NHS Digital Data Release Register - reformatted

University Of Edinburgh projects

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


R5 - MR1109 - UK Biobank — DARS-NIC-08472-V9S6K

Opt outs honoured: No - consent provided by participants of research study, No - data flow is not identifiable, Identifiable, No (Consent (Reasonable Expectation))

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC, Health and Social Care Act 2012, Health and Social Care Act 2012 – s261(2)(c), Informed Patient consent to permit the receipt, processing and release of data by NHS Digital, Health and Social Care Act 2012 - s261(5)(c), Health and Social Care Act 2012 – s261(2)(c)

Purposes: (Charity)

Sensitive: Sensitive, and Non Sensitive, and Non-Sensitive

When:2017.06 — 2022.05. DSA runs 2020-04-01 — 2021-01-31

Access method: Ongoing, One-Off

Data-controller type: UK BIOBANK

Sublicensing allowed: Yes

Datasets:

  1. MRIS - List Cleaning Report
  2. MRIS - Cause of Death Report
  3. MRIS - Cohort Event Notification Report
  4. MRIS - Members and Postings Report
  5. Hospital Episode Statistics Accident and Emergency
  6. Bridge file: Hospital Episode Statistics to Diagnostic Imaging Dataset
  7. Hospital Episode Statistics Admitted Patient Care
  8. Diagnostic Imaging Dataset
  9. Hospital Episode Statistics Outpatients
  10. Hospital Episode Statistics Critical Care
  11. Mental Health Services Data Set
  12. MRIS - Scottish NHS / Registration
  13. Mental Health and Learning Disabilities Data Set
  14. National Diabetes Audit
  15. Emergency Care Data Set (ECDS)
  16. Civil Registration - Deaths
  17. Demographics
  18. Cancer Registration Data
  19. GPES Data for Pandemic Planning and Research (COVID-19)
  20. Bridge file: Hospital Episode Statistics to Mental Health Minimum Data Set
  21. Improving Access to Psychological Therapies Data Set
  22. Mental Health Minimum Data Set
  23. COVID-19 Hospitalization in England Surveillance System
  24. COVID-19 Vaccination Status

Objectives:

UK Biobank, a registered charity, is one of the world’s largest medical research resources http://www.ukbiobank.ac.uk/. It was established in 2003. It is funded by the Wellcome Trust, the Department of Health and the Medical Research Council. The recruitment of its 500,000 participants, aged between 45 and 69, took place between 2007 and 2010, whose health is now being followed long term. Access to the resource opened in 2012, since which time there have been over 300 approved applications and over 2,700 researchers have registered to use the resource.

The overall purpose of the research is to create a prospective epidemiological resource of 500,000 people aged 45 -69 from around the UK. The methods to be used for the identification, invitation and assessment of participants have been developed following extensive consultation with leading research groups in the UK and internationally, and with research participants and representatives of the general population. All participants in the UK Biobank study have given fully informed consent for access to and long-term storage of information from their medical and other health-related records, and use of this and other information for health-related research purposes; long-term storage and use of their blood and urine samples for health-related research purpose; and recontact by UK Biobank to invite them (but without any obligation) to answer further questions or take part in further assessments. A copy of the consent form is available in the DAAG pack.

UK Biobank is a unique resource, because of the combination of its very large size and the range and detail of data that it contains on its participants, including extensive phenotype and genotype information on each of them. Further, rather than recruiting participants with specific diseases or risk factors, UK Biobank is a prospective population-based resource established to support research into the causes of a wide range of diseases affecting people in middle and older age. Thus, the ability to link to participant’s health records, so that specific outcomes occurring during long-term follow-up of the participants can be identified and appropriate disease-based research carried out, is critical.

UK Biobank’s priority is to combine extensive and precise measurement of exposures, along with the detailed and rigorous follow-up for a wide range of health related outcomes, and to promote innovative science by maximising secure access to deidentified data.

