Linking the National Registry of Rare Kidney Diseases with Hospital Episode Statistics for Research (Consent)

The Renal Association requires access to NHS England Data for the purpose of linking The National Registry of Rare Kidney Diseases (RaDaR) to address five research questions that it is hoped can benefit patient care for chronic kidney disease.

The UK Renal Registry (UKRR) is part of the Renal Association, a not-for-profit organisation registered with the Charity Commission (https://register-of-charities.charitycommission.gov.uk/charity-search/-/charity-details/800733). The UK Kidney Association was formed in 2021, an amalgamation of the Renal Association (RA) and the British Renal Society (BRS). The UK Kidney Association (trading name of the Renal Association) is the legal entity which owns and operates the two registries, the UK Renal Registry, and National Registry of Rare Kidney Diseases.

The Renal Association is the data controller of the UKRR database and was established in 1995 to improve the care of patients with kidney disease. The registry collects data from the United Kingdom’s 70 adult and 13 paediatric renal centres, as well as hospital laboratories in England.

The following research questions are:

1. Investigate risk factors (including the impact of renal treatment, morbidities and infections including COVID-19) for clinical outcomes of adults and children with rare kidney disease.

The UKRR’s study team (henceforth 'study team') comprises medical director, research director, clinical research fellows and statisticians. The linkage will enable the study team to better understand the reasons why some patients with kidney disease progress faster towards kidney failure and/or have worse clinical outcomes than others. This will help the study team to understand how risk factors could be managed to slow the progression of kidney disease and to have a targeted quality improvement approach to better patient outcomes. For patients with established kidney failure, understanding risk factors that can be modified will be valuable in ensuring they experience the best outcomes and quality of life.

2. Predict future outcomes for adults and children with rare kidney disease using novel statistical modelling methods on big datasets.

Modelling outcomes of kidney disease in various scenarios, e.g. different renal replacement therapy (RRT) modalities or for those with diabetes as a morbidity versus those without can help clinicians offer treatments to patients that might slow progression and/or improve their clinical outcomes. Understanding how morbidities change over time in the kidney patient population is vital for predicting future outcomes and care needs for kidney patients.

3. Understand trends and variations (geographical, socio-economic, ethnic, seasonal, time and by renal centre) in the care and outcomes of adults and children with rare kidney disease and changing underlying morbidities to identify health inequities.

Understanding variation in outcomes in relation to demographic and other factors can help to address inequalities in kidney care. Being able to add in the hospitalisation, length of stay and morbidities in future analyses of inequalities would help to further understand and quantify inequalities in access to care for kidney patients. Seasonality of AKI mortality in community and hospital acquired AKI and trends in excess mortality in patients starting RRT will be studied.

4. Estimate the cost of rare kidney diseases in adults and children, taking into account morbidities.

The burden of kidney disease in the UK is substantial and the cost of providing RRT, in particular, is high. The linkage will enable us to quantify this cost and the change over time, not only for England, but also by trust and kidney centre.

5. Validate measures of risk factors, outcomes and treatment modalities using different data sources for adults and children with rare kidney diseases.

Being able to validate RaDaR data using NHS England's HES and Civil Registration Mortality data, particularly cause of death and morbidities, which have long proved difficult to collect from renal centres, will allow the Renal Association to highlight issues with the data submitted to the UKRR. Research on data quality will help the Renal Association to understand which variables are best suited to address research questions 1-5.

Timely referral to kidney care is essential for planning and preparation of dialysis start or kidney transplantation. Validating and improving missing dates of referral using HES Outpatient appointment data will add greatly to the understanding of referral patterns in England.

The five research questions all relate to the same cohort, namely, all adults and children in England with a rare kidney disease, some of whom are on kidney replacement therapy and others who are not.

How decisions are made about projects and use of HES data and mortality data sets:

Researchers wishing to use RaDaR to investigate a specific rare disease are required to form a Rare Disease Group (RDG). The Rare Disease Committee (RDC) of the Renal Association will oversee the data application process managed by RaDaR staff members in line with RaDaR’s data sharing policy. The RDG Lead will be asked to sign and abide by a Standard Operating Policy, monitored by RDC RaDaR staff. The RDG will specify their required disease-specific data fields. Generic data fields are the responsibility of the Rare Disease Committee and will be designed and modified where necessary. The RDG will require separate research ethical committee approval to involve patients in any further research studies.

