NHS Digital Data Release Register - reformatted

Renal Registry projects

3 data files in total were disseminated unsafely (information about files used safely is missing for TRE/"system access" projects).


Linking the UK Renal Registry and Hospital Episode Statistics for research — DARS-NIC-406158-Q2J0X

Opt outs honoured: Anonymised - ICO Code Compliant (Section 251 NHS Act 2006)

Legal basis: Health and Social Care Act 2012 - s261 - 'Other dissemination of information'

Purposes: No (Charity)

Sensitive: Sensitive, and Non-Sensitive

When:DSA runs 2022-05-19 — 2025-05-18

Access method: Ongoing

Data-controller type: THE RENAL ASSOCIATION

Sublicensing allowed: No

Datasets:

  1. Civil Registration (Deaths) - Secondary Care Cut
  2. Hospital Episode Statistics Admitted Patient Care
  3. Hospital Episode Statistics Critical Care
  4. Hospital Episode Statistics Outpatients

Objectives:

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 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 UKRR has a current agreement (DARS-NIC-94250-L8W8T) with NHS Digital for Hospital Episode Statistic (HES) and Civil Registration Mortality data which is for audit purposes to enhance benchmarking of renal centres against national audit standards. DARS-NIC-94250-L8W8T states: "Other agreements between the Renal Association and NHS Digital may permit re-use of this data for further purposes." This agreement (DARS-NIC-406158-Q2J0X) is being submitted separately for the purpose of research only. To strengthen the UKRR’s corresponding research programme, the UKRR is applying to link the UKRR database to HES and Civil Registration Mortality data released under DARS-NIC-94250-L8W8T for the research purposes detailed below, namely to:

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

The UKRR’s study team (henceforth 'study team') comprises approximately 15 people (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 kidney disease using novel statistical modelling methods on big datasets, including the impact of infections such as COVID-19 and changing underlying morbidities.

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 (HES morbidities data), 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 kidney disease, including the impact of infections such as COVID-19 and changing underlying morbidities.

Understanding variation in outcomes in relation to demographic and other factors can help to address inequalities in kidney care – see the recent report the UKRR jointly authored with Kidney Research UK – kidneyresearchuk.org/wp-content/uploads/2019/09/Health_Inequalities_lay_report_FINAL_WEB_20190311.pdf. 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) Use patient reported measures, such as patient activation (PAM), patient reported outcome (PROM) and patient reported experience (PREM), to understand the impact of kidney disease on adults and children, taking into account morbidities.

Kidney disease is not just about clinical outcomes – it is also about the wellbeing and quality of life experienced by people with kidney disease (World Health Organization www.who.int/healthinfo/survey/whoqol-qualityoflife/en/). The UKRR collects various PREM, PAM and PROM data about patients – renal.org/audit-research/data-permissions/data/ukrr-ckd-patient-measures-dataset, which the quality improvement arm of the Renal Association uses to work with renal centres to make changes that enhance the activation, outcomes and experiences of patients receiving treatment for kidney disease. PREM data is fully anonymised and cannot be linked. PAM and PROM data will be linked to the HES data. Using HES data, the study team will be able to better understand and describe the association between morbidities and their impact on patient reported measures and quality of life, which is very important to patients with kidney disease.

5) Quantify the financial cost to the healthcare system of kidney disease 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.

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

Being able to validate UKKR data using 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.

Having HES and Civil Registration Mortality data for the above 6 research questions would allow the study team to use powerful statistical methods and to generalise the findings.

The UKRR holds secondary use permissions under section 251 of the NHS Act (2006) for collecting patient data for audit and research purposes without consent and relies on the following legal bases for processing patient data for research purposes under the Regulation (EU) 2016/679 (General Data Protection Regulation as incorporated into UK law under the Data Protection Act 2018).

For processing of general categories of personal data, the UKRR relies on article 6(1)(f) legitimate interests. The UKRR processes data for the purposes of conducting and supporting high quality clinical research to improve the treatment and outcomes of people with kidney disease. Processing personal data is therefore necessary for UKRR's legitimate interests. The data to which access is requested are proportionate and necessary to achieve those interests. UKRR has completed a legitimate interests assessment (LIA) and is satisfied that the interests of the data subjects do not override UKRR’s legitimate interests; that they would reasonably expect the processing and it would not cause unjustified harm. The UKRR closely monitors potential threats to the data it processes and implements appropriate measures and safeguards to minimise the risks, including compliance with the National Data Guardian standards for the secure and appropriate use of patient health and social care information, and pseudonymisation or anonymisation of all patient data.

For processing of special category personal data, the UKRR relies on article 9(2)(j) archiving, research and statistics – processing for scientific research purposes in the public interest. For the purposes of the UKRR’s research function, the registry relies primarily on the ‘statistical analysis’ portion of the article, because the analysis of the data received from renal centres and hospital laboratories is a vital component of research studies. As per Part 1 of Schedule 1 of the Data Protection Act 2018, the processing is carried out in accordance with Article 89(1) of the UK GDPR and is in the public interest.

The linkage between the UKRR database and HES and Civil Registration Mortality data will strengthen the research analyses and will allow the study team to be able to conduct research at the UKRR to address the above-listed 6 questions, all of which rely crucially on information on morbidities and if/when patients were admitted to hospital.

The data linkage will help to:

– Identify underlying morbidities in patients (this is currently not possible because UKRR morbidity data are about 50% incomplete, with considerable variation between renal centres)
– Enable adjustment of case-mix when comparing clinical outcomes of patients
– Determine whether patients were admitted to hospital and why
– Enable hospital admissions and length of stay to be compared – time spent in hospital is a major concern for all patients with kidney disease and varies considerably between centres
– Factor in lateness of presentation with end-stage kidney disease (ESKD) requiring dialysis/kidney transplantation when comparing clinical outcomes of patients (this is currently not possible because UKRR presentation data are less than 80% complete, with again wide centre variation)
– Enable the reporting of cause of death, which is currently not completely returned by all centres
– Determine whether rates of acute kidney injury (AKI) (and harm associated with AKI) vary from hospital to hospital and, if so, whether this is explained by different rates of AKI and severity of AKI in the community versus in hospital
– Understand the quality and consistency of renal care given by morbidity profile of patients and to what extent some centres appear to avoid complications.
Participation of renal centres in England is mandated through NHS commissioning specialised services A06 Renal Services (www.england.nhs.uk/commissioning/spec-services/npc-crg/group-a/a06/). Participation of hospital laboratories is mandated by NHS England following a level 3 patient safety alert (www.england.nhs.uk/akiprogramme/aki-algorithm).

Initially, the UKRR only collected data on people receiving renal replacement therapy (RRT – dialysis (haemodialysis and peritoneal dialysis) or a kidney transplant), but in recent years data collection has been expanded to also include:

– all cases of acute kidney injury (AKI) in people in primary and secondary care in England from 2015 (following a level 3 patient safety alert issued by NHS England – see above). Approximately 550,000 cases are alerted per year.
– all cases of pre-dialysis chronic kidney disease (CKD – stages 4 to 5) in people in secondary care in England and Wales from 2016 (at the request of the National Clinical Reference Group). There were approximately 50,000 individual cases in total, from ~17 renal centres between 2016-2020.
Though the Renal Association approvals cover CKD stages 1-5, for the purpose of this linkage, only stages 4-5 are included.

The study team analyses the UKRR data for audit and research purposes (under separate Agreements) and publishes the results in various reports and medical journals – see renal.org/audit-research/annual-report and renal.org/audit-research/publications-presentations. Research at the UKRR relies on having good data on morbidity.

