Follow-up of participants in the After Diagnosis Diabetes Research Support System-2 (ADDRESS-2) Cohort

Imperial College London requires access to NHS England data for the purpose of the following research project: Follow-up of participants in the After Diagnosis Diabetes Research Support System-2 (ADDRESS-2) Cohort

The following is a summary of the aims of the research project provided by Imperial College London: ADDRESS-2 started to recruit in 2011 as a second phase of the After Diabetes Diagnosis REsearch Support System. The aims were to maximise the opportunities for people newly with type 1 diabetes to get involved in research, both through recruitment to trials and deep characterisation at the point of diagnosis. Participants were recruited primarily through secondary care centres and provided informed consent to be contacted for research opportunities, to provide information to characterise the early stages of type 1 diabetes as part of the study and for additional information on their diabetes to be collected from NHS data for inclusion in the study.

The following NHS England Data will be accessed:

• Hospital Episode Statistics Admitted Patient Care (HES APC) – necessary to provide data on the number of admissions post diagnosis for diabetic ketoacidosis, other diabetes associated conditions and social deprivation status (based on area).

• Demographics – necessary for their registration status in the NHS, taken from the personal demographics service and to provide fact and date of death, where applicable, to minimise the risk of attempting to contact deceased participants.

• National Diabetes Audit (NDA) – necessary for follow-up diabetes status to be collected.

• Mental Health Services Data Set (MHSDS) and Improving Access to Psychological Therapies (IAPT) v2 – necessary because while the NDA has the remit of auditing care for diabetes, there are only clearly understood markers for physical health monitored in clinics. In this dataset, the mental health issues connected to living with type one diabetes are monitored only via referrals and a flag for the presence of SMI, as well as by proxy through medications. The MHSDS and IAPT linkage would cover data on mental health conditions developed by participants and enable elucidation of the impact of type 1 diabetes on these. Their linkage to ADDRESS-2 is as part of the data on ‘long term health status’ which was consented to by all participants.

The request for MHDS and IAPT datasets is to explore hypothesis around the long-term impact of chronic health conditions like T1D on patient’s long-term health. The ADDRESS-2 team would want to look at the relationship between psychological complications and diabetes management, or lack thereof, and its subsequent impact to the development of diabetes complications.

The level of the Data will be identifiable which is necessary to link to consented participants.

The Data will be minimised as follows:

• Limited to a study cohort identified by Imperial College London based on consent materials.

• Limited to a cohort of 9,936 participants, including all participants that were adults at consent, paediatric participants still <16 years old and those paediatric participants that reconsented at 16 years old,

• Limited to data between date of when consent is signed and latest available.

• Limited to the following geographic areas: England,

• Limited to conditions relevant to the study identified by specific ICD or OPCS 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 data linkage of the ADDRESS-2 cohort, which is the largest combined adult and paediatric cohort of incident type 1 diabetes in the UK with almost 10,0000 participants, uniquely enables ADDRESS-2 team to answer questions around the progression of T1D and its complications for the UK populations. These participants have all consented to their data being linked to datasets held by NHSE for the follow-up of their long-term health status. With such a large and uniquely places cohort of participants this cohort will be able to identify the range of risk factors that affect the trajectory of diabetes outcomes and adverse events. These findings could have the potential to inform preventative interventions and help us tackle the onset and progression of T1D. In addition, the linkage of data in both children and adult onset may enable ADDRESS-2 team to understand the differences in disease progression across all ages. Most of the current research has been conducted in only children or only adults; however, the ADDRESS-2 team are distinctly placed to explore both within the ADDRESS-2 cohort and therefore further hypothesis differences in the aetiopathogenesis of T1D between children and adults, which could have impacts on both the treatment and management of T1D.

The funding is provided by Diabetes UK. The funding is specifically for the study described. Funding is in place until 30 April 2025, to be extended via a no cost extension to 31 March 2026. Funding to continue the work described will be sought on an ongoing basis.

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

The ADDRESS-2 management committee includes numerous senior type 1 diabetes specialists from other organisations that are acting in an advisory role for the correct and continued use of the ADDRESS-2 samples and data. The specialists will not be able to access the data.

Data will be accessed by Undergraduate, Masters or PhD students enrolled with Imperial College London. Any student working with the Data held under this Data Sharing Agreement (DSA) must have completed relevant data protection and confidentiality training and are subject to Imperial College London’s policies on data protection and confidentiality. Any students 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 students. These students would only work on the Data for the purposes described in this DSA.

ADDRESS-2 has a Patient Advocate Group (PAG) who have been involved and informed of ADDRESS-2 activities and discussions around the paediatric reconsent and the use of the ADDRESS-2 data to be linked to NHSE datasets. They have been very supportive of the objectives outlined and have not raised any substantiative concerns.