Researchers who are not part of a Rare Disease Group, including those from universities and commercial companies, can apply to the Renal Association via the data application process for off-line access to HES data aggregated with small numbers suppressed. Such applications must also be approved by the Lead Clinician of the relevant Rare Disease Group

RaDaR has a Data Release Group (DRG) tasked with reviewing applications from researchers wishing to use RaDaR data. Whilst these applications might include an interest in HES data, any analyses involving HES data will be conducted by statisticians employed directly by the Renal Association only.

To date, there have not been any requests for access for research which falls outside of these topics. Researchers with topics that falls within the questions listed in purpose section do not get access to the RaDaR-HES linked data, but RaDaR statisticians will perform the analysis and aggregated data summary results will be shared with researchers.

If research topics are outside of the research questions listed in the purpose section, the request for analysis would be declined by the DRG.

This request is covered across two DSAs to facilitate the mixed national data opt outs needed or the cohort involved:

> DARS-NIC-564296-L7V1M (this DSA): Covers consented cohort (opt outs not applied)

> DARS-NIC-787477-W3G5Z: Covers consultee cohort (opt outs applied)

The following NHS England Data will be accessed:

Hospital Episode Statistics (HES)

• Admitted Patient Care (APC), Outpatients (OP), Critical Care (CC), Accident and Emergency (A&E) and Emergency Care (ECDS)

– necessary to provide information on hospitalisations, critical and emergency care, around the time of diagnosis to understand the impact and progression of rare kidney diseases.

• Civil Registration Secondary Care Mortality –– necessary to understand survival and causes of death for people with rare kidney diseases.

The level of the Data will be:

• Identifiable – because the RaDaR hold the patient identifiers and the pseudonymised data separately, however, there is a means to re-identify patients. However, RaDaR will make no attempt to re-identify the patients,

The Data will be minimised as follows:

• Limited to a study cohort of approximately 36,000 participants identified by RaDaR, recruited from England, Wales, Scotland and Northern Ireland

• Limited to adults and children diagnosed with rare kidney disease.

• Limited to data from 1997 to latest available, with annual data releases.

• Limited to Data fields mapped to the specific research questions looking at evaluating for hospitalisations, outpatient appointments, death information and critical and emergency care.

If, upon turning 16, a participant does not wish to provide consent for continued participation in RaDaR, their records within RaDaR would be frozen, collecting no additional data about their kidneys or overall health; this would include not linking their records with any additional datasets, such as HES. The data already collected and held by RaDaR prior to consent being withdrawn would remain in the database and could be included in pseudonymised or anonymised analyses. Where a patient for whom data has already been linked with HES withdraws their consent, RaDaR will remove the linked data for said patient from their servers and from any future linkage cohorts.

Although recruitment to RaDaR started in 2010, the most people with rare kidney diseases were diagnosed much earlier and hospitalisation information from around time of diagnosis and after diagnosis is important to understand the impact and progression of the rare kidney diseases. This will give the Renal Association sufficient numbers/stability for the long-term survival estimates. Also, because of the rarity of the kidney diseases collected by RaDaR, there can often be a degree of uncertainty or noise in observations from one year to the next.

It is therefore useful to see trends over a long time (research question 3). The mortality rate for many of these rare kidney diseases is high or expected to be high compared to the general population, and this affects the certainty of estimates for long term survival further (a key metric for people with a rare kidney disease), which the study team need to understand outcomes in the oldest patients (research question 1, and to project future health needs – research question 2).

Historical data are needed to determine comorbidities and new (accrued) comorbidities over time as these have long term effects on outcomes for patients with rare kidney diseases.

The Renal Association is the Data Controller of RaDaR.

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

Article 6(1)(f) - processing is necessary for the purposes of the legitimate interests pursued by the controller or by a third party.

“The UK Renal Registry (UKRR) is part of the UKKA Association (UKKA) has determined the processing is necessary for its legitimate interests in being able to provide tools and services that will benefit healthcare organisations.” They will use the data to provide a high-quality clinical database for the treatment and care of renal diseases in the UK.

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.

There are no funders or commissioners involved in the research function of RaDaR at present.

Arrow Business Communications Limited trading as ARO provides IT hosting services to the Renal Association and will store the Data as contracted by the Renal Association.

