The Oxford Risk Factors And Non Invasive Imaging Study (ORFAN) Arm 4
University of Oxford · Academic
In term In term in the September 2026 edition: the latest version runs to 6 March 2027.
- Reference
- DARS-NIC-409610-J6L1F
- Current version
- v2.5
- Term of current version
- 7 March 2024 to 6 March 2027
- Start date
- 25 March 2021
- Data controller
- Sole Data Controller
- Commercial purposes
- No
- Sublicensing
- No
- Files released to date
- 90
Why the data was released
Objective for processing
The Oxford Risk Factors And Non Invasive Imaging Study (ORFAN) at large has been operational since 2015. Originally the study was limited to arms 1, 2 and 3. Arm 4 has been developed conceptually from 2018 and came into practical existence from 2019 to both address outstanding scientific questions that cannot be answered with the limited pool of participants in arms 1-3, and to further develop and validate novel biomarkers that have emerged from ORFAN Arms 1-3 and Oxford Heart Vessel and Fat research group (Ox-HVF) studies coordinated by the University of Oxford (see below). ORFAN Arm 4 is funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and The British Heart Foundation (BHF).
ORFAN Arm 4 study is a multi-centre observational cohort study involving patients who have had a computed tomography (CT) angiography or CT chest scan.
The University of Oxford is applying to NHS England, in order to link data subjects within the scope of the study with data held by NHS England. This linkage is necessary in order to develop and validate cardiovascular disease risk assessment tools that will lead to earlier detection of disease risk and prevent heart attacks and strokes, amongst other cardiovascular diseases. These tools are for usage in the clinical environment and are intended to change patient care for the better.
The purpose of the project is to develop new and better biomarkers of cardiovascular disease risk using novel approaches to the analysis of CT scans. The overriding purpose of this work is to reduce the large burden of morbidity and mortality that cardiovascular disease such as heart attack and stroke have in our society.
The NHS England data requested in this agreement could contribute in a fundamental way to the achievement of this purpose by allowing the research team to know which diseases and clinical events had occurred prior to the CT scan of relevance to the study, and which diseases and clinical events have occurred for participants following the CT scan. This data is critical to the successful development of image analysis tools as it enables accurate differentiation of participant characteristics (namely imaging characteristics detected from within the CT scans) that can be utilised to predict patient risk.
A further major purpose of the ORFAN Arm 4 project is to understand the cardiovascular disease ramifications of COVID-19 infection. The study team know that deleterious impacts on blood vessels and the heart due to acute COVID-19 infection are commonly reported, but they do not know the long-term impacts or how to predict which patients are most at risk of morbidity due to such disease effects. Access to data related to COVID-19 infection and later cardiovascular disease diagnosis and clinical events, along with relevant CT scans of such patients’ hearts and vessels, will enable a much more accurate assessment of this risk for individual patients.
THE ORFAN STUDY PROTOCOL AND OBJECTIVES
The study has two main objectives:
1) To investigate whether biomarkers, including imaging biomarkers, of metabolic risk can predict major adverse cardiovascular events
2) To identify novel biomarkers able to predict cardiovascular disease pathogenesis and extent of pre-existing vascular disease, including in those with COVID-19 infection.
The specific primary objective of the ORFAN study is to investigate whether biomarkers of disease risk can predict major adverse cardiovascular events.
In order to achieve this objective, the primary outcome measures for the study are:
1. Measurements of plasma/imaging markers of cardiometabolic risk - not directly relevant for this agreement, although the data requested will be linked to the pseudonymised plasma and imaging data already held by the applicant
2. Atherosclerosis progression by Computerised Tomography - not directly relevant for this agreement, although the data requested will be linked to the relevant pseudonymised imaging data already held by the applicant
3. Major adverse cardiovascular events over 10 years - relevant for this agreement.
The relevant study secondary objective is to identify novel biomarkers able to predict cardiovascular disease pathogenesis and extent of pre-existing vascular disease
The secondary outcome measures that are relevant to this agreement:
1. Measurement of modification to cardiovascular disease pathogenesis and modulation of pre-existing vascular disease that is attributable to infection with coronavirus disease 2019 (COVID-19), and other pre-existing vascular disease.
The ORFAN Study was assigned COVID-19 Cardiovascular Disease UK Flagship Project status by the NIHR-BHF in May 2020 and has received ethical approval to pursue a scientific inquiry into the specific risk that is conveyed by COVID-19 infection in regard to stroke and coronary artery disease. The data from this agreement will form a major part of this inquiry as it will support the study team to understand the heart disease risk that COVID infection confers, and enable the creation of biomarkers for assessing patients individual risk of heart disease complication following COVID-19 infection.
The ORFAN study at large consists of 4 Arms of study. Arms 1, 2 and 3 include a total of 15,500 prospectively recruited participants who are directly consented to be included within the study. The ORFAN Study research arms 1,2 and 3 include directly consented patients for whom the University of Oxford collects and processes data for research purposes. The outcome data of these participants are collected through NHS England with whom a data sharing agreement has been signed (DARS-NIC-392669-T1F8B). This agreement herein does not include the collection, processing or storage of any data associated with patients in ORFAN Arms 1, 2 or 3.
ORFAN is part of the Oxford cohort for Heart, Vessels and Fat (Ox-HVF), which means the results from this study may be interpreted together with the findings of other Ox-HVF projects. The Ox-HVF cohort is a cluster of clinical studies run from the University of Oxford that together provide results which allow for the deployment of a multi-level strategy to understand the mechanisms of cardiovascular disease, specifically heart attack and stroke.
This agreement concerns ORFAN Arm 4 only, which is a retrospective study arm which includes up to 250,000 adult participants (200,000 - in the UK; 50,000 – internationally; this agreement only concerns participants located within England and Wales) who have undergone CT chest, abdomen and pelvis scans for clinical purposes at a participating NHS Trust radiology department. The ORFAN study team are focused on CT coronary angiograms in this project - scans that only include the heart and surrounding blood vessels and tissues.
ORFAN Arm 4 focuses on collecting CT images, patient demographics and clinical information including clinical outcomes and medication usage to aid the development of new CT image analysis algorithms and software tools for the practical application of these algorithms via both traditional and artificial intelligence approaches. ORFAN Arm 4 will provide the required statistical power to allow automation of image analysis processes such as the automated calculation of image analysis techniques developed by the University of Oxford. This includes the perivascular Fat Attenuation Index, the coronary artery Fat Radiomic* Profile and the Atriomic Stroke Algorithm (a novel risk algorithm interrogates the heart atria (the top chambers of the heart) to extract radiomic features, hence ‘atriomic’), as well as the development of new imaging biomarkers - this is the focus of this project. The development of these algorithms and tools has, and will lead to much improved patient care for those at risk of heart attack and stroke.
* In the field of medicine, radiomics is a discipline and collection of methods concerned with the extraction of a large number of statistical features from radiographic medical images using data-characterisation algorithms. These features, termed radiomic features, have the potential to uncover disease characteristics that fail to be appreciated by the naked eye.
Following the COVID-19 pandemic, the ORFAN study programme pivoted to include relevant research objectives related to the non-invasive assessment of cardiovascular damage caused by infection with the virus. This work has been designated by the NIHR and the British Heart Foundation as a COVID-19 Cardiovascular Disease UK Flagship Project. The influence of COVID-19 infection on the outcome measures of the study will be explored, and novel tools to assess the impact of COVID-19 infection on blood vessels and the heart will be developed. This agreement is of fundamental importance for the success of ORFAN Arm 4. Access to NHS England held data will enable the accurate ascertainment of disease status for all relevant study conditions within all participants. The breadth of relevant diseases and clinical activity for this research is large due to the complexity of accurately adjusting imaging analysis for all conditions.
The analysis that will occur will involve the adjustment of patient risk profiles for all clinical events and medication usage prior to the CT scan of interest, and adjustment of all clinical events and medication usage following the CT scan of interest. It is not possible to accurately build risk assessment models without both the prior and post CT scan patient data.
The use of NHSBSA data (Medicines dispensed in Primary Care) in ORFAN Arm 4 is in keeping with the direction for data usage for analysing the safety and effectiveness of medicines. The team's usage of this data is to understand the effectiveness and safety profile of medications for the reduction of pathological disease processes around the heart such as inflammation and fibrosis. These processes are directly linked to heart attack, stroke and atrial fibrillation. Many currently prescribed medications are likely to have this positive effect, however without access to the NHSBSA datasets and the other data in ORFAN Arm 4 (such as patient CT scans) it is not known if this effect is beneficial to patient care and on what scale (i.e. effectiveness) and if patients receiving such medications have any increased risk of adverse events (i.e. safety profile).
As an example, a specific project that will make use of Arm 4 data that has also received significant funding is explained here. This project is the development and clinical translation of the Atriomic Stroke Algorithm, which has received a BHF Translational award (TG/19/2/34831 – ‘Using radiomics and artificial intelligence to predict cardio-embolic stroke’) to validate a novel imaging biomarker for the direct prediction of stroke risk from CT images. This project intends to make use of ORFAN Arm 4 data to provide the most accurate risk assessment of individual stroke risk available. This award has unlocked new technical ability in the ORFAN project as it has funded a very powerful computer capable of processing many thousands of CT scans for deep-learning purposes. Deep-learning is the field of artificial intelligence concerned with the automated interpretation of images. In the same way that a computer can identify if a photo portrays a cat or a dog, a computer can also identify if a CT scan portrays a heart or a stomach, to use a rudimentary example. In this project, the computer will learn to identify patients with inflammation around their heart – inflammation that places them at increased risk of stroke. This computer has been purchased and installed at the University of Oxford for this project. The award also funds suitably qualified engineers to work on the ORFAN study utilising this computer for CT scan analysis purposes.
The University of Oxford research team, who will receive the pseudonymised data from NHS England, will never receive linkage files that enable the matching of the participants clinical information with their identifiable information.
The sole Data Controller is the University of Oxford who also process the data. The team is led by the Professor of Cardiovascular Medicine at the University of Oxford.
There is a third-party company, Caristo Diagnostics Ltd, which is a University of Oxford spin-out company from the Antoniades Laboratory. The Antoniades Laboratory is the research group from which the ORFAN Study is coordinated. The Laboratory includes researchers, clinical staff, administrators, data scientists, machine learning experts and PhD candidates all based at the Radcliffe Department of Medicine in the University of Oxford. This company is involved in the wider ORFAN study, along with other research studies coordinated from the Antoniades laboratory as part of the Ox-HVF stable of studies. This company will NOT be involved in any processing of NHS England data relating to this agreement and will have no data shared with it. Caristo Diagnostics Ltd also do not play any role in determining the means by which any data will be processed under this agreement.
There are no funders or commissioners directly involved in the collection or processing of data. The ORFAN study has received funding from a number of sources, however the British Heart Foundation has awarded monies specifically for ORFAN Arm 4. The specific project is the development and clinical translation of the Atriomic Stroke Algorithm via a BHF Translational award (TG/19/2/34831 – ‘Using radiomics and artificial intelligence to predict cardio-embolic stroke’). This project intends to make use of ORFAN Arm 4 data to provide the most accurate risk assessment of individual stroke risk available, as is in keeping with the ORFAN scientific aims. The British Heart Foundation has no control over the methodology of the study nor direct access to NHS England data and is therefore not considered a Data Controller.
The international sites involved in the wider ORFAN study are only contributors to ARM 2 - 3. This agreement is relevant to ORFAN Arm 4 only and the international sites have no involvement at all. No international, or domestic, organisations detailed in the protocol have access to the NHS England data except for the University of Oxford who is the sole data controller who processes the data.
The lawful basis for processing data under GDPR has been reviewed and the University of Oxford process data under Article 6(1)(e): "processing is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the controller" as they are a Public Authority.
Additionally, the University of Oxford process the Special Category Health Data under Article 9(2)(j): "processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject" as the data are required for statistical purposes in the public interest.
The public interest relevant to this work is that the research stands to greatly improve the way in which patients – that is, the public of the UK – receive care in relation to heart attack and stroke. These are the top causes of morbidity and mortality in our community and there is huge public interest in improving patient risk assessment and the management of that risk to save lives.
Update under v2:
The Civil Registrations of Death - Secondary Care Cut dataset has been replaced with the automated Civil Registrations of Death dataset.
Processing activities
The purpose of this agreement is to carry out health data related research. The agreement is to provide patient identifiable data for the purposes of linkage to health data held by NHS England. To achieve this clinical care teams from 14 NHS Trusts who are collaborating on the study will provide the minimum required patient identifiers to NHS England (NHS Number and Date of Birth, and Post Code), with 8 of the Trusts providing data under this iteration (version 1) of the agreement. This is the only flow of identifiable data that will be received by NHS England.
This amendment also allows for the expansion of the cohort, as approved by the relevant REC and the HRA CAG. The cohort was originally approved for a total of 75,000 patients from England and Wales. The cohort is now approved for a total of 200,000 patients from England and Wales. In practice, the first drop of data from NHS England will include some 110,000 patients, and the second will include the full 200,000 (inclusive of the original 110,000). The 10 NHS Trust sites which will be participating in the first drop are identified below.
Under this (version 1) Agreement, only data from 10 collaborating NHS Trusts (marked with *) will flow to NHS England. There is an intention to include the further 3 Trusts in this data flow over the following year preceding the second drop of data.
The following NHS Trusts are collaborating on the study:
Oxford University Hospitals*
Royal United Hospitals Bath*
Milton Keynes University Hospital*
University Hospitals of Leicester*
Barts Health*
Royal Brompton and Harefield*
Leeds Teaching Hospitals*
Royal Papworth Hospital*
Guy's and St Thomas’ *
Sandwell & West Birmingham Hospitals*
University Hospitals Birmingham
Manchester University
The Royal Wolverhampton
The data subjects are adults (18-99 year old) who have undergone a relevant CT scan at a NHS Trust where the local clinical team is collaborating on the ORFAN Study Arm 4.
The relevant CT scans include only clinically indicated and successfully performed scans, specifically a CT angiogram (CTA) or CT chest, abdomen and pelvis scan.
The data required is concerned with identifying what diagnoses, clinical events and therapy occurred both prior to the relevant CT scan (from 2005 onwards) and after the CT scan. The data required includes hospital episodes (emergency department attendances, inpatient admissions, critical care admissions, and outpatient clinics), with the focus on diagnoses made during those episodes and procedures that occurred at those episodes. The data required also includes medicine prescribed in the community both prior to and after the CT scan as this greatly influences risk of future disease through the reduction of risk. To address the research objective of how COVID-19 infection influences cardiovascular disease risk the study team will request data related to COVID-19 infection and its severity. Death data is also needed to understand which patients in the study have passed away. Otherwise these patients will be incorrectly included in certain analysis. The data sets requested from NHS England are:
- Civil Registrations of Death (in place of Civil Registration (Deaths) - Secondary Care Cut )
- COVID-19 Hospitalization in England Surveillance System (CHESS)
- Emergency Care Data Set (ECDS)
- Hospital Episode Statistics Accident and Emergency
- Hospital Episode Statistics Admitted Patient Care
- Hospital Episode Statistics Critical Care
- Hospital Episode Statistics Outpatients
- Medicines dispensed in Primary Care (NHSBSA data).
The University of Oxford requires the following ethnic category and sex variables sensitive fields for the stated datasets:
ECDS: Ethnic category
HES OP: Ethnic category and Sex of patient
HES APC: Ethnic category and Sex of patient
HES AE: Sex of patient
COVID-19 Hospitalization in England Surveillance System: Ethnicity and Sex
Medicines dispensed in Primary Care: Gender
This ensures that the University of Oxford has the required data to investigate the difference in cardiovascular disease outcomes related to COVID-19 infection and cardiovascular complications. This comes following the release of observational data suggesting that both ethnicity and sex is a major predictor of adverse outcomes, both cardiovascular and otherwise, from COVID-19. The inclusion ensures that the cohort can be utilised to investigate these different impacts. Excluding these variables the study would have lacked the statistical power to investigate these differences. The work to create imaging based risk prediction signatures must be informed by understanding of underlying disease, and if ethnicity and/or sex is leading to different disease processes then different risk signatures will need to be developed to best suit the individual. To apply risk signature blind to ethnicity and sex would be unacceptable. The inclusion of both sex and gender variables is by design, as both biological sex and self-assigned gender can act as relevant variables that influence individual health, particularly relevant when assessing contagious diseases such as COVID-19.
The study team is aware that the definition for sex and gender fields may differ across the datasets disseminated under this agreement. The team will take care to ensure this is considered, otherwise this may have a significant negative impact on the research and the expected benefits.
The first drop of all historical data would be after this agreement is signed off, with some 110,000 participants from 10 Trusts, and a second drop using the complete Arm 4 ORFAN cohort of 13 Trusts and up to 200,000 patients in October 2023.
The ORFAN Arm 4 data is analysed only for the purposes of the ORFAN project – to develop and validate imaging biomarkers of cardiovascular disease risk. The ORFAN Arm 4 data as received from NHS England will be analysed alongside the actual CT images from the linked patients. This is performed in a completely pseudonymised manner with the only link between the data extracted from NHS England and the original CT scan being the study ID originally assigned by the local NHS Trust clinical care team where the patient received care.
The second follow up of patient outcomes via NHS England data will further enable the correct ascertainment of individual patient risk through further refinement of imaging biomarkers as increasing numbers of patients suffer from clinical events of relevance to the ORFAN Study.
METHODOLOGY
For the first drop of NHS England data at the start of the agreement, the clinical care teams at each collaborating NHS Trust will generate a list of their own patients who met the participation requirements for ORFAN Arm 4. This list will be established and stored within the local NHS Trust firewall at the site where the patient was treated in the first instance. The clinical care teams will assign a unique ORFAN Arm 4 study ID to each participant. When ready and instructed to do so, the clinical care teams will send their ORFAN Arm 4 patient list, including identifiers: NHS Number, Date of Birth, and Postcode, plus ORFAN Study ID. Cohorts will be sent in via the Secure Electronic File Transfer (SEFT) service. 10 Trusts will initially provide their cohorts to NHS England.
NHS England combines the 10 Trusts' cohorts to create one full ORFAN Arm 4 cohort. NHS England will then link and extract the required data fields from the required data products and remove identifiers (leaving the Study ID).
NHS England send the pseudonymised data extracts to the Study team at University of Oxford via SEFT. No data is sent back to the 10 NHS Trusts that provided the patients that are included in the cohort.