Since 2018 the UKRR has had permission to link the UKRR with HES and Civil Registration Mortality data for audit purposes. These data are used in the CKD annual report to adjust survival for case-mix to identify renal centres with significantly poorer patient survival – the most recent annual report was published in August 2021 (https://ukkidney.org/audit-research/annual-report/23rd-annual-report-data-31122019).

HES data were also recently used in the UKRR’s inaugural AKI report to identify which people with an AKI required hospital treatment and to investigate the degree of correlation between AKI coding in the UKRR database and AKI coding in HES. This report was published in July 2020 (renal.org/audit-research/publications-presentations/report/acute-kidney-injury-aki-england-report-nationwide). HES data was also used in the 'Getting It Right First Time' (GIRFT) report that described hospitalisation and length of stay for hospitalised patients with AKI (https://ukkidney.org/resource/renal-girft-national-report) .

Possessing HES and Civil Registration Mortality data for the above 6 research questions will enable the study team to generalise findings beyond individual renal centres, which has potential benefits for the thousands of people with kidney disease in England and further afield.

Aside from the audit work, having HES and Civil Registration Mortality data for research purposes will allow the study team to use powerful statistical methods and to generalise the findings. The key differences to the audit work are that these six research questions seek to generalise to other renal populations and investigate causal associations.

The six research questions detailed above all relate to the same cohort, namely, all adults and children in England with kidney disease (~2.5 million historic and new patients). HES and Civil Registration Mortality data are therefore requested for:

(i) Adults and children in England who are on RRT (kidney transplant or dialysis).
(ii) Adults and children in England with CKD (stages 1-5), including those with ESKD who do not receive RRT.
(iii) Adults and children in England with an AKI.

The UKRR is not permitted to hold individual data about people without kidney disease. Analyses are therefore designed to identify the risk factors associated with various outcomes for patients with kidney disease.

The purpose of the project is to conduct research only for the 6 research questions described above for the benefit of patients with kidney disease.

Data about all kidney patients in England is required, i.e. all adults and children with ESKD, CKD and AKI. These data will be linked to the UKRR database of kidney patients in England to strengthen research analyses.

The HES and civil registration datasets requested are:

– HES Admitted Patient Care, period 1997/98 to 2020/21 or most recent, with further annual data releases. The UKRR commenced collection of new patients starting RRT in 1997 and so to identify variation and improvement over time, data are requested from 1997 onwards.
– HES Critical Care, period 2014/15 to 2020/21 or most recent, with further annual data releases. The UKRR began collecting AKI data in 2015 and so the study team have only requested critical care data from 2015 onwards.
– HES Outpatients, period 2003/04 to 2020/21 or most recent, with further annual data releases. Outpatient episodes are only available from 2003.
– Civil Registration (Deaths) Secondary Care cut, annual data releases requested.

The research questions require a patient-level linkage so that the cohort of patients can be evaluated for hospitalisations, outpatient appointments, death information and critical care.

The UKRR started collecting data about people on RRT in 1997 and has therefore requested HES and Civil Registration Mortality data (where available) from this year onwards. This will give the UKRR sufficient numbers/stability for the long-term survival estimates. Historical data are needed to determine comorbidities and new (accrued) comorbidities over time as these have long term effects on outcome for patients with chronic kidney disease. Comorbidities over time is also required for the research question on risk prediction. Also, because ESKD is a relatively rare condition – about 100 new cases per million of the population each year start RRT – 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. Seasonality of AKI mortality in community and hospital acquired AKI and trends in excess mortality in patients starting RRT will be studied (research question 3). ESKD also has a high mortality rate, so few people will survive to 10 years, especially those on dialysis and those in the older age groups. This affects the certainty of estimates for long term survival further (a key metric for people with ESKD), which the study team need to understand outcomes in the oldest patients (research question 1, and to project future health needs – research question 2).


The UKRR collects data from every kidney centre in the UK and so collects data on 100% of people on RRT in the UK. This includes patients in the 50 adult and 10 paediatric renal centres in England. To enable the UKRR to include all English patients in analyses the UKRR are requesting HES and Civil Registration Mortality data for all kidney patients in England.


The UKRR can confirm that there is no alternative, less intrusive way of obtaining data for case-mix adjusted outcomes, e.g. cause of death, length of stay, hospitalisations, referral patterns, outpatient appointments and hospital acquired AKI. Despite many efforts at national meetings and correspondence with clinical directors and renal centres, the completeness of many data items submitted to the UKRR is not improving and in some instances is declining.

All data items requested in the UKRR-HES-Civil Registration Mortality linkage have been specifically chosen to answer the questions described above and the UKRR have not requested any data items which are not required. Over 20 years of data is requested because several renal conditions are rare and therefore many years of data are required to yield clinically meaningful results.


The organisations involved with the storage and management of the UKRR database are the Renal Association and North Bristol NHS Trust. Their roles are explained below.

The data controller of the UKRR database is the Renal Association (the legal entity under which the UKRR sits). The Renal Association is also the data processor for research, with its staff processing the data from collection, through validation, to analysis and publication. The Renal Association also engages North Bristol NHS Trust and AIMES as additional data processors for the purposes described in 'Processing Activities'.

The Renal Association has a Patient Council that meets every 2-3 months. The Patient Council propose research questions of interest to patients. The Renal Association research strategy is discussed with the Patient Council before it gets approved and implemented. The Patient Council annually reviews all patient information, such as the privacy notice, information on who the UK Renal Registry is, how patient data are used and information on patient opt-out. The Patient Council also reviews all submitted and approved data applications. Any substantial changes in data access procedures and data flows will be discussed by the Patient Council before a Confidentiality Advisory Group amendment is submitted. The UK Kidney Association are also developing a partnership with the ‘Kidney Patients Involvement Network’ that will give patients a further voice in what research to undertake. The UKRR are re-presented in joint annual patient meetings with NHS Blood and Transplant where research are discussed.

It is recognised that UK renal centres are the respective data controllers of the data submitted to the UKRR and that the renal IT system providers, who assist renal centres, are data processors on their behalf. The role of data controller for the respective patient care data sets is transferred from the renal centres to the Renal Association at the point of data submission.

Expected Benefits:

Kidney disease is common, affecting 1 in 8 people at some point in their life (kidneycareuk.org/about-kidney-health/conditions/ckd/). The research that the HES and Civil Registration Mortality data would make possible covers patients at all stages of kidney disease and so the outputs detailed below have the potential to positively benefit large numbers of people in England and, by extrapolation, even larger numbers further afield. The proposed research questions focus on trying to: (i) improve the outcomes of people with kidney disease; (ii) predict outcomes (iii) reduce health inequalities; (iv) improve patient experience; (v) quantify cost of treatments; and (vi) improve the quality of the data the study group collect at the UKRR to enhance the audit function.

In line with the UKRR's legitimate interest for processing the data, it is anticipated that the following groups might benefit from the processing:

1) Patients. All UKRR research in conducted with the goal of improving the quality of treatments, care and outcomes for patients. Using UKRR and NHS Digital data minimises the impact on patients because most of the research can be carried out without additional contact or additional appointments for patients, which is especially important for those on dialysis who already require regular visits to renal centres.

2) The NHS. Any major research finding should impact on the way on the way care is delivered, and therefore also benefits the NHS, and any health systems providing renal care to patients.

