Childhood Arthritis Prospective Study (CAPS): NHS data linkage

The University of Manchester requires access to NHS England data for the purpose of the following research project:

Childhood Arthritis Prospective Study (CAPS): NHS data linkage

The following is a summary of the aims of the research project provided by The University of Manchester:

The Childhood Arthritis Prospective Study (CAPS) is an inception cohort of children and young people with juvenile idiopathic arthritis (JIA), established in the early 2000’s. The overall aim is to identify the predictors of outcome, both short- and long-term, following presentation with childhood onset inflammatory arthritis and to identify the relative contributions of socio-demographic, clinical, psychological, laboratory and genetic factors and treatment in explaining outcome.

The data collected in this national cohort study contains invaluable information on what happens to children and young people from the moment they are diagnosed with JIA.

This study will also provide unique opportunities to identify previously unidentified genes that are important in JIA outcome. This long term prospective study would provide current and reliable information on short and long-term outcome for children with JIA in terms of:

a) physical damage

b) disability/function

c) quality of life

d) Psychological impact on child/family-disease triangle

d) drug response/drug toxicity.

In 2019, due to end of funding, CAPS stopped registering new patients and stopped collecting follow-up forms. However, as, CAPS is an invaluable source of data from the point of JIA diagnosis over time, there is a need to request further data. As currently, lack of information on what happens to children with JIA as they become adults is a major source of anxiety for patients and their families.

The Data will be used to address the following research questions:

1) Do children continue to have arthritis as adults?

2) How many JIA adults visit healthcare professionals for mental health?

3) Does chronic arthritis influence whether JIA adults can have children?

4) How often do complications of JIA (including but not limited to uveitis, joint replacements, infections, malignancy, early death), occur in adulthood?

Answering these questions is essential for young adults with JIA, and their parents, as there is a need for more information on what to expect for the future.

Through linking CAPS with NHS datasets, additional outcomes in these individuals could be analysed, not just in childhood but to establish what happens to these children as they become adults with JIA. With these answers and establishing high-quality up-to-date important information, the CAPS Study wishes to educate patients and families on what to expect, empowering them to make informed decisions regarding their own disease management, and plan for their future without fear.

The following NHS England Data will be accessed:

- Hospital Episode Statistics (HES)

o Admitted Patient Care (APC)

o Accident & Emergency (A&E)

o Critical Care (CC)

o Outpatients (OP)

- Emergency Care Data Set (ECDS)

- Maternity Services Data Sets (MSDS) v1.5 and v2

- Mental Health Services Data Set (MHSDS)

- Civil Registration Mortality

- Cancer Registration

HES Data sets are necessary to evaluate:

- How many children with JIA continued to have arthritis as adults. Subsequently, clinicians could give more accurate information to those newly diagnosed on how likely they are to still have disease.

- How life-long arthritis many impact adults with JIA on quality of life and day-to-day function, therefore, better resources could be put in place to support individuals throughout the course of their lives. Alongside charities, provisions could be put in place to help young adults manage in higher education, potentially living away from their support network, and in their future careers.

- How often do complications of JIA occur compared with young people without JIA, including infection, eye inflammation, orthopaedic procedures, cancer and early death. Therefore, clinicians could make more educated plans (alongside patients) regarding how long to stay on treatment and any risks. Resources could be implemented to help prevent potential vision loss or prepare for future joint replacements, and any screening necessary for potential risk of cancers, to best support an adult with chronic childhood arthritis.

• Maternity Services Data Set – necessary to evaluate if JIA influences whether they can have children. Therefore, the CAPS Study could provide resources to the fertility team on how best to support these adults in planning a family.

• Mental Health Services Data Set – necessary to evaluate many adults with JIA are using mental health services. Therefore, the CAPS Study team could explore (with young people) which interventions might help them.

• Civil Registration Mortality – necessary to maintain mortality outcomes for long term follow up.

• Cancer Registration – necessary for identification of any cancer diagnosis.

The level of the Data will be:

• Identifiable – Identifiable Date of Birth of Baby in HES APC is being requested alongside, Person Date of Death, so that birthing outcomes in these patients can be investigated.

For clarity the data will only be identifiable in a scenario where the mother has had a baby. Returns for all other members of the cohort would be STUDY ID with pseudonymised data.

In the future, there may be a future consideration to re-instating the project and by updating the clinical data with the NHS England data the CAPS Study would not wish to contact parents regarding their deceased child.

The Data will be minimised as follows:

• Limited to a study cohort of ~1800 patients who originally consented to the CAPS Study at The University of Manchester.