For the second drop of NHS England data in October 2023, NHS England retrieves the full ORFAN Arm 4 cohort from storage and adds the additional patients as submitted by the remaining 3 NHS Trust sites that did not participate in the original upload for drop 1. NHS England links and extracts the required data fields from the required data products and removes identifiers (leaving the Study ID). NHS England send the pseudonymised data extracts to the Study team at University of Oxford via SEFT. This second drop will include all historical data for the patients not included in drop 1, but only data for the periods 2020/21, 2021/22, and 2022/23 for those who were already included in drop 1. This will prevent the duplication of data linkage.
There is no subsequent flow of pseudonymised data from the data recipient, the University of Oxford, to any other organisation.
DATA MINIMISATION
The study team consider the data they have requested as adequate for the scientific aims of the ORFAN Study protocol, and will achieve the purposes of creating novel risk prediction tools for common cardiovascular diseases. All data requested is relevant to the risk of cardiovascular disease and its complications, and most importantly the request is limited to the achievement of the ORFAN Study aims only.
The NHS England datasets requested will be linked to the ORFAN Arm 4 cohort of approx. 110,000 for the first drop and 200,000 participants for the second drop.
The study only request linkage to datasets held by NHS England that are fundamental to the scientific aims of the ORFAN Arm 4 study. No requested linkages are superfluous to the study or hold data that will not be utilised in statistical models as proposed in the ORFAN Study protocol. The datasets requested cannot be reduced because all datasets as requested hold necessary data for the successful completion of the ORFAN Arm 4 project.
The scientific purpose of the ORFAN Arm 4 requires pseudonymised data only, and no identifiable data is requested.
The number of years requested corresponds to the scientific aims of the ORFAN Study. The study team need to know the background medical conditions, hospitalisations and procedures that the participants had in order to adjust the statistical analysis to account for prior risk. This is necessary when creating risk algorithms that seek to predict an individual's risk of a specific medical condition. The study team request data linkage for the years supported by the CAG. This is from 2005 through until the current time, with repeat extraction supported for 10 years following the commencement of CAG support. The ORFAN Study team has compromised on how many years to request linkage for, as the more retrospective years of linkage included within the study, the more accurate the risk prediction algorithms would become. However, 16 years of previous risk of events (2005 through 2021) will provide enough relevant information regarding the participants in ORFAN Arm 4 to allow successful adjustment of the risk algorithms. For example, if a patient had a stroke 5 years prior to the CT scan this will mean that patient is analysed in a different way to patients who did not have such an event.
This study must consider geographic differences in exposure to cardiovascular disease risk factors, differences in socio-economic status and differences in access to health care. It would not be acceptable to include all 200,000 participants from the Oxford University Hospital (OUH) NHS Trust as this analysis would be prone to bias. On more practical terms, it is not possible to enrol patients from a single or smaller number of NHS Trusts due to the fact that most CT radiology services only have several thousand patients relevant to inclusion in the study. For example, the OUH NHS Trust has at most 6,000 relevant participants who could be enrolled in ORFAN Arm 4. For this reason, the study team must extend to multiple NHS Trusts so that the total number of participants is appropriate to achieve the scientific aims of the study.
The study team are only considering participants from across England and Wales. The cohort needs to include all episodes of care across this area as events that occurred at any relevant hospital must be considered in the algorithm. The cohort is limited to those aged 18 years and over. The cohort is primarily limited by the fact inclusion requires a participant to have received a study relevant clinical computed tomography (CT) scan. For the most part, for ORFAN Arm 4, this means the participant must have received a clinical CT coronary angiogram (a specific CT scan of the heart).
The ORFAN Study requires all episodes of care, both elective and emergent, to achieve the purpose, bar maternity episodes. The study team do not require maternity episodes and do not require unborn child and neonatal records. Elective episodes are important as these often capture procedures of relevance to cardiovascular disease risk.
The study team have selected the minimum number of fields per dataset that are required for the successful fulfilment of the ORFAN Study scientific objectives. These fields are all necessary for the adjustment of the risk algorithms for cardiovascular disease and as such these fields will be used in the models, or to adjust specific risk factors by severity and/or the confounding of treatment (medical and surgical) prior to being fed into the models. Dates of death can be transformed into the format MM/YYYY.
Following receipt of the linked pseudonymised data from NHS England by the ORFAN Study team at the University of Oxford, the study team will perform statistical analysis to develop disease risk models in accordance with the scientific objectives of the ORFAN Study as outlined in the ORFAN Study protocol approved by the Health Research Association’s (HRA) Research Ethics Committee. This processing will include importing the data into statistical data analysis software. The analysis will include the development of models for the prediction of disease such as stroke and heart attack and will involve the simultaneous analysis of CT imaging data (not sourced from NHS England).
There will be linkage of the NHS England data to the CT scan of the relevant patient that rendered them eligible for inclusion in ORFAN. This linkage occurs through the unique ORFAN Study ID originally assigned to the patient by the patient’s own clinical care team at the NHS Trust where they were treated. Along with sending the minimum required patient identifiers to NHS England for linkage, the local clinical care teams will also extract, pseudonymise and assign the corresponding unique patient ID to the relevant CT scan, and then send this scan to the ORFAN Study team. This will enable the ORFAN study team to analyse the scan in combination with the data received from NHS England, a key aspect in achieving the scientific aims of the study.
The ORFAN study team will also request data from national registries (or NHS England when available) such as National Institute for Cardiovascular Outcomes Research (NICOR) and the Sentinel Stroke National Audit Programme (SSNAP), both controlled by Healthcare Quality Improvement Partnership (HQIP) and intend to link the pseudonymised NHS England data to ORFAN study participants events recorded in these national registries. This linkage will be through the unique ORFAN study ID only, not identifiable data. Linkage of NHS England data with NICOR / SSNAP data, would be subject to an amendment of this data sharing agreement prior to the linkage taking place.
There will be no matching of data to publicly available data sources. There will be no requirement or attempt to re-identify any study individuals in ORFAN Arm 4. No ORFAN Arm 4 patients will ever be contacted by the ORFAN Study team, or anyone else on behalf of the ORFAN study team.
Data processing will only be carried out by those who are substantive employees, with formal contracts, of the data processors or the data controller, the University of Oxford.
Once pseudonymised data is received from NHS England by the ORFAN Study team at the University of Oxford, the data is saved without any manipulation on secure University of Oxford servers located in University premises, namely the Acute Vascular Imaging Centre at the John Radcliffe Hospital, Oxford. This back up is only for disaster recover purposes and is not accessible to any ORFAN researchers/others bar senior University IT staff working in the Division of Cardiovascular Medicine. Both servers are in environment-controlled rooms, with uninterruptable power supplies and fire/flood monitoring. All server rooms require swipe card and physical keypad access, and users are credentialed by both the University of Oxford and the Oxford University Hospital NHS Trust.
The main copy and the back-up copy of the data is controlled by the study team lead, Professor of Cardiovascular Medicine, as the named ORFAN data controller. The study team lead will assign access to the dataset to credentialed researchers actively working on the ORFAN Arm 4 project.
The data will be held on servers owned by the University of Oxford, with the primary storage at the Acute Vascular Imaging Centre at the John Radcliffe Hospital and the secure back up at the Oxford Centre for Clinical Magnetic Resonance Research, also at the John Radcliffe Hospital but in a separate stand-alone building.
No third party organisations listed in the ORFAN Study protocol will receive pseudonymised data that has come to the University of Oxford from NHS England for ORFAN Arm 4. The University of Oxford and their ORFAN Study group is the only and final recipient of such data.
The investigators listed in the ORFAN Study protocol do not all retain rights to access ORFAN Arm 4 study data. Only the core ORFAN Study Team at the University of Oxford who have undertaken the appropriate training and have formal contracts in place with the University of Oxford may be eligible to access pseudonymised data disseminated to the University of Oxford from NHS England.
Data will not be made available to any third parties other than those specified except in the form of aggregated outputs with small numbers suppressed in line with the HES Analysis Guide.
Update under v2:
The cohort comprises 90,552 participants from 9 collaborating trusts. Recruitment of collaborating sites is ongoing with a final target cohort size of 200,000.
Expected output
The major outputs from this data processing are twofold:
1) The creation of novel disease risk calculating algorithms (patient assessment algorithms and the necessary software tools to practically apply the algorithms) for conditions such as heart attack and stroke ready for incorporation into patient care within health services, and
2) the communication of these outputs via scientific and lay-person publications.
The research outputs to convey the results will be led by peer reviewed publications in leading international journals, presentations in international and national scientific meetings and subsequent media reporting and public engagement lead by the University of Oxford.
Journals being targeted to submit to/publish in:
i) The New England Journal of Medicine (NEJM) (impact factor 74.7)
ii) The Journal of the American Medical Association (JAMA) (impact factor 45.5)
iii) The Lancet (impact factor 60.4)
iv) Circulation (impact factor 23.6)
v) Journal of the American College of Cardiology (JACC) (impact factor 20.5)
vi) British Medical Journal (BMJ) (impact factor 30.2)
vii) European Heart Journal (EHJ) (impact factor 22.7)
The study team intend major findings of this work to be published in the top-tier general medicine journals (NEJM, JAMA, Lancet, BMJ) as opposed to more cardiac specific findings which will be aimed at the top cardiology journals (Circulation, JACC, EHJ). This enables far greater readership and targeting of impact. All publications in major journals such as those listed here will be open access, meaning any reader from anywhere on Earth can access the full text of the research article without any cost.
Congresses and conferences targeted to submit work to:
i) Scientific sessions of the American Heart Association
ii) Scientific sessions of the European Society of Cardiology
iii) Scientific sessions of the American College of Cardiology
iv) Scientific sessions of the British Cardiac Society
The outputs from this work will be both immediate - with publications in high impact journals within 2-3 years of the commencement of the agreement as well as long-term - when diagnostic biomarkers are implemented in clinical practice. As the ORFAN study is expected to continue collecting outcomes data for at least the next 10 years, the cohort will continue to generate outputs as more events accumulate over time. These long-term impacts have the potential to change clinical practice worldwide and save lives from improved assessment of cardiovascular disease risk.
Specific algorithms that the ORFAN Study team wish to create and/or validate through the ORFAN arm 4 study include:
1) An algorithm for the specific risk assessment of ischaemic stroke in those with and without atrial fibrillation (provisionally called the Atriomic Stroke Algorithm)
2) An algorithm for the specific risk assessment of cardiovascular complications in those with COVID-19 infection
3) An algorithm for the likelihood of success of invasive catheter ablation in those with atrial fibrillation
4) Validation of the perivascular Fat Attenuation Index (FAI) algorithm for heart attack risk. The FAI algorithm is an already established algorithm for the accurate assessment of heart attack risk, discovered in the ORFAN Study. FAI involves the assessment of CT scan features, in particular attenuation – the CT term for density of fat surrounding the coronary vessels.
5) Validation of the Fat Radiomic Profile (FRP) algorithm for heart attack risk. The FRP algorithm is another already established algorithm for long-term heart attack risk discovered in the ORFAN Study. This algorithm relies upon many radiomic features extracted from CT scans from around the coronary vessels. These features cannot be seen by the naked eye, and so require computer extraction and assessment which is what the FRP computes.
6) Likely other algorithms related to specific at risk population depending on data quality and statistical power
All such algorithms are stand-alone patient assessment tools, and any intellectual property created from within the ORFAN Study will be owned by the University of Oxford, and associated intellectual property will be controlled by the University for licensing to health services for inclusion in clinical practice.
The ORFAN research team at the University of Oxford has no personal intention to monetise or generate income from the research outputs generated from the ORFAN Arm 4 study. Were discoveries to be made in the ORFAN Arm 4 study, individual researchers within the ORFAN team would be listed inventors on any patents that the University of Oxford may file.
The study team expect to be publishing important findings related to the development of novel disease risk assessment for cardiovascular disease within 2-3 years of the DSA commencing. It is possible this may occur earlier if the extraction of data in the first year produces enough scientific power for robust results. The study team expect novel diagnostic and risk assessment tools to be incorporated into clinical practice within 5 years from the DSA commencing, and further major publications related to the use of the tools developed from within the ORFAN study by the end of the 10 year data retention date.
The level of data contained in the outputs is aggregate data with small number suppression applied as per the disclosure rules for the various data sets that have been augmented via statistical processes. No individual participants data is ever published individually, with the nature of this scientific work demanding high numbers of participants data for the testing and validation of disease risk calculators.
The dissemination activities of the ORFAN Study team are focused on high-impact peer reviewed journals and oral research presentations at international conferences. Other activities through which the ORFAN study findings are communicated include through NHS Trust clinical grand-round meetings (at NHS Trusts who deliver services relevant to those explored in the study), NHS Trust newsletters (delivered to staff emails) and through high level meetings with NHS executives and clinical leads at NHS Trusts (to discuss the suitability for the clinical tools to be tested within the clinical environment at their Trusts). This work also involves audit related work to model the impact of novel tools developed from within ORFAN on current service usage, as has occurred within Oxford University Hospitals NHS Trust already.
To target the lay audience, the ORFAN team uses the following approaches and is guided by the Research Services team at the University of Oxford and the Public Engagement team at the Cardiovascular Medicine Division of the University of Oxford:
a) Website (www.oxhvf.com): this is updated with all the most up to date information regarding the outputs of the research. This is a public-facing website, and the public can read about the latest outputs of the study.
b) Newsletters: when major findings or general outputs are available, the ORFAN team post newsletters both on the website and in hard-copy form to ORFAN Arm 1-3 participants. This is not possible for Arm 4, as the University of Oxford do not hold patient identifiable information. Media attention including articles in BBC News, The Guardian, The Financial Times and CBN concerning work published in the prestigious journal ‘Science Translational Medicine’ are the sorts of topics highlighted in newsletters (see example from the Antoniades Lab: https://test188076.files.wordpress.com/2018/01/newsletter-adiporedox-15-09-2017.pdf).
c) Press releases: the ORFAN team have an active involvement in outreach activities of the University of Oxford, Oxford University Innovations and the British Heart Foundation communications team, and the major findings from their study lead to press releases. From there they are distributed to the lay press.
d) Workshops and patient and public involvement: the ORFAN team participate in workshops for patients as part of the Biomedical Research Centre in Oxford. Through these workshops they inform the patients about their research and ask for their involvement in the design of protocols, feedback on research procedures and more. This is also done through Patient and Public involvement (PPI) panels.
e) Social media – the ORFAN Study group frequently share results and outputs to their social media presence on Twitter, Facebook and LinkedIn.
Exploitation of results/outputs:
All intellectual property and knowhow is owned by the University of Oxford, as the sponsor of the ORFAN Study. The University of Oxford, through Oxford University Innovation, maintains the ability to licence any technology that is created within the ORFAN Study for commercial use or for use within health services such as the NHS.
Update under v2:
The initial results from analysis of the first data drop has been performed and was presented in international conference (American Heart Association 2023). The study team aim to publish the full findings in Q2 of 2024.
Expected measurable benefits
The dissemination of the data stands to have a huge impact on the provision of cardiovascular care within the UK and further afield. The creation of novel means to assess a patient’s individual risk for heart attack and stroke could revolutionise the way that clinicians currently deal with these deadly diseases. Current means to inform a patient of their risk for both heart attack and stroke rely on population-wide data based upon demographics (such as age) and clinical measures such as blood pressure. Although these are important risk factors, these clinical tools fail to consider some of the most fundamental causes of heart disease that can now be detected, such as inflammation around the heart and the effect of adipose tissue adjacent to the heart muscle, and hence provide poor accuracy for patients.
The personalisation of risk assessment, as the ORFAN study sets to create via access to NHS England data and other sources, unlocks personalised clinical approaches that can provide the right therapy or monitoring for the right patient, at the right time, more often than is currently achieved – saving clinical time and health service resources while improving the health outcome for the patient. The COVID-19 arm of ORFAN Arm 4 is set up to explore the cardiovascular consequences of COVID-19 infection and stands to provide important benefits to patients in regards to the personalised assessment of disease risk for Covid patients following their acute illness with the virus. This benefit stands to be hugely important to the UK, with very high Covid rates and unknown consequences for heart disease and how to assess risk for individual patients.
The dissemination of ORFAN Study findings is in the public interest due to the profound benefits that this work could have on patient care for those at risk of very common conditions including heart attack and stroke. These conditions remain the top two leading causes of death in our society, and efforts to reduce early mortality have stalled in recent years. The ORFAN Study intends to create tools for the most accurate assessment of cardiovascular disease risk available to patients. The dissemination of these tools to clinicians, once appropriately validated, is entirely within the interests of the UK public so that they can receive better care. The dissemination of the requested NHS England data for this project is fundamental to the success of the scientific aims, and is firmly in the interest of the UK public.
The outputs hope to facilitate the improvement of patient care in the interests of the UK public. The benefits of processing this data are to develop tools that stand to directly improve patient care in regards to common cardiovascular disease including heart attack and stroke. The dissemination of the research findings should enable uptake of these technologies within the UK and abroad, and provide better management options to patients so that they can avoid the morbidity and mortality associated with cardiovascular disease.
The linkage of NHS England data to patients identified by local NHS Trust clinical care teams as being suitable for inclusion in the ORFAN Study arm 4 is fundamental to the achievement of the scientific aims of the ORFAN Study, particularly to create novel disease risk assessment tools for heart attack and stroke. The statistical power to test and validate the novel risk assessment tools is not possible without the requested data. The study team hope that the
analysis of these data as disseminated by NHS England will enable the creation of the necessary tools, as the study team will be able to adjust the analysis for the relevant clinical events/disease diagnoses/medications that the patient had prior to the CT scan and after the CT scam. Without this information, the analysis is not possible and there would be no advancement of this scientific field and no advancement of early risk assessment through imaging biomarkers for heart attack and stroke.
ORFAN Arms 1, 2 and 3 all involve the direct consent of patients, and the direct follow up of these patients over time. It is not feasible for enough participants to be enrolled into these consented study arms to enable the research to successfully fulfil the scientific objectives and create tools for clinical usage. ORFAN Arm 4, and the requested dissemination of NHS England data as a part of that arm, will facilitate the necessary statistical power to develop and test the tools that emerge from ORFAN Arms 1-3 and the other complementary studies within the Oxford Heart Vessel and Fat research group (Ox-HVF) coordinated by the University of Oxford.
An obvious continuation of this same project would be to test the perivascular Fat Attenuation Index in the ORFAN Arm 4 cohort, to investigate if the biomarker is able to accurately predict patients who will go on to suffer from heart attack following their CT scan. Such an experiment requires large numbers of participants, with complete datasets of background risk factors and events (diagnoses prior to the CT scan), the CT scan itself, and outcomes data (diagnoses/events following the CT scan).
The Study expect to be publishing key findings related to the development of novel disease risk assessment for cardiovascular disease within 2-3 years of the DSA commencing. The study team expect novel diagnostic and risk assessment tools to be incorporated into clinical practice within 5 years from the DSA commencing, and further publication of the use of these tools from within the ORFAN study, reliant on this agreement by 10 years.