Participants are now being followed through fully approved linkages to death and cancer registries. Flagging of the cohort with these data sources in England Wales and Scotland has been performed with the data provision ongoing. UK Biobank obtained at baseline and holds identifiable information on its participants (with an appropriately high level of security and monitored restricted access to a few, named and approved individuals). It is very important for UK Biobank to be able to maintain as accurate information as possible about participants contact details (including postal address) and registered GP practice (which were up to date for the whole cohort at the time of recruitment but there will be undoubtedly have been changes since then. There are several reasons for this requirement:
- Ongoing approved linkages to primary care data require accurate information about registered GP practice (as practice as well as PCT level) to ensure that data about a particular participant are requested from the correct practice.
- Direct contact with GPs may be required to seek further details about particular health related outcomes identified through linkages to coded primary care data.
- To enable GPs to be confident in their assessing primary care data about participants registered in their practices, Biobank will need to be able to provide GP practices with up to date listings of UK Biobank participants in their practices, and – where requested – evidence of their consent.
- Follow-up in a cohort study needs to be as complete as possible. This is to avoid both unnecessary reduction in size of the cohort (which reduces statistical power of data analyses), and loss-to-follow-up bias (which can cause misleading research results). Part of UK Biobank’s follow-up strategy relies on intermittent re-contact with UK Biobank’s participants to invite them to complete brief questionnaires about health related exposures or outcomes. It is important that UK Biobank have correct and up-to-date participant contact details for this. Although UK Biobank encourage participants to inform UK Biobank when they move, this is not a failsafe method of ensuring the most accurate information.
- UK Biobank are committed to ensuring participants continue to be kept aware of progress and developments in UK Biobank, to obtaining their opinions on proposed enhancements to the study, and to providing them with information on how to contact UK Biobank should they have any questions. UK Biobank do this in part through Biobank’s annual newsletter, sent via e-mail and/or regular mail. Clearly, UK Biobank need up to date contact details (especially postal address) to do this. UK Biobank's wish to avoid contacting participants at the wrong address, as this may cause confusion or even occasional distress.
- Important potential research questions about the effects of environmental exposures on health require information about current and previous postal address since this allows these exposures to be estimated (from postcodes). These include, for example, valuable studies of the health effects of living close to power cables, aspects of the local environment such as nearby local public amenities and green space, and exposure to background radiation.

Yielded Benefits:

UK Biobank has approved over 850 applications since it first opened to researches in 2012. List of the approved applications can be found here: http://www.ukbiobank.ac.uk/approved-research/ In addition in 2017 alone there have been over 70 publications from researchers using the UK Biobank resources on a wide variety of topics including genetics, diet, exercise, mental health, respiratory disease and many more topics. You can see the full list of publications based on the resource here: http://www.ukbiobank.ac.uk/published-papers/

Expected Benefits:

UK Biobank is a major national health resource, and a registered charity in its own right, with the aim of improving the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses – including cancer, heart diseases, stroke, diabetes, arthritis, osteoporosis, eye disorders, depression and forms of dementia. UK Biobank recruited 500,000 people aged between 40-69 years in 2006-2010 from across the country to take part in this project. They have undergone measures, provided blood, urine and saliva samples for future analysis, detailed information about themselves and agreed to have their health followed. This is an increasingly powerful resource that is helping – and will continue over many years to help - scientists discover why some people develop particular diseases and others do not.
UK Biobank has joined other world leaders in research at the launch of the Dementias Platform UK, a powerful new tool for studying dementia. The ground-breaking collaboration between industry and academia has been established by the Medical Research Council (MRC) and bolstered by government funding. UK Biobank will be one of the key resources used to help scientists:
• Get a better understanding of who is at risk of developing dementia and why the progression of the disease varies from person to person;
• Explore the anatomy of the disease to help develop new medicines and enable more accurate diagnosis
• Look into how existing drugs which are used to treat other conditions might help to treat the progression of dementia and improve symptoms.

All research projects that have already been completed using UK Biobank are required to be displayed at http://www.ukbiobank.ac.uk/approved-research/ . This shows the many projects achieved using UK Biobank.

Compliance with HSCIC requirements under The 2014 Care Act
• As a research resource, the benefits that will be generated from researchers using UK Biobank are potentially very considerable to the population of the United Kingdom and the National Health Service. UK Biobank’s public service remit, which in due course will benefit the UK population and the health care system, is set out unambiguously on the introductory page of its 2007 Ethics and Governance Framework:
“UK Biobank aims to build a major resource that can support a diverse range of research intended to improve the prevention, diagnosis, and treatment of illness and the promotion of health throughout society.
Lifestyle and environmental information, medical history, physical measurements, and biological samples are to be collected from about 500,000 people aged 40 to 69 at presentation and then, with consent, their health will be followed for many years through medical and other health related records. The biological samples will be stored so that they can be used for a wide range of biochemical and genetic analyses in the future. Scientists have known for many years that our risks of developing different diseases are due to the complex combination of different factors: our lifestyle and environment; our personal susceptibility (genes); and the play of chance (luck).

