D27 - QResearch COVID-19 linkage

This agreement specifically relates to QResearch COVID-19 research projects undertaken in relation to the 2020 pandemic. Under this agreement QResearch data linked to NHS Digital data will be used solely for the purpose of research into COVID-19. Other QResearch uses of NHS Digital data are covered by a separate data sharing agreement (DARS-NIC-240279-Y2V2N).

QResearch is a database of linked medical records that has been used and continues to be used by a variety of research projects undertaken by UK universities, from reviewing the safety of antidepressant medicines to studying factors to predict variations in survival rates for cancer patients.

Monthly HES and mortality data are requested to link to the existing QResearch database so that it can be used for medical research. The QResearch database consists of the coded pseudonymised electronic health records from primary care patients registered with approximately 1,500 general practices spread throughout the UK.

QResearch was originally a not for profit collaboration originally between the University of Nottingham and Egton Medical Information Systems (EMIS) but the University of Nottingham’s roles and responsibilities have since been transferred to the University of Oxford. Strategic decisions about the GP data are taken by a Management Board representing the interests of EMIS and the University of Oxford. The University of Oxford is the sole data controller for the datasets which are linked to QResearch (deaths, cancer and hospital data) and the single point of access to the data, with ICNARC as joint data controller for COVID-19 projects using linked ICNARC data.

In addition to coded data from the GP electronic record, the QResearch database also contains the linked cause of death derived from the death certificate data which was originally supplied directly by the Office of National Statistics (ONS) but NHS Digital has since assumed ownership for this data, and cancer registration data supplied directly by Public Health England, following approval by Trent MREC and Secretary of State for Health. From October 2018, new mortality data (referred to as Civil Registration data) will be supplied by NHS Digital. Any mortality originally supplied by ONS data will be considered data supplied by NHS Digital and only NHS Digital can approve ongoing access to this data and its use for specific purposes.

The data linkages for QResearch were extended in 2011 to include additional health information from secondary care including HES. This agreement grants additional permission to link NHS Digital data to an existing database of data from 185 intensive care units nationally which has the clinical data for all those admitted with severe disease requiring ventilation. This is known as the Intensive Care National Audit and Research Centre (ICNARC) database and the COVID-19 testing database held by PHE. ICNARC will be a joint data controller (along with the University of Oxford) solely for COVID-19 projects involving the use of this linked data, and not for any other purposes.

The patient level data linked to QResearch is only accessed by academics employed by University of Oxford, as well as authorised individuals employed by the University of Nottingham. In all cases, data can only be accessed on site at the University of Oxford. However, the researchers involved in a given project (contributing to the research question, design, interpretation and writing of the paper for publication but not handling the data) may be employed by other UK universities. The HES and mortality data stay on site at the University of Oxford and are only handled by University of Oxford staff, ICNARC where they are a joint data controller, the data processor contracted to the University of Oxford (Dancing House Consulting) and authorised researchers employed by the University of Nottingham. The University of Oxford may have a collaborator at another university on the project team advising on clinical aspects or interpretation of findings, but they will not receive any data. In addition, the external researcher may initiate a COVID-19 project but the University of Oxford has sole autonomy for determining the purposes for which the HES and/or civil registration data will be processed and analysis will be done by University of Oxford staff with the data located at the University of Oxford. The sole exception to this is for COVID-19 projects using linked ICNARC data, for which ICNARC will be a joint data controller. For these COVID-19 projects ICNARC statisticians will have a role in the design, analysis and interpretation of the data under the overall direction of University of Oxford, and they will be co-authors on arising papers. ICNARC will not be involved in any decisions regarding other research projects which do not use their ITU data. Data will not be used for any solely commercial purposes and all applications for the use of HES and/or mortality linked data are subject to a governance process explained in the Processing Activities section.

Only University of Oxford staff, their data processor, Dancing House Consulting, ICNARC, and authorised researchers employed by the University of Nottingham will have access to HES and/or mortality record level data. External researchers will only have access to tabular outputs that are aggregate with small numbers suppressed in line with the HES Analysis Guide. Record level data are not shared with researchers outside of the University of Oxford.