The purpose and means for processing the data are determined by the Renal Association. The RaDaR accepts applications from employees of academic, clinical and commercial organisations. Researchers interested in aggregated RaDaR data apply to the RaDaR Data Analysis Group who will analyse the data on their behalf and share the aggregated results. The aggregated data that will be released will be only be linked to HES RaDaR data, and will not be to HES data alone.

Data will be accessed by The RaDaR research team which comprises of RaDaR chair, vice-chair, clinical research fellow, two statisticians, RaDaR manager and two data managers who work together to plan and conduct analyses, and write up the findings for publication in reports, medical journals and patient information, and for presentation at various national and international meetings.

All analysis will be performed by substantive employees of the Renal Association.

A Public and Patient Involvement and Engagement group helped refine the purpose of the research. However, RaDaR work closely with the Renal Association patient council to ensure that the research carried out falls within the reasonable expectations of patients and if the consensus is that the patient council are not comfortable, then the research will not be done. As part of the review process, it is a requirement for the applicant to have had PPIE input into their request.

RaDaR engages with its participants through multiple methods to inform them of what’s happening with their data and upcoming changes and plans. One way is through patient meetings; RaDaR has an annual user group meeting with presentation from patients and Rare Disease Groups. The Rare Disease Groups also have regular meetings including patients to get their input on matter related to research linked to their rare disease. Alongside these meetings we also keep the patient population informed through quarterly newsletters and regular updates to the Rare Renal website.

RaDaR will transfer data to NHS England. The data will consist of identifying details, NHS Number, Date of Birth and RaDaR Study ID, for the cohort to be linked with NHS England data.

NHS England will provide the relevant records from the HES, APC, CC, OP A&E, ECDS and mortality datasets to RaDaR.

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.

The Renal Association will extract a subset of the HES Data containing aggregated data and make this available to the researchers within the same organisation via the RaDaR Data Release Group (DRG).

The Data will be stored on The Renal Association’s server hosted at Arrow Business Communications Limited trading under brand name (ARO) and will not be combined with RaDaR data apart from for specific analyses.

The Renal Association uses offsite back-up services provided by North Bristol NHS Trust and Arrow Business Communications Limited (ARO).

In the event that Data will be accessed 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).

The data will not leave England/Wales at any time.

Employees of RaDaR are only permitted to access aggregated data including information derived from NHS England Data. Such datasets will adhere to the relevant small number suppression rules to minimise the risk of individuals being identified.

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

The Data will be linked with the RaDaR data for specific research analyses. Aside from that they will be kept separately from any other Renal Association held data.

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 RaDaR will analyse the Data for the purposes described above.

The expected outputs of the processing will be:

Planned analyses using HES data include (numbers in parentheses relate to the five research questions with subgroup analyses according to rare renal disease diagnosis:

– Long-term outcomes (rate of progression kidney disease, End Stage Kidney Disease and survival) of people with rare kidney diseases (1) and variation of this by time/centre (3)

– Impact of morbidity, treatments and infection on long term outcomes for each rare disease (1)

– Development of a prognostic model for predicting prognosis for patients with rare kidney diseases (2)

– Modelling of cause-specific hazards to estimate cumulative incidence functions (2)

– Trends in excess morbidity and mortality in patients diagnoses with rare kidney disease (3)

– Estimated cost of rare kidney disease care (4)

– Validation of dates of first referral to kidney care, reported comorbidities and treatments in RaDaR database (5).

From these analyses the study team will produce:

– Peer reviewed publications, as many as possible open access, information about which is available through the Renal Association’s website, renal.org/audit-research/publications-presentations. Potential journals include Nephrology Dialysis Transplantation and Kidney International.

– Presentations at meetings and conferences – examples at which the RaDaR research team regularly presents are:

o UK Kidney Week

o The British Renal Society's annual conference

o European Renal Association-European Dialysis and Transplant Association annual conference

o American Society of Nephrology annual conference

o British Transplant Society annual conference

o Webinars, e.g. renal.org/audit-research/publications-presentations/presentations

o Rare Disease Patient events

– Newsletters – the Renal Association produces monthly newsletters that are used to disseminate new analyses and publications to the UK’s renal community.