Because UK Biobank will involve thousands of people who develop any particular disease, it will be able to show more reliably than ever before why some people develop that disease while others do not. This should help to find new ways to prevent death and disability from many different conditions. “
• This remit is re-iterated in UK Biobank’s 2012 Access Procedures, which state:
“UK Biobank’s purpose is to build a major resource that can support a diverse range of research intended to improve the prevention, diagnosis and treatment of illness and the promotion of health throughout society”. This intent is paraphrased in the Consent Form (www.ukbiobank.ac.uk/consent) and related information materials as being “health-related” and in the “public interest”. Researchers who apply to use the Resource will be required to explain explicitly how their research project supports this stated purpose.”
• In the intervening period between 2007 and 2016, the resource has been built, enhanced and has been open to researchers for just over 3 years. There is simply no other resource currently available, which enables researchers to study such a wide range of diseases with such rich and extensive data. What UK Biobank does is to enable researchers to conduct research in a highly cost-effective manner, rather than duplicate spending and effort on sample and case collection.

Outputs:

Access to the resource
UK Biobank’s access policy is set out in the Ethics and Governance Framework. Its Access Procedures were prepared during 2010 to 2011 and were the subject of extensive discussion and dialogue with its funders, the REC and the EGC. The Access Procedures were also put out to public consultation, including consultation with UK Biobank participants.

In summary:
- Every researcher has to register and apply to UK Biobank. If successful, they have to execute UK Biobank's Material Transfer Agreement (MTA) (http://www.ukbiobank.ac.uk/wp-content/uploads/2012/09/Material-
Transfer-Agreement.pdf (for information presented to DAAG in the supporting documentation). The application process is the same irrespective of the nature of the applicant and the applicant's location. The MTA governs the legal relationship between UK Biobank and each researcher and, inter alia, ensures that the researcher complies with all the applicable data protection requirements relating to all participant data that they receive. In addition to audit provisions (i.e. UK Biobank is entitled to audit any applicant if it transpires that a transgression has or may have taken place) the MTA contains explicit provisions stating that UK Biobank will bar a transgressing institution from any further use of the resource as well as publicly informing its governing bodies, funders et al ;

- The criteria are that the applicant must be a bona fide researcher conducting health-related research in the public interest. Note that the researcher may be based internationally, but that the terms under which that international researcher may access the data is set out within the MTA and are the same as those for a UK researcher. The adjudication of each application is made by UK Biobank’s Access and Scientific teams, with independent ethical advice (from the University of Oxford’s multidisciplinary bioethics research centre, Ethox: http://www.ndph.ox.ac.uk/research/ethox-centre) as well as input from UK Biobank’s independent Ethics and Governance Council, and the whole process is overseen by UK Biobank’s Access Sub Committee (http://www.ukbiobank.ac.uk/access-to-the-resource/), which contains both scientific and legal / ethical expertise;

- Any data released to researchers is pseudonymised and encrypted. The researcher is only permitted to use the data for a particular (approved) research project for a particular (approved) time frame after which the researcher must securely destroy the data. The results of the research have to come back to UK Biobank – where they are then accessible by other researchers – and the researcher is obliged to publish their work;

- In other words, any data supplied by UK Biobank to a researcher can only be used for the research project in question and for a limited time through UK Biobank’s access procedures (http://www.ukbiobank.ac.uk/wp-content/uploads/2012/09/Access-Procedures-2011.pdf, provided for convenience as document B3). Further, any such data cannot be sub-licensed or made available by researchers to any other party under any circumstances. This is all covered in UK Biobank’s MTA, which is non-negotiable.

- Participants have been aware that that the data is made available to researchers anywhere in the world as well as commercial researchers at the time of consent. To demonstrate the information which was made available to each participant:

- Our one page screen notes, (also in the resources section of the website) which each participant would view prior to starting the consent process at the assessment centre stated that “Over the coming years, a very wide range of tests would be done on your blood and urine samples by approved researchers from the UK and elsewhere (including commercial companies)”;

- Page 8 of the Information Leaflet under the section “Who will be able to use my information and samples” makes it clear that researchers from overseas and commercial researchers can access the resource. The first box in the UK Biobank consent form, also on the website, states that “I have read and understand the Information Leaflet, and have had the opportunity to ask questions”;

- In addition on the UK Biobank website on the participants page (http://www.ukbiobank.ac.uk/participants/) includes the following information: Who is using the resource?

"UK Biobank is being used by a huge range of scientists from around the world studying lots of different health problems (including those in the US, Australia, France, Spain, Russia & Japan).

The resource is open to any bona fide researcher undertaking health related research, wherever they might be. Currently, most researchers are UK-based and working in academia. UK Biobank hopes more researchers from overseas and working in industry will find the resource of value, and use it to improve the health of future generations.