The outputs are hoped to change the clinical approach to patients at risk of heart attack and stroke who have been referred to receive a CT scans that includes their heart. The tools that the ORFAN study intends to create are for the advanced interpretation of these scans, and are hoped to provide clinician with information related to individual disease risk for the specific patient. This information is not currently available from these scans. This information can then be used to change lifestyle and medical therapy as appropriate and/or to change monitoring of that specific patient as appropriate, with the aim being to reduce the patients individual risk for harm. A simplified example of how such tools can impact on an individual patient’s care is provided: A patient has chest pain and is referred for a CT scan of their heart; CT scans are the National Institute for Health and Care Excellence (NICE) and European Society of Cardiology (ESC) recommended first line investigation for chest pain. The scan shows clear coronary arteries free from blockage however when the novel Fat Attenuation Index (FAI) is assessed on the scan the patient is found to have highly inflamed coronary arteries. This patient is likely at elevated risk of heart attack despite no visible blockages. This patient could then be placed on anti-inflammatory medication and monitored carefully for a period as opposed to discharge without any change in therapy and monitoring, as is currently the status quo for a patient with arteries free of blockage. The FAI is a previously developed novel CT measure of coronary artery inflammation developed by the Antoniades laboratory using ORFAN and other studies.
The development of such imaging biomarkers enables more personalised disease risk assessment for patients. These biomarkers are concerned with individualised assessment of risk for common conditions such as heart attacks, strokes and atrial fibrillation. Risk assessments for such conditions are currently based on classical approaches to risk factors that provide blunt population level risk data that are difficult for clinicians and patients to interpret. Risk assessments that make use of biological processes that directly relate to the disease, such as measuring the level of inflammation surrounding the coronary arteries, as is possible with the Fat Attenuation Index, and relating this to other information such as a patients age and cholesterol level, can provide highly accurate and personal risk assessments that clinicians and patients can utilise to reduce risk of events. These risk assessments can be utilised to enact closer monitoring of patients, to motivate lifestyle changes and to guide pharmacological therapies in a way that has not previously been possible.
45’000 CTA scans (CT scans of the heart) are performed in UK per year to manage chest pain, expected to increase to >350’000 when the 2016 NICE guidelines are fully implemented. The 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes recommends CTA as the first line test for the diagnosis of coronary artery disease in all symptomatic patients. This class 1 recommendation will further see the use of CTA increase across Europe. Currently, 80% of CTAs reveal no significant coronary disease, a number that is expected to increase with increasing scan rates. In addition, non-contrast CT scans of hearts are routinely used for screening the population for coronary calcification, as part of risk stratification. As these scans are all focused on the coronaries, any other information is missed. By way of example utilising stroke: An automated technology that can provide risk stratification for stroke and heart attack as a standard element of clinical CTA reporting, may predict (and potentially prevent) up to 900 strokes/year based upon current uptake of CTA in the UK. The study team expect that the method could identify patients with atrial myopathy at risk for cardio-embolic stroke, over and above clinical risk prediction tools such as the widely utilised CHA2DS2-VASc score, so they can be referred for ECG monitoring or possible anticoagulation therapy to prevent events. The proposed technologies to be developed in the ORFAN study can be applied retrospectively to existing cardiac CT scans, acquired with or without contrast, or prospectively as part of usual clinical care.
The financial impact of heart attack and stroke on UK society is very large. Again, utilising the stroke example: 1 in 6 people in the UK will have a stroke during their lifetime, with enormous socioeconomic impact. The average cost of stroke per person is £40,000 in the first 12 months after the event (cost of incident stroke), followed by a lifetime average cost of £25,000/person/year. Grossly, the overall annual cost of stroke to UK society is £26 billion. The rate of first-time strokes in people >45 years old is expected to increase by 59% in the next 15 years, with worldwide stroke-related illness, disability and early death set to double by 2035. The prevention of every stoke via enhanced tools for the detection of risk stands to save enormous resources within the UK’s NHS, and could be an immensely valuable tool for clinicians to wield to both prevent events, but also to better target therapies to those that actually need them – preventing waste.
The possible benefits are hoped to be achieved by the study sponsor, the University of Oxford. Intellectual property developed through this work will be owned by the University of Oxford. Benefit will be measured in the short-term by the impact of peer-reviewed academic publications and presentations of the work at international cardiology conferences. The final result of this work is anticipated to be a number of automated risk algorithms that empower both patients and clinicians with highly accurate prediction of disease events, such as a heart attack or stoke, within the following 5 years. This risk prediction is currently very poor and enhanced prediction ability is critical for managing patients in regard to lifestyle changes, monitoring and the initiation or escalation of medical therapy. The long-term benefit will be measured by the total number of patients for whom the disease assessment tools are applied to clinically, and how many clinical events are assessed to have been prevented through the technology. This longer-term impact will require specific study to understand, and the ORFAN study will enable this through the 10-year follow-up period as requested in this DSA. It should be possible to adjudicate which patients do go on to suffer clinical events via the requested annual NHS England data extractions, hence allowing an ongoing enquiry into the effectiveness of the diagnostic and risk assessment tools that the study team propose to develop.
Results related to the development of novel imaging tools for the prediction of heart attack and stroke will be available within 2 years of the commencement of the DSA. The results are hoped to be published and subsequently updated in the following years once further clinical outcomes data is collected from NHS England, as requested. The project is forecast to be finally concluded at the end of the 10 year follow up period as agreed to within the agreement, at which time all final analysis of the outcomes will occur and final validation papers will likely be published, although the study team anticipate by then the tools developed for the assessment of individual patient risk to be adopted clinically and clinical trials to be ongoing as to the effectiveness of the tools.
Benefits reported so far
The University of Oxford ORFAN team have previously produced multiple results included from Arms 1, 2 and 3 of the ORFAN study that have been published academically and reported upon within the lay press. Some noteworthy examples include:
Evidence that obesity may not be necessarily bad for all patients, and those patients with high body mass index may be protected against cardiovascular mortality because fat in the body may secrete protective substances. This is called the obesity paradox and has major implications for the treatment of patients with heart diseases (published in the journal Diabetes in 2015).
The University of Oxford (ORFAN team) has recently identified a significant therapeutic target for the treatment of heart diseases, and that discovery led to intense research to develop new drugs to modify this target (presented in the European Society of Cardiology 2018 Congress, and received the Best Poster Award).
The University of Oxford ORFAN group has developed a novel imaging biomarker (see Antonopoulos et al in Science Translational Medicine, 2017), namely the Fat Attenuation Index (FAI), which has been shown to be a marker of vascular inflammation at early disease stages. Validation of this biomarker in large cohorts of patients with residual cardiovascular risk showed that FAI is able to detect patients at high risk for cardiac mortality and is also predictive of non-fatal heart attacks. This permits reclassification of an individual's risk, above and beyond the current state-of-the-art diagnostic tools, with strong implications for guiding medical management in patients and guiding the use of primary and secondary prevention measures. The development of this technology is a significant example that highlights the strength and unique ability of the Ox-HVF cohort in combining data across different and diverse fields - from clinical and epidemiological data to basic science and imaging data to outcome data - to create new, boundary-pushing ideas that promote health and serve the public interest. Of note, FAI was featured by iNews as one of the ten health innovations that could soon be on the NHS, and has been featured by the BHF as a technology soon to enter clinical practice (https://www.bhf.org.uk/what-we-do/our-research/research-successes/artificial-intelligence-and-heart-attack). FAI has been identified as a technology that can provide significant financial benefits to health systems (https://www.ft.com/content/6ff32188-8821-4272-80b9-53ac81463d97). FAI has been included into the recent Up-To-Date clinical guidance for use in patients with chest pain (Hoffmann, U. & Manning, W.J., 2022, ‘Cardiac imaging with computed tomography and magnetic resonance in the adult’, UpToDate.com, updated February 2022 & accessed 15 March 2022, URL: https://www.uptodate.com/contents/cardiac-imagingwith-computed-tomography-and-magnetic-resonance-in-the-adult) and can be used to detect patients who may need intense medical therapy to prevent future heart attacks.”
Update under v2:
Through publication of findings in appropriate media, the findings of this research have added to the body of evidence on cardiovascular disease risk.
1. Establishing epicardial adipose tissue as a marker of unhealthy visceral obesity to predict cardiovascular risks such as stroke.
- Presentations: European Society of Cardiology Congress 2021; the American Heart Association Scientific Sessions 2021; the British Atherosclerosis Society 2021 Annual meeting.
- Publications: West et al., JACC Cardiovascular Imaging, 2023.
2. Prediction of in-hospital mortality from COVID-19 with imaging biomarker on CT scans.
- Publications: Kotanidis et al., Lancet Digital Health, 2022 (doi: 10.1016/S2589-7500(22)00132-7)
3. Using cardiac CT scans for prediction of future heart attacks.
- Presentations: the American Heart Association congress 2023.
- About 300,000 cardiac CT scans are expected to be performed in the UK per year. Currently, the majority (~80%) of the scans show no significant coronary artery disease and are achieved in the hospital system. Analysing imaging biomarkers in theses scans in relation to the linked clinical data supported by NHS England enables the use of these resources to tailor preventative treatment in vulnerable patients.
- Integrating metrics of coronary inflammation (FAI Score) with traditional cardiovascular risk factors in an artificial-intelligence enhanced risk stratification tool were shown to be predictive of heart attacks that was recorded in the NHS England data. This had gained significant media coverage including Financial times, Guardian, Evening Standard, the Independent, and the British Heart Foundation) https://www.bhf.org.uk/what-we-do/news-from-the-bhf/news-archive/2023/november/ai-tool-could-help-prevent-thousands-of-heart-attacks#:~:text=The%20team%20used%20a%20new,predict%20risk%20of%20cardiac%20events.)
Datasets on the current version
Legal basis for provision: Health and Social Care Act 2012 - s261 - 'Other dissemination of information'
| Dataset | Type of data | Sensitivity | Frequency | Confidential data |
|---|---|---|---|---|
| Civil Registrations of Death | Anonymised - ICO Code Compliant | Sensitive | Ongoing | Section 251 NHS Act 2006 |
| Civil Registrations of Death - Secondary Care Cut | Anonymised - ICO Code Compliant | Sensitive | Ongoing | Section 251 NHS Act 2006 |
| COVID-19 Hospitalization in England Surveillance System | Anonymised - ICO Code Compliant | Sensitive | One-Off | Section 251 NHS Act 2006 |
| Emergency Care Data Set (ECDS) | Anonymised - ICO Code Compliant | Sensitive | Ongoing | Section 251 NHS Act 2006 |
| Hospital Episode Statistics Accident and Emergency (HES A and E) | Anonymised - ICO Code Compliant | Non-Sensitive | One-Off | Section 251 NHS Act 2006 |
| Hospital Episode Statistics Admitted Patient Care (HES APC) | Anonymised - ICO Code Compliant | Non-Sensitive | Ongoing | Section 251 NHS Act 2006 |
| Hospital Episode Statistics Critical Care (HES Critical Care) | Anonymised - ICO Code Compliant | Non-Sensitive | Ongoing | Section 251 NHS Act 2006 |
| Hospital Episode Statistics Outpatients (HES OP) | Anonymised - ICO Code Compliant | Non-Sensitive | Ongoing | Section 251 NHS Act 2006 |
| Medicines dispensed in Primary Care (NHSBSA data) | Anonymised - ICO Code Compliant | Non-Sensitive | Ongoing | Section 251 NHS Act 2006 |
Files released
Files released counts only files released externally by DARS. Access granted in NHS England's own systems, such as its Secure Data Environment, is not included.
Patient opt-outs were applied to all 90 files released under this agreement, across every version. About opt-outs
Files released against version 2.5 of this agreement, summarised by dataset.
| Dataset | Files | First released | Last released | Opt-outs applied |
|---|---|---|---|---|
| Civil Registrations of Death | 3 | March 2024 | March 2026 | Yes |
| Medicines dispensed in Primary Care (NHSBSA data) | 3 | August 2024 | July 2026 | Yes |
| Emergency Care Data Set (ECDS) | 2 | November 2024 | November 2025 | Yes |
| Hospital Episode Statistics Admitted Patient Care (HES APC) | 2 | October 2024 | October 2025 | Yes |
| Hospital Episode Statistics Critical Care (HES Critical Care) | 2 | October 2024 | September 2025 | Yes |
| Hospital Episode Statistics Outpatients (HES OP) | 2 | October 2024 | September 2025 | Yes |
Version history
The register lists each renewal of this agreement as a separate row. This site has 3 versions.
DARS-NIC-409610-J6L1F-v2.5 7 March 2024 to 6 March 2027
- Title
- The Oxford Risk Factors And Non Invasive Imaging Study (ORFAN) Arm 4
- Commercial
- No
- Sublicensing
- No
- Datasets
- 9
- Files released
- 14
Datasets: Civil Registrations of Death; Civil Registrations of Death - Secondary Care Cut; COVID-19 Hospitalization in England Surveillance System; Emergency Care Data Set (ECDS); Hospital Episode Statistics Accident and Emergency (HES A and E); Hospital Episode Statistics Admitted Patient Care (HES APC); Hospital Episode Statistics Critical Care (HES Critical Care); Hospital Episode Statistics Outpatients (HES OP); Medicines dispensed in Primary Care (NHSBSA data)
What changed from DARS-NIC-409610-J6L1F-v1.9
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Start date | 2024-03-07 | |
| End date | 2027-03-06 |
Datasets:
+ Civil Registrations of Death · − HES:Civil Registration (Deaths) bridge
Objective for processing
[2 paragraphs unchanged]
The University of Oxford is applying to NHS
Digital,
England,
in order to link data subjects within the scope of the study with data held by NHS
Digital.
England.
This linkage is necessary in order to develop and validate cardiovascular disease
[29 words unchanged]
clinical environment and are intended to change patient care for the better.
[1 paragraph unchanged]
The NHS
Digital
England
data requested in this agreement could contribute in a fundamental way to
[68 words unchanged]
within the CT scans) that can be utilised to predict patient risk.
[14 paragraphs unchanged]
The ORFAN study at large consists of 4 Arms of study. Arms
[45 words unchanged]
research purposes. The outcome data of these participants are collected through NHS
Digital
England
with whom a data sharing agreement has been signed (DARS-NIC-392669-T1F8B). This agreement
[10 words unchanged]
any data associated with patients in ORFAN Arms 1, 2 or 3.
[4 paragraphs unchanged]
Following the COVID-19 pandemic, the ORFAN study programme pivoted to include relevant
[75 words unchanged]
fundamental importance for the success of ORFAN Arm 4. Access to NHS
Digital
England
held data will enable the accurate ascertainment of disease status for all
[19 words unchanged]
due to the complexity of accurately adjusting imaging analysis for all conditions.
[3 paragraphs unchanged]
The University of Oxford research team, who will receive the pseudonymised data from NHS
Digital,
England,
will never receive linkage files that enable the matching of the participants clinical information with their identifiable information.
[1 paragraph unchanged]
There is a third-party company, Caristo Diagnostics Ltd, which is a University
[76 words unchanged]
studies. This company will NOT be involved in any processing of NHS
Digital
England
data relating to this agreement and will have no data shared with
[12 words unchanged]
the means by which any data will be processed under this agreement.
There are no funders or commissioners directly involved in the collection or
[95 words unchanged]
control over the methodology of the study nor direct access to NHS
Digital
England
data and is therefore not considered a Data Controller.
The international sites involved in the wider
ORFRAN
ORFAN
study are only contributors to ARM 2 - 3. This agreement is relevant to
ORFRAN
ORFAN
Arm 4 only and the international sites have no involvement at all. No international, or domestic, organisations detailed in the protocol have access to the NHS
Digital
England
data except for the University of Oxford who is the sole data controller who processes the data.
[3 paragraphs unchanged]
Update under v2:
The Civil Registrations of Death - Secondary Care Cut dataset has been replaced with the automated Civil Registrations of Death dataset.
Processing activities
The purpose of this agreement is to carry out health data related
[8 words unchanged]
data for the purposes of linkage to health data held by NHS
Digital.
England.
To achieve this clinical care teams from 14 NHS Trusts who are collaborating on the study will provide the minimum required patient identifiers to NHS
Digital
England
(NHS Number and Date of Birth, and Post Code), with 8 of
[14 words unchanged]
the only flow of identifiable data that will be received by NHS
Digital.
England.
This amendment also allows for the expansion of the cohort, as approved
[35 words unchanged]
England and Wales. In practice, the first drop of data from NHS
Digital
England
will include some 110,000 patients, and the second will include the full
[10 words unchanged]
sites which will be participating in the first drop are identified below.
Under this (version 1) Agreement, only data from 10 collaborating NHS Trusts (marked with *) will flow to NHS
Digital.
England.
There is an intention to include the further 3 Trusts in this data flow over the following year preceding the second drop of data.
[16 paragraphs unchanged]
The data required is concerned with identifying what diagnoses, clinical events and
[126 words unchanged]
be incorrectly included in certain analysis. The data sets requested from NHS
Digital
England
are:
-
Civil Registrations of Death (in place of
Civil Registration (Deaths) - Secondary Care Cut
)
[17 paragraphs unchanged]
The ORFAN Arm 4 data is analysed only for the purposes of
[11 words unchanged]
cardiovascular disease risk. The ORFAN Arm 4 data as received from NHS
Digital
England
will be analysed alongside the actual CT images from the linked patients.
[6 words unchanged]
pseudonymised manner with the only link between the data extracted from NHS
Digital
England
and the original CT scan being the study ID originally assigned by the local NHS Trust clinical care team where the patient received care.
The second follow up of patient outcomes via NHS
Digital
England
data will further enable the correct ascertainment of individual patient risk through
[8 words unchanged]
of patients suffer from clinical events of relevance to the ORFAN Study.
[1 paragraph unchanged]
For the first drop of NHS
Digital
England
data at the start of the agreement, the clinical care teams at
[104 words unchanged]
Transfer (SEFT) service. 10 Trusts will initially provide their cohorts to NHS
Digital.
England.
NHS
Digital
England
combines the 10 Trusts' cohorts to create one full ORFAN Arm 4 cohort. NHS
Digital
England
will then link and extract the required data fields from the required data products and remove identifiers (leaving the Study ID).
NHS
Digital
England
send the pseudonymised data extracts to the Study team at University of
[11 words unchanged]
NHS Trusts that provided the patients that are included in the cohort.