3) The UKRR directly benefits from the processing of patient data for research by allowing its staff, namely its employed statisticians and research fellows to carry out research projects using the data. Not only does this allow these individuals to utilise and improve upon their skillsets and publish works under their name, it also allows the UKRR to demonstrate the practical applications of the data it has collected, furthering its goal of improving the quality of care and outcomes of patients with kidney disease.

Dissemination of the results of analyses addressing these 6 questions is key to improving the care of people with kidney disease, because the study team need to reach key stakeholders to enable implementation of changes in care and patient management (or data management for question 6).
Below are examples of how research outputs are hoped can benefit patient care for each of the 6 research questions:

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

The specific analysis of long-term outcomes of COVID-19 survivors on RRT and the resulting publication it is anticipated will help both patients and healthcare providers understand the long-term consequences of this new disease, and it is hoped will ensure kidney patients receive the most appropriate care and will also enable planning of services.

2. Predict future outcomes for adults and children with kidney disease using novel statistical modelling methods on big datasets, including the impact of infections such as COVID-19 and changing underlying morbidities.

The development of a prognostic model for dialysis patients starting RRT will hopefully inform patient choice, as well as policies related to patient choice, for example it may allow development of an algorithm that is anticipated will be made available to physicians.

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 kidney disease, including the impact of infections such as COVID-19 and changing underlying morbidities.

Any trend and variation of care requires investigation with regards to potential inequalities that may need to be addressed. 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 casemix. Outputs in the form of papers and reports to commissioners are essential to change care processes.

4. Use patient reported measures, such as patient activation (PAM), patient reported outcome (PROM) and patient reported experience (PREM), to understand the impact of kidney disease on adults and children, taking into account morbidities.

HES morbidity data is expected to help the study team to understand the impact of a patient’s morbidities on their experience of kidney disease, something that up to now hasn’t been possible. Dissemination of these findings through papers, conferences, and dedicated webinars will hopefully inform quality improvement initiatives to help patients cope with their chronic medical condition.

5. Quantify the cost of kidney disease in adults and children, taking into account morbidities.

Understanding the financial impact of COVID-19 on kidney care is anticipated to help the study team to quantify the burden of the pandemic on renal services, so it is hoped that they can be better prepared for future such outbreaks. Key outputs will be papers and a dedicated report to inform commissioners.

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

The validation of dates of first referral to renal care is hoped to help determine if those who present late to renal services have worse outcomes, which will be fed back to commissioners. It is expected to inform future data capture by the UKRR. Also, a research paper is key because external researchers use a range of different data sources on renal care and the research will hopefully help them interpret the positive predictive value of a given variable.

Four members of the UKRR’s study team (statisticians and clinical fellows) are currently undertaking PhDs. The two statisticians are substantive employees of the Renal Association, and the two clinical fellows are on honorary contracts (their substantive employer is the University of Bristol). University of Bristol will ensure that both clinical fellows and their substantive employers sign the NHS Digital honorary contract that applies specifically to the use of NHS Digital data by a non-substantive employee of the Renal Association. In collaboration with senior members of the study team, the PhD students plan to conduct some analyses for their PhDs that include the HES data. All UKRR statisticians and clinical fellows who are undertaking PhDs have appropriate training in data security and information governance. The objectives of these PhDs are as follows:

1) Address the issue of missing data in the CKD and AKI datasets held by the registry in order to improve the quality of these data
2) Determinants of unplanned dialysis start
o Investigate the impact of AKI to unplanned dialysis start
o Examine the association between late referral and unplanned dialysis start in CKD and RRT cohort
o Examine the effect of multi-morbidity on dialysis start
3) Develop statistical methods to capture diverse health needs/treatment pathways

The PhD projects also explore and quantify the potential underestimation of coverage of the UKRR AKI Master Patient Index (MPI) dataset, to uncover the limitations in AKI algorithm, and the gap between the AKI algorithm and clinical assessment through the help of Hospital Episode Statistics (HES) data. Through multilevel modelling, with the help of geographical epidemiology, the PhD will use statistical techniques to quantify the missing data problems with the AKI-MPI, to get a better estimate of AKI rates in each area.

Linking the HES data with the AKI-MPI, it should be possible to compare the difference between hospitalised patients who also had AKI (N17) coded in the HES data and those who did not, to understand the clinical characteristics of the latter AKI patients in more depth. This will help to achieve a better understanding of the clinical diagnosis and AKI algorithm, which could potentially explain part of the variation in each area’s AKI rate.

AKI is a common and heterogeneous syndrome with a high short-term mortality rate. Improving the AKI-MPI will provide more confidence in the interpretation of area AKI rates. This will help identify areas that are outliers with the greatest need, for potential prevention interventions or quality of clinical care improvement. This facilitates prioritisation of resource allocation, to achieve positive impacts on patient outcomes.

Outputs:

The UKRR’s study team 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. The study team works closely with the Renal Association’s Patient Council, a group comprising approximately 15 people with kidney disease that meets four times per year with representatives of the UKRR (renal.org/patients/patient-council).

There is no lay person on the Data Release Group (DRG), however the outcomes of the DRG meeting (i.e. approved data releases) are included in the agenda of the Renal Association Patient Council for review. Patient Council is always scheduled a week or two after the DRG. This allows for lay review and feedback on proposed data releases.

Planned analyses using HES and Civil Registration Mortality data include (numbers in parentheses relate to the six research questions detailed in the ‘Objective for processing’ section):

– Impact of morbidity on type of care given around the time of dialysis start (1)
– Long-term outcomes of COVID-19 survivors on RRT (1) and variation of this by time/centre (3)
– Impact of morbidity on COVID-19 ethnic disparities in renal care (1) and variation of this by time/centre (3)
– Development of a prognostic model for dialysis patients starting RRT (2)
– Modelling of cause-specific hazards to estimate cumulative incidence functions (2)
– Seasonality of AKI mortality in community and hospital acquired AKI (3)
– Trends in excess mortality in patients starting RRT (3)
– Impact of morbidity on self-reported symptom clusters on RRT (4)
– Impact of COVID-19 on the cost of renal care (5)
– Validation of dates of first referral to renal care (6).

From these analyses the study team will produce:

– Reports e.g. renal.org/audit-research/publications-presentations/reports
– 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 UKRR study 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 Clinical directors’ annual forum.
– 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.

Only aggregate data will be published in research papers or other outputs, with small numbers suppressed.

a) Dissemination of results/outputs

Working with the Renal Association’s communications officer and the Renal Association’s Patient Council, the study team will strive to disseminate results of analyses containing HES and Civil Registration Mortality data as widely as possible. The audience is clinicians, patients, commissioners and clinical directors. Findings will be disseminated through the many channels already routinely used at the UKRR by the study team. These channels are those listed above (reports, publications, conferences etc) as well as:

– Patient Council – key analyses are discussed at quarterly meetings and participants are encouraged to distribute and promote findings through their local networks. The Patient Council also has close links with Kidney Care UK, with whom the Renal Association works closely
– Website – www.renal.org – the UKRR is one of the largest and longest standing registries in the world and so the website receives a lot of traffic, both nationally and internationally. The website was overhauled this year and relaunched in October 2020 and includes various sections aimed at health professionals, researchers, commissioners and patients
– Website – https://ukkidney.org/audit-research/projects/ukrr - projects that use UKRR data are published here
– Social media (Twitter)
– Press releases

By making the findings of the research accessible to as broad an audience as possible, the study team expect this will encourage further research and, if of benefit, changes to clinical guidelines.

b) Communication of results/outputs

Two-way communication with key stakeholders takes place with commissioners, clinicians and patients. The UKRR works closely with the Patient Council each year to produce, for example, patient summaries of the UKRR CKD annual report (https://ukkidney.org/audit-research/annual-report/23rd-annual-report-data-31122019) and an infographic summarising the impact of COVID-19 on patients on haemodialysis (renal.org/health-professionals/covid-19/covid-19-data). Patients influence the way dissemination of audit and research findings are achieved and also have the opportunity to highlight which research questions are of key importance to them.
Commissioners, clinicians and researchers actively engage with the Renal Association on the research being conducted at the UKRR, and the UKRR works closely with the renal community on a number of 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 6 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 6 that should be embedded in renal software systems, the study team will make these open access to achieve maximum benefit and quick implementation.