You can find out about the research currently under way, and where it is being done, by clicking on our interactive map in the Approved Research section of this web site. The Publications section provides a summary of findings that have been written up in specialist research journals, or been presented to conferences. "

- Finally the UK Biobank Approved research page (http://www.ukbiobank.ac.uk/approved-research-2/) contains two maps, one of the UK and one of the whole world. This allows participants to click on a map and see who is doing research in UK Biobank and where they are located in the world.

Processing:

UK Biobank’s IT infrastructure ensures that the most up-to-date security technology is used to maintain confidentiality of participant data, with regularly up-dated firewalls, antivirus software and other data encryption protocols to ensure on-going compliance with the Data Protection Act and other regulatory requirements. Periodic penetrance testing, as part of a regular security audits, is carried out by an independent third party to ensure that no data can be accessed by unauthorised individuals.

Importantly, the main administrative database, which includes identifiable information on participants (allowing for linkage to health-related records, re-contact for further data collection and keeping participants informed of study progress) is located and maintained separately from the research database (which contains all the data of potential interest for researchers but no data from which any participant could be identified). Access to the administrative database is closely monitored and is strictly limited to a very small number of named staff.

Data once processed may be provided to researchers according to the UK Biobank access policy and procedures, which were developed through extensive consultation, including public consultation and consultation with UK Biobank participants. Further detail is given within the Outputs section.

Any proposed research project, whether led from an academic institution, a company, a charity, or a collaborative combination of any of these, is only approved for access to data held by UK Biobank (which data can only be used for the purposes of approved research project) following a clear demonstration that the primary aim of the project is to generate results that are for the benefit of the public’s health and for the promotion of health throughout society. Since the UK Biobank resource is based on 500,000 UK-based participants (90% of whom were recruited in England and registered with the English NHS), the public health and health promotion benefits arising from the results of approved research based on the UK Biobank resource will be apply most directly to recipients of health services and social care in England, although many of the benefits will also have broader applicability to populations beyond those of England and the UK.


UK Prospective Diabetes Study (UKPDS) Legacy Study: long-term follow-up of participants into electronic health records — DARS-NIC-265261-W7P8W

Opt outs honoured: Identifiable, Yes (Section 251 NHS Act 2006)

Legal basis: Health and Social Care Act 2012 – s261(7); National Health Service Act 2006 - s251 - 'Control of patient information'., Health and Social Care Act 2012 – s261(7); Health and Social Care Act 2012 – s261(7)

Purposes: (Academic)

Sensitive: Sensitive

When:2021.10 — 2022.04. DSA runs 2021-01-25 — 2024-01-24

Access method: One-Off

Data-controller type: UNIVERSITY OF OXFORD

Sublicensing allowed: No

Datasets:

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

Objectives:

The purpose of this application is to link participants in the UK Prospective Diabetes Study (UKPDS) trial to all death and hospitalisation health records in order to measure the effect of the treatments in this study on death, major medical illnesses, and costs of treatment.

The use of the data requested in this agreement is in accordance with Article 6(1)e as processing is necessary for a task carried out in the public interest. The aim of the study is to provide reliable evidence about the very long-term effects of blood pressure and glucose-lowering treatments on important health outcomes in people with diabetes. This promotes the public interest aiming to improve the treatment of estimated 5 million people with diabetes by the year 2025. Further details can be found on the UKPDS website (https://www.dtu.ox.ac.uk/OurTrials/UKPDSLegacy)

Processing of the data is in accordance with Article 9(2)(j) exemption, i.e. that the processing of the data is necessary for scientific research. The scientific aim of the study is to provide reliable evidence about the very long-term effects of blood pressure and glucose-lowering treatments on important health outcomes. This will help to inform people with diabetes about the long term consequence of blood pressure lowering and glucose lowering treatment, so they can make better decisions about their care. Further details can be found on the UKPDS website (https://www.dtu.ox.ac.uk/OurTrials/UKPDSLegacy)

The research team have taken the opinion of the South East Scotland Research Ethics Service (18/SS/0127), who have granted approval to the study in its current form, and of the Confidentiality Advisory Group (CAG) (18/CAG/0182).

The University of Oxford propose to link participants in the trial to their health data held within hospitalisation and death records curated by NHS Digital. By doing so, The University of Oxford will be able to determine the effects of higher versus lower blood pressure and glucose on future health and health care resource use. The University of Oxford will compare the incidence of major disease in different arms of the trial, in participants with different baseline factors (both clinical and genetic), and with difference disease occurrence during follow-up.

