Lynch Syndrome Research Registry Pilot Study

Imperial College London requires access to NHS England data for the purpose of the following research project: Lynch Syndrome Research Registry Pilot Study.

Lynch Syndrome (LS) is an inherited disorder associated with an increased risk of many types of cancer, particularly bowel cancer, as well as cancer of the womb. In the UK, there are only 6,000 known LS patients, however, it is estimated that there are ~176,000 undiagnosed cases. Given their high risk of bowel cancer, these patients require close monitoring, also known as ‘surveillance’, by colonoscopy - a thin tube with a camera used to examine the bowel lining.

The study was undertaken in 4 English NHS hospital sites (St Mark’s, Newcastle, Manchester & Birmingham). Eligible adult participants with a confirmed genetic LS diagnosis, who had previously taken part in the Cancer Prevention Project 3 (CaPP3) trial and consented to be contacted, were sent an invitation letter, consent form, patient information sheet and questionnaire asking whether they would be interested in participating. 257 patients responded and consented to take part over a 9-month period.

This Imperial College London sponsored pilot study is funded by the charities 40tude and Cancer Research UK and was setup with the intention of helping to review and improve how LS patients are managed; to provide data to support the BCSP (national Bowel Cancer Screening Programme’s) role in taking on and managing LS surveillance; and to provide a unique resource to conduct and support future research into LS.

The following is a summary of the aims of the Observational, questionnaire-based study.

- Build a registry of patients with LS;

- Better understand how LS patients are currently being monitored and managed;

- Address the variation in care people with LS receive, and gain a better understanding of the issues which lead to variation;

- Work collaboratively with the multi-disciplinary teams, BCSP and other organisations involved in the LS patient care pathway;

- Develop a registry that is functional and suitable for adoption within the NHS;

- Create a research dataset to conduct and support future research projects and collaborations;

- Create a model that can be applied to manage other high-risk conditions.

The collection of data will support the following research questions:

1. How can they optimise the data collection process and functionality of the registry database for both users and researchers?

2. What would be required to better support the national BCSP and their role in taking on and managing LS surveillance?

3. What proportion of the registry pilot data collected directly from participants and local sites can be provided by the National Disease Registration service (NDRS) and NHS England on a national scale?

4. Can they capture colonoscopy quality assurance data and ascertain disease-specific colonoscopic quality indicators in LS patients?

5. What proportion of LS patients have been tested for Helicobacter pylori (H Pylori) - an important risk factor in the development of gastric cancer?

6. What options are appropriate for the gynaecological management of female LS patients, particularly when considering patients with PMS2 pathogenic variants?

7. What proportion of LS patients have had a cancer diagnosis?

8. What proportion of LS patients are taking aspirin, why are they taking it and at what dosage or frequency?

The following NHS England Data will be accessed:

• NDRS Cancer Registration - necessary to directly address aims 3, 4 and 7.

• NDRS HES Linked Hospital Episode Statistics Admitted Patient Care (HES APC) - necessary to directly address aims 3, 4 and 7.

• NDRS HES Linked Hospital Episode Statistics Outpatients (HES OP) - necessary to directly address aims 3, 4 and 7.

The level of the Data will be:

• Identifiable – necessary because although the data from NHS England under this DSA will be pseudonymised under a unique study ID number, the CSPRG (Cancer Screening and Prevention Research Group) already hold identifiers for all participants under consent. It would therefore be possible for the applicant to reidentify cohort members. In addition, identifiable data that they have already collected from participants will need to be transferred to NHS England for the cohort to be linked with NHS England data.

The Data will be minimised as follows:

• Limited to a study cohort identified by the CSPRG, 257 individuals with a confirmed LS diagnosis, who consented to participate.

• Limited to data between 1995 – Latest Available

• Limited to conditions relevant to the study identified by specific ICD or OPCS codes; all cancer related ICD-10 codes, all endoscopy and associated surgery related OPCS-4 codes.

Imperial College London is the research sponsor and the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above.

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

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

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

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

This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care.