• Limited to data between 2000/2001 (where available) - 2024/2025 annual data to cover JIA diagnosis and patient outcomes, from birth to current day will be provided. This will ensure that all data for patients is captured from their date of JIA diagnosis onwards.

The University of Manchester 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 is provided by Versus Arthritis. The funding is specifically for the study described. The funding is in place until 30th January 2030.

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

The University of Manchester store Data in the Data Safe Haven.

Data will be accessed by:

• The CAPS study team and PhD Students enrolled with University of Manchester. The individuals have completed mandatory data protection and confidentiality training and is subject to the University of Manchester's policies on data protection and confidentiality.

The individuals accessing the data will do so under the supervision of a substantive employee of the University of Manchester. The University of Manchester would be responsible and liable for any work carried out by the individual. The PhD students would only work on the data for the purposes described in this Data Sharing Agreement (DSA).

A Public and Patient Involvement and Engagement group helped refine the purpose of the research. The group strongly supported the collection of the data for the purposes described above.

In the original study NHS patients, families and charities were consulted about the CAPS Study, as follows:

Design of the research:

During the preparation of the application for funding to link CAPS with NHS datasets, adults with childhood-onset arthritis, parents, and charities were approached for their views. Focus groups were held with patients and parents to understand their core research priorities and how we could use this data to achieve them.

CAPS have also received views from 61 adults with JIA via an anonymous survey regarding the use of confidential patient information as per this project requests. When looking at whether participants would be happy for the research team to continue to access NHS records after the age of 16 years old without asking for explicit consent from participants (relying solely on original parental / guardian consent), the majority responded that they would be happy with this, with over a quarter of those assuming that the linkage was already continuing into adulthood. Results of this survey will be published for public viewing.

In addition to three personal letters from adults with JIA, we have received a joint letter of support from four national charities on behalf of the thousands of patients and family members that they support.

Management of the research and Analysis of Results:

Throughout analysis of this linked data, patients will continue to be involved. For the long-term outcomes in adults with JIA, there are multiple patient partners involved that will aid the management and interpretation of research. Patient and parent groups will also be included for views on and interpretation of research findings.

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

NHS England will provide the relevant records from the HES, CC, APC, A&E, ECDS. OP, MSDS and MHSDS, Cancer Registration and Mortality datasets to the University of Manchester.

The Data will:

• contain directly identifying data items including Baby's Date of Birth and Date of Death, which is required to complement the MSDS data extract, so that birthing outcomes in these patients can be investigated. In addition to Study ID.

The Data will not be transferred to any other location.

The Data will be stored on servers at University of Manchester in the Data Safe Haven (DSH).

UOM DSH uses offsite back-up services provided two Data Centres provided by UOM, managed by Equinix and Ascendas Riat.

The Data will be accessed by authorised personnel onsite at the University of Manchester and via remote access.

The Controller 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 is restricted to employees and PhD students of Manchester University who have authorisation from Chief Investigator are only permitted to access pseudonymised data only.

All patient identifying information is stored on a separate database linked to unique identifying number. Access to the database is restricted only to the study coordinator and Chief Investigator (both employees of the University of Manchester).

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

The Data will be linked at person record level with CAPS Study data. Data within the Data Safe Haven is pseudonymised (linked to the CAPS study patient identified).

However, for any patients for which a death is recorded in the Death Register, the derived date of death (month-year) will be extracted and entered into primary study database to ensure that future analyses of CAPS patients are applicable to those who are alive. Access to identifiable data is restricted only to the study coordinator and Chief Investigator (both employees of the University of Manchester).

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.

All students and researchers analysing data have no access to personal identifiable information.

Researchers from the University of Manchester will analyse the Data for the purposes described above.

The expected outputs of the processing will be:

· Presentations at least one conference abstract presentation at a national or international rheumatology conference, such as the British Society for Rheumatology (BSR) or the European Alliance of Associations for Rheumatology (EULAR) annual conferences.

· Conferences: such as the British Paediatric Rheumatology Research Meeting, or the UK Research in Musculoskeletal Epidemiology (UK-RiME).

· Journals: peer-review rheumatology journals, such as the Lancet Rheumatology, Annals of the Rheumatic Diseases, Rheumatology, or other equivalent journal.

Outputs from this study has already been published in high-impact journals, the full list which can be found here: http://www.caps-jia.org.uk/publications

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 dissemination plan for each research project will be developed alongside the patient partners and will be unique to each topic depending on how best to circulate the results to those living with the condition. Options include adding publication details, lay summary and infographic to the CAPS website, sharing with charity partners to distribute to their networks via emails and on their website, and sharing on social media. Once the publication has been accepted by a journal, the dissemination plan for that project will commence.