Only aggregate data will be published in research papers or other outputs, small numbers (cells equalling or fewer than 5) suppressed to reduce the risk of patient reidentification.

a) Dissemination of results/outputs

Working with the Renal Association’s communications officer, the RaDaR research team will strive to disseminate results of analyses as widely as possible, through the channels detailed below.

- clinicians, patients, commissioners, pharmaceutical industry to inform priorities for novel therapy development and clinical directors. Findings will be disseminated through the many channels already routinely used at the RaDaR by the research team

These channels are:

- Peer reviewed publications, as many as possible open access, information about which is available through the Renal Association’s website, renal.org/audit-research/publications-presentations. Potential journals include Nephrology Dialysis Transplantation and Kidney International.

– Reports e.g. renal.org/audit-research/publications-presentations/reports

– Website – www.ukkidney.org

– Social media (Twitter)

– Press releases

– Webinars, e.g. renal.org/audit-research/publications-presentations/presentations

– Newsletters – the Renal Association produces monthly newsletters that are used to disseminate new analyses and publications to the UK’s renal community.

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.

b) Communication of results/outputs

Two-way communication with key stakeholders takes place with clinicians and patients. Clinicians and researchers actively engage with the Renal Association on the research being conducted by RaDaR, and the RaDaR works closely with the renal community on several research ideas and projects. Communication channels that specifically target two-way communication are webinars and dedicated meetings with key stakeholders.

c) Exploitation of results/outputs

Whilst the study team strive to carry out research for these five questions, they are not yet at the stage where they can exploit findings and novel ways of analysis. Where an algorithm results from the work on research questions 2 or 5 that should be embedded in renal software systems, the study team will make this open access to achieve maximum benefit and quick implementation.

The Renal Association aim to start publishing some results of analyses within 12 months of receipt of HES data and mortality data, around March 2025.

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 proposed research questions focus on trying to: (i) improve the outcomes of people with rare kidney disease; (ii) predict outcomes (iii) reduce health inequalities related to rare kidney disease; (iv) quantify cost of care; and (v) improve the quality of the data the study group collect at RaDaR to enhance the audit function.

Dissemination of the results of analyses addressing these five questions and expected measurable benefits is key to improving the care of people with rare kidney disease. The RaDaR research team needs to reach key stakeholders to enable implementation of changes in care and patient management (or data management for question 5).

Below are examples of how research outputs it is hoped can benefit patient care for each of the five research questions:

1. Investigate risk factors (including the impact of renal treatment, morbidities and infections including COVID-19) for clinical outcomes of adults and children with rare kidney disease.

The analysis of clinical outcomes and impact of risk factors of patients with rare kidney disease and the resulting publication is anticipated to help both patients and healthcare providers understand natural history of rare kidney diseases. It is hoped this information will ensure rare kidney disease patients receive the most appropriate care and will also enable planning of services.

2. Predict future outcomes for adults and children with rare kidney disease using novel statistical modelling methods on big datasets.

The development of a prognostic model for people diagnosed with a rare kidney disease will hopefully inform patient choice, as well as policies related to patient choice, for example it may allow development of an algorithm to predict outcomes that is anticipated will be made available to physicians and patients.

3. Understand trends and variations (geographical, socio-economic, ethnic, seasonal, time and by renal centre) in the care and outcomes of adults and children with rare kidney disease and changing underlying morbidities to identify health inequities

Variation in outcomes of care means that there is a potential worst and best practice of care that should be investigated to inform uniformly better patient care. HES data are essential to this to adjust for case-mix. It is critical to improve health in equities in kidney care, particularly in underserved communities. Outputs in the form of papers and reports to commissioners highlighting these health care gaps are essential to change care processes.

4. Estimate the cost of rare kidney diseases in adults and children, taking into account morbidities. Understanding the financial impact rare renal disease care is anticipated to help the study team to quantify the burden rare diseases on renal and other health care services, so they care provide appropriate resource to optimise outcomes. Key outputs will be papers and a dedicated report to inform commissioners.

5. Validate measures of risk factors, outcomes and treatment modalities using different data sources for adults and children with rare kidney disease.

The validation of dates of first referral to kidney care is hoped to help determine if those who have delayed diagnosis of their rare disease or present late to kidney services have worse outcomes, which will be fed back to commissioners. It is expected to inform future data capture by RaDaR.

Yielded Benefits is not a requirement for new applications.