For the second drop of NHS
Digital
England
data in October 2023, NHS
Digital
England
retrieves the full ORFAN Arm 4 cohort from storage and adds the
[11 words unchanged]
that did not participate in the original upload for drop 1. NHS
Digital
England
links and extracts the required data fields from the required data products and removes identifiers (leaving the Study ID). NHS
Digital
England
send the pseudonymised data extracts to the Study team at University of
[34 words unchanged]
included in drop 1. This will prevent the duplication of data linkage.
[3 paragraphs unchanged]
The NHS
Digital
England
datasets requested will be linked to the ORFAN Arm 4 cohort of approx. 110,000 for the first drop and 200,000 participants for the second drop.
The study only request linkage to datasets held by NHS
Digital
England
that are fundamental to the scientific aims of the ORFAN Arm 4
[39 words unchanged]
necessary data for the successful completion of the ORFAN Arm 4 project.
[6 paragraphs unchanged]
Following receipt of the linked pseudonymised data from NHS
Digital
England
by the ORFAN Study team at the University of Oxford, the study
[70 words unchanged]
involve the simultaneous analysis of CT imaging data (not sourced from NHS
Digital).
England).
There will be linkage of the NHS
Digital
England
data to the CT scan of the relevant patient that rendered them
[32 words unchanged]
were treated. Along with sending the minimum required patient identifiers to NHS
Digital
England
for linkage, the local clinical care teams will also extract, pseudonymise and
[28 words unchanged]
to analyse the scan in combination with the data received from NHS
Digital,
England,
a key aspect in achieving the scientific aims of the study.
The ORFAN study team will also request data from national registries (or NHS
Digital
England
when available) such as National Institute for Cardiovascular Outcomes Research (NICOR) and
[10 words unchanged]
Healthcare Quality Improvement Partnership (HQIP) and intend to link the pseudonymised NHS
Digital
England
data to ORFAN study participants events recorded in these national registries. This linkage will be through the unique ORFAN study ID only, not identifiable data. Linkage of NHS
Digital
England
data with NICOR / SSNAP data, would be subject to an amendment of this data sharing agreement prior to the linkage taking place.
[2 paragraphs unchanged]
Once pseudonymised data is received from NHS
Digital
England
by the ORFAN Study team at the University of Oxford, the data
[84 words unchanged]
both the University of Oxford and the Oxford University Hospital NHS Trust.
[2 paragraphs unchanged]
No third party organisations listed in the ORFAN Study protocol will receive pseudonymised data that has come to the University of Oxford from NHS
Digital
England
for ORFAN Arm 4. The University of Oxford and their ORFAN Study group is the only and final recipient of such data.
The investigators listed in the ORFAN Study protocol do not all retain
[39 words unchanged]
to access pseudonymised data disseminated to the University of Oxford from NHS
Digital.
England.
HES and ECDS DISCLOSURE CONTROL / SMALL NUMBER SUPPRESSION
In order to protect patient confidentiality, when presenting results calculated from HES record level data, outputs will contain only aggregate level data with small numbers suppressed in line with HES Analysis Guide. When publishing HES data, you must make sure that:
· cell values from 1 to 7 are suppressed at a local level to prevent possible identification of individuals from small counts within the table.
· Zeros (0) do not need to be suppressed.
· All other counts will be rounded to the nearest 5.
[1 paragraph unchanged]
MEDICINES DISPENSED IN PRIMARY CARE DISCLOSURE CONTROL / SMALL NUMBER SUPPRESSION
Update under v2:
The medicines data is not deemed disclosive and information on a GP level is available in the public domain. However, should the published information pose a risk of re-identification, the following suppression methodology should be applied:
The cohort comprises 90,552 participants from 9 collaborating trusts. Recruitment of collaborating sites is ongoing with a final target cohort size of 200,000.
• Zeros should be shown.
• 1-7 to be rounded to 5.
• Any other numbers rounded to nearest 5.
• Rounding unnecessary for averages etc.
• Percentages calculated from rounded values.
• If zeros need to be suppressed, round to 5.
COVID-19 Hospitalisations in England Surveillance System (CHESS) DISCLOSURE CONTROL POLICY
NHS Digital will only disseminate CHESS data collected from PHE where the information is linked to other information controlled by NHS Digital.
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).
Expected output
[39 paragraphs unchanged] Update under v2: The initial results from analysis of the first data drop has been performed and was presented in international conference (American Heart Association 2023). The study team aim to publish the full findings in Q2 of 2024.
Expected measurable benefits
[1 paragraph unchanged]
The personalisation of risk assessment, as the ORFAN study sets to create via access to NHS
Digital
England
data and other sources, unlocks personalised clinical approaches that can provide the
[96 words unchanged]
consequences for heart disease and how to assess risk for individual patients.
The dissemination of ORFAN Study findings is in the public interest due
[88 words unchanged]
that they can receive better care. The dissemination of the requested NHS
Digital
England
data for this project is fundamental to the success of the scientific aims, and is firmly in the interest of the UK public.
[1 paragraph unchanged]
The linkage of NHS
Digital
England
data to patients identified by local NHS Trust clinical care teams as
[49 words unchanged]
not possible without the requested data. The study team hope that the
analysis of these data as disseminated by NHS
Digital
England
will enable the creation of the necessary tools, as the study team
[48 words unchanged]
of early risk assessment through imaging biomarkers for heart attack and stroke.
ORFAN Arms 1, 2 and 3 all involve the direct consent of
[39 words unchanged]
for clinical usage. ORFAN Arm 4, and the requested dissemination of NHS
Digital
England
data as a part of that arm, will facilitate the necessary statistical
[22 words unchanged]
Vessel and Fat research group (Ox-HVF) coordinated by the University of Oxford.
[6 paragraphs unchanged]
The possible benefits are hoped to be achieved by the study sponsor,
[182 words unchanged]
do go on to suffer clinical events via the requested annual NHS
Digital
England
data extractions, hence allowing an ongoing enquiry into the effectiveness of the diagnostic and risk assessment tools that the study team propose to develop.
Results related to the development of novel imaging tools for the prediction
[28 words unchanged]
the following years once further clinical outcomes data is collected from NHS
Digital,
England,
as requested. The project is forecast to be finally concluded at the
[55 words unchanged]
clinical trials to be ongoing as to the effectiveness of the tools.
Benefits reported
The University of Oxford ORFAN team have previously produced multiple results included from Arms 1, 2 and 3 of the
OFRAN
ORFAN
study that have been published academically and reported upon within the lay press. Some noteworthy examples include:
[3 paragraphs unchanged]
Update under v2:
Through publication of findings in appropriate media, the findings of this research have added to the body of evidence on cardiovascular disease risk.
1. Establishing epicardial adipose tissue as a marker of unhealthy visceral obesity to predict cardiovascular risks such as stroke.
- Presentations: European Society of Cardiology Congress 2021; the American Heart Association Scientific Sessions 2021; the British Atherosclerosis Society 2021 Annual meeting.
- Publications: West et al., JACC Cardiovascular Imaging, 2023.
2. Prediction of in-hospital mortality from COVID-19 with imaging biomarker on CT scans.
- Publications: Kotanidis et al., Lancet Digital Health, 2022 (doi: 10.1016/S2589-7500(22)00132-7)
3. Using cardiac CT scans for prediction of future heart attacks.
- Presentations: the American Heart Association congress 2023.
- About 300,000 cardiac CT scans are expected to be performed in the UK per year. Currently, the majority (~80%) of the scans show no significant coronary artery disease and are achieved in the hospital system. Analysing imaging biomarkers in theses scans in relation to the linked clinical data supported by NHS England enables the use of these resources to tailor preventative treatment in vulnerable patients.
- Integrating metrics of coronary inflammation (FAI Score) with traditional cardiovascular risk factors in an artificial-intelligence enhanced risk stratification tool were shown to be predictive of heart attacks that was recorded in the NHS England data. This had gained significant media coverage including Financial times, Guardian, Evening Standard, the Independent, and the British Heart Foundation) https://www.bhf.org.uk/what-we-do/news-from-the-bhf/news-archive/2023/november/ai-tool-could-help-prevent-thousands-of-heart-attacks#:~:text=The%20team%20used%20a%20new,predict%20risk%20of%20cardiac%20events.)
DARS-NIC-409610-J6L1F-v1.9 3 March 2022 to 24 March 2024
- Title
- The Oxford Risk Factors And Non Invasive Imaging Study (ORFAN) Arm 4
- Commercial
- No
- Sublicensing
- No
- Datasets
- 9
- Files released
- 76
Datasets: Civil Registrations of Death - Secondary Care Cut; COVID-19 Hospitalization in England Surveillance System; Emergency Care Data Set (ECDS); HES:Civil Registration (Deaths) bridge; Hospital Episode Statistics Accident and Emergency (HES A and E); Hospital Episode Statistics Admitted Patient Care (HES APC); Hospital Episode Statistics Critical Care (HES Critical Care); Hospital Episode Statistics Outpatients (HES OP); Medicines dispensed in Primary Care (NHSBSA data)
What changed from DARS-NIC-409610-J6L1F-v0.3
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Start date | 2022-03-03 | |
| COVID-19 Hospitalization in England Surveillance System: legal basis | Health and Social Care Act 2012 - s261 - 'Other dissemination of information' | |
| COVID-19 Hospitalization in England Surveillance System: sensitivity | Sensitive | |
| Civil Registrations of Death - Secondary Care Cut: legal basis | Health and Social Care Act 2012 - s261 - 'Other dissemination of information' | |
| Emergency Care Data Set (ECDS): legal basis | Health and Social Care Act 2012 - s261 - 'Other dissemination of information' | |
| Emergency Care Data Set (ECDS): sensitivity | Sensitive | |
| HES:Civil Registration (Deaths) bridge: legal basis | Health and Social Care Act 2012 - s261 - 'Other dissemination of information' | |
| Hospital Episode Statistics Accident and Emergency (HES A and E): legal basis | Health and Social Care Act 2012 - s261 - 'Other dissemination of information' | |
| Hospital Episode Statistics Admitted Patient Care (HES APC): legal basis | Health and Social Care Act 2012 - s261 - 'Other dissemination of information' | |
| Hospital Episode Statistics Critical Care (HES Critical Care): legal basis | Health and Social Care Act 2012 - s261 - 'Other dissemination of information' | |
| Hospital Episode Statistics Outpatients (HES OP): legal basis | Health and Social Care Act 2012 - s261 - 'Other dissemination of information' | |
| Medicines dispensed in Primary Care (NHSBSA data): legal basis | Health and Social Care Act 2012 - s261 - 'Other dissemination of information' |
Objective for processing
The Oxford Risk Factors And Non Invasive Imaging Study (ORFAN) at large
[54 words unchanged]
and validate novel biomarkers that have emerged from ORFAN Arms 1-3 and
other Ox-HVF
Oxford Heart Vessel and Fat research group (Ox-HVF)
studies
coordinated by the University of Oxford
(see below). ORFAN Arm 4 is funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and The British Heart Foundation (BHF).
[1 paragraph unchanged]
The
study
University of Oxford
is applying to NHS
Digital
Digital,
in order to link
data subjects within the scope of the
study
participant's patient identifiers
with data held by NHS Digital. This linkage is necessary in order
[35 words unchanged]
clinical environment and are intended to change patient care for the better.
[9 paragraphs unchanged]
1. Measurements of plasma/imaging markers of cardiometabolic risk - not directly relevant for this
application,
agreement,
although the data requested will be linked to the pseudonymised plasma and imaging data already held by the applicant
2. Atherosclerosis progression by Computerised Tomography - not directly relevant for this
application,
agreement,
although the data requested will be linked to the relevant pseudonymised imaging data already held by the applicant
[2 paragraphs unchanged]
The secondary outcome measures that are relevant to this
application:
agreement:
[4 paragraphs unchanged]
This agreement concerns ORFAN Arm 4 only, which is a retrospective study arm which includes up to
100,000
250,000
adult participants
(75,000
(200,000
- in the UK;
25,000
50,000
– internationally; this
application
agreement
only concerns participants located within England and Wales) who have undergone CT
[29 words unchanged]
scans that only include the heart and surrounding blood vessels and tissues.
[4 paragraphs unchanged]
The use of NHSBSA data (Medicines dispensed in Primary Care) in ORFAN Arm 4 is in keeping with the direction for data usage for analysing the safety and effectiveness of medicines. The team's usage of this data is to understand the effectiveness and safety profile of medications for the reduction of pathological disease processes around the heart such as inflammation and fibrosis. These processes are directly linked to heart attack, stroke and atrial fibrillation. Many currently prescribed medications are likely to have this positive effect, however without access to the NHSBSA datasets and the other data in ORFAN Arm 4 (such as patient CT scans) it is not known if this effect is beneficial to patient care and on what scale (i.e. effectiveness) and if patients receiving such medications have any increased risk of adverse events (i.e. safety profile).
[3 paragraphs unchanged]
There is a third-party company, Caristo Diagnostics Ltd, which is a University of Oxford spin-out company from the Antoniades Laboratory.
The Antoniades Laboratory is the research group from which the ORFAN Study is coordinated. The Laboratory includes researchers, clinical staff, administrators, data scientists, machine learning experts and PhD candidates all based at the Radcliffe Department of Medicine in the University of Oxford.
This company is involved in the wider ORFAN study, along with other research studies coordinated from the
Professor
Antoniades laboratory as part of the Ox-HVF stable of studies. This company
[34 words unchanged]
the means by which any data will be processed under this agreement.
[1 paragraph unchanged]
The lawful basis for processing data under GDPR has been reviewed and been assessed as acceptable. The University of Oxford process data under Article 6(1)(e): "processing is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the controller" as they are a Public Authority.
The international sites involved in the wider ORFRAN study are only contributors to ARM 2 - 3. This agreement is relevant to ORFRAN Arm 4 only and the international sites have no involvement at all. No international, or domestic, organisations detailed in the protocol have access to the NHS Digital data except for the University of Oxford who is the sole data controller who processes the data.
The lawful basis for processing data under GDPR has been reviewed and the University of Oxford process data under Article 6(1)(e): "processing is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the controller" as they are a Public Authority.
[2 paragraphs unchanged]
Processing activities
The purpose of this agreement is to carry out health data related
[16 words unchanged]
data held by NHS Digital. To achieve this clinical care teams from
13
14
NHS Trusts who are collaborating on the study will provide the minimum required patient identifiers to NHS Digital (NHS Number and Date of Birth, and Post
Code).
Code), with 8 of the Trusts providing data under this iteration (version 1) of the agreement.
This is the only flow of identifiable data that will be received by NHS Digital.
The collaborating 13 NHS Trusts with local clinical care teams participating in ORFAN Arm 4 are:
This amendment also allows for the expansion of the cohort, as approved by the relevant REC and the HRA CAG. The cohort was originally approved for a total of 75,000 patients from England and Wales. The cohort is now approved for a total of 200,000 patients from England and Wales. In practice, the first drop of data from NHS Digital will include some 110,000 patients, and the second will include the full 200,000 (inclusive of the original 110,000). The 10 NHS Trust sites which will be participating in the first drop are identified below.
Oxford University Hospitals
Under this (version 1) Agreement, only data from 10 collaborating NHS Trusts (marked with *) will flow to NHS Digital. There is an intention to include the further 3 Trusts in this data flow over the following year preceding the second drop of data.
Royal United Hospitals Bath
The following NHS Trusts are collaborating on the study:
Milton Keynes University Hospital
Oxford University Hospitals*
University Hospitals of Leicester
Royal United Hospitals Bath*
Barts Health
Milton Keynes University Hospital*
Royal Brompton and Harefield
University Hospitals of Leicester*
Leeds Teaching Hospitals
Barts Health*
Royal Papworth Hospital
Royal Brompton and Harefield*
Guy's and St Thomas’
Leeds Teaching Hospitals*
The Royal Wolverhampton
Royal Papworth Hospital*
Sandwell & West Birmingham Hospitals
Guy's and St Thomas’ *
Sandwell & West Birmingham Hospitals*
[2 paragraphs unchanged]
There is a single cohort group that will be included in the ORFAN Arm 4 study, however the participants of this cohort group will come from a number of different NHS Trusts across England. The data subjects are adults (18-99 year old) who have undergone a relevant CT scan at a NHS Trust where the local clinical team is collaborating on the ORFAN Study Arm 4.
The Royal Wolverhampton
The data subjects are adults (18-99 year old) who have undergone a relevant CT scan at a NHS Trust where the local clinical team is collaborating on the ORFAN Study Arm 4.
[1 paragraph unchanged]
The data required is concerned with identifying what diagnoses, clinical events and
[101 words unchanged]
to COVID-19 infection and its severity. Death data is also needed to
know what
understand which
patients in the study have passed
away, otherwise
away. Otherwise
these patients will be incorrectly included in certain analysis. The data sets requested from NHS Digital are:
[5 paragraphs unchanged]
- Hospital Episode Statistics
Admitted
Critical Care
[2 paragraphs unchanged]
The first drop of all historical data would be after this agreement is signed off, and a second drop using THE SAME full Arm 4 ORFAN cohort in October 2023 for the periods 2020/21, 2021/22, and 2022/23.
The University of Oxford requires the following ethnic category and sex variables sensitive fields for the stated datasets:
ECDS: Ethnic category
HES OP: Ethnic category and Sex of patient
HES APC: Ethnic category and Sex of patient
HES AE: Sex of patient
COVID-19 Hospitalization in England Surveillance System: Ethnicity and Sex
Medicines dispensed in Primary Care: Gender
This ensures that the University of Oxford has the required data to investigate the difference in cardiovascular disease outcomes related to COVID-19 infection and cardiovascular complications. This comes following the release of observational data suggesting that both ethnicity and sex is a major predictor of adverse outcomes, both cardiovascular and otherwise, from COVID-19. The inclusion ensures that the cohort can be utilised to investigate these different impacts. Excluding these variables the study would have lacked the statistical power to investigate these differences. The work to create imaging based risk prediction signatures must be informed by understanding of underlying disease, and if ethnicity and/or sex is leading to different disease processes then different risk signatures will need to be developed to best suit the individual. To apply risk signature blind to ethnicity and sex would be unacceptable. The inclusion of both sex and gender variables is by design, as both biological sex and self-assigned gender can act as relevant variables that influence individual health, particularly relevant when assessing contagious diseases such as COVID-19.
The study team is aware that the definition for sex and gender fields may differ across the datasets disseminated under this agreement. The team will take care to ensure this is considered, otherwise this may have a significant negative impact on the research and the expected benefits.
The first drop of all historical data would be after this agreement is signed off, with some 110,000 participants from 10 Trusts, and a second drop using the complete Arm 4 ORFAN cohort of 13 Trusts and up to 200,000 patients in October 2023.