Each research question will be addressed separately with individual timelines and deadlines for each (to be confirmed). However, the current funding for this research is available until the end of January 2030 for which all these research questions are hoped to be answered and published on.

Currently, the specific research questions that are in plan include:

(1) Identify the impact of JIA on mental health in adulthood:

To address important questions for young adults regarding mental health, his analysis will estimate the proportion of adults with JIA who are visiting health care professionals for their (severe) mental health problems. It will use the health records of individuals who are in contact with mental health services via the mental health services dataset (MHSDS), as well as HES hospital admissions and outpatient visits (appointments: “child and adolescent psychiatry”, “psychotherapy”, “adult mental illness”), and events reported by clinicians directly to CAPS. Expected dates: analysis start September 2025, completion date December 2026.

(2) Mortality rates in people with JIA:

Using the death register, in addition to any deaths already reported to CAPS, this analysis will calculate the mortality rate of individuals diagnosed with JIA, and using the ONS mortality rates, identified whether those with JIA have an increased mortality rate compared with what you would expect given their age and gender, and whether there are certain patients that are at increased risk, i.e. those with systemic JIA. Expected dates: analysis start September 2025, completion date December 2026.

(3) Rates of malignancies in people with JIA:

Using the cancer register data, in addition to any malignancies already reported to CAPS, this analysis will calculate the rate of malignancies in individuals diagnosed with JIA, particularly looking at how risk of malignancy changes from diagnosis onwards. Expected dates: analysis start January 2026, completion date April 2027.

(4) Calculate the proportion of people with JIA that continue to access care during adulthood:

Using the NHS England Hospital Episode Statistics (HES), patients with CAPS who continue to visit Rheumatology and/or Ophthalmology outpatient clinics will be identified. This marker of attendance of appointments will provide a surrogate for ongoing disease in adulthood that requires continued outpatient care with a consultation. This will include those who continue to have active disease or who may be in remission but require ongoing therapy, monitoring, or assessment. Expected dates: analysis start June 2026, completion date September 2027.

(5) Rates of hospitalised infections in people diagnosed with JIA:

Using the HES primary diagnosis data from the A&E, admitted patient, and critical care datasets, patients who experience hospitalised infections will be identified and rates of infection calculated. Expected dates: analysis start January 2027, completion date January 2029.

(6) Pregnancy outcomes in people with JIA:

To provide valuable information to patients concerned about family planning, this analysis will use HES primary diagnosis codes and the maternity services dataset (MSDS) to estimate how many adults with JIA have had a pregnancy, to identify their birth outcomes, and potential impact of JIA treatment on pregnancy. Expected date: analysis start January 2028, completion date January 2030.

(7) Identify whether people with JIA are experiencing orthopaedic interventions:

Using procedure codes and primary diagnosis codes from all HES datasets, individuals who undergo orthopaedic interventions (i.e. joint replacement) will be identified. Expected dates: analysis start June 2028, completion date September 2029.

(8) How does uveitis affect individuals with JIA:

Using the HES data for Ophthalmology appointments, and primary diagnoses, in addition to data already reported to CAPS, the rate of uveitis in JIA will be calculated and those particularly at risk identified. In addition, to understand the impact of uveitis into adulthood, outcomes such as blindness will be identified. Expected dates: analysis start September 2028, completion date January 2030.

The findings of this research study are expected to contribute to evidence-based decision-making for policy-makers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of health care users relevant to the subject matter of the study.

The use of the data could:

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

• advance understanding of the need for, or effectiveness of, preventative health and care measures for particular populations or conditions such as Childhood Arthritis.

• 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).

The data obtained by linking with NHS datasets will be used to enrich the data that is already collected by the CAPS Study.

BENEFITS TO PATIENTS

Over 1,500 participants have been recruited to the study, already providing invaluable information from the point of diagnosis with JIA. With many of the CAPS participants now adults, it is fundamentally important to patients and families that researchers use all the data available to them to provide information on outcomes in these participants.

Without this linkage, our research and knowledge will stop at the age of 16 years old, just when young people are starting to build their own lives and when such information will be critical to them. This means that compared with research in people who have their disease onset in adulthood – where long-term data capture can continue indefinitely through data linkage agreed in the initial study consent – in the absence of this linkage, research into paediatric onset diseases are unfairly penalised.

PUBLIC BENEFITS

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

Yielded Benefits is not a requirement for new applications.