Research undertaken using the extended database continues to be processed using the existing arrangements with respect to scientific review and annual reports to Trent MREC. Research has to be peer reviewed, original, hypothesis driven or hypothesis testing, intended for publication in an academic peer reviewed journal.

All research undertaken using the QResearch database and linked data are subject to independent peer review and the results of all research are published.

Under this agreement, primary care data from The Phoenix Partnership (TPP) from general practices which use the SytmOne computer system will be included in QResearch linkage in addition to data from EMIS practices. This will give a larger population of patients and enable more coverage of patients who subsequently go into hospital and onto Intensive Treatment Unit (ITU) with and without COVID-19.

EMIS and TPP process the GP data from the original data controllers (GP practices) and sends it to the University of Oxford. EMIS and TPP are not able to access or process any GP data once it is located at the University of Oxford.

EMIS and TPP are neither a data processor nor a data controller for the data provided by NHS Digital under this Agreement. EMIS and TPP are not able to access the HES data under any circumstances. EMIS and TPP have given permission for the GP data it supplies to be linked with the data from NHS Digital for purposes determined by the Principal Investigator at the University of Oxford.

Before providing data to the University of Oxford, NHS Digital use the Open Pseudonymiser tool to pseudonymise the HES data. NHS Digital retains the salt key for this pseudonymisation, meaning that the University of Oxford are unable to re-identify the data but as described below they are able to link with GP data that was pseudonymised using the same Open Pseudonymiser tool. The University of Oxford will not be provided with a copy of the pseudonymisation salt.

NHS Digital provide the pseudonymised data to the University of Oxford which is then linked to the QResearch database at individual patient level using a pseudonymised version of the NHS number which has been supplied in both GP data and the HES data. The data linkage is undertaken by an employee of the University of Oxford. No data items which would identify the data subjects are received by QResearch as the data is pseudonymised-at-source and at NHS Digital. Date of birth is rounded to year of birth before receipt by the University of Oxford.

The resulting data are then used for undertaking primary research relating to COVID-19. The linked data are only accessed by approved research staff with substantive contracts employed by University of Oxford, the contracted data processor (Dancing House Consulting), ICNARC (for COVID-19 projects using linked ICNARC data) and authorised researchers employed by the University of Nottingham. Data is only processed on site on secure servers at the University of Oxford. No individual level data will be shared or stored outside the University of Oxford or supplied to any third party.

Applications for HES and/or civil registration data linked to QResearch GP data are restricted to academics employed by University of Oxford to undertake research. At least one member of the research team must be a medically qualified academic registered with the General Medical Council who signs the guarantee. Eligibility of applications is assessed according to the following criteria.

• You agree NOT to attempt to identify patient(s) or practice(s)?

• You undertake to provide a copy of the final report of the project and copies of any publications within one year of the project completion?

• You agree NOT to release the data to any third party including the funder, sponsor or other such body?

• You agree not to use the data for any other project except that which is expressly described in your protocol

• Do you have a statistician on the project team who has contributed to the design of the study and will advise on the analysis?

• Is the research a benefit to the UK Health and Social care system

All applications are reviewed by the QResearch Scientific Committee, which is overseen by the QResearch Advisory Board (which includes patients and general practice representatives). If an application does not meet the above criteria it would mean that application would be rejected and the data would not be shared. Details of the Scientific Committee and Advisory Board terms of reference and membership are published on the QResearch website, along with Advisory Board minutes.

Researchers originate a research question or hypothesis; write an outline protocol; and contact QResearch to discuss the feasibility of undertaking the study. If the study is feasible, QResearch will give a broad estimate of the costs of providing the analysis and will provide a letter to accompany any application for funding. The researcher then secures the necessary funding and completes the QResearch application form, including a detailed protocol and data specification. This application is sent for scientific review and feedback is given to the researcher. The researcher makes any necessary modifications to the protocol and approval is obtained, the researcher is given a timescale for the analysis. Once the researcher has the analysis, they have to approve it within one month of receipt.