The Renal Association aim to start publishing results of analyses within 12 months of receipt of HES and Civil Registration Mortality data.

Processing:

All organisations party to this agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract ie: employees, agents and contractors of the Data Recipient who may have access to that data).

All relevant data flows for this Agreement occur under the UKRR's audit Agreement DARS-NIC-94250-L8W8T. The data flows are as follows:

- For linkage of the UKRR database with HES and Civil Registration Mortality data, personal identifiers for patients in the UKRR cohort of English kidney patients will be securely uploaded by the UKRR to NHS Digital’s Secure Electronic File Transfer (SEFT) data portal. Patient identifiers will be limited to date of birth and NHS number. The UKRR study ID will also be uploaded, but this is an anonymised study ID.

- Upon receipt of the UKRR patient identifiers, NHS Digital will send back to the UKRR the agreed clinical and mortality data with patient identifiers removed and the UKRR study ID attached. Identifiers will be stored separately from the pseudonymised data that is to be used under DARS-NIC-406158-Q2J0X, with access to identifiers limited to the UK Renal Registry Systems Team.

- An extract of linked data up to 2021/22 will be sent to the UKRR at the start of the Data Sharing Agreement (DARS-NIC-94250-L8W8T-v2). A further dissemination of linked HES/Civil Registration Mortality data from 2022 - 2024 will be sent to the UKRR on an annual basis.

The data is held on UKRR servers in two separate data centres. The data centres host the hardware and provide connectivity.

AIMES host the physical hardware in a Secure Datacentre. AIMES have ISO27001 certification (UK8000045), NHS Data Security and Protection Toolkit Compliance and are a G-Cloud Assured Supplier. The Virtual Machines are backed up to a backup server in a secondary location at the same address on a daily basis. These backups are encrypted with access to the keys limited to the UKRR Systems Team.

North Bristol Trust hosts the physical hardware in a purpose built secure data centre. The data centre is a controlled environment and access to the building is monitored and access to both the building and to the different security zones is logged. Physical access to this room is restricted by hospital security protocols to senior IT staff and substantive employees/ honorary contract holders from the Renal Association who are employed in the UKRR function. Any access to the servers is logged. The computer server has its own tape backup system, with the tape rotated on a daily basis by the hospital IT staff. These tapes are encrypted and stored along with the hospital system backups, in the hospital’s fire proof safe. Employees of North Bristol NHS Trust do not have access to the Renal Association’s server.

To achieve the purpose stated in the previous section (‘Objective for processing’), HES and Civil Registration Mortality data would be used to determine variables about patients known to the UKRR including:

– the presence of co-morbid conditions
– whether a patient was seen by kidney or other specialities prior to RRT or after sustaining an AKI episode
– the nature of outpatient care for people with CKD
– the number, duration and reason for hospital admissions
– whether an episode of AKI occurred before or during a hospital admission
– whether patients have had dialysis access surgery and interventions
– whether patients have had other relevant surgery, such as cardiac and orthopaedic surgery and interventions
– the number and outcome of pregnancies.

The UKRR has requested over 20 years of data to monitor trends over long periods of time, with the two most important being:

– care and outcomes of patients incident to RRT, i.e. people starting dialysis or receiving a first kidney transplant in England, and those already on RRT
– survival of new and existing patients on RRT.

HES and Civil Registration Mortality data will only be linked with UKRR-held data for specific research analyses. (The UKRR annually collects patient outcomes and experience measures (PREM, PAM and PROM data) for the kidney patients for whom the UKRR hold data. PAM and PROM data forms part of the renal dataset that will be linked to the HES and Civil Registration Mortality data.) Aside from that HES and Civil Registration Mortality data will be kept separately from any other UKRR-held data.

The UKRR’s legal basis for research allows routine linkage, not only with NHS Digital, but also with NHS Blood and Transplant (NHSBT) and UK Health Security Agency (UKHSA) for the UKRR to receive a small number of data items:

(i) NHSBT to ensure the UKRR is aware of and able to monitor the outcomes of all patients in the UK who have a kidney transplant or who are wait-listed for a kidney transplant. In a reciprocal and documented arrangement, NHSBT and the UKRR share a small number of data items.
(ii) UKHSA to enable the UKRR to monitor levels of the following infections and bacteraemias in kidney patients in England: E. coli, MRSA, MSSA, C. difficile and COVID-19. In a documented arrangement, the UKRR sends personal identifiers (as agreed in the data sharing agreement) for people on its database to UKHSA and they return the bacteraemia and infections data to the UKRR.

In order to effectively analyse e.g. kidney transplant patients or RRT patients highly susceptible to infections, HES and Civil Registration Mortality data may not only be linked with English data collected by the UKRR, but also with UKRR-held data provided by NHSBT and UKHSA. Some patients who are very sick and on dialysis are not placed on the waiting list for transplantation. When looking at whether infections in transplant patients are primarily driven by immunosuppression (in contrast to the cause of increased susceptibility for dialysis patients), those on the waiting list and then transplanted could be compared with those too sick to be eligible.

Being UK-wide, the UKRR also holds data about kidney patients who are treated in renal centres in Northern Ireland, Scotland and Wales. The Renal Association confirm that these data will be kept entirely separate from HES and Civil Registration Mortality data.

Statisticians and researchers conducting analyses will only have access to pseudonymised data.

Any analyses that plan to include HES and Civil Registration Mortality data must go through the UKRR’s Health Research Authority Confidentiality Advisory Group approved data use process, which is documented on the Renal Association website (renal.org/audit-research/how-access-data/ukrr-data/apply-access-ukrr-data). All research must fall within the scope of the six research questions stated in this Agreement.

In brief:

(i) For each analysis, the UKRR research fellow or statistician must submit an expression of interest (EoI) to the UKRR’s Data Release Group (DRG). The DRG is chaired by the UK Kidney Association's (UKKA) Medical Director. Membership of the DRG includes the UKKA’s director of informatics research, the data protection officer and senior members of the statistical team, the IT team, the finance team and the research team, as well as representatives from the British Association for Paediatric Nephrology (BAPN).
(ii) If the EoI is approved by the DRG the applicant will be invited to submit a full application form and data protection impact assessment (DPIA) at least four weeks prior to the next quarterly DRG meeting.
(iii) At the DRG, the group collectively completes an assessment form, one section of which is dedicated to assessing the risk of re-identification – low, medium or high. Any analysis judged to have a high risk of reidentification is referred to the Health Research Authority Confidentiality Advisory Group for them to decide how to progress. For applications rated low or medium, feedback is provided by the DRG to applicants to ensure the risk of identification is as low as possible. Risk of re-identification is based primarily upon the potential of small numbers in outputs, or if the cohort is from a particularly small or specialised population.