The funding comes from multiple sources. Previous and current funders include:

• 40tude – Funding was in place until 2024

• Cancer Research UK – Funding is in place until June 2028

Co-investigators are involved with the study design and protocol development, and will contribute towards outputs and publications, including the final study report and any associated manuscripts. They will not have access to NHS England data only aggregated data. The organisations involved include: Newcastle Hospitals NHS Trust, St Marks Hospital NHS Trust, Newcastle University, North Tees & Hartlepool NHS Trust, Manchester University NHS Trust.

Data will be accessed by substantive employees of Imperial College London and a PhD student enrolled with the CSPRG. The individual has completed mandatory data protection and confidentiality training and is subject to CSPRG’s policies on data protection and confidentiality. The individual accessing the data will do so under the supervision of a substantive employee of Imperial College London. Imperial College London would be responsible and liable for any work carried out by the individual. The PhD student would only work on the data for the purposes described in this Data Sharing Agreement (DSA).

Public and Patient Involvement Engagement Group :

The group consists of five core patient public representatives for this project. All five patient representatives have been diagnosed with Lynch syndrome, of these, two have also received a diagnosis of bowel cancer. They include a mixture of ages (20–50 years old), come from a diverse range of backgrounds and communities and bring different levels of personal experiences and skills necessary for this project. These include previous experience working with databases and public speaking. A patient representative was also recruited with no previous experience of Public Patient Involvement (PPI) in a research study. All patient representatives have been actively involved in developing and shaping the content of the research proposal. The patient representatives were asked to review the proposal electronically and send comments back to the research team. All five patient representatives who read the proposal stated how this is a ‘worthwhile, relevant and timely application’ and how PPI plans are entirely appropriate. With the help of social media and continued engagement with organisations such as Lynch Syndrome UK, an additional three patients and members of the public were recruited to attend two larger group workshops. These were subsequently held to discuss recruitment strategies, co-develop patient recruitment materials and website content, and obtain feedback on the design and usability of the registry database.

Two patient representatives also expressed further interest in reviewing the study protocol and were given an opportunity to review and provide feedback on the final draft.

The national data opt-out does not apply where explicit consent has been obtained from the patient for the specific purpose.

Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out.

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

NHS England will provide the relevant records from the datasets below to Imperial College London:

• NDRS Cancer Registration

• Linked Hospital Episode Statistics Admitted Patient Care (HES APC)

• Linked Hospital Episode Statistics Outpatients (HES OP)

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 (data sourced from local hospitals St Mark’s, Newcastle, Manchester & Birmingham).

The Data will not be transferred to any other location.

Imperial College London uses onsite back-up services provided by Imperial College London ICT.

The Data will be stored on servers at Imperial College London.

The Data will be accessed either onsite at the premises of the CSPRG, or by authorised personnel via remote access.

The Data will be accessed either onsite at the premises of the CSPRG, or by authorised personnel via remote access.

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

For remote access:

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

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

- Remote access is only via secure connections (secured via 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 Data will not leave England/Wales at any time.

Access is restricted to individuals within the CSPRG of Imperial College London who have authorisation from the Principal Investigator. All such individuals are either substantive employees of Imperial College London, or a PhD student with access restricted to a pseudonymised dataset. All personnel accessing the Data have been appropriately trained in data protection and confidentiality.

Institute of Cancer Research in London, Western General Hospital in Edinburgh, St Mark’s Hospital NHS Trust in London are not permitted to access the Data.

The Data will be linked at person record level with data such as demographics, baseline medical history, LS and cancer diagnosis data and surveillance history. This data has been sourced from local hospitals St Mark’s, Newcastle, Manchester & Birmingham.

The identifying details will be stored in a separate database to the linked dataset used for analysis. Researchers will not have access to the identifying details and all analyses will use the pseudonymised dataset.

Researchers from the Cancer Screening and Prevention Research Group at Imperial College London will process the Data for the purposes described above.