The UKPDS was a randomised, multi-centre trial of glucose-lowering and antihypertensive therapies in 5,102 patients with newly diagnosed type 2 diabetes that ran in 23 clinical centres for twenty years from 1977 to 1997.

UKPDS has been a major project, that has influenced diabetes guidelines in the UK and around the world (www.dtu.ox.ac.uk/ukpds). Both the Health Economic Research Unit and the Diabetes Trials Unit have a strong research interest in determining the effects of treatments for diabetes, and have published many influential studies.

The UKPDS trial investigators would therefore now like to evaluate the effects of the randomised treatments on dementia and other measures of long-term health. Therefore, the University of Oxford propose the extended follow up of all UKPDS participants into Electronic Health Records and other routinely collected health data.

The purpose of the project is to:

1. To determine whether participants randomly allocated to tight, rather than less tight, blood pressure control have a lower risk of dementia.
2. To determine whether participants randomly allocated to intensive, rather than conventional, glucose control have a lower risk of dementia.
3. To determine whether tight blood pressure control or intensive glucose control reduces the long-term risk of major vascular diseases in diabetes.
4. To determine whether tight blood pressure control or intensive glucose control reduces long-term health resource use and total burden of disease in diabetes.
5. To investigate use of health care resources in secondary care by patients with diabetes.

University of Oxford decided against requesting Mental Health data because it was not available for such a long time, and varied in coverage over the potential period of follow up. It was therefore determined that HES and mortality data will hold enough dementia data for the purposes highlighted above.

The study’s purpose is to examine the effect of baseline clinical variables on major health events, including major vascular events (including, but not limited to strokes of different types and myocardial infarction), cancers, renal disease and dementia. In order to ascertain these events, chiefly though ICD-10 coding. ICD-10 consists of a tabular list of diseases, the study team propose that it accesses hospital admission, and death records. The study team have found in previous work that the majority of cases of chronic disease (including dementia) can be found in admitted patient care, and death records. Data is needed on individuals in order to adjust for differing factors at baseline. The chief comparison will be between participants allocated to blood pressure and glucose lowering regimens and participants allocated to control regimens.


The University of Oxford propose that the linkage of individual participants by their identifying information (name, NHS number, date of birth, sex) should be performed by NHS Digital. The University of Oxford propose that NHS Digital return data to the university at the Nuffield Department of Population Health at the University of Oxford with each participant’s trial identity number with data from the linkage, i.e. a pseudonymised level of data.

The study team propose that to obtain data from each participant from the time they began to take part in the trial (the first participant was randomised in 1977) to the date of linkage. This will allow them to: (i) compare the occurrence of events recorded by the study during follow up with events recorded by Electronic Health Records; (ii) compare the very long-term incidence of major disease by randomised treatments and baseline factors. Further data releases will allow the study team to continue follow up into the extremely long term.

Participants were resident and recruited from across the UK, who may have moved between nations since recruitment, and therefore the data held will be linked across the country.

Linking participants to their data held by NHS Digital is the least intrusive way of achieving the stated purposes; in fact there is no other way that this could be performed without leading to considerable bias in the assessment of important outcomes. The University of Oxford believe that re-approaching participants for further consent would lead to potentially very large biases in ascertainment of major health conditions (because of non-responder biases particularly amongst those in poorest health, or have died), potentially lead to distress, and therefore have sought permission from the Health Research Authority (HRA) CAG for this linkage. The University of Oxford propose to link only to those datasets that contain information on medical diagnoses.

The Data Controller and Processor will be the University of Oxford. The Primary Investigator is employed by The University of Oxford. All processing of NHS Digital data will be within the University of Oxford. Analyses will be performed within the University of Oxford department the Nuffield Department of Population Health, by researchers within that department and researchers with contracts with that department. Advice on analysis and manuscript will be provided by researchers within the Diabetes Trials Unit. The project is funded by the Nuffield Department of Population Health.

The funders of the study and individual outside the study team will only have access to tabular data with small numbers suppressed. This so that people who wish to meta-analyse studies, who are currently not predictable (it may be no-one), are able to do so. The type of data that would be shared would be very similar to what would be in a published paper. Sharing this level of data is very important for openness of the scientific endeavour and would suppress small numbers.

Yielded Benefits:

The UK Prospective Diabetes Study (UKPDS) was a landmark randomised, multicentre trial of glycaemic therapies in 5,102 patients with newly diagnosed type 2 diabetes. It ran for twenty years (1977 to 1997) in 23 UK clinical sites and showed conclusively that the complications of type 2 diabetes, previously often regarded as inevitable, could be reduced by improving blood glucose and/or blood pressure control. The study has led to 118 manuscripts as of December 2020, covering many aspects of diabetes care (https://www.dtu.ox.ac.uk/ukpds/) The key benefits for patients with type 2 diabetes was to demonstrate that lower blood pressure and more intensive glucose control were of benefit. These treatments are the cornerstone of modern diabetes practice.