First and foremost, the Renal Association does not want to reidentify patients. All data available for analysis are pseudonymised and only aggregate data are published in research papers or other outputs, with small numbers suppressed. These approaches and processes ensure that the inadvertent risk of reidentification of patients is extremely low. Any Data Sharing Agreements put in place between the Renal Association and a data recipient subsequent to an EoI will state that no attempt should be made to re-identify or contact patients.

Only substantive employees of the Renal Association working within the UKRR or employees from other organisations who have an honorary contract with the Renal Association and a specific clause in their contract with their substantive employer will have access to these data for processing. There will be no subsequent flows of HES and Civil Registration Mortality data.

The HES and Civil Registration Mortality data will not be matched to publicly available data.

There will be no requirement or attempt to re-identify individuals from UKRR-held data.

All employees of the Renal Association complete annual training about the fundamentals of information governance by completing the Data Security Awareness level one module on the Health Education England training platform. Any non-substantive Renal Association employees will be required to complete at least this level of training prior to accessing any HES and Civil Registration Mortality data.

Only members of the Renal Association’s statistics team will have access to the pseudonymised HES and Civil Registration Mortality data for linkage with other UKRR data for analyses. They use a secure working environment. No data are ever stored on desktops or laptops. With the current working from home arrangements, members of the statistics team use a virtual private network (VPN) via a North Bristol Trust laptop to access data on the Renal Association server. The statistics programme sits on their desktop in the Renal Association office. All processing occurs by remote signing on to the desktop. Access to folders is restricted to those members of staff who will do the statistical analysis using the HES and Civil Registration Mortality data. All staff have unique logon details to their laptop and desktop and laptops are encrypted. Those with honorary contracts will be able to access a subset of record-level HES/mortality data. Those on honorary contracts are expected to respect the terms of access they sign.

The Renal Association’s data protection officer works closely with the Renal Association’s researchers and statisticians to ensure that data are analysed and published appropriately.

There will be no data linkage undertaken with NHS Digital data provided under this agreement that is not already noted in the agreement.


Commissioning through Evaluation (CtE) Rituximab for Idiopathic Membranous Nephropathy (IMN) — DARS-NIC-386376-Z1H5J

Opt outs honoured: Anonymised - ICO Code Compliant, No (Consent (Reasonable Expectation))

Legal basis: Health and Social Care Act 2012 – s261(2)(c)

Purposes: No (Charity)

Sensitive: Sensitive, and Non-Sensitive

When:DSA runs 2021-09-20 — 2024-09-19 2022.02 — 2022.02.

Access method: One-Off

Data-controller type: NHS ENGLAND (QUARRY HOUSE), THE RENAL ASSOCIATION

Sublicensing allowed: No

Datasets:

  1. Civil Registration (Deaths) - Secondary Care Cut
  2. Emergency Care Data Set (ECDS)
  3. HES:Civil Registration (Deaths) bridge
  4. Hospital Episode Statistics Accident and Emergency
  5. Hospital Episode Statistics Admitted Patient Care
  6. Hospital Episode Statistics Critical Care
  7. Hospital Episode Statistics Outpatients

Objectives:

The Commissioning through Evaluation (CtE) programme ‘Rituximab for the treatment of idiopathic membranous nephropathy (IMN) in adults’ has been commissioned to help NHS England (NHSE) decide whether to routinely commission rituximab and its biosimilars for the treatment of IMN. Currently in the UK, rituximab is only prescribed for IMN patients for whom all other options of immunosuppressive treatment have failed, or there is a contraindication for prescribing them.

Membranous nephropathy (MN) occurs when the small blood vessels in the kidney, which filter wastes from the blood, become damaged and thickened, this causes proteins to leak from the damaged blood vessels into the urine. MN has been identified as a leading cause of nephrotic syndrome (NS) in adults, these are a group of symptoms that signify that the kidneys are not functioning properly. If an underlying cause is not identified, the disorder is termed idiopathic (a term used for diseases with an unknown cause). The traditional treatment of MN has been shown to increase rates of remission from the disease and slow kidney function loss in patients with persistent NS. However, the side effects, which include increased risk of cancer, are severe. Data from clinical trials on the effectiveness of rituximab for patients with IMN is so far limited, although several trials are currently underway (GEMRITUX, MENTOR and STARMEN), with some promising initial results.

- Gemritux: High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy | American Society of Nephrology (asnjournals.org)
- Mentor: A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR) - PubMed (nih.gov)
- Starmen: The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy - Kidney International (kidney-international.org)

Clinical outcome data for the IMN patients recruited to the rituximab CtE programme will be collected by the Renal Association through its National Registry of Rare Kidney Diseases (RaDaR). RaDaR is an initiative designed to pull together information from patients with certain rare kidney diseases to develop a better understanding of how these illnesses affect people and to support research into these diseases. RaDaR is operated and governed by the Renal Association, a not for profit organisation registered with the Charity Commission as a membership organisation for healthcare professionals caring for people with kidney disease.

All analyses and the evaluation report will be undertaken by the King’s Technology Evaluation Centre (KiTEC), a NICE external assessment centre (EAC) based at King’s College London.

The Renal Association is applying for Hospital Episode Statistics (HES), ECDS Data (an extension of HES Accident and Emergency Data) and Civil Registration data (hereafter, for ease, collectively referred to as HES/ECDS/CRD) to enable KiTEC to answer the following 4 questions so that NHSE can make its commissioning decision:

1. How often is re-treatment with rituximab and its biosimilars necessary for people with IMN to maintain partial or complete remission and what is the timing of the treatment, when needed?
2. Does treatment of people with IMN with rituximab and its biosimilars for the clinical indication covered by the CtE rituximab protocol result in fewer hospitalisations in comparison with best supportive care?
3. Does the use of rituximab and its biosimilars for people with IMN for the clinical indication covered by the CtE rituximab protocol present different safety issues from their established uses?
4. What is the actual cost and relative cost effectiveness of treatment of people with IMN with rituximab and its biosimilars for the clinical indication covered by the CtE rituximab protocol?

For processing of general categories of personal data, the CtE rituximab programme relies on article 6(1)(f) legitimate interests – the legitimate interests of the rare kidney health and social care services in England to provide high standards of care to patients with IMN. Some patients with IMN are not suitable or do not respond to conventional treatments. In the UK, rituximab is not currently licensed for use for people with IMN. If the CtE programme for rituximab can provide evidence of the effectiveness of rituximab and its biosimilars and that it’s safe to use, NHS England may routinely fund rituximab for patients with IMN. This will open up another treatment against IMN, which would be especially important for those people with IMN who do not respond well to currently available treatments.

For processing of special category personal data, the CtE rituximab programme relies on article 9(2)(j) archiving, research, and statistics – processing for scientific evaluation purposes in the public interest. For the purposes of the evaluation function, CtE rituximab relies primarily on the ‘statistical analysis’ portion of the article, because the analysis of the data received from RaDaR is a vital component of the project.

Only aggregate data will be published in the evaluation report and other outputs, with small numbers (cells equalling or less than 5) suppressed where it has been formally assessed by the data processors that the potential risk of re-identification of patients outweighs the potential benefits of publishing the information. This means that there are no moral or ethical issues involved with publishing these data. The risk of harm to the public by the dissemination is negligible. There has been recent research indicating the relationship of rituximab to adverse outcomes in COVID-19 and reduced vaccine efficacy.