[3 paragraphs unchanged]
For the first drop of NHS Digital data at the start of
[15 words unchanged]
of their own patients who met the participation requirements for ORFAN Arm
4, this
4. This
list will be established and stored within the local NHS Trust firewall
[36 words unchanged]
clinical care teams will send their ORFAN Arm 4 patient list, including
identifiers
identifiers:
NHS Number, Date of Birth, and Postcode, plus
OFAN
ORFAN
Study ID. Cohorts will be sent in via
the
Secure Electronic File Transfer (SEFT) service.
13
10
Trusts
in total
will
initially
provide their cohorts to NHS Digital.
NHS Digital combines the
13
10
Trusts' cohorts to create one full ORFAN Arm 4
cohort
cohort. NHS Digital will then link
and
links and extracts
extract
the required data fields from the required data products and
removed
remove
identifiers (leaving the Study ID).
NHS Digital send the pseudonymised data extracts to the Study team at University of Oxford via SEFT. No data is sent back to the
13
10
NHS Trusts that provided the patients that are included in the cohort.
For the second drop of NHS Digital data in October 2023, NHS Digital retrieves the full ORFAN Arm 4 cohort from storage and
adds the additional patients as submitted by the remaining 3 NHS Trust sites that did not participate in the original upload for drop 1. NHS Digital
links and extracts the required data fields from the required data products and
removed
removes
identifiers (leaving the Study ID). NHS Digital send the pseudonymised data extracts to the Study team at University of Oxford via SEFT.
This second drop will include all historical data for the patients not included in drop 1, but only data for the periods 2020/21, 2021/22, and 2022/23 for those who were already included in drop 1. This will prevent the duplication of data linkage.
[3 paragraphs unchanged]
The NHS Digital datasets requested will be linked to the ORFAN Arm 4 cohort of approx.
75,000 participants.
110,000 for the first drop and 200,000 participants for the second drop.
The study only request linkage to datasets held by NHS Digital that
[9 words unchanged]
Arm 4 study. No requested linkages are superfluous to the study or
that
hold data that will not be utilised in statistical models as proposed in the ORFAN Study protocol. The datasets
requests can not
requested cannot
be reduced because all datasets as requested hold necessary data for the successful completion of the ORFAN Arm 4 project.
The scientific purpose of the ORFAN Arm 4
require
requires
pseudonymised data only, and no identifiable data is requested.
The number of years requested corresponds to the scientific aims of the ORFAN Study. The study team
require
need
to know the background medical conditions, hospitalisations and procedures that the participants
[155 words unchanged]
a different way to patients who did not have such an event.
This study must consider geographic differences in exposure to cardiovascular disease risk
[8 words unchanged]
access to health care. It would not be acceptable to include all
75,000
200,000
participants from the Oxford University Hospital (OUH) NHS Trust as this analysis
[82 words unchanged]
of participants is appropriate to achieve the scientific aims of the study.
The study team are only considering participants from across England and Wales.
[51 words unchanged]
received a study relevant clinical computed tomography (CT) scan. For the most
part
part,
for ORFAN Arm
4
4,
this means the participant must have received a clinical CT coronary angiogram (a specific CT scan of the heart).
[2 paragraphs unchanged]
Following receipt of the linked pseudonymised data from NHS Digital by the
[46 words unchanged]
Committee. This processing will include importing the data into statistical data analysis
software using R (a programming language) and SPSS (SPSS Statistics is an IBM software package used for interactive, or batched, statistical analysis).
software.
The analysis will include the development of models for the prediction of
[10 words unchanged]
the simultaneous analysis of CT imaging data (not sourced from NHS Digital).
There will be linkage of the NHS Digital data to the CT
[51 words unchanged]
NHS Digital for linkage, the local clinical care teams will also extract,
de-identify
pseudonymise
and assign the corresponding unique patient ID to the relevant CT scan,
[29 words unchanged]
Digital, a key aspect in achieving the scientific aims of the study.
The ORFAN study team will also request data from national registries (or
[18 words unchanged]
Audit Programme (SSNAP), both controlled by Healthcare Quality Improvement Partnership (HQIP) and
will
intend to
link the pseudonymised NHS Digital data to ORFAN study participants events recorded in these national registries. This linkage
is
will be
through the unique ORFAN study ID only, not identifiable data.
Linkage of NHS Digital data with NICOR / SSNAP data, would be subject to an amendment of this data sharing agreement prior to the linkage taking place.
[2 paragraphs unchanged]
Once pseudonymised data is received from NHS Digital by the ORFAN Study
[23 words unchanged]
namely the Acute Vascular Imaging Centre at the John Radcliffe Hospital, Oxford.
An exact copy is saved on another secure University of Oxford server, namely the researcher server of the Oxford Centre for Clinical Magnetic Resonance Research, also at the John Radcliffe Hospital but in a separate building.
This back up is only for disaster recover purposes and is not
[45 words unchanged]
both the University of Oxford and the Oxford University Hospital NHS Trust.
[20 paragraphs unchanged]
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).
Expected output
[29 paragraphs unchanged]
THE LEVEL OF DATA THAT WILL BE CONTAINED IN THE OUTPUTS:
[9 paragraphs unchanged]
All intellectual property and knowhow is owned by the University of Oxford, as the sponsor of the ORFAN Study. The University of Oxford, through Oxford University Innovation, maintains the ability to licence any technology that is created within the ORFAN Study for commercial use or for use within health services such as the NHS.The major outputs from this data processing are twofold:
1) The creation of novel disease risk calculating algorithms algorithms (patient assessment algorithms and the necessary software tools to practically apply the algorithms) for conditions such as heart attack and stroke ready for incorporation into patient care within health services, and
2) the communication of these outputs via scientific and lay-person publications.
The research outputs to convey the results will be led by peer reviewed publications in leading international journals, presentations in international and national scientific meetings and subsequent media reporting and public engagement lead by the University of Oxford.
Journals being targeted to submit to/publish in:
i) The New England Journal of Medicine (NEJM) (impact factor 74.7)
ii) The Journal of the American Medical Association (JAMA) (impact factor 45.5)
iii) The Lancet (impact factor 60.4)
iv) Circulation (impact factor 23.6)
v) Journal of the American College of Cardiology (JACC) (impact factor 20.5)
vi) British Medical Journal (BMJ) (impact factor 30.2)
vii) European Heart Journal (EHJ) (impact factor 22.7)
The study team intend major findings of this work to be published in the top-tier general medicine journals (NEJM, JAMA, Lancet, BMJ) as opposed to more cardiac specific findings which will be aimed at the top cardiology journals (Circulation, JACC, EHJ). This enables far greater readership and targeting of impact. All publications in major journals such as those listed here will be open access, meaning any reader from anywhere on Earth can access the full text of the research article without any cost.
Congresses and conferences targeted to submit work to:
i) Scientific sessions of the American Heart Association
ii) Scientific sessions of the European Society of Cardiology
iii) Scientific sessions of the American College of Cardiology
iv) Scientific sessions of the British Cardiac Society
The outputs from this work will be both immediate - with publications in high impact journals within 2-3 years of the commencement of the agreement as well as long-term - when diagnostic biomarkers are implemented in clinical practice. As the ORFAN study is expected to continue collecting outcomes data for at least the next 10 years, the cohort will continue to generate outputs as more events accumulate over time. These long-term impacts have the potential to change clinical practice worldwide and save lives from improved assessment of cardiovascular disease risk.
Specific algorithms that the ORFAN Study team wish to create and/or validate through the ORFAN arm 4 study include:
1) An algorithm for the specific risk assessment of ischaemic stroke in those with and without atrial fibrillation (provisionally called the Atriomic Stroke Algorithm)
2) An algorithm for the specific risk assessment of cardiovascular complications in those with COVID-19 infection
3) An algorithm for the likelihood of success of invasive catheter ablation in those with atrial fibrillation
4) Validation of the perivascular Fat Attenuation Index (FAI) algorithm for heart attack risk. The FAI algorithm is an already established algorithm for the accurate assessment of heart attack risk, discovered in the ORFAN Study. FAI involves the assessment of CT scan features, in particular attenuation – the CT term for density, of fat surrounding the coronary vessels.
5) Validation of the Fat Radiomic Profile (FRP) algorithm for heart attack risk. The FRP algorithm is a another already established algorithm for long-term heart attack risk discovered in the ORFAN Study. This algorithm relies upon many radiomic features extracted from CT scans from around the coronary vessels. These features cannot be seen by the naked eye, and so require computer extraction and assessment which is what the FRP computes.
6) Likely other algorithms related to specific at risk population depending on data quality and statistical power
All such algorithms are stand-alone patient assessment tools, and any intellectual property created from within the ORFAN Study will be owned by the University of Oxford, and associated intellectual property will be controlled by the University for licensing to health services for inclusion in clinical practice.
The ORFAN research team at the University of Oxford has no personal intention to monetise or generate income from the research outputs generated from the ORFAN Arm 4 study. Were discoveries to be made in the ORFAN Arm 4 study, individual researchers within the ORFAN team would be listed inventors on any patents that the University of Oxford may file.
The study team expect to be publishing important findings related to the development of novel disease risk assessment for cardiovascular disease within 2-3 years of the DSA commencing. It is possible this may occur earlier if the extraction of data in the first year produces enough scientific power for robust results. They expect novel diagnostic and risk assessment tools to be incorporated into clinical practice within 5 years from the DSA commencing, and further major publications related to the use of the tools developed from within the ORFAN study by the end of the 10 year data retention date.
THE LEVEL OF DATA THAT WILL BE CONTAINED IN THE OUTPUTS:
The level of data contained in the outputs is aggregate data with small number suppression applied as per the disclosure rules for the various data sets that has been augmented via statistical processes. No individual participants data is ever published individually, with the nature of this scientific work demanding high numbers of participants data for the testing and validation of disease risk calculators.
The dissemination activities of the ORFAN Study team are focussed on high-impact peer reviewed journals and oral research presentations at international conferences. Other activities through which the ORFAN study findings are communicated include through NHS Trust clinical grand-round meetings at NHS Trusts who deliver services relevant to those explored in the study, NHS Trust newsletters delivered to staff emails and through high level meetings with NHS executives and clinical leads at NHS Trusts to discuss the suitability for the clinical tools to be tested within the clinical environment at their Trusts. This work also involves audit related work to model the impact of novel tools developed from within ORFAN on current service usage, as has occurred within Oxford University Hospitals NHS Trust already.
To target the lay audience, the ORFAN team uses the following approaches and is guided by the Research Services team at the University of Oxford and the Public Engagement team at the Cardiovascular Medicine Division of the University of Oxford:
a) Website (www.oxhvf.com); this is updated with all the most up to date information regarding the outputs of the research. This is a public-facing website, and the public can read about the latest outputs of the study.
b) Newsletters; when major findings or general outputs are available, the ORFAN team post newsletters both on the website and in hard-copy form to ORFA Arm 1-3 participants. This is not possible for Arm 4, as we do not hold patient identifiable information. Media attention including articles in BBC News, The Guardian, The Financial Times and CBN concerning work published in the prestigious journal ‘Science Translational Medicine’ are the sorts of topics highlighted in newsletters (see example from the Antoniades Lab: https://test188076.files.wordpress.com/2018/01/newsletter-adiporedox-15-09-2017.pdf).
c) Press releases; the ORFAN team have an active involvement in outreach activities of the University of Oxford, Oxford University Innovations and the British Heart Foundation communications team, and the major findings from their study lead to press releases, and from there they are distributed to the lay press.
d) Workshops and patient and public involvement; the ORFAN team participate in workshops for patients as part of the Biomedical Research Centre in Oxford, and through that they inform the patients about their research and ask for their involvement in the design of protocols, feedback on research procedures and more, through Patient and Public involvement (PPI) panels
e) Social media – the ORFAN Study group frequently share results and outputs to their social media presence on Twitter, Facebook and LinkedIn.
Exploitation of results/outputs:
[1 paragraph unchanged]
Expected measurable benefits
The dissemination of the data stands to have a huge impact on
[44 words unchanged]
patient of their risk for both heart attack and stroke rely on
population wide
population-wide
data based
on
upon
demographics (such as age) and clinical measures such as blood pressure. Although
[37 words unchanged]
adjacent to the heart muscle, and hence provide poor accuracy for patients.
[5 paragraphs unchanged]
ORFAN Arm 4 compliments the other arms of the ORFAN study where direct patient consent is obtained.
ORFAN Arms 1, 2 and 3 all involve the direct consent of
[86 words unchanged]
Vessel and Fat research group (Ox-HVF) coordinated by the University of Oxford.
Such synergy within the Ox-HVF projects facilitates rapid translation of basic science into clinically useful tools.
An obvious continuation of this same project would be to test the
[57 words unchanged]
the CT scan itself, and outcomes data (diagnoses/events following the CT scan).
[1 paragraph unchanged]
The outputs are hoped to change the clinical approach to patients at
[121 words unchanged]
referred for a CT scan of their heart; CT scans are the
NICE
National Institute for Health
and
ESC
Care Excellence (NICE) and European Society of Cardiology (ESC)
recommended first line investigation for chest pain. The scan shows clear coronary
[92 words unchanged]
artery inflammation developed by the Antoniades laboratory using ORFAN and other studies.
[5 paragraphs unchanged]
Benefits reported
The University of Oxford ORFAN team have previously produced multiple results
included from Arms 1, 2 and 3 of the OFRAN study
that have been published academically and reported upon within the lay press. Some noteworthy examples include:
Evidence that obesity may not be necessarily bad for all patients, and
[34 words unchanged]
treatment of patients with heart diseases (published in the journal Diabetes in
2015, link to press coverage about the obesity paradox: https://www.telegraph.co.uk/news/science/science-news/11657811/Why-obesity-protects-against-heart-diseaseand-heart-attack.html).
2015).
[1 paragraph unchanged]
The University of Oxford ORFAN group has developed a novel imaging biomarker
[130 words unchanged]
and epidemiological data to basic science and imaging data to outcome data
(requested in the current application)
- to create new, boundary-pushing ideas that promote health and serve the
[10 words unchanged]
one of the ten health innovations that could soon be on the
NHS (https://inews.co.uk/news/health/the-ten-health-innovations-that-could-soon-be-on-the-nhs/). bFAI
NHS, and has been featured by the BHF as a technology soon to enter clinical practice (https://www.bhf.org.uk/what-we-do/our-research/research-successes/artificial-intelligence-and-heart-attack). FAI has been identified as a technology that can provide significant financial benefits to health systems (https://www.ft.com/content/6ff32188-8821-4272-80b9-53ac81463d97). FAI
has been included into the recent Up-To-Date clinical guidance for use in patients with chest pain
(https://www.uptodate.com/contents/cardiac-imagingwith-computed-tomography-and-magnetic-resonance-in-the-adult)
(Hoffmann, U. & Manning, W.J., 2022, ‘Cardiac imaging with computed tomography and magnetic resonance in the adult’, UpToDate.com, updated February 2022 & accessed 15 March 2022, URL: https://www.uptodate.com/contents/cardiac-imagingwith-computed-tomography-and-magnetic-resonance-in-the-adult)
and can be used to detect patients who may need intense medical therapy to prevent future heart attacks.”
Objective for processing
The Oxford Risk Factors And Non Invasive Imaging Study (ORFAN) at large has been operational since 2015. Originally the study was limited to arms 1, 2 and 3. Arm 4 has been developed conceptually from 2018 and came into practical existence from 2019 to both address outstanding scientific questions that cannot be answered with the limited pool of participants in arms 1-3, and to further develop and validate novel biomarkers that have emerged from ORFAN Arms 1-3 and Oxford Heart Vessel and Fat research group (Ox-HVF) studies coordinated by the University of Oxford (see below). ORFAN Arm 4 is funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and The British Heart Foundation (BHF).
ORFAN Arm 4 study is a multi-centre observational cohort study involving patients who have had a computed tomography (CT) angiography or CT chest scan.
The University of Oxford is applying to NHS Digital, in order to link data subjects within the scope of the study with data held by NHS Digital. This linkage is necessary in order to develop and validate cardiovascular disease risk assessment tools that will lead to earlier detection of disease risk and prevent heart attacks and strokes, amongst other cardiovascular diseases. These tools are for usage in the clinical environment and are intended to change patient care for the better.
The purpose of the project is to develop new and better biomarkers of cardiovascular disease risk using novel approaches to the analysis of CT scans. The overriding purpose of this work is to reduce the large burden of morbidity and mortality that cardiovascular disease such as heart attack and stroke have in our society.
The NHS Digital data requested in this agreement could contribute in a fundamental way to the achievement of this purpose by allowing the research team to know which diseases and clinical events had occurred prior to the CT scan of relevance to the study, and which diseases and clinical events have occurred for participants following the CT scan. This data is critical to the successful development of image analysis tools as it enables accurate differentiation of participant characteristics (namely imaging characteristics detected from within the CT scans) that can be utilised to predict patient risk.
A further major purpose of the ORFAN Arm 4 project is to understand the cardiovascular disease ramifications of COVID-19 infection. The study team know that deleterious impacts on blood vessels and the heart due to acute COVID-19 infection are commonly reported, but they do not know the long-term impacts or how to predict which patients are most at risk of morbidity due to such disease effects. Access to data related to COVID-19 infection and later cardiovascular disease diagnosis and clinical events, along with relevant CT scans of such patients’ hearts and vessels, will enable a much more accurate assessment of this risk for individual patients.
THE ORFAN STUDY PROTOCOL AND OBJECTIVES
The study has two main objectives:
1) To investigate whether biomarkers, including imaging biomarkers, of metabolic risk can predict major adverse cardiovascular events
2) To identify novel biomarkers able to predict cardiovascular disease pathogenesis and extent of pre-existing vascular disease, including in those with COVID-19 infection.
The specific primary objective of the ORFAN study is to investigate whether biomarkers of disease risk can predict major adverse cardiovascular events.
In order to achieve this objective, the primary outcome measures for the study are:
1. Measurements of plasma/imaging markers of cardiometabolic risk - not directly relevant for this agreement, although the data requested will be linked to the pseudonymised plasma and imaging data already held by the applicant
2. Atherosclerosis progression by Computerised Tomography - not directly relevant for this agreement, although the data requested will be linked to the relevant pseudonymised imaging data already held by the applicant
3. Major adverse cardiovascular events over 10 years - relevant for this agreement.
The relevant study secondary objective is to identify novel biomarkers able to predict cardiovascular disease pathogenesis and extent of pre-existing vascular disease
The secondary outcome measures that are relevant to this agreement:
1. Measurement of modification to cardiovascular disease pathogenesis and modulation of pre-existing vascular disease that is attributable to infection with coronavirus disease 2019 (COVID-19), and other pre-existing vascular disease.