Outputs:

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide

The University of Oxford expect at least 3 publications to address each of the following questions:
1. To determine whether participants randomly allocated to tight, rather than less tight, blood pressure control have a lower risk of dementia.
2. To determine whether participants randomly allocated to intensive, rather than conventional, glucose control have a lower risk of dementia.
3. To determine whether tight blood pressure control or intensive glucose control reduces the long-term risk of major vascular diseases in diabetes
4. To determine whether tight blood pressure control or intensive glucose control reduces long-term health resource use and total burden of disease in diabetes
5. To investigate use of health care resources in secondary care by patients with diabetes

Once data is received, the University of Oxford expect that it will take between 2 and 3 years to deliver these analyses. The UKPDS trial investigators will publish these outputs in major clinical journals (e.g., Lancet, BMJ, Stroke etc.) and present them in international meetings by study end, target 2 to 3 years after a full dataset is received. It is anticipated these would contribute to national guidelines on reducing risk in people with diabetes, and will be communicated to charities (e.g., Diabetes UK) that are active in giving advice to people with diabetes.

The data will be aggregated with small number suppression in accordance with the HES analysis guide. The University of Oxford will not present data on individual participants. however, will present actual and modelled data in graphical and tabular format in line with the HES analysis guidelines on suppression.

The Diabetes Trials Unit and NDPH contribute widely to health policy, particularly in the area of vascular risk prevention. They contribute to debate with academic papers, conference participation, lectures to the public and advice to government (including NHS Digital). The University of Oxford will share all outputs through all of the listed channels: website and newsletters, open lectures and talks, exhibition at public events, posters, press/media engagement and other public promotion of the research, stakeholder mailing list.

Processing:

The Nuffield Department of Population Health (NDPH), University of Oxford will transfer participant identifiers with linked trial ID numbers to NHS Digital through a secure route approved by the receiving bodies. The entire UKPDS cohort (5102) will be transferred, in case of relocation of Scottish participants to England. The University of Oxford will receive data back to the Nuffield Department of Population Health in an encrypted format via NHS Digital encrypted transfer solution. The data will be encrypted during receiving, storage and processing. Each participant will be identified by trial identifier only at this stage, not with name, date of birth etc. The University of Oxford will construct a dataset from the original UKPDS trial dataset with covariates for this analysis, where each participant is identified only by the anonymised trial identifier, including baseline clinical, genetic, and event-based data. Data on individual participants held in the Nuffield Department of Population Health will be linked to data on the same individual provided by NHS Digital. Analyses will be performed with these data to achieve the stated scientific aims of estimating the effects of treatment in the UKPDS on major health outcomes, and health economic outcomes. All analyses will be performed using pseudo-anonymised trial identifiers.

All data will be transferred, handled and processed in agreement with the NHS Digital Data Sharing Framework Contract. Data will be received by the NDPH, University of Oxford. Using existing ICD-10 code lists for different clinical phenotypes, the study team will define the date and the nature of disease events for each participant. The study team will link the list of processed disease outcomes with existing datasets of baseline clinical, genetic and biomarkers data, and the occurrence of disease events within trial. Data are pseudonymised prior to analysis.

The Nuffield Department of Population Health, University of Oxford will link this dataset with the information received from NHS Digital with pseudonymised trial identifiers.

NDPH has successfully acquired analysed and appropriately stored data from HES for previous large long-term studies such as HPS2-THRIVE and HPS3-REVEAL. NDPH researchers are experienced in handling confidential and participant sensitive data and have appropriate training in Information Governance.

The NDPH servers are protected against unauthorised external access by an appropriate strength firewall. Access to patient identifiable information is protected by the appropriate authentication procedures (user IDs and passwords). Authentication is only given to personnel with a need to access the required data. Only personnel involved in the long-term follow-up study for UKPDS (processing and analysing data) will have access to this data, which will be members of the statistical and health economics teams NDPH has a Corporate Level Security Policy that has been fully adopted by management and will apply fully to the long-term follow-up study. The data protection Registration Number is Z575783X. NDPH investigators are fully aligned with all data management and security policies.