Linking the CtE rituximab data to HES/ECDS/CRD data will enable KiTEC to answer the following 4 evaluation questions on behalf of NICE and NHSE:
1. How often is re-treatment with rituximab and its biosimilars necessary for people with IMN to maintain partial or complete remission and what is the timing of the treatment, when needed? – Linkage with HES Outpatients for appointment dates, diagnosis, main speciality etc. is needed to answer this question.
2. Does treatment of people with IMN with rituximab and its biosimilars for the clinical indication covered by the CtE rituximab protocol result in fewer hospitalisations in comparison with best supportive care? – Hospitalisations will be accessed through linkage with HES APC and AE / ECDS datasets.
3. Does the use of rituximab and its biosimilars for people with IMN for the clinical indication covered by the CtE rituximab protocol present different safety issues from their established uses? – Linkage of the Civil Registration data for date and cause of death will assist in providing answers to this question.
4. What is the actual cost and relative cost effectiveness of treatment of people with IMN with rituximab and its biosimilars for the clinical indication covered by the CtE rituximab protocol? – Answering this question requires linkage with HES OP/AE/APC and ACC and ECDS datasets.

The CtE programme was launched in September 2013 and provides funding for a limited number of patients to access medical treatments and technologies not routinely commissioned within the NHS (National Health Service England 2014). Rituximab is one such treatment and the programme spans 2018-2021.

The data for patients recruited to the rituximab CtE programme are collected in the Renal Association’s RaDaR database (until 2021). These data, plus the HES/ECDS/CRD data, will be shared with KiTEC who will link the datasets and then conduct the analyses and write the evaluation report, which will assist NHSE in making its commissioning decision.

The number of patients receiving rituximab as part of the CtE programme was fixed and dependent on the funding available from NHSE.
A total of 52 sites were selected by NHSE to provide rituximab treatment and 190 patients with IMN were recruited to participate in the CtE. All 190 patients were recruited in 39 kidney centres across all regions in England.
The 190 people participating in the rituximab CtE programme are all adults, who are eligible to receive rituximab for the treatment of their IMN at one of the 52 participating kidney centres in England. They have either native or transplanted kidneys.
All consented for their data to be entered onto the CtE register within RaDaR for inclusion in the analyses and evaluation report.

The purpose of the linkage with RaDaR is to enable KiTEC to answer the 4 evaluation questions so that NHSE can decide whether rituximab and its biosimilars should be routinely prescribed to people with IMN.

Data about the patients treated with rituximab in the CtE programme is required, i.e. the 190 adult patients with IMN in England recruited at one of the 52 participating kidney centres in England.

The datasets and data items requested are aligned with the CtE programme's aims and evaluation questions. Recruiting for CtE rituximab patients started in 2018 and finished in 2019, allowing up to 2 years of follow-up (to 2021). The date of IMN diagnosis varies between patients and obtaining hospital information prior to recruitment to the programme is very important to understand hospitalisations and outpatient appointments prior to inclusion in the programme.

• HES Admitted Patient Care, period 2016/17-2020/21. Hospitalisation data will be used to answer the questions about (1) whether treatment with rituximab results in fewer hospitalisations compared with best supportive care (question 2) and (2) actual and relative cost effectiveness of treatment with rituximab (question 4).

• HES Critical Care, period 2016/17-2020/21. Data will be used to answer the question about actual and relative cost effectiveness of treatment with rituximab (question 4).

• HES Outpatients, period 2016/17-2020/21. Outpatient appointments will be used to answer the questions about (1) re-treatment to maintain partial or complete remission and the timing when needed (question 1) and (2) actual and relative cost effectiveness of treatment with rituximab (question 4).

• HES Accident & Emergency Care/ECDS data, period 2016/17-2020/21. Data will also be used to answer the questions about (1) whether treatment with rituximab results in fewer hospitalisations compared with best supportive care (question 2) and (2) actual and relative cost effectiveness of treatment with rituximab (question 4).

• Civil Registration (Deaths) Secondary Care Cut. Data will be used to answer the question about whether rituximab presents different safety issues from its established uses

The HES/ECDS/CRD linkage is required at a patient level so that the cohort of patients can be evaluated for hospitalisations, outpatient appointments, accident & emergencies, death information and critical care.
Patient identifiers that will be shared with NHS Digital for linkage are NHS number, date of birth, sex and postcode. Data returned to the Renal Association from HES/ECDS/CRD will be pseudonymised and will include a HES ID and a study ID.

Recruiting for the CtE rituximab programme started in 2018 and finished in 2019. Patients will be followed-up for up to 2 years. The date of IMN diagnosis varies between patients and getting hospital information prior to recruitment to the CtE rituximab programme that started in 2018 is very important to understand hospitalisations and outpatient appointments prior to recruitment. Data are therefore requested from 2016/17 to 2020/21.

NHS England wants to prospectively evaluate the efficacy of Rituximab in patients with idiopathic membranous nephropathy across renal units nationally, therefore all 52 kidney centres in England were invited by NHS England to take part and recruit patients for the CtE Rituximab programme. 190 patients were recruited in 39 kidney centres across all regions in England.

The CtE rituximab data collection through RaDaR is the most efficient, least intrusive, and most cost-effective way of collecting the data. A linkage with HES/ECDS/CRD is necessary to answer the four evaluation questions because centres recruiting patients are unable to provide the required detailed hospital and death information. Obtaining these data through HES/ECDS/CRD is the least intrusive way to achieve the aims of the CtE rituximab programme.

The cohort of 190 patients recruited for the CtE Rituximab programme will be linked to the HES/ECDS/CRD data. There were strict clinical criteria for patients to be recruited to the CtE and the cohort of 190 recruited patients is from a wide range of age groups. Recruitment for the CtE started in September 2018 and HES data are only requested for 2 years before recruitment to capture prior hospitalisations and relapses to the most recent data at time of linkage.

All data items requested in the HES/ECDS/CRD linkage have been specifically chosen to answer the four evaluation questions described above. The Renal Association have not requested any data items that is not needed. Only pseudonymised Civil registration data relating to the 190 patients has been requested. The fields selected from the Civil Registrations datasets have been limited to only the fields required to meet the objectives of this research such as date of death, place of death, cause of death etc.

The organisations involved with the management and storage of the RaDaR and HES/ECDS/CRD data are the Renal Association, AIMES Management Services and the King’s Technology Evaluation Centre (KiTEC). KiTEC is a collaboration between several King’s College London departments and the Medical Physics Department of Guy’s and St Thomas’ NHS Foundation Trust (GSTT). Their roles are explained below:

RaDaR falls under the Renal Association. Data are processed by the Renal Association and KiTEC. The CtE rituximab data are collected in RaDaR and these data are stored on servers at AIMES Management Services (see processing activities below for the detail). The HES/ECDS/CRD data will also be stored on the Renal Association server at AIMES Management Services prior to secure sharing with KiTEC.

Pseudonymised RaDaR and HES/ECDS/CRD data will be shared securely with KiTEC and the data will be stored on servers at King’s College London. Once transferred, the HES/ECDS/CRD data will be deleted from the Renal Association’s server.

The Renal Association (the legal entity under which RaDaR sits) is the data controller for the RaDaR database and the CtE rituximab data collection. There are 2 processors for the CtE rituximab data collection: RaDaR that falls under the Renal Association and KiTEC. The Renal Association and KiTEC are both data processors for the HES/ECDS/CRD data.