The ORFAN Study was assigned COVID-19 Cardiovascular Disease UK Flagship Project status by the NIHR-BHF in May 2020 and has received ethical approval to pursue a scientific inquiry into the specific risk that is conveyed by COVID-19 infection in regard to stroke and coronary artery disease. The data from this agreement will form a major part of this inquiry as it will support the study team to understand the heart disease risk that COVID infection confers, and enable the creation of biomarkers for assessing patients individual risk of heart disease complication following COVID-19 infection.
The ORFAN study at large consists of 4 Arms of study. Arms 1, 2 and 3 include a total of 15,500 prospectively recruited participants who are directly consented to be included within the study. The ORFAN Study research arms 1,2 and 3 include directly consented patients for whom the University of Oxford collects and processes data for research purposes. The outcome data of these participants are collected through NHS Digital with whom a data sharing agreement has been signed (DARS-NIC-392669-T1F8B). This agreement herein does not include the collection, processing or storage of any data associated with patients in ORFAN Arms 1, 2 or 3.
ORFAN is part of the Oxford cohort for Heart, Vessels and Fat (Ox-HVF), which means the results from this study may be interpreted together with the findings of other Ox-HVF projects. The Ox-HVF cohort is a cluster of clinical studies run from the University of Oxford that together provide results which allow for the deployment of a multi-level strategy to understand the mechanisms of cardiovascular disease, specifically heart attack and stroke.
This agreement concerns ORFAN Arm 4 only, which is a retrospective study arm which includes up to 250,000 adult participants (200,000 - in the UK; 50,000 – internationally; this agreement only concerns participants located within England and Wales) who have undergone CT chest, abdomen and pelvis scans for clinical purposes at a participating NHS Trust radiology department. The ORFAN study team are focused on CT coronary angiograms in this project - scans that only include the heart and surrounding blood vessels and tissues.
ORFAN Arm 4 focuses on collecting CT images, patient demographics and clinical information including clinical outcomes and medication usage to aid the development of new CT image analysis algorithms and software tools for the practical application of these algorithms via both traditional and artificial intelligence approaches. ORFAN Arm 4 will provide the required statistical power to allow automation of image analysis processes such as the automated calculation of image analysis techniques developed by the University of Oxford. This includes the perivascular Fat Attenuation Index, the coronary artery Fat Radiomic* Profile and the Atriomic Stroke Algorithm (a novel risk algorithm interrogates the heart atria (the top chambers of the heart) to extract radiomic features, hence ‘atriomic’), as well as the development of new imaging biomarkers - this is the focus of this project. The development of these algorithms and tools has, and will lead to much improved patient care for those at risk of heart attack and stroke.
* In the field of medicine, radiomics is a discipline and collection of methods concerned with the extraction of a large number of statistical features from radiographic medical images using data-characterisation algorithms. These features, termed radiomic features, have the potential to uncover disease characteristics that fail to be appreciated by the naked eye.
Following the COVID-19 pandemic, the ORFAN study programme pivoted to include relevant research objectives related to the non-invasive assessment of cardiovascular damage caused by infection with the virus. This work has been designated by the NIHR and the British Heart Foundation as a COVID-19 Cardiovascular Disease UK Flagship Project. The influence of COVID-19 infection on the outcome measures of the study will be explored, and novel tools to assess the impact of COVID-19 infection on blood vessels and the heart will be developed. This agreement is of fundamental importance for the success of ORFAN Arm 4. Access to NHS Digital held data will enable the accurate ascertainment of disease status for all relevant study conditions within all participants. The breadth of relevant diseases and clinical activity for this research is large due to the complexity of accurately adjusting imaging analysis for all conditions.
The analysis that will occur will involve the adjustment of patient risk profiles for all clinical events and medication usage prior to the CT scan of interest, and adjustment of all clinical events and medication usage following the CT scan of interest. It is not possible to accurately build risk assessment models without both the prior and post CT scan patient data.
The use of NHSBSA data (Medicines dispensed in Primary Care) in ORFAN Arm 4 is in keeping with the direction for data usage for analysing the safety and effectiveness of medicines. The team's usage of this data is to understand the effectiveness and safety profile of medications for the reduction of pathological disease processes around the heart such as inflammation and fibrosis. These processes are directly linked to heart attack, stroke and atrial fibrillation. Many currently prescribed medications are likely to have this positive effect, however without access to the NHSBSA datasets and the other data in ORFAN Arm 4 (such as patient CT scans) it is not known if this effect is beneficial to patient care and on what scale (i.e. effectiveness) and if patients receiving such medications have any increased risk of adverse events (i.e. safety profile).
As an example, a specific project that will make use of Arm 4 data that has also received significant funding is explained here. This project is the development and clinical translation of the Atriomic Stroke Algorithm, which has received a BHF Translational award (TG/19/2/34831 – ‘Using radiomics and artificial intelligence to predict cardio-embolic stroke’) to validate a novel imaging biomarker for the direct prediction of stroke risk from CT images. This project intends to make use of ORFAN Arm 4 data to provide the most accurate risk assessment of individual stroke risk available. This award has unlocked new technical ability in the ORFAN project as it has funded a very powerful computer capable of processing many thousands of CT scans for deep-learning purposes. Deep-learning is the field of artificial intelligence concerned with the automated interpretation of images. In the same way that a computer can identify if a photo portrays a cat or a dog, a computer can also identify if a CT scan portrays a heart or a stomach, to use a rudimentary example. In this project, the computer will learn to identify patients with inflammation around their heart – inflammation that places them at increased risk of stroke. This computer has been purchased and installed at the University of Oxford for this project. The award also funds suitably qualified engineers to work on the ORFAN study utilising this computer for CT scan analysis purposes.
The University of Oxford research team, who will receive the pseudonymised data from NHS Digital, will never receive linkage files that enable the matching of the participants clinical information with their identifiable information.
The sole Data Controller is the University of Oxford who also process the data. The team is led by the Professor of Cardiovascular Medicine at the University of Oxford.
There is a third-party company, Caristo Diagnostics Ltd, which is a University of Oxford spin-out company from the Antoniades Laboratory. The Antoniades Laboratory is the research group from which the ORFAN Study is coordinated. The Laboratory includes researchers, clinical staff, administrators, data scientists, machine learning experts and PhD candidates all based at the Radcliffe Department of Medicine in the University of Oxford. This company is involved in the wider ORFAN study, along with other research studies coordinated from the Antoniades laboratory as part of the Ox-HVF stable of studies. This company will NOT be involved in any processing of NHS Digital data relating to this agreement and will have no data shared with it. Caristo Diagnostics Ltd also do not play any role in determining the means by which any data will be processed under this agreement.
There are no funders or commissioners directly involved in the collection or processing of data. The ORFAN study has received funding from a number of sources, however the British Heart Foundation has awarded monies specifically for ORFAN Arm 4. The specific project is the development and clinical translation of the Atriomic Stroke Algorithm via a BHF Translational award (TG/19/2/34831 – ‘Using radiomics and artificial intelligence to predict cardio-embolic stroke’). This project intends to make use of ORFAN Arm 4 data to provide the most accurate risk assessment of individual stroke risk available, as is in keeping with the ORFAN scientific aims. The British Heart Foundation has no control over the methodology of the study nor direct access to NHS Digital data and is therefore not considered a Data Controller.
The international sites involved in the wider ORFRAN study are only contributors to ARM 2 - 3. This agreement is relevant to ORFRAN Arm 4 only and the international sites have no involvement at all. No international, or domestic, organisations detailed in the protocol have access to the NHS Digital data except for the University of Oxford who is the sole data controller who processes the data.
The lawful basis for processing data under GDPR has been reviewed and the University of Oxford process data under Article 6(1)(e): "processing is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the controller" as they are a Public Authority.
Additionally, the University of Oxford process the Special Category Health Data under Article 9(2)(j): "processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject" as the data are required for statistical purposes in the public interest.
The public interest relevant to this work is that the research stands to greatly improve the way in which patients – that is, the public of the UK – receive care in relation to heart attack and stroke. These are the top causes of morbidity and mortality in our community and there is huge public interest in improving patient risk assessment and the management of that risk to save lives.
Expected output
The major outputs from this data processing are twofold:
1) The creation of novel disease risk calculating algorithms (patient assessment algorithms and the necessary software tools to practically apply the algorithms) for conditions such as heart attack and stroke ready for incorporation into patient care within health services, and
2) the communication of these outputs via scientific and lay-person publications.
The research outputs to convey the results will be led by peer reviewed publications in leading international journals, presentations in international and national scientific meetings and subsequent media reporting and public engagement lead by the University of Oxford.
Journals being targeted to submit to/publish in:
i) The New England Journal of Medicine (NEJM) (impact factor 74.7)
ii) The Journal of the American Medical Association (JAMA) (impact factor 45.5)
iii) The Lancet (impact factor 60.4)
iv) Circulation (impact factor 23.6)
v) Journal of the American College of Cardiology (JACC) (impact factor 20.5)
vi) British Medical Journal (BMJ) (impact factor 30.2)
vii) European Heart Journal (EHJ) (impact factor 22.7)
The study team intend major findings of this work to be published in the top-tier general medicine journals (NEJM, JAMA, Lancet, BMJ) as opposed to more cardiac specific findings which will be aimed at the top cardiology journals (Circulation, JACC, EHJ). This enables far greater readership and targeting of impact. All publications in major journals such as those listed here will be open access, meaning any reader from anywhere on Earth can access the full text of the research article without any cost.
Congresses and conferences targeted to submit work to:
i) Scientific sessions of the American Heart Association
ii) Scientific sessions of the European Society of Cardiology
iii) Scientific sessions of the American College of Cardiology
iv) Scientific sessions of the British Cardiac Society
The outputs from this work will be both immediate - with publications in high impact journals within 2-3 years of the commencement of the agreement as well as long-term - when diagnostic biomarkers are implemented in clinical practice. As the ORFAN study is expected to continue collecting outcomes data for at least the next 10 years, the cohort will continue to generate outputs as more events accumulate over time. These long-term impacts have the potential to change clinical practice worldwide and save lives from improved assessment of cardiovascular disease risk.
Specific algorithms that the ORFAN Study team wish to create and/or validate through the ORFAN arm 4 study include:
1) An algorithm for the specific risk assessment of ischaemic stroke in those with and without atrial fibrillation (provisionally called the Atriomic Stroke Algorithm)
2) An algorithm for the specific risk assessment of cardiovascular complications in those with COVID-19 infection
3) An algorithm for the likelihood of success of invasive catheter ablation in those with atrial fibrillation
4) Validation of the perivascular Fat Attenuation Index (FAI) algorithm for heart attack risk. The FAI algorithm is an already established algorithm for the accurate assessment of heart attack risk, discovered in the ORFAN Study. FAI involves the assessment of CT scan features, in particular attenuation – the CT term for density of fat surrounding the coronary vessels.
5) Validation of the Fat Radiomic Profile (FRP) algorithm for heart attack risk. The FRP algorithm is another already established algorithm for long-term heart attack risk discovered in the ORFAN Study. This algorithm relies upon many radiomic features extracted from CT scans from around the coronary vessels. These features cannot be seen by the naked eye, and so require computer extraction and assessment which is what the FRP computes.
6) Likely other algorithms related to specific at risk population depending on data quality and statistical power
All such algorithms are stand-alone patient assessment tools, and any intellectual property created from within the ORFAN Study will be owned by the University of Oxford, and associated intellectual property will be controlled by the University for licensing to health services for inclusion in clinical practice.
The ORFAN research team at the University of Oxford has no personal intention to monetise or generate income from the research outputs generated from the ORFAN Arm 4 study. Were discoveries to be made in the ORFAN Arm 4 study, individual researchers within the ORFAN team would be listed inventors on any patents that the University of Oxford may file.
The study team expect to be publishing important findings related to the development of novel disease risk assessment for cardiovascular disease within 2-3 years of the DSA commencing. It is possible this may occur earlier if the extraction of data in the first year produces enough scientific power for robust results. The study team expect novel diagnostic and risk assessment tools to be incorporated into clinical practice within 5 years from the DSA commencing, and further major publications related to the use of the tools developed from within the ORFAN study by the end of the 10 year data retention date.
The level of data contained in the outputs is aggregate data with small number suppression applied as per the disclosure rules for the various data sets that have been augmented via statistical processes. No individual participants data is ever published individually, with the nature of this scientific work demanding high numbers of participants data for the testing and validation of disease risk calculators.
The dissemination activities of the ORFAN Study team are focused on high-impact peer reviewed journals and oral research presentations at international conferences. Other activities through which the ORFAN study findings are communicated include through NHS Trust clinical grand-round meetings (at NHS Trusts who deliver services relevant to those explored in the study), NHS Trust newsletters (delivered to staff emails) and through high level meetings with NHS executives and clinical leads at NHS Trusts (to discuss the suitability for the clinical tools to be tested within the clinical environment at their Trusts). This work also involves audit related work to model the impact of novel tools developed from within ORFAN on current service usage, as has occurred within Oxford University Hospitals NHS Trust already.
To target the lay audience, the ORFAN team uses the following approaches and is guided by the Research Services team at the University of Oxford and the Public Engagement team at the Cardiovascular Medicine Division of the University of Oxford:
a) Website (www.oxhvf.com): this is updated with all the most up to date information regarding the outputs of the research. This is a public-facing website, and the public can read about the latest outputs of the study.
b) Newsletters: when major findings or general outputs are available, the ORFAN team post newsletters both on the website and in hard-copy form to ORFAN Arm 1-3 participants. This is not possible for Arm 4, as the University of Oxford do not hold patient identifiable information. Media attention including articles in BBC News, The Guardian, The Financial Times and CBN concerning work published in the prestigious journal ‘Science Translational Medicine’ are the sorts of topics highlighted in newsletters (see example from the Antoniades Lab: https://test188076.files.wordpress.com/2018/01/newsletter-adiporedox-15-09-2017.pdf).
c) Press releases: the ORFAN team have an active involvement in outreach activities of the University of Oxford, Oxford University Innovations and the British Heart Foundation communications team, and the major findings from their study lead to press releases. From there they are distributed to the lay press.
d) Workshops and patient and public involvement: the ORFAN team participate in workshops for patients as part of the Biomedical Research Centre in Oxford. Through these workshops they inform the patients about their research and ask for their involvement in the design of protocols, feedback on research procedures and more. This is also done through Patient and Public involvement (PPI) panels.
e) Social media – the ORFAN Study group frequently share results and outputs to their social media presence on Twitter, Facebook and LinkedIn.
Exploitation of results/outputs:
All intellectual property and knowhow is owned by the University of Oxford, as the sponsor of the ORFAN Study. The University of Oxford, through Oxford University Innovation, maintains the ability to licence any technology that is created within the ORFAN Study for commercial use or for use within health services such as the NHS.
Benefits reported
The University of Oxford ORFAN team have previously produced multiple results included from Arms 1, 2 and 3 of the OFRAN study that have been published academically and reported upon within the lay press. Some noteworthy examples include:
Evidence that obesity may not be necessarily bad for all patients, and those patients with high body mass index may be protected against cardiovascular mortality because fat in the body may secrete protective substances. This is called the obesity paradox and has major implications for the treatment of patients with heart diseases (published in the journal Diabetes in 2015).
The University of Oxford (ORFAN team) has recently identified a significant therapeutic target for the treatment of heart diseases, and that discovery led to intense research to develop new drugs to modify this target (presented in the European Society of Cardiology 2018 Congress, and received the Best Poster Award).
The University of Oxford ORFAN group has developed a novel imaging biomarker (see Antonopoulos et al in Science Translational Medicine, 2017), namely the Fat Attenuation Index (FAI), which has been shown to be a marker of vascular inflammation at early disease stages. Validation of this biomarker in large cohorts of patients with residual cardiovascular risk showed that FAI is able to detect patients at high risk for cardiac mortality and is also predictive of non-fatal heart attacks. This permits reclassification of an individual's risk, above and beyond the current state-of-the-art diagnostic tools, with strong implications for guiding medical management in patients and guiding the use of primary and secondary prevention measures. The development of this technology is a significant example that highlights the strength and unique ability of the Ox-HVF cohort in combining data across different and diverse fields - from clinical and epidemiological data to basic science and imaging data to outcome data - to create new, boundary-pushing ideas that promote health and serve the public interest. Of note, FAI was featured by iNews as one of the ten health innovations that could soon be on the NHS, and has been featured by the BHF as a technology soon to enter clinical practice (https://www.bhf.org.uk/what-we-do/our-research/research-successes/artificial-intelligence-and-heart-attack). FAI has been identified as a technology that can provide significant financial benefits to health systems (https://www.ft.com/content/6ff32188-8821-4272-80b9-53ac81463d97). FAI has been included into the recent Up-To-Date clinical guidance for use in patients with chest pain (Hoffmann, U. & Manning, W.J., 2022, ‘Cardiac imaging with computed tomography and magnetic resonance in the adult’, UpToDate.com, updated February 2022 & accessed 15 March 2022, URL: https://www.uptodate.com/contents/cardiac-imagingwith-computed-tomography-and-magnetic-resonance-in-the-adult) and can be used to detect patients who may need intense medical therapy to prevent future heart attacks.”
DARS-NIC-409610-J6L1F-v0.3 25 March 2021 to 24 March 2024
- Title
- The Oxford Risk Factors And Non Invasive Imaging Study (ORFAN) Arm 4
- Commercial
- No
- Sublicensing
- No
- Datasets
- 9
- Files released
- 0
Datasets: Civil Registrations of Death - Secondary Care Cut; COVID-19 Hospitalization in England Surveillance System; Emergency Care Data Set (ECDS); HES:Civil Registration (Deaths) bridge; Hospital Episode Statistics Accident and Emergency (HES A and E); Hospital Episode Statistics Admitted Patient Care (HES APC); Hospital Episode Statistics Critical Care (HES Critical Care); Hospital Episode Statistics Outpatients (HES OP); Medicines dispensed in Primary Care (NHSBSA data)
Objective for processing
The Oxford Risk Factors And Non Invasive Imaging Study (ORFAN) at large has been operational since 2015. Originally the study was limited to arms 1, 2 and 3. Arm 4 has been developed conceptually from 2018 and came into practical existence from 2019 to both address outstanding scientific questions that cannot be answered with the limited pool of participants in arms 1-3, and to further develop and validate novel biomarkers that have emerged from ORFAN Arms 1-3 and other Ox-HVF studies (see below). ORFAN Arm 4 is funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and The British Heart Foundation (BHF).
ORFAN Arm 4 study is a multi-centre observational cohort study involving patients who have had a computed tomography (CT) angiography or CT chest scan.
The study is applying to NHS Digital in order to link study participant's patient identifiers with data held by NHS Digital. This linkage is necessary in order to develop and validate cardiovascular disease risk assessment tools that will lead to earlier detection of disease risk and prevent heart attacks and strokes, amongst other cardiovascular diseases. These tools are for usage in the clinical environment and are intended to change patient care for the better.