Identifiers will need to be retained whilst linkages are made between UKPDS datasets (the University of Oxford anticipate this will take up to a year) before all data are identified primarily with the study ID, in order to pseudo-anonymise the long-term follow-up dataset. We anticipate this will not be necessary, but if there are linkage problems, or inconsistencies in the data provided, the identifiers may need to be provided again to NHS Digital.

The study team will link data from individuals to existing trial databases, which hold information on the baseline clinical, genetic, biochemical, and Health Economic characteristics of participants, and in-trial health events.

Data processing will only be carried out by substantive employees of the data processor(s) and or data controller who have been appropriately trained in data protection and confidentiality.

No data will be stored at premises which are owned by an organisation which is not named in the agreement. All information is stored securely by University of Oxford and is kept confidential. Access to the computer database is by unique combinations of usernames and passwords and only authorised study personnel can access information about participants. The building is secure with authorised swipe card access only. No individuals will be identified in any study reports.

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)”

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

Data will only be accessed and processed by substantive employees of University of Oxford and will not be accessed or processed by any other third parties not mentioned in this agreement


REstart or STop Antithrombotics Randomised Trial (RESTART) — DARS-NIC-149576-G6M4B

Opt outs honoured: No - consent provided by participants of research study, Identifiable, No (Consent (Reasonable Expectation))

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

Purposes: (Academic)

Sensitive: Non Sensitive, and Sensitive, and Non-Sensitive

When:2019.06 — 2019.06. DSA runs 2018-12-21 — 2021-12-20

Access method: One-Off

Data-controller type: UNIVERSITY OF EDINBURGH

Sublicensing allowed: No

Datasets:

  1. Hospital Episode Statistics Admitted Patient Care
  2. Civil Registration - Deaths
  3. HES:Civil Registration (Deaths) bridge
  4. Civil Registration (Deaths) - Secondary Care Cut

Objectives:

The University of Edinburgh will use the data for the REstart or STop Antithrombotics Randomised Trial.

RESTART is studying the potentially beneficial effects of starting antiplatelet drugs (one or more of aspirin, clopidogrel or dipyridamole, chosen by the patients physician), on the risks of a heart attack, stroke and other clotting problems as well as their effect on the risk of a brain haemorrhage happening again, for adults surviving a stroke due to bleeding in the brain and who were taking a prescribed antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of illnesses such as angina, heart attack or stroke before their bleed.
A magnetic resonance imaging (MRI) sub-study will also study whether the presence of brain microbleeds modify the effects of antiplatelet drugs.

537 consented participants were recruited from 103 recruiting sites in NHS hospitals throughout the UK and randomly allocated to take an antiplatelet or avoid taking antiplatelets. All participants are followed up for at least 6 months after randomisation either by postal or telephone questionnaire to check for the occurrence of any relevant events or outcomes and their medications. In addition, participants GPs, and the hospital which recruited them, provide information on any relevant adverse events which occur during the follow up period including hospital admissions and deaths. These events will be compared in those taking an antiplatelet and those avoiding it to compare the event rate.

Recruitment commenced on the 22nd May 2013 and closed at midday on the 31st May 2018 with 537 participants (97 from Scotland). Follow-up will be completed for events that occur by the end of November 2018.

This proposal for NHS Digital data along with the data from NHS Scotland will enable RESTART to more accurately determine the number of outcome events which occur after the date of a patient’s randomisation, until the time of this data extract or the last period of data available. It is already known that the primary source of ascertainment of these outcome events (annual postal questionnaires to participants’ general practitioners) misses some events that participants have reported. Therefore, RESTART seeks secondary data to improve the accuracy of its data on the occurrence of the trial’s major outcomes, which will improve the scientific validity of the trial’s findings. The primary objective of the trial is to estimate, when all participants have completed at least 6 months of follow-up, the relative and absolute effects of antiplatelet drugs on the risk of brain haemorrhage happening again associated with a policy of starting antiplatelet drugs after the acute phase of brain haemorrhage. Ultimately, RESTART intends to determine whether antiplatelet drugs are beneficial for patients after brain haemorrhage because the gains from prevention of clotting problems outweigh the risks of bleeding at any site.

A brain MRI sub-study is incorporated into the trial protocol to determine whether patients with tiny deposits of blood in the brain called 'microbleeds' on an MRI brain scan have an increased risk of having a recurrent brain haemorrhage if prescribed antiplatelet drugs following a brain haemorrhage.
This specific proposal will allow RESTART to identify any missing primary and secondary outcome events in the trial which were not reported using the primary sources of follow-up (patient and GP follow-up, ad hoc reports from patients or research staff at participating sites) and determine the long-term survival of participants. This will enable RESTART to determine whether antiplatelet drugs are a safe and effective treatment.