Imperial College London will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number, Date of Birth, Gender, date of recruitment and a unique CSRE Database ID) for the cohort to be linked with NHS England data.

NHS England will provide the relevant records from the HES APC, NDA, Demographics, MHSDS and IAPT v2 datasets to Imperial College London. The Data will contain directly identifying data items including Names, NHS Number, Date of Birth, Address and Postcode which are required to link the Data at record level with data already held by the recipient.

The Data will not be transferred to any other location.

The Data will be stored on servers at Imperial College London Certified Secure Research Environment (CSRE).

Virtus Secure Data Centres Limited host the Imperial College London data servers. Virtus Secure Data Centres Limited is not permitted to access the Data.

The Data will be accessed 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 (e.g., VPNs or secure protocols) to protect data;

- Multifactor authentication (MFA) is required for remote access;

- Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access;

- All remote access is undertaken within the scope of the organisation’s DSPT (or other security arrangements as per this DSA) and complies with the organisation’s remote access policy.

The above applies in addition to any condition set out elsewhere within the DSA (e.g. who may carry out processing, and for what purpose).

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

Access to confidential patient identifiable data is restricted to substantive employees of Imperial College London, who are part of the ADDRESS-2 Central Team.

Substantive employees and/or students of Imperial College London are permitted to access pseudonymised data only who have authorisation from ADDRESS-2’s Data Manager.

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

The Data will be linked to the pseudonymised ADDRESS-2 dataset held by Imperial College London.

The identifying details will be stored in a separate database to the linked dataset used for analysis. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset.

Researchers from Imperial College London will process the Data for the purposes described above.

The expected outputs of the processing will be:

• Submissions to peer reviewed journals at the end of the study,

• Presentations at Diabetes UK, the European Association for the Study of Diabetes and the American Diabetes Association

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

• Website updates

ADDRESS-2 remains open to recruitment until April 2025, with applications underway to extend this. Informative analysis could begin as soon as linkage was complete with a data cut from April 2024 which is currently being cleaned and prepared. Thereafter, an annual data clean would be carried out and uploaded to the CSRE through which pseudonymised linkage will take place. Imperial College London would expect that results could be complete and published within 24 months of linkage.

The impact that longitudinal studies of type 1 diabetes and its complications can have on health care was demonstrated by the Diabetes Control and Complications Trial, and linkage between ADDRESS-2’s database and the proposed NHS England datasets would enable a similar analysis of how a wide range of factors which can be measured at diagnosis similarly impact on similar outcomes. The depth of characterisation at diagnosis in ADDRESS-2 has already been used to look for links in the early stages after diagnosis with type 1 diabetes, and linking this to routinely collected clinical data would allow us to do the same with longer term trajectories of type 1 diabetes outcomes. This should allow new risk factors and potential intervention targets to be identified: candidate measurements for better-focused risk assessments and preventive measures which could either become the subject of future dedicated trials or implemented directly in care.

Messaging in plain English and ongoing public involvement previously referenced will also produce public perception of measures which could reduce long-term morbidities for people living with type 1 diabetes, with potential advantages to their individual wellbeing as well as reduced public health expenditure. The team will develop the health promotion messages generated by the planned analyses and who to target them with experts by experience and public health experts, and monitor their success.

Updated contact details meanwhile will assist ADDRESS-2 in supporting recruitment to other studies of type 1 diabetes in the UK, as well as the development of strategies and approaches to increase access to research the study team are planning. This data would boost the cohort’s value in supporting studies of prevalent diabetes by ensuring that any invitations to take part in type 1 diabetes research, which have been consented to and requested by ADDRESS-2’s participants, are received. It would also ensure that any current paediatric participants can be effectively contacted to reconsent at the age of 16.

Expected benefits will be achieved primarily by dissemination of the findings in scientific journals, which will be read and acted upon by the wider healthcare and research community, according to the results of the analysis. Diabetes and its complications are among the most common causes of long-term morbidity, with type 1 diabetes spending accounting for £1.8 billion in 2012 and the cost of treating complications 3-4 times higher than routine type 1 diabetes care. This shows that there is huge potential for impact on health care, which could start to be seen within ten years.

The ADDRESS-2 has a study website that is well maintained, and the website is updated to include the publications of any scientific papers. The ADDRESS-2 study team have also historically, released participant newsletters to inform them of current T1D research and of any study specific activities. It is hoped that with the personal demographic dataset linkage, and the subsequent updated contact details for the participants the ADDRESS-2 team will be able to continue to provide them with a more engaged update around research and layman. The ADDRESS-2 team have also worked with Diabetes UK, the funder, to publicise opportunities to take part in research and the results of such studies. This linkage being complete is also a key milestone in our current grant which means they have kept aware of progress and want be involved in sharing results emerging from the work.

Yielded Benefits is not a requirement for new applications.