The purpose of the project is to develop new and better biomarkers of cardiovascular disease risk using novel approaches to the analysis of CT scans. The overriding purpose of this work is to reduce the large burden of morbidity and mortality that cardiovascular disease such as heart attack and stroke have in our society.
The NHS Digital data requested in this agreement could contribute in a fundamental way to the achievement of this purpose by allowing the research team to know which diseases and clinical events had occurred prior to the CT scan of relevance to the study, and which diseases and clinical events have occurred for participants following the CT scan. This data is critical to the successful development of image analysis tools as it enables accurate differentiation of participant characteristics (namely imaging characteristics detected from within the CT scans) that can be utilised to predict patient risk.
A further major purpose of the ORFAN Arm 4 project is to understand the cardiovascular disease ramifications of COVID-19 infection. The study team know that deleterious impacts on blood vessels and the heart due to acute COVID-19 infection are commonly reported, but they do not know the long-term impacts or how to predict which patients are most at risk of morbidity due to such disease effects. Access to data related to COVID-19 infection and later cardiovascular disease diagnosis and clinical events, along with relevant CT scans of such patients’ hearts and vessels, will enable a much more accurate assessment of this risk for individual patients.
THE ORFAN STUDY PROTOCOL AND OBJECTIVES
The study has two main objectives:
1) To investigate whether biomarkers, including imaging biomarkers, of metabolic risk can predict major adverse cardiovascular events
2) To identify novel biomarkers able to predict cardiovascular disease pathogenesis and extent of pre-existing vascular disease, including in those with COVID-19 infection.
The specific primary objective of the ORFAN study is to investigate whether biomarkers of disease risk can predict major adverse cardiovascular events.
In order to achieve this objective, the primary outcome measures for the study are:
1. Measurements of plasma/imaging markers of cardiometabolic risk - not directly relevant for this application, although the data requested will be linked to the pseudonymised plasma and imaging data already held by the applicant
2. Atherosclerosis progression by Computerised Tomography - not directly relevant for this application, although the data requested will be linked to the relevant pseudonymised imaging data already held by the applicant
3. Major adverse cardiovascular events over 10 years - relevant for this agreement.
The relevant study secondary objective is to identify novel biomarkers able to predict cardiovascular disease pathogenesis and extent of pre-existing vascular disease
The secondary outcome measures that are relevant to this application:
1. Measurement of modification to cardiovascular disease pathogenesis and modulation of pre-existing vascular disease that is attributable to infection with coronavirus disease 2019 (COVID-19), and other pre-existing vascular disease.
The ORFAN Study was assigned COVID-19 Cardiovascular Disease UK Flagship Project status by the NIHR-BHF in May 2020 and has received ethical approval to pursue a scientific inquiry into the specific risk that is conveyed by COVID-19 infection in regard to stroke and coronary artery disease. The data from this agreement will form a major part of this inquiry as it will support the study team to understand the heart disease risk that COVID infection confers, and enable the creation of biomarkers for assessing patients individual risk of heart disease complication following COVID-19 infection.
The ORFAN study at large consists of 4 Arms of study. Arms 1, 2 and 3 include a total of 15,500 prospectively recruited participants who are directly consented to be included within the study. The ORFAN Study research arms 1,2 and 3 include directly consented patients for whom the University of Oxford collects and processes data for research purposes. The outcome data of these participants are collected through NHS Digital with whom a data sharing agreement has been signed (DARS-NIC-392669-T1F8B). This agreement herein does not include the collection, processing or storage of any data associated with patients in ORFAN Arms 1, 2 or 3.
ORFAN is part of the Oxford cohort for Heart, Vessels and Fat (Ox-HVF), which means the results from this study may be interpreted together with the findings of other Ox-HVF projects. The Ox-HVF cohort is a cluster of clinical studies run from the University of Oxford that together provide results which allow for the deployment of a multi-level strategy to understand the mechanisms of cardiovascular disease, specifically heart attack and stroke.
This agreement concerns ORFAN Arm 4 only, which is a retrospective study arm which includes up to 100,000 adult participants (75,000 - in the UK; 25,000 – internationally; this application only concerns participants located within England and Wales) who have undergone CT chest, abdomen and pelvis scans for clinical purposes at a participating NHS Trust radiology department. The ORFAN study team are focused on CT coronary angiograms in this project - scans that only include the heart and surrounding blood vessels and tissues.
ORFAN Arm 4 focuses on collecting CT images, patient demographics and clinical information including clinical outcomes and medication usage to aid the development of new CT image analysis algorithms and software tools for the practical application of these algorithms via both traditional and artificial intelligence approaches. ORFAN Arm 4 will provide the required statistical power to allow automation of image analysis processes such as the automated calculation of image analysis techniques developed by the University of Oxford. This includes the perivascular Fat Attenuation Index, the coronary artery Fat Radiomic* Profile and the Atriomic Stroke Algorithm (a novel risk algorithm interrogates the heart atria (the top chambers of the heart) to extract radiomic features, hence ‘atriomic’), as well as the development of new imaging biomarkers - this is the focus of this project. The development of these algorithms and tools has, and will lead to much improved patient care for those at risk of heart attack and stroke.
* In the field of medicine, radiomics is a discipline and collection of methods concerned with the extraction of a large number of statistical features from radiographic medical images using data-characterisation algorithms. These features, termed radiomic features, have the potential to uncover disease characteristics that fail to be appreciated by the naked eye.
Following the COVID-19 pandemic, the ORFAN study programme pivoted to include relevant research objectives related to the non-invasive assessment of cardiovascular damage caused by infection with the virus. This work has been designated by the NIHR and the British Heart Foundation as a COVID-19 Cardiovascular Disease UK Flagship Project. The influence of COVID-19 infection on the outcome measures of the study will be explored, and novel tools to assess the impact of COVID-19 infection on blood vessels and the heart will be developed. This agreement is of fundamental importance for the success of ORFAN Arm 4. Access to NHS Digital held data will enable the accurate ascertainment of disease status for all relevant study conditions within all participants. The breadth of relevant diseases and clinical activity for this research is large due to the complexity of accurately adjusting imaging analysis for all conditions.
The analysis that will occur will involve the adjustment of patient risk profiles for all clinical events and medication usage prior to the CT scan of interest, and adjustment of all clinical events and medication usage following the CT scan of interest. It is not possible to accurately build risk assessment models without both the prior and post CT scan patient data.
As an example, a specific project that will make use of Arm 4 data that has also received significant funding is explained here. This project is the development and clinical translation of the Atriomic Stroke Algorithm, which has received a BHF Translational award (TG/19/2/34831 – ‘Using radiomics and artificial intelligence to predict cardio-embolic stroke’) to validate a novel imaging biomarker for the direct prediction of stroke risk from CT images. This project intends to make use of ORFAN Arm 4 data to provide the most accurate risk assessment of individual stroke risk available. This award has unlocked new technical ability in the ORFAN project as it has funded a very powerful computer capable of processing many thousands of CT scans for deep-learning purposes. Deep-learning is the field of artificial intelligence concerned with the automated interpretation of images. In the same way that a computer can identify if a photo portrays a cat or a dog, a computer can also identify if a CT scan portrays a heart or a stomach, to use a rudimentary example. In this project, the computer will learn to identify patients with inflammation around their heart – inflammation that places them at increased risk of stroke. This computer has been purchased and installed at the University of Oxford for this project. The award also funds suitably qualified engineers to work on the ORFAN study utilising this computer for CT scan analysis purposes.
The University of Oxford research team, who will receive the pseudonymised data from NHS Digital, will never receive linkage files that enable the matching of the participants clinical information with their identifiable information.
The sole Data Controller is the University of Oxford who also process the data. The team is led by the Professor of Cardiovascular Medicine at the University of Oxford.
There is a third-party company, Caristo Diagnostics Ltd, which is a University of Oxford spin-out company from the Antoniades Laboratory. This company is involved in the wider ORFAN study, along with other research studies coordinated from the Professor Antoniades laboratory as part of the Ox-HVF stable of studies. This company will NOT be involved in any processing of NHS Digital data relating to this agreement and will have no data shared with it. Caristo Diagnostics Ltd also do not play any role in determining the means by which any data will be processed under this agreement.
There are no funders or commissioners directly involved in the collection or processing of data. The ORFAN study has received funding from a number of sources, however the British Heart Foundation has awarded monies specifically for ORFAN Arm 4. The specific project is the development and clinical translation of the Atriomic Stroke Algorithm via a BHF Translational award (TG/19/2/34831 – ‘Using radiomics and artificial intelligence to predict cardio-embolic stroke’). This project intends to make use of ORFAN Arm 4 data to provide the most accurate risk assessment of individual stroke risk available, as is in keeping with the ORFAN scientific aims. The British Heart Foundation has no control over the methodology of the study nor direct access to NHS Digital data and is therefore not considered a Data Controller.
The lawful basis for processing data under GDPR has been reviewed and been assessed as acceptable. The University of Oxford process data under Article 6(1)(e): "processing is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the controller" as they are a Public Authority.
Additionally, the University of Oxford process the Special Category Health Data under Article 9(2)(j): "processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject" as the data are required for statistical purposes in the public interest.
The public interest relevant to this work is that the research stands to greatly improve the way in which patients – that is, the public of the UK – receive care in relation to heart attack and stroke. These are the top causes of morbidity and mortality in our community and there is huge public interest in improving patient risk assessment and the management of that risk to save lives.
Expected output
The major outputs from this data processing are twofold:
1) The creation of novel disease risk calculating algorithms (patient assessment algorithms and the necessary software tools to practically apply the algorithms) for conditions such as heart attack and stroke ready for incorporation into patient care within health services, and
2) the communication of these outputs via scientific and lay-person publications.
The research outputs to convey the results will be led by peer reviewed publications in leading international journals, presentations in international and national scientific meetings and subsequent media reporting and public engagement lead by the University of Oxford.
Journals being targeted to submit to/publish in:
i) The New England Journal of Medicine (NEJM) (impact factor 74.7)
ii) The Journal of the American Medical Association (JAMA) (impact factor 45.5)
iii) The Lancet (impact factor 60.4)
iv) Circulation (impact factor 23.6)
v) Journal of the American College of Cardiology (JACC) (impact factor 20.5)
vi) British Medical Journal (BMJ) (impact factor 30.2)
vii) European Heart Journal (EHJ) (impact factor 22.7)
The study team intend major findings of this work to be published in the top-tier general medicine journals (NEJM, JAMA, Lancet, BMJ) as opposed to more cardiac specific findings which will be aimed at the top cardiology journals (Circulation, JACC, EHJ). This enables far greater readership and targeting of impact. All publications in major journals such as those listed here will be open access, meaning any reader from anywhere on Earth can access the full text of the research article without any cost.
Congresses and conferences targeted to submit work to:
i) Scientific sessions of the American Heart Association
ii) Scientific sessions of the European Society of Cardiology
iii) Scientific sessions of the American College of Cardiology
iv) Scientific sessions of the British Cardiac Society
The outputs from this work will be both immediate - with publications in high impact journals within 2-3 years of the commencement of the agreement as well as long-term - when diagnostic biomarkers are implemented in clinical practice. As the ORFAN study is expected to continue collecting outcomes data for at least the next 10 years, the cohort will continue to generate outputs as more events accumulate over time. These long-term impacts have the potential to change clinical practice worldwide and save lives from improved assessment of cardiovascular disease risk.
Specific algorithms that the ORFAN Study team wish to create and/or validate through the ORFAN arm 4 study include:
1) An algorithm for the specific risk assessment of ischaemic stroke in those with and without atrial fibrillation (provisionally called the Atriomic Stroke Algorithm)
2) An algorithm for the specific risk assessment of cardiovascular complications in those with COVID-19 infection
3) An algorithm for the likelihood of success of invasive catheter ablation in those with atrial fibrillation
4) Validation of the perivascular Fat Attenuation Index (FAI) algorithm for heart attack risk. The FAI algorithm is an already established algorithm for the accurate assessment of heart attack risk, discovered in the ORFAN Study. FAI involves the assessment of CT scan features, in particular attenuation – the CT term for density of fat surrounding the coronary vessels.
5) Validation of the Fat Radiomic Profile (FRP) algorithm for heart attack risk. The FRP algorithm is another already established algorithm for long-term heart attack risk discovered in the ORFAN Study. This algorithm relies upon many radiomic features extracted from CT scans from around the coronary vessels. These features cannot be seen by the naked eye, and so require computer extraction and assessment which is what the FRP computes.
6) Likely other algorithms related to specific at risk population depending on data quality and statistical power
All such algorithms are stand-alone patient assessment tools, and any intellectual property created from within the ORFAN Study will be owned by the University of Oxford, and associated intellectual property will be controlled by the University for licensing to health services for inclusion in clinical practice.
The ORFAN research team at the University of Oxford has no personal intention to monetise or generate income from the research outputs generated from the ORFAN Arm 4 study. Were discoveries to be made in the ORFAN Arm 4 study, individual researchers within the ORFAN team would be listed inventors on any patents that the University of Oxford may file.
The study team expect to be publishing important findings related to the development of novel disease risk assessment for cardiovascular disease within 2-3 years of the DSA commencing. It is possible this may occur earlier if the extraction of data in the first year produces enough scientific power for robust results. The study team expect novel diagnostic and risk assessment tools to be incorporated into clinical practice within 5 years from the DSA commencing, and further major publications related to the use of the tools developed from within the ORFAN study by the end of the 10 year data retention date.
THE LEVEL OF DATA THAT WILL BE CONTAINED IN THE OUTPUTS:
The level of data contained in the outputs is aggregate data with small number suppression applied as per the disclosure rules for the various data sets that have been augmented via statistical processes. No individual participants data is ever published individually, with the nature of this scientific work demanding high numbers of participants data for the testing and validation of disease risk calculators.
The dissemination activities of the ORFAN Study team are focused on high-impact peer reviewed journals and oral research presentations at international conferences. Other activities through which the ORFAN study findings are communicated include through NHS Trust clinical grand-round meetings (at NHS Trusts who deliver services relevant to those explored in the study), NHS Trust newsletters (delivered to staff emails) and through high level meetings with NHS executives and clinical leads at NHS Trusts (to discuss the suitability for the clinical tools to be tested within the clinical environment at their Trusts). This work also involves audit related work to model the impact of novel tools developed from within ORFAN on current service usage, as has occurred within Oxford University Hospitals NHS Trust already.
To target the lay audience, the ORFAN team uses the following approaches and is guided by the Research Services team at the University of Oxford and the Public Engagement team at the Cardiovascular Medicine Division of the University of Oxford:
a) Website (www.oxhvf.com): this is updated with all the most up to date information regarding the outputs of the research. This is a public-facing website, and the public can read about the latest outputs of the study.
b) Newsletters: when major findings or general outputs are available, the ORFAN team post newsletters both on the website and in hard-copy form to ORFAN Arm 1-3 participants. This is not possible for Arm 4, as the University of Oxford do not hold patient identifiable information. Media attention including articles in BBC News, The Guardian, The Financial Times and CBN concerning work published in the prestigious journal ‘Science Translational Medicine’ are the sorts of topics highlighted in newsletters (see example from the Antoniades Lab: https://test188076.files.wordpress.com/2018/01/newsletter-adiporedox-15-09-2017.pdf).
c) Press releases: the ORFAN team have an active involvement in outreach activities of the University of Oxford, Oxford University Innovations and the British Heart Foundation communications team, and the major findings from their study lead to press releases. From there they are distributed to the lay press.
d) Workshops and patient and public involvement: the ORFAN team participate in workshops for patients as part of the Biomedical Research Centre in Oxford. Through these workshops they inform the patients about their research and ask for their involvement in the design of protocols, feedback on research procedures and more. This is also done through Patient and Public involvement (PPI) panels.
e) Social media – the ORFAN Study group frequently share results and outputs to their social media presence on Twitter, Facebook and LinkedIn.
Exploitation of results/outputs:
All intellectual property and knowhow is owned by the University of Oxford, as the sponsor of the ORFAN Study. The University of Oxford, through Oxford University Innovation, maintains the ability to licence any technology that is created within the ORFAN Study for commercial use or for use within health services such as the NHS.The major outputs from this data processing are twofold:
1) The creation of novel disease risk calculating algorithms algorithms (patient assessment algorithms and the necessary software tools to practically apply the algorithms) for conditions such as heart attack and stroke ready for incorporation into patient care within health services, and
2) the communication of these outputs via scientific and lay-person publications.
The research outputs to convey the results will be led by peer reviewed publications in leading international journals, presentations in international and national scientific meetings and subsequent media reporting and public engagement lead by the University of Oxford.
Journals being targeted to submit to/publish in:
i) The New England Journal of Medicine (NEJM) (impact factor 74.7)
ii) The Journal of the American Medical Association (JAMA) (impact factor 45.5)
iii) The Lancet (impact factor 60.4)
iv) Circulation (impact factor 23.6)
v) Journal of the American College of Cardiology (JACC) (impact factor 20.5)
vi) British Medical Journal (BMJ) (impact factor 30.2)
vii) European Heart Journal (EHJ) (impact factor 22.7)
The study team intend major findings of this work to be published in the top-tier general medicine journals (NEJM, JAMA, Lancet, BMJ) as opposed to more cardiac specific findings which will be aimed at the top cardiology journals (Circulation, JACC, EHJ). This enables far greater readership and targeting of impact. All publications in major journals such as those listed here will be open access, meaning any reader from anywhere on Earth can access the full text of the research article without any cost.
Congresses and conferences targeted to submit work to:
i) Scientific sessions of the American Heart Association
ii) Scientific sessions of the European Society of Cardiology
iii) Scientific sessions of the American College of Cardiology
iv) Scientific sessions of the British Cardiac Society
The outputs from this work will be both immediate - with publications in high impact journals within 2-3 years of the commencement of the agreement as well as long-term - when diagnostic biomarkers are implemented in clinical practice. As the ORFAN study is expected to continue collecting outcomes data for at least the next 10 years, the cohort will continue to generate outputs as more events accumulate over time. These long-term impacts have the potential to change clinical practice worldwide and save lives from improved assessment of cardiovascular disease risk.
Specific algorithms that the ORFAN Study team wish to create and/or validate through the ORFAN arm 4 study include:
1) An algorithm for the specific risk assessment of ischaemic stroke in those with and without atrial fibrillation (provisionally called the Atriomic Stroke Algorithm)
2) An algorithm for the specific risk assessment of cardiovascular complications in those with COVID-19 infection
3) An algorithm for the likelihood of success of invasive catheter ablation in those with atrial fibrillation
4) Validation of the perivascular Fat Attenuation Index (FAI) algorithm for heart attack risk. The FAI algorithm is an already established algorithm for the accurate assessment of heart attack risk, discovered in the ORFAN Study. FAI involves the assessment of CT scan features, in particular attenuation – the CT term for density, of fat surrounding the coronary vessels.
