both the transition from pre-diabetes to T2D and the complications of T2D can be reduced by lifestyle changes and/or medications. Risk calculators have been developed that use characteristics such as age, family history of diabetes, and body mass index to calculate risk of developing T2D. These can now be supplemented with a polygenic risk score for T2D calculated from the genome array Our Future Health will run on participants.

At enrolment participants in Our Future Health agree to be re-contacted and are told they will receive personal health information – if they wish. Our Future Health propose to offer participants who do not already know they have T2D their risk based on a calculator currently hosted by Diabetes UK that has been used online by over 3 million people. This will be supplemented with unique information from the Polygenic Risk Score*.

* The Polygenic Risk Score is a simple calculator which is owned and managed by Diabetes UK.

In order to assess the impact of providing this information, Our Future Health will follow-up with a subset of participants to assess their psychological responses to the information and whether they use it to contact their GP practice. Our Future Health will monitor, through primary health care records, what actions are taken based on the information and how many new diagnoses of pre-diabetes or T2D are made and what clinical actions are taken. This will inform NHS practice, particularly whether the polygenic risk score adds meaningfully to the numbers of new diagnoses. These data will also be needed for health economic evaluation of this polygenic risk score.

Since GP level Data around this topic is not available currently, Our Future Health have requested the National Diabetes Audit Dataset in order to help achieve the aims of the proposal regarding Type 2 Diabetes incidence and management in the UK.

>National Disease Registration Service (NDRS) Cancer Registration Data, including:

>> Cancer Registry,

>> Cancer Registration (pre-1995),

>> Cancer Pathway,

>> Systemic Anti-Cancer Therapy Dataset (SACT),

>> National Radiotherapy Data Set (RTDS), and

> Annual drops of Somatic Molecular Dataset.

Necessary because the NDRS Cancer registration Data sets above provide almost complete capture of cancer diagnoses in the UK. These Datasets provide patient and tumour level information including pathology reports, molecular testing results, treatment records, and hospital activity records.

The identifiable data (e.g., name, date of birth, full postcode, and NHS number) will not be included in the data viewable on the OFH TRE to registered researchers working on approved studies. The registered researcher will only ever be provided with a study-specific, unique identification number for each participant. This is designed to prevent registered researchers who have been granted access to the Our Future Health TRE from identifying participants.

DATA MINIMISATION

To maximise the societal benefits of the resource, Our Future Health seeks all available (historical) data available for participants across their lifetime within the above datasets.

For the cohort to have the most benefit to society, it needs to be reflective of the whole population. Hence, this Data Sharing Agreement (DSA) is for linkage to healthcare data from the whole of England. Separate DSA applications will be made for Wales, Scotland, and Northern Ireland.

It is not practical to collect the depth of healthcare data Our Future Health seeks directly from the participants themselves. Participants are being asked to complete a health-related questionnaire, which primarily focuses on elements not covered in the datasets being requested for linkage (e.g., family medical history, drug history). It would not be possible to collect this data from 5 million people, nor to do so in a way that would provide levels of consistency that would be considered scientifically valuable. Even if it were possible to include all the variables of interest in a questionnaire, it would be unduly burdensome to expect participants to remember all relevant information and update it on a quarterly basis.

Our Future Health takes the protection of data, and the individual, seriously.  Recognising the increased risks of re-identification associated with linking health data to genomic data, Our Future Health consulted the ICO and incorporated their advice into their de-identification policy, established to ensure the risk of unintentional re-identification is minimised. Our Future Health took part in an ICO SANDBOX exercise. As part of this, Our Future Health informed the ICO that it had concluded that the personal data in the TRE will be pseudonymous. Our Future Health also stated that it is not possible to anonymise genetic information whilst retaining its utility for research. The ICO agreed with the assessment that it is likely that the personal data Our Future Health enters into the TRE will be pseudonymous (and not anonymous). Furthermore, Our Future Health is of the opinion that regardless of whether genetic data can be regarded as directly or indirectly identifiable, they are applying the same protections to genetic data, both when processed directly by Our Future Health and when accessible by third party researchers, as if it were directly identifiable data. Our Future Health will seek to strike the balance between restricting access (for minimisation purposes) and ensuring the full research potential of the programme, as anticipated by the participants who consent, is achieved by supporting hitherto unknown patterns and causal relationships to be identified.

Any release of genomic data into the TRE will be reviewed by an internal group, prior to release, to assess the specific risks of re-identification presented, and agree mitigations required.  While Our future Health acknowledges that genomic data is, by definition, identifiable, it requires a reference data set to confirm identity.  By implementing strong and careful de-identification of other data Our Future He

Our Future Health will be a long-term cohort, designed to support a wide range of potential studies into disease development, identification, and treatment. It will provide a resource and facilitate both basic and translational research across the UK, on a very large, national scale. In line with the objectives and aims described in 5a, with most cases, Our Future Health will not be generating the outputs. Rather, these will be generated by the researchers who have approval from the Our Future Health Access Board to use the Our Future Health resource. Outputs will include peer-reviewed journal articles as well as presentations at conferences.

Outputs produced from the Our Future Health dataset will be presented in aggregate form only with suppression of small numbers in line with Office for National Statistics guidance and the HES analysis guide to avoid inadvertent identification. In cases where founding members have indicated preference for the release of non-identifiable but person-level data, this form of outputs may be made available (but will not be publicly available). These conditions will be detailed in a governance policy describing the statistical non-disclosure policies (please refer to above mentioned Access process description).

Our Future Health has dedicated communications and partnerships teams that will ensure substantial reach and awareness across the research community. This includes regular and in-depth engagement with numerous organisations and networks across the life sciences industry, academia, public sector, research charities and patient groups. Networking and presentations at conferences are envisioned to be a significant part of work to disseminate findings. Newsletters, bulletins and updates on digital platforms and social media will be provided to aim for regular and ongoing dissemination across the wider research community.

Submission of research to peer-reviewed journals will be another stream of dissemination for research and insight to gather traction and exposure to the research that is being carried out by approved researchers. Unless there is a justifiable reason for not doing so which has been agreed with the Access Board, researchers who use Our Future Health will be required to disseminate the results of their research as rapidly and widely as possible, subject to ethics and confidentiality considerations. They will be encouraged to discuss their research findings with other scientists and the public, and to share relevant materials as openly as possible. This means that Our Future Health will constantly grow in breadth and depth, to the benefit of other researchers in future.

In addition to publishing their work, Researchers are required to provide a plain language summary of their research at the point of application. This will be made publicly available at the point of approval.

Researchers will also be required to provide Our Future Health with a copy of all of results data of their research based on the Our Future Health data and samples (including any negative results data and relevant supporting data) for incorporation into a central database, upon completion of the research.

The abovementioned plans for dissemination of research outputs will be allocated to all registered research partners of Our Future Health who access and produce outputs from the programme. Our Future Health plans to provide infrastructure to third party researchers and facilitate dissemination of results through peer-reviewed publications, conferences, newsletters and ongoing updates and communications.

Registered Researchers will agree to publicise their results to promote the Our Future Health Resource and maximise its usage, whilst making knowledge advancements available to other scientists and researchers to maximise the output.

Our Future Health expects the first research outputs from the cohort to be published in 2024.

Yielded Benefits is not a requirement for new applications.