The CtE rituximab programme data will be collected by RaDaR (IMN is one of the rare kidney diseases on RaDaR). Once follow-up is completed, the RaDaR data will be pseudonymised and shared securely with KiTEC. The HES/ECDS/CRD data will also be shared securely with KiTEC. KiTEC will link the 2 datasets and will then be responsible for the analysis and publication of results.

The RaDaR CtE rituximab data are stored on the Renal Association’s server at AIMES Management Services. The HES/ECDS/CRD data will be also be stored at AIMES, albeit on a temporary basis – once they have been sent securely to KiTEC for statistical analysis and evaluation, the HES/ECDS/CRD data will be deleted from AIMES.

The data will not be shared with any other organisation not named in this agreement and the linked RaDaR-HES/ECDS/CRD dataset will not leave the secure servers at KiTEC. Only substantive employees of both organisations (Renal Association and KiTEC) will have access to the data.

The HES/ECDS/CRD data will be stored temporarily at AIMES Management Services until they are sent securely to KiTEC. They will then be deleted and held solely by KiTEC.
CtE rituximab is commissioned by NICE to support NHSE in its CtE programme and summary results will be shared with NHSE and NICE.

The CtE rituximab programme is funded by NHS England and they are a joint data controller but will not process the data. Kidney centres in England were invited by NHSE to participate in the CtE rituximab programme. Those centres that contracted with NHSE to participate in the CtE are funded by NHSE to recruit patients, administer rituximab and provide data of a high completeness and quality to the RaDaR CtE rituximab group. NHSE also provides the funding to RaDaR for the administration of the RaDaR CtE rituximab data. NHSE and commissioners funded this work with the aim of prospectively evaluating the clinical effectiveness of rituximab and its biosimilars in patients with idiopathic membranous nephropathy across kidney units nationally and to assist NHSE in making its commissioning decisions.

Expected Benefits:

Membranous nephritis remains a leading cause of nephrotic syndrome in adults. About one quarter of cases are felt to be secondary to a pre-disposing disease, an infection, or medical therapy. In most other cases, an underlying reason for the lesion is idiopathic (IMN). There are established treatments for IMN. However, none are completely effective, and all have side-effects, some severe, such as increased risk of cancer. Recently, rituximab has surfaced as a potential treatment option for IMN. There is some emerging evidence showing there may be benefit in the use of rituximab for the treatment of IMN. However, there is currently insufficient evidence for NHSE to commission the treatment for the NHS. The key objective of KiTEC is to analyse clinical outcomes data related with rituximab treatment for patients participating to the CtE. It is hoped that this analysis will provide results regarding the clinical effectiveness of rituximab (as well as other outcomes of interest), which will assist NHSE in making its commissioning decision.

NHS England/NICE: It is hoped that the outputs from the rituximab CtE will help NHS England make future commissioning decisions for IMN care and rituximab treatment for IMN across the country and for NICE to consider guidelines for IMN treatment with rituximab.

Some patients with IMN are not suitable or do not respond to conventional treatments. In the UK, rituximab is not currently licensed for use for people with IMN. If the CtE programme for rituximab can provide evidence of the effectiveness of rituximab and its biosimilars and that it’s safe to use, NHS England may routinely fund rituximab for patients with IMN. It is hoped that this will open up another treatment against IMN, which would be especially important for those people with IMN who do not respond well to currently available treatments. It is hoped that by adding another treatment option (rituximab) for IMN would help to improve quality of life or life expectancy of those patients.

This is a prospective multi-centre national database (register) project to obtain the evidence related to rituximab that will address the gap in evidence. Outputs to be produced from the HES/ECDS and mortality linked data are to assist NHSE to evaluate the clinical effectiveness and safety of rituximab treatment and to assist NHSE in making a commissioning decision about rituximab treatment. Ultimately, the research aims to be instructive for clinicians treating IMN patients. The research may also help NICE to consider guidelines for IMN treatment and rituximab. Should the evaluation of rituximab show evidence of benefit to patients, making rituximab available earlier on in the treatment pathway will benefit patient outcome and health. The results of the final analysis are due to be reported and sent to NICE by February 2022.

Outputs:

Outputs to be produced from the HES and mortality linked data are a report to assist NHSE in evaluating the clinical effectiveness and safety of rituximab treatment for IMN patients. This will enable them to make a commissioning decision about rituximab treatment. This report will be made publicly available by NHSE (via their website) originally for public consultation and comments and afterwards as the final policy.

NICE will also use the findings to consider guidelines for IMN treatment and rituximab. NICE will evaluate the summary report produced by KiTEC to consider guidelines for IMN treatment and Rituximab'.

Other outputs are the submission of the summary results to a peer reviewed journal. An academic paper will be published in an open-access high impact nephrology journal on the methodology, analyses and results, including the impact of rituximab on the induction of remission (partial or complete) of nephrotic syndrome and on the decline of kidney function.

KiTEC intends to publish before the end of 2022. They do not plan to publish interim results.
For each paper published, a short presentation will be developed to summarise the findings for a range of stakeholders, including health technology assessment practitioners. Findings may be presented at relevant conferences such as the HTAi Annual Meeting. The KiTEC website will provide links to our open access papers and summaries of findings. Publications will also be listed on individuals’ King’s College London Pure pages.

All outputs will be at the aggregate level with small numbers (cells equalling or less than 5) suppressed. All reports to NHSE will be summary data and NHSE will not receive any patient level data from HES or RaDaR.

There is no scope to exploit the results and outputs beyond what has been described above as the purpose of this project does not result in further intellectual property development.

Processing:

All organisations party to this agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by "Personnel" (as defined within the Data Sharing Framework Contract i.e.: employees, agents and contractors of the Data Recipient who may have access to that data).

To enable linkage of the CtE rituximab patients from RaDaR with HES/ECDS/CRD, personal identifiers for patients in the CtE programme (English kidney patients with IMN) will be securely uploaded by RaDaR to NHS Digital’s Secure Electronic File Transfer (SEFT) data portal. Patient identifiers will be limited to date of birth, NHS number, sex and postcode. The CtE study ID will also be uploaded, but this is an anonymised study ID.

Upon receipt of the CtE rituximab programme patient identifiers, NHS Digital will send back to the Renal Association the agreed clinical and mortality data with patient identifiers removed and the CtE study ID included. The clinical data refers to the ‘Admitted Patient Care (APC)’, ‘Outpatient’, ‘Critical Care’ and ‘AE/ECDS datasets and mortality data to the NHS Digital ‘Civil Registration (deaths)’ dataset, all to be linked by NHS Digital to the cohort of 190 CtE rituximab patients.

Data for the CtE rituximab programme that are collected by RaDaR include demographic data, comorbidities, information about the IMN diagnosis and treatment, blood test results and adverse events. From this database, RaDaR will extract the NHS-number, date of birth, gender, postcode and study-id (anonymous number) for the cohort of 190 recruited patients to upload to NHS Digital’s SEFT platform for linkage. The HES/ECDS/CRD data to be downloaded from SEFT will be for the cohort of 190 patients matched with the requested HES/ECDS/CRD datasets and the CtE study-id, no other patient identifiers.