5) Validation of the Fat Radiomic Profile (FRP) algorithm for heart attack risk. The FRP algorithm is a another already established algorithm for long-term heart attack risk discovered in the ORFAN Study. This algorithm relies upon many radiomic features extracted from CT scans from around the coronary vessels. These features cannot be seen by the naked eye, and so require computer extraction and assessment which is what the FRP computes.
6) Likely other algorithms related to specific at risk population depending on data quality and statistical power
All such algorithms are stand-alone patient assessment tools, and any intellectual property created from within the ORFAN Study will be owned by the University of Oxford, and associated intellectual property will be controlled by the University for licensing to health services for inclusion in clinical practice.
The ORFAN research team at the University of Oxford has no personal intention to monetise or generate income from the research outputs generated from the ORFAN Arm 4 study. Were discoveries to be made in the ORFAN Arm 4 study, individual researchers within the ORFAN team would be listed inventors on any patents that the University of Oxford may file.
The study team expect to be publishing important findings related to the development of novel disease risk assessment for cardiovascular disease within 2-3 years of the DSA commencing. It is possible this may occur earlier if the extraction of data in the first year produces enough scientific power for robust results. They expect novel diagnostic and risk assessment tools to be incorporated into clinical practice within 5 years from the DSA commencing, and further major publications related to the use of the tools developed from within the ORFAN study by the end of the 10 year data retention date.
THE LEVEL OF DATA THAT WILL BE CONTAINED IN THE OUTPUTS:
The level of data contained in the outputs is aggregate data with small number suppression applied as per the disclosure rules for the various data sets that has been augmented via statistical processes. No individual participants data is ever published individually, with the nature of this scientific work demanding high numbers of participants data for the testing and validation of disease risk calculators.
The dissemination activities of the ORFAN Study team are focussed on high-impact peer reviewed journals and oral research presentations at international conferences. Other activities through which the ORFAN study findings are communicated include through NHS Trust clinical grand-round meetings at NHS Trusts who deliver services relevant to those explored in the study, NHS Trust newsletters delivered to staff emails and through high level meetings with NHS executives and clinical leads at NHS Trusts to discuss the suitability for the clinical tools to be tested within the clinical environment at their Trusts. This work also involves audit related work to model the impact of novel tools developed from within ORFAN on current service usage, as has occurred within Oxford University Hospitals NHS Trust already.
To target the lay audience, the ORFAN team uses the following approaches and is guided by the Research Services team at the University of Oxford and the Public Engagement team at the Cardiovascular Medicine Division of the University of Oxford:
a) Website (www.oxhvf.com); this is updated with all the most up to date information regarding the outputs of the research. This is a public-facing website, and the public can read about the latest outputs of the study.
b) Newsletters; when major findings or general outputs are available, the ORFAN team post newsletters both on the website and in hard-copy form to ORFA Arm 1-3 participants. This is not possible for Arm 4, as we do not hold patient identifiable information. Media attention including articles in BBC News, The Guardian, The Financial Times and CBN concerning work published in the prestigious journal ‘Science Translational Medicine’ are the sorts of topics highlighted in newsletters (see example from the Antoniades Lab: https://test188076.files.wordpress.com/2018/01/newsletter-adiporedox-15-09-2017.pdf).
c) Press releases; the ORFAN team have an active involvement in outreach activities of the University of Oxford, Oxford University Innovations and the British Heart Foundation communications team, and the major findings from their study lead to press releases, and from there they are distributed to the lay press.
d) Workshops and patient and public involvement; the ORFAN team participate in workshops for patients as part of the Biomedical Research Centre in Oxford, and through that they inform the patients about their research and ask for their involvement in the design of protocols, feedback on research procedures and more, through Patient and Public involvement (PPI) panels
e) Social media – the ORFAN Study group frequently share results and outputs to their social media presence on Twitter, Facebook and LinkedIn.
Exploitation of results/outputs:
All intellectual property and knowhow is owned by the University of Oxford, as the sponsor of the ORFAN Study. The University of Oxford, through Oxford University Innovation, maintains the ability to licence any technology that is created within the ORFAN Study for commercial use or for use within health services such as the NHS.
Benefits reported
The University of Oxford ORFAN team have previously produced multiple results that have been published academically and reported upon within the lay press. Some noteworthy examples include:
Evidence that obesity may not be necessarily bad for all patients, and those patients with high body mass index may be protected against cardiovascular mortality because fat in the body may secrete protective substances. This is called the obesity paradox and has major implications for the treatment of patients with heart diseases (published in the journal Diabetes in 2015, link to press coverage about the obesity paradox: https://www.telegraph.co.uk/news/science/science-news/11657811/Why-obesity-protects-against-heart-diseaseand-heart-attack.html).
The University of Oxford (ORFAN team) has recently identified a significant therapeutic target for the treatment of heart diseases, and that discovery led to intense research to develop new drugs to modify this target (presented in the European Society of Cardiology 2018 Congress, and received the Best Poster Award).
The University of Oxford ORFAN group has developed a novel imaging biomarker (see Antonopoulos et al in Science Translational Medicine, 2017), namely the Fat Attenuation Index (FAI), which has been shown to be a marker of vascular inflammation at early disease stages. Validation of this biomarker in large cohorts of patients with residual cardiovascular risk showed that FAI is able to detect patients at high risk for cardiac mortality and is also predictive of non-fatal heart attacks. This permits reclassification of an individual's risk, above and beyond the current state-of-the-art diagnostic tools, with strong implications for guiding medical management in patients and guiding the use of primary and secondary prevention measures. The development of this technology is a significant example that highlights the strength and unique ability of the Ox-HVF cohort in combining data across different and diverse fields - from clinical and epidemiological data to basic science and imaging data to outcome data (requested in the current application) - to create new, boundary-pushing ideas that promote health and serve the public interest. Of note, FAI was featured by iNews as one of the ten health innovations that could soon be on the NHS (https://inews.co.uk/news/health/the-ten-health-innovations-that-could-soon-be-on-the-nhs/). bFAI has been included into the recent Up-To-Date clinical guidance for use in patients with chest pain (https://www.uptodate.com/contents/cardiac-imagingwith-computed-tomography-and-magnetic-resonance-in-the-adult) and can be used to detect patients who may need intense medical therapy to prevent future heart attacks.”
Register history
When this agreement appeared in, or was edited in, each monthly edition of the register. Built by comparing every edition this site holds, the earliest of which is July 2021.
-
July 2021 —
already listed in the earliest edition this site holds, so it may be older. 1 version: DARS-NIC-409610-J6L1F-v0.3
-
February 2022
Amended DARS-NIC-409610-J6L1F-v0.3
- Objective for processing:
reworded
Show the change
The Oxford Risk Factors And Non Invasive Imaging Study (ORFAN) at large [11 words unchanged] arms 1, 2 and 3. Arm 4 has been developed conceptually from
2018,2018 and came into practical existence from 2019 to both address outstanding scientific [15 words unchanged] to further develop and validate novel biomarkers that have emerged from ORFANArmArms 1-3 and other Ox-HVF studies (see below). ORFAN Arm 4 is funded [6 words unchanged] Research (NIHR) Oxford Biomedical Research Centre and The British Heart Foundation (BHF). [1 paragraph unchanged] The study is applying to NHS Digital in order to link study participant's patient identifiers with data held by NHSDigitalDigital. This linkage is necessary in order to develop and validate cardiovascular disease risk assessment tools that [25 words unchanged] clinical environment and are intended to change patient care for the better. [1 paragraph unchanged] The NHS Digital data requested in this agreement could contribute in a fundamental way to the achievement of this purpose by allowing the research team to knowwhatwhich diseases and clinical events had occurred prior to the CT scan of relevance to the study, andwhat diseasewhich diseases and clinical events have occurred for participants following the CT scan. This [6 words unchanged] development of image analysis tools as it enables accurate differentiation of participantcharacteristics, namelycharacteristics (namely imaging characteristics detected from within the CTscans,scans) that can be utilised to predict patient risk. A further major purpose of the ORFAN Arm 4 project is to [67 words unchanged] clinical events, along with relevant CT scans of such patients’ hearts andvesselsvessels, will enable a much more accurate assessment of this risk for individual patients. [6 paragraphs unchanged] 1. Measurements of plasma/imaging markers of cardiometabolic risk - not directly relevant for this application, although the data requested will be linked to thepseudo-anonymisedpseudonymised plasma and imaging data already held by the applicant 2. Atherosclerosis progression by Computerised Tomography - not directly relevant for this application, although the data requested will be linked to the relevantpseudo-anonymisedpseudonymised imaging data already held by the applicant [4 paragraphs unchanged] The ORFAN Study was assigned COVID-19 Cardiovascular Disease UK Flagship Project status by the NIHR-BHF in May 2020 and has received ethical approval to pursue a scientific inquiry into the specific risk that is conveyed by COVID-19 infection in regard to stroke [5 words unchanged] data from this agreement will form a major part of this inquirysoas it will support the study teamcanto understand the heart disease risk that COVID infection confers, andwillenable the creation of biomarkers for assessing patients individual risk of heart disease complication following COVID-19 infection. [1 paragraph unchanged] ORFAN is part of the Oxford cohort for Heart, Vessels and Fat [26 words unchanged] clinical studies run from the University of Oxford that together provide resultsallowingwhich allow for the deployment of a multi-level strategy to understand the mechanisms of cardiovascular disease, specifically heart attack and stroke. This agreement concerns ORFAN Arm 4 only, which is a retrospective study [38 words unchanged] at a participating NHS Trust radiology department. The ORFAN study team arefocussedfocused on CT coronary angiograms in this project - scans that only include the heart and surrounding blood vessels and tissues. ORFAN Arm 4 focuses on collecting CT images, patient demographics and clinical [52 words unchanged] the automated calculation of image analysis techniques developed by the University ofOxford includingOxford. This includes the perivascular Fat Attenuation Index, the coronary artery Fat Radiomic* Profile and [38 words unchanged] of this project. The development of these algorithms and tools has, andwill,will lead to much improved patient care for those at risk of heart attack and stroke. [3 paragraphs unchanged] As an example, a specific project that will make use of Arm [112 words unchanged] is the field of artificial intelligence concerned with the automated interpretation ofimages, inimages. In the same way that a computer can identify if a photo portrays a cat or a [70 words unchanged] on the ORFAN study utilising this computer for CT scan analysis purposes. The University of Oxford researchteamteam, who will receive the pseudonymised data from NHSDigitalDigital, will never receive linkage files that enable the matching of the participants clinical information with their identifiable information. [6 paragraphs unchanged] - Expected output:
reworded
Show the change
[1 paragraph unchanged] 1) The creation of novel disease risk calculating algorithms (patient assessment algorithms and the necessary software tools to practically apply the algorithms) for conditions such as heart attack and stroke ready for incorporation into patient care within health services, and 2) the communication of these outputs via scientific and lay-person publications. The research outputs to convey the results will be led by peer reviewed publications in leading international journals, presentations in international and national scientific meetings and subsequent media reporting and public engagement lead by the University of Oxford. Journals being targeted to submit to/publish in: i) The New England Journal of Medicine (NEJM) (impact factor 74.7) ii) The Journal of the American Medical Association (JAMA) (impact factor 45.5) iii) The Lancet (impact factor 60.4) iv) Circulation (impact factor 23.6) v) Journal of the American College of Cardiology (JACC) (impact factor 20.5) vi) British Medical Journal (BMJ) (impact factor 30.2) vii) European Heart Journal (EHJ) (impact factor 22.7) The study team intend major findings of this work to be published in the top-tier general medicine journals (NEJM, JAMA, Lancet, BMJ) as opposed to more cardiac specific findings which will be aimed at the top cardiology journals (Circulation, JACC, EHJ). This enables far greater readership and targeting of impact. All publications in major journals such as those listed here will be open access, meaning any reader from anywhere on Earth can access the full text of the research article without any cost. Congresses and conferences targeted to submit work to: i) Scientific sessions of the American Heart Association ii) Scientific sessions of the European Society of Cardiology iii) Scientific sessions of the American College of Cardiology iv) Scientific sessions of the British Cardiac Society The outputs from this work will be both immediate - with publications in high impact journals within 2-3 years of the commencement of the agreement as well as long-term - when diagnostic biomarkers are implemented in clinical practice. As the ORFAN study is expected to continue collecting outcomes data for at least the next 10 years, the cohort will continue to generate outputs as more events accumulate over time. These long-term impacts have the potential to change clinical practice worldwide and save lives from improved assessment of cardiovascular disease risk. Specific algorithms that the ORFAN Study team wish to create and/or validate through the ORFAN arm 4 study include: 1) An algorithm for the specific risk assessment of ischaemic stroke in those with and without atrial fibrillation (provisionally called the Atriomic Stroke Algorithm) 2) An algorithm for the specific risk assessment of cardiovascular complications in those with COVID-19 infection 3) An algorithm for the likelihood of success of invasive catheter ablation in those with atrial fibrillation 4) Validation of the perivascular Fat Attenuation Index (FAI) algorithm for heart attack risk. The FAI algorithm is an already established algorithm for the accurate assessment of heart attack risk, discovered in the ORFAN Study. FAI involves the assessment of CT scan features, in particular attenuation – the CT term for density of fat surrounding the coronary vessels. 5) Validation of the Fat Radiomic Profile (FRP) algorithm for heart attack risk. The FRP algorithm is another already established algorithm for long-term heart attack risk discovered in the ORFAN Study. This algorithm relies upon many radiomic features extracted from CT scans from around the coronary vessels. These features cannot be seen by the naked eye, and so require computer extraction and assessment which is what the FRP computes. 6) Likely other algorithms related to specific at risk population depending on data quality and statistical power All such algorithms are stand-alone patient assessment tools, and any intellectual property created from within the ORFAN Study will be owned by the University of Oxford, and associated intellectual property will be controlled by the University for licensing to health services for inclusion in clinical practice. The ORFAN research team at the University of Oxford has no personal intention to monetise or generate income from the research outputs generated from the ORFAN Arm 4 study. Were discoveries to be made in the ORFAN Arm 4 study, individual researchers within the ORFAN team would be listed inventors on any patents that the University of Oxford may file. The study team expect to be publishing important findings related to the development of novel disease risk assessment for cardiovascular disease within 2-3 years of the DSA commencing. It is possible this may occur earlier if the extraction of data in the first year produces enough scientific power for robust results. The study team expect novel diagnostic and risk assessment tools to be incorporated into clinical practice within 5 years from the DSA commencing, and further major publications related to the use of the tools developed from within the ORFAN study by the end of the 10 year data retention date. THE LEVEL OF DATA THAT WILL BE CONTAINED IN THE OUTPUTS: The level of data contained in the outputs is aggregate data with small number suppression applied as per the disclosure rules for the various data sets that have been augmented via statistical processes. No individual participants data is ever published individually, with the nature of this scientific work demanding high numbers of participants data for the testing and validation of disease risk calculators. The dissemination activities of the ORFAN Study team are focused on high-impact peer reviewed journals and oral research presentations at international conferences. Other activities through which the ORFAN study findings are communicated include through NHS Trust clinical grand-round meetings (at NHS Trusts who deliver services relevant to those explored in the study), NHS Trust newsletters (delivered to staff emails) and through high level meetings with NHS executives and clinical leads at NHS Trusts (to discuss the suitability for the clinical tools to be tested within the clinical environment at their Trusts). This work also involves audit related work to model the impact of novel tools developed from within ORFAN on current service usage, as has occurred within Oxford University Hospitals NHS Trust already. To target the lay audience, the ORFAN team uses the following approaches and is guided by the Research Services team at the University of Oxford and the Public Engagement team at the Cardiovascular Medicine Division of the University of Oxford: a) Website (www.oxhvf.com): this is updated with all the most up to date information regarding the outputs of the research. This is a public-facing website, and the public can read about the latest outputs of the study. b) Newsletters: when major findings or general outputs are available, the ORFAN team post newsletters both on the website and in hard-copy form to ORFAN Arm 1-3 participants. This is not possible for Arm 4, as the University of Oxford do not hold patient identifiable information. Media attention including articles in BBC News, The Guardian, The Financial Times and CBN concerning work published in the prestigious journal ‘Science Translational Medicine’ are the sorts of topics highlighted in newsletters (see example from the Antoniades Lab: https://test188076.files.wordpress.com/2018/01/newsletter-adiporedox-15-09-2017.pdf). c) Press releases: the ORFAN team have an active involvement in outreach activities of the University of Oxford, Oxford University Innovations and the British Heart Foundation communications team, and the major findings from their study lead to press releases. From there they are distributed to the lay press. d) Workshops and patient and public involvement: the ORFAN team participate in workshops for patients as part of the Biomedical Research Centre in Oxford. Through these workshops they inform the patients about their research and ask for their involvement in the design of protocols, feedback on research procedures and more. This is also done through Patient and Public involvement (PPI) panels. e) Social media – the ORFAN Study group frequently share results and outputs to their social media presence on Twitter, Facebook and LinkedIn. Exploitation of results/outputs: All intellectual property and knowhow is owned by the University of Oxford, as the sponsor of the ORFAN Study. The University of Oxford, through Oxford University Innovation, maintains the ability to licence any technology that is created within the ORFAN Study for commercial use or for use within health services such as the NHS.The major outputs from this data processing are twofold: [39 paragraphs unchanged]
- Objective for processing:
reworded
-
May 2022
1 version added: DARS-NIC-409610-J6L1F-v1.9
-
April 2024
1 version added: DARS-NIC-409610-J6L1F-v2.5
"Amended in place" means NHS England changed the record without issuing a new version number. The register publishes no changelog for those edits; this site infers them by comparing editions. An edit is attributed to the edition it first appears in, not to the date it was made.
Cite this page
NHS England (2026) Data Uses Register, September 2026 edition, agreement DARS-NIC-409610-J6L1F, “The Oxford Risk Factors And Non Invasive Imaging Study (ORFAN) Arm 4”. Read via NHS Data Access Explorer (unofficial), https://healthdatauses.uk/agreements/dars-nic-409610-j6l1f/ (accessed [date]).
This address stays the same, but the page is rebuilt with each monthly edition, so the citation names the edition it shows. Every edition's data is kept in the facts store.
Source: datausesregister_september2026.xlsx, September 2026 edition of the NHS England Data Uses Register. Search that workbook for DARS-NIC-409610-J6L1F to see the original rows.