The Data will not be accessed by external researchers. However, requests to respond to queries based on the registry data will be considered. All responses provided will contain only anonymised aggregate data with small numbers suppressed. Such requests from commercial organisations may be considered. However, requests from commercial organisations are not something that has happened in the past and is not planned. There are no charges for production and release of aggregated data, although if the release required a significant amount of staff time to prepare then a contribution toward staff costs might be requested.

The expected outputs of the processing will be:

• A report of findings to Health Research Authority – Research Ethics Committees and the Trial Steering Committee, alongside annual scientific milestone reports to the funder, Cancer Research UK.

• Submissions to peer reviewed journals.

• Presentations at Annual Lynch Syndrome (LS) Conferences i.e.: the LS UK patient conference.

• A database to be utilised as a resource for health research.

The outputs will not contain NHS England Data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Workshops involving patients and the public.

• Webinars open to both patients and researchers

• Social media - X/Twitter: @CSPRG_Imperial; Facebook: @cancerscreeningandpreventionresearchgroup; Bluesky: @imperial-csprg.bsky.social and LinkedIn https://www.linkedin.com/company/csprg/

• Public events, including conferences and meetings such as the Lynch Syndrome UK national patient conference

• Posters displayed at conferences and meetings

• Patient Information leaflets available at

- The LS registry pilot website (https://lynchregistry.org.uk/) also provides study specific information and results for recruited participants and the general public.

- The CSPRG website https://csprg.org.uk/

- Imperial College London communications (various) – website news, internal faculty/department newsletters, Imperial partner communication channels (Imperial Biomedical Research Centre, Imperial NHS Trust)

The target date for outputs is Q4 2025/Q1 2026.

Results may also be presented to the research community and service providers via high-impact, peer reviewed journals and presented at national and international scientific and clinical meetings as appropriate. Furthermore, the CSPRG are collaborating with numerous leading experts across the country who are also involved in promoting the National LS Registry and Expert Network, as part of the National LS Transformation Programme.

The study investigators also plan to promote their research and share results to patient groups by attending annual LS patient information days and conferences, such as the LS UK patient conference. They will work together with several charities (see ‘Benefits’) and use their group website (csprg.org.uk) and social media channels (X/Twitter: @CSPRG_Imperial; Facebook: @cancerscreeningandpreventionresearchgroup; Bluesky: @imperial-csprg.bsky.social and LinkedIn) to raise awareness and to reach the wider LS community as well as other potentially interested audiences.

The LS registry pilot website (https://lynchregistry.org.uk/) also provides study specific information and results for recruited participants and the general public.

The use of the data could:

• Help the system to better understand the health and care needs of Lynch Syndrome patients.

• Advance understanding of regional and national trends in health and social care needs of LS patients.

• Advance understanding of the need for, or effectiveness of, preventative health and care measures for particular populations, in this case those diagnosed with Lynch Syndrome.

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

• Provide a mechanism for checking the quality of care. This could include identifying areas of good practice to learn from, or areas of poorer practice which need to be addressed.

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

This study funded by the charities 40tude and Cancer Research UK will help us to answer several important research questions around how LS patients are currently managed, which are expected to contribute to evidence-based decision-making for policymakers, local decision-makers (such as doctors), and patients, to improve care, treatment and the experience of healthcare users relevant to Lynch Syndrome.

The study database will also create a unique resource to conduct and support future research into LS and the associated risk of cancer, including Colorectal Cancer, endometrial and other LS-related cancers, which will help the healthcare system to better understand the health and care needs of LS patients and support further research. This currently includes a PhD project investigating patient views, experiences, and challenges of colonoscopy surveillance.

It is the study investigators intention that the registry pilot, and associated research results, will be used to inform and assist the national BCSP in their role managing LS surveillance and further development of a national LS registry. As discussed in ‘Outputs’, the study investigators plan to promote the research and share results to patient groups by attending annual LS patient information days and conferences, such as the LS UK patient conference. They have already engaged with several charities such as LSUK, 40tude, Cancer Research UK and Bowel Cancer UK and plan to use their group website, study website and social media channels to raise awareness and to reach the wider LS community as well as other potentially interested audiences.

Yielded Benefits is not a requirement for new applications.