The HES/ECDS/CRD data downloaded from SEFT by RaDaR will be stored securely on the Renal Association’s servers in the data centre at Aimes Management Services and HES/ECDS/CRD data will be securely transferred (using a secure file exchange platform) to KiTEC. Once KiTEC received the data from RaDaR and proceeded with the analysis, RaDaR will securely delete the HES/ECDS/CRD data from their server. There will be no onward flow of the HES/ECDS/CRD data from RaDaR to any other organisations. RaDaR will share the CtE rituximab RaDaR collected clinical data with KiTEC: all patient identifiers will be removed and the study id included. KiTEC will analyse the HES/ECDS/CRD data and will link it via the study-id with the clinical data collected and shared with them by RaDaR for the CtE rituximab programme. KiTEC will store the HES/ECDS/CRD data securely on King’s College London servers. There will be no onward flow of the HES/ECDS/CRD data from KiTEC to any other organisations.

As detailed above, the Renal Association will upload patient identifiers for those patients in the CtE rituximab programme (NHS number, date of birth, sex, postcode, study id) to NHS Digital. NHS Digital will return clinical information about each patient – the data will be pseudonymised with the study-id included.

The HES/ECDS/CRD data will be stored on the Renal Association’s server at the AIMES Management Services data centre. AIMES Management Services will process the data for backup and storage functions only.

The HES/ECDS/CRD data will then be securely transferred from the Renal Association to KiTEC for analysis. KiTEC will only receive pseudonymised data and all data received will be stored securely. Data will only be accessed by individuals within KiTEC who have authorisation to access the data for the purpose(s) described, all of whom are substantive employees of KiTEC within King’s College London. No HES/ECDS/CRD linked CtE rituximab data will leave the KiTEC servers. All analyses using the HES/ECDS/CRD data will be performed by substantive employees of KiTEC. The NHS Digital data will leave the RA servers when RaDaR securely shares the pseudonymised CtE-HES linked data with KiTEC who will perform the analyses and write the evaluation report

Patients were recruited for the CtE rituximab programme at English hospitals and registered on the RaDaR database by research nurses. Recruitment of CtE rituximab patients has been completed. Hospitals update the information on RaDaR for CtE rituximab with follow-up data. Substantive Renal Association employees validate the data and provide recruiting hospitals with regular reports on quality and completeness of the data at baseline and during follow-up visits. Once follow-up visits are completed and all data collected (estimated May 2021), the database will be closed.

The Renal Association will share RaDaR and HES/ECDS/CRD data with KiTEC who will analyse and produce summary results (aggregated) for the evaluation report which they will share with NHSE and NICE. They will also publish the results in a peer reviewed journal. All results will be checked for any risk for re-identification by ensuring that small numbers rules are adhered to and categories used for reporting don't pose a risk of re-identification of individuals.

To achieve the purpose stated in the previous section (‘Objective for processing’), HES, ECDS and Civil Registration data would be used by KiTEC for patients recruited to the CtE rituximab programme:
• HES Outpatients for appointment dates, diagnosis, main speciality etc. is needed to determine if retreatment is necessary to maintain partial or complete remission and what the timing is of that treatment when needed.
• HES APC and A&E and ECDS datasets will be used to assess if treatment with rituximab results in fewer hospitalisations in comparison with best supportive care.
• Civil Registration data for date and cause of death will be used to provide answers to the question of safety issues around rituximab.
• HES Outpatient, A&E, APC, CC and ECDS datasets will be used to determine the actual and relative cost effectiveness of the rituximab treatment.

The above analyses will be performed only by KiTEC.

Data collected by the Renal Association’s RaDaR for the CtE rituximab programme will be shared with KiTEC. Prior to sharing, the data will be pseudonymised with all patient identifiers removed.

KiTEC will link the CtE rituximab programme clinical data from RaDaR with the HES matched data to be able to answer the questions as detailed above.

Access to patient identifiers is limited to Renal Association staff working directly with the CtE rituximab programme, all of whom are substantive employees of the Renal Association and have been appropriately trained in data protection and confidentiality. KiTEC employees who will analyse the linked data will only have access to pseudonymised data with the study-id. The CtE rituximab programme clinical data from RaDaR will be shared with KiTEC, but this is also pseudonymised data with the study-id and no other patient identifiers.

NHS Digital data will never leave the servers of the Renal Association in the data centre at Aimes Management Services or KiTEC and will only be used in analyses conducted by substantive employees of KiTEC.

First and foremost, the Renal Association and KiTEC do not want to reidentify patients. All data available for analysis by KiTEC are pseudonymised. Results of the analysis by KiTEC will be in the form of aggregated outputs and will be completely anonymised, to be published in academic paper(s) in an open access journal, with small numbers suppressed in line with the HES Analysis Guide. Record level HES and Civil Registration Mortality data will not be released to any external organisation not listed in this application. These approaches and processes ensure that the inadvertent risk of reidentification of patients is extremely low. NHSE will not receive any patient level or any HES/ECDS/CRD data and only summary results in the final report from KiTEC will be shared with them.

The HES, ECDS, and Civil Registration Mortality data will not be matched to publicly available data.

There will be no requirement or attempt to re-identify individuals from HES/ECDS/CRD held data by employees of the Renal Association or KiTEC. The data from NHS Digital will not be used for any other purpose other than that outlined in this agreement.

Record level HES/ECDS mortality data will not be released to any external organisation not mentioned in this agreement.

Only substantive employees of the Renal Association working within RaDaR and who have been appropriately trained in data protection and confidentiality, have access to the data for processing. All analyses involving HES/mortality data will be undertaken by substantive employees of KiTEC who are appropriately trained in data protection and confidentiality.
Both organisations have completed and met the required standards of the Data Security and Protection Toolkit, including staff training.

All data processing will be carried out by substantive employees of KiTEC and RaDaR. All analyses involving HES, ECDS and Civil Registration Mortality data will only be undertaken by substantive employees of KiTEC.

All employees of the Renal Association and KiTEC complete annual training in data protection and confidentiality.

The HES/ECDS/CRD data will be stored on the Renal Association’s server at AIMES Management Servers in a protected folder on the server with the password known only to the Renal Association’s systems administrator.

KiTEC substantive employees will have access to the pseudonymised HES/ECDS/CRD data for analyses. They use a secure working environment. No data are ever stored on desktops or laptops. With the current working from home arrangements, members of the KiTEC team will use a virtual private network (VPN) to access the data on the King’s College London servers for processing. Access to folders is restricted to those members of staff who will do the statistical analysis using the data. All staff have unique log-on details to their laptop and desktop and laptops are encrypted.

All organisations where data is stored are named in the agreement and detailed as above.

The HES/ECDS/CRD data will be stored on the Renal Association’s server at the AIMES Management Services data centre. AIMES Management Services host the physical hardware in a Secure Data centre and provide connectivity. AIMES have ISO27001 certification (UK8000045), NHS IG Data Security and Protection Toolkit Compliance and are a G-Cloud Assured Supplier. The Virtual Machines are backed up to a backup server in a secondary location at the same address on a daily basis. These backups are encrypted with access to the keys limited to the Renal Association’s Systems Team. AIMES Management Services will process the data for backup and storage functions only.

The HES/ECDS/CRD data will also be securely transferred to KiTEC for analysis. KiTEC will only receive pseudonymised data and all data received will be stored securely. All university computers where data will be stored are password protected. The areas where the computers are located have restricted ID protected access. Data will only be accessed by individuals within KiTEC who have authorisation to access the data for the purpose(s) described, all of whom are substantive employees of KiTEC within King’s College London. No HES/ECDS/CRD linked CtE rituximab data will leave the KiTEC servers. All analyses using the data will be performed by substantive employees of KiTEC. NHSE will not receive any patient level or any HES/ECDS/CRD data and only summary results in the final report from KiTEC will be shared with them.