Expected Benefits:

More than one third of the adults with a stroke due to bleeding into the brain – known as brain haemorrhage – are taking drugs to prevent clotting when they have a brain haemorrhage. These patients had previously suffered illnesses like angina, heart attack, or stroke due to blood vessel blockage, which is why they are treated with drugs to prevent further clots occurring. These drugs are usually stopped when the brain haemorrhage occurs. But when patients recover from brain haemorrhage, they and their doctors are often uncertain about whether to restart these drugs to prevent further clots occurring, or whether to avoid them in case they increase the risk of brain haemorrhage happening again.

RESTART will study the potentially beneficial effects of antiplatelet drugs such as aspirin on the risks of heart attack, stroke and other clotting problems as well as their effect on the risk of a brain haemorrhage happening again.

If RESTART can reliably demonstrate this it will help patients make better decisions about their treatment and inform clinicians and patients about potential preventative treatment pathways.

Outputs:

All outputs will consist of aggregate data only with small numbers suppressed in line with the HES analysis guide.
After database lock in the second week of January 2019, the final trial results will be submitted to The Lancet in February/March 2019 after approval by the Steering Committee. If the data is not received from NHS Digital by the second week then the results will be used in a subsequent publication later in the year. The results will be presented at the European Stroke Organisation Conference in May 2019, hopefully alongside simultaneous publication in The Lancet (or other prominent peer-reviewed medical journal, if not accepted by The Lancet). The trial report will be published open access, to enable professional and lay audiences to access it.

The results will be shared with participants/carers (who have expressed a wish for this to be done) in June 2019. This report will be prepared with reference to the HRA guidelines, and with input from the Chief Investigator's patient reference group.

Presentations will be made to non-medical audiences after publication of the trial report, although the dates and venues have not yet been determined.

A final report will be prepared for the trial funder, based on aggregate data and the final results, and submitted to the British Heart Foundation in May 2019.

When processing has been completed, the following will have been created:
1. A trial database which will be kept securely in the University of Edinburgh Safe Haven - patient level data identifiable.
2. A completely pseudonymised version of the patient-level data used for the primary analysis will be made available, behind access controls that require approval by the Trial Steering Committee, for use by the wider research community upon reasonable request. These outputs are primarily for health professionals to guide their patient care and for those developing evidence based guidelines. This output does not include record level data provided by NHS Digital, the processing of which has been detailed in the processing activities section of the application.
3. Pseudonymised data which is for use solely for the RESTART trial by the University of Edinburgh (and includes NHS Digital data).
4. Presentations for healthcare staff and lay audiences - aggregated data only
5. Open access papers in peer reviewed journals - aggregated data only.

Processing:

The processing of NHS Digital data will be carried out within the University of Edinburgh Safe Haven. A similar application is being made to the Public Benefit and Privacy Panel for Health and Social Care for data relating to patients recruited in Scotland.

RESTART will supply NHS Digital with patients’ identifiers (forename, surname, date of birth, NHS No., postcode, and RESTART study id [i.e. pseudonymous identifier]) to facilitate the linkage and the participant’s date of randomisation to limit the data extraction from this date to the end of the available follow up period. RESTART will not request data on any patient who has withdrawn consent following recruitment.

The data received back from NHS Digital will include the RESTART trial ID (as provided) and any dates of admission to NHS hospitals and the primary diagnosis leading to these admissions from HES Admitted Patient Care, as well as Mortality data (including Date of Death and Cause of Death). The data will be securely transferred to the University of Edinburgh Safe Haven.

A copy of the RESTART trial dataset will be transferred to the Safe Haven. The Data manager will link these dataset with the data provided by NHS Digital, using the RESTART study number. The two datasets will then be compared in order to find the Outcome Events (Intracranial events, Extracranial Cardiovascular events, and Death of any cause which are present in the NHS data but not in the RESTART trial dataset. If the record-level data provided by NHS Digital indicate that any of these outcomes might have occurred, University of Edinburgh will obtain source data from participating sites to verify or refute the occurrence of these outcomes. For any outcomes that are verified, two fields will be manually populated in the trial database for relevant participants after characterising the outcome (outcome event type and date); this will not involve importing record-level data provided by NHS Digital. This will be the only linkage with the NHS Digital data.

RESTART has a study-specific database that is password protected and held securely on University Datastore. Access is routinely reviewed and revoked when any team member leaves RESTART.

Data will only be accessed and processed by substantive employees of the University of Edinburgh and will not be accessed or processed by any other third parties not mentioned in this agreement.

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).