As described in the section above, the QResearch database is also linked to mortality and cancer registration data. The database was first linked to ONS mortality data in 2007 and cancer data in 2011 (subsequently supplied by Public Health England since 2015). The data fields received from mortality data are: pseudonymised NHS number; year of birth, date of death; ICD10 cause of death. The cancer data includes pseudonymised NHS number; sex; year of birth; date of death; diagnosis date; cancer site and type; cancer stage and grade; cancer behaviour; cancer diagnosed only on death certificate; cancer treatment (surgery, hormone, chemotherapy, other).

To enable COVID-19 research, data will also be linked to the ICNARC database and the COVID-19 testing database held by PHE. No other data linkage is permitted without further amendment to the data sharing agreement with NHS Digital. There is no requirement to re-identify individuals from the data and no attempts will ever be made to do this.

The data processor Dancing House Consulting undertakes IT consultancy on behalf of the data controller, including administration of data backups, database administration, and secure destruction of data. Dancing House Consulting do not undertake data linkage or analysis of the data.

All outputs are restricted to aggregate data with small numbers supressed in line with the HES Analysis Guide.

Regular reviews against the ICO code on anonymisation (2012) will be undertaken to ensure that the data remain anonymised and all appropriate controls are in place to minimise any risk of re-identification.

The data from NHS Digital will not be used for any other purpose other than that outlined in this Agreement, and the specific QResearch projects outlined within the data sharing agreement DARS-NIC-240279-Y2V2N while that agreement remains active.

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).

The outputs are research papers which are published in peer reviewer academic scientific journals and presented at academic conferences. All research is published in academic journals with a link from the QResearch website on an ongoing basis. The publications are accompanied by with press releases from the relevant organisations and highlighted on social media.

Results are also shared with policy makers and NICE guideline committees on a regular basis via their stakeholder consultations in order to support development of relevant guidelines.

Results are also regularly shared with patient participants on the QResearch Advisory Board and PPI representatives on individual research projects.

The results tables within the papers will only contain statistical information with cell counts of > 5, being suppressed in line with the ICO code on anonymisation. Outputs will only contain aggregate level data with small numbers suppressed in line with the HES analysis guide.

No indicators are produced which show performance of an organisation – indeed the identity of the GP practices contributing to QResearch are not shared with any third party.

This data linkage with ICNARC seeks to match against data on prior long-term medication and chronic disease, information contained in the QResearch databases derived from the de-identified general practice health records. The aim is to provide useful knowledge that patients, GPs and intensive care doctors can use to reduce the risk of severe COVID-19 infection within this pandemic.

Specifically it will help research to understand whether drugs commonly taken for chronic conditions such as hypertension or diabetes may exacerbate or reduce the severity of COVID-19 disease. It is hoped this study will be able to identify alternative drugs for patients with chronic conditions, as well as possible drugs to treat COVID-19; and recognise high-risk patients in primary care.

Around 14 percent of the adult population in England take anti-hypertensive medications, and around five percent receive medication to treat diabetes. The prevalence increases with age, making usage particularly common in those at risk of for severe COVID-19 infections. In many cases drugs from a different class could be used instead. If these drugs are increasing the risk of severe infection, they represent one of the few modifiable risk factors for severe COVID-19 infection. Medical and research communities need rapid large-scale accumulation of data on the outcomes of patients who develop COVID-19 infection whilst taking these drugs to allow appropriate risk assessment and clinical decision making for these patient groups. Other drugs in common use in primary care patients are believed to have anti-viral activity to COVID-19, such as hydroxychloroquine, used in rheumatoid arthritis, and lopinavir-ritonavir, used in the treatment of HIV.

There are also immune-suppressive therapies that may either increase the risk of severe illness by preventing the body’s response to infection, or attenuate the hyperinflammation syndrome associated with COVID-19 disease, so preventing severe disease.

The incidence of severe disease in patient groups taking these medications urgently needs to be established to guide both their management and investigation of COVID-19 treatment strategies.

ICNARC is already providing up-to-date information on the admission characteristics and outcomes of all patients with severe COVID-19 infection treated on an ICU in England, Wales and Northern Ireland.

Not stated in the register.