EVAREST/BSE-NSTEP Study Cohort to gather follow up data

The University of Oxford are requesting NHS England pseudonymised record level data for the Study: Echocardiography: Value and Accuracy at REst and STress “EVAREST”

BACKGROUND:

Stress echocardiography is a commonly used test to assess for heart disease. It is performed routinely across the country in many different ways. The University of Oxford are examining how stress echocardiography is used in the diagnosis of heart disease, whether there are differences in how the test is performed between hospitals and how the results of the stress echocardiogram guides patients’ care. The EVAREST study should allow University of Oxford to gather information about how this test was performed and how it has helped doctors give patients the most appropriate care. University of Oxford will also examine how stress echocardiography is performed across the country.

STUDY AIMS

The primary objective of this study is to characterise the change in extracellular MVs and associated blood biomarkers during standardised stress echocardiogram protocols and understand the relevance of this change as a predictive marker of coronary disease. However, the request for data in this agreement relates to part of the secondary objectives of the study, namely to investigate the use of stress echocardiography as a clinical procedure in the UK (Group 1-3).

Identifying the long-term outcome data from these patients post functional imaging, is an integral piece of this research project. This analysis will look to assess performance and accuracy of stress echocardiography practice in the UK, which will also include an analysis on the costs associated with the long-term patient care pathway of those who have received a stress echocardiogram.

ORGANISATIONS AND RESPONSIBILITIES

The University of Oxford will be the sole data controller for this agreement and will also be processing the data. The study team are based within the Cardiovascular Clinical Research Facility (CCRF) within the University of Oxford. The sole sponsor and funder for the data analysis section of this project is the University of Oxford.

The British Society of Echocardiography act as an advisory board for the purposes of the study, but are not the sponsor of the study, nor do they decide the purpose and means of processing the data, and do not/will not have access to record-level data from NHS England. The University of Oxford have reviewed ICO requirements / definition of a Data Controller and are satisfied that the British Society of Echocardiography are not a data controller.

In the past, the study has variously been funded by an National Institute for Health and Care Research (NIHR) - Health Education England (HEE) Healthcare Science Research Fellowship, Ultromics Ltd and Lantheus Medical Imaging Inc but these organisations are no longer involved with the study and will have no access to record level NHS England data. The University of Oxford have reviewed ICO requirements / definition of a Data Controller and are satisfied that these organisaitons are not a data controller.

DATA REQUESTED

The University of Oxford are requesting access to the following record level pseudonymised NHS England datasets from the period 2018/19 to latest available data:

- Hospital Episode Statistics (HES) HES Admitted Patient Care (APC)

- HES Outpatients (OP)

- HES Critical Care (CC)

- Emergency Care Dataset (ECDS)

- Diagnostic Imaging Dataset (DIDS)

- Civil Registration (Deaths) Data

The data requested will create a clinical picture of the immediate and subsequent cardiac history for each patient enrolled in the study. This data will be aligned with the initial clinical reasoning and interpretation of cardiac disease/risk to help identify the initial success of the functional testing (stress echocardiography).

The overarching EVAREST project seeks to investigate the accuracy and feasibility of stress echocardiography as a functional imaging modality for cardiology. This requires primarily a large cohort (there are multiple methods of performing stress echocardiography) and a substantial follow-up period in which it is possible to identify any patterns of disease or trends with associated outcomes/risk factors. These will ultimately help improve the accuracy of the test when being performed if it highlights the needs for alterative testing methods, or greater weighting on certain risk factors or demographics.

In order to ascertain the immediate, short term and long-term outcomes in patients having undergone stress echocardiography, this study requires a detailed and long-term follow-up plan. This includes acquiring data surrounding potential cardiac pathways post stress echocardiography, death, admission to Emergency Department (ED) for chest pain and any cardiac imaging or diagnostic testing that may have been undertaken and subsequently altered a patient’s treatment pathway.

This will ensure that this study can build a cardiac history for each participant, and compare this to their initial presentation, the immediate results of the stress echocardiography and the subsequent intervention strategies should this be implemented.

With regards to the acquisition of this data, whilst some could be obtained from the individual patient notes, it is likely that patients will have moved across Trust boundaries, be seen at different NHS hospitals for acute admissions etc during the lengthy follow-up period, and as a result, NHS England is content that the request is the most appropriate and least intrusive method for obtaining the high-quality data required to make these informed observations.

The study team have worked to minimise the data that is requested so that only data requested relating to cardiac investigations/events, in addition to death data. The disease in investigation is common and will help to minimise risk with patient identification. A pseudonymised study ID is used by the University of Oxford, so that once the data is linked and extracted, the study team can analyse the data meaningfully using only a Study ID.

COHORT

This EVAREST programme of work started in 2014 and seeks to obtain 10-year follow-up data on all participants who have consented to follow-up data from NHS England.

Study Participants were added to three groups. Groups 1 and 2 collectively (Phase 1 of the study) consists of 8,000 participants referred for stress echocardiogram by their clinical consultant in order to establish likelihood of coronary artery disease (CAD). Recruitment started in early 2015 and completed in March 2020.

Group 3 (Phase 2 of the study) consists of up to 15,000 participants referred for stress echocardiogram for the investigation of any disease. This includes, but is not limited to, stress echocardiography to assess ischaemia, valvular function, left ventricular outflow tract obstruction, diastology*, myocardial perfusion and tissue viability.

*diastology - The scientific study of the heart muscle when it is not contracting but is in diastole (at rest)

The cohort provided to NHS England will be approximately 6,000 individuals from the above 3 groups. 3,000 from phase 1 and 3,000 from phase 2.

The cohort consists of patients over the age of 18, eligible for recruitment having undergone stress echocardiography at one of the designated recruitment centres.

If a participant requests to withdraw from the study, this will be notated within the Castor eDC system used as part of the study. There is a specific withdrawal Case Report Form (CRF) that will be used for these requests. The participant will have an opportunity to provide a reason for their withdrawal if they so choose. The study team will also ask the participant if the study has permission to keep data after the withdrawal. If the participant does not consent to this, then the database will alert the study team member to delete all data from within the eDC that has been collected to date for that participant with the exception of details of their original consent and withdrawal.

LEGAL BASIS FOR COMMON LAW DUTY OF CONFIDENTIALITY

The study team at University of Oxford will be providing one cohort for this request containing approximately 6,000 individual records. Consent to data linkage has been sought for all participants in phases 1 and 2.

For those study participants in phase 1 (groups 1 and 2) recruited between June 2015 and 21 October 2019 (originally about 8,000 individuals ), consent was originally sought for a 12 month follow up, and then these study participants were re-consented for a further 10 years follow-up period. Only those that re-consented (approximately 3,000) will be a part of the cohort sent to NHS England. Of the phase 1 study participants, the consent documents provide for requesting NHS England data for a maximum of 10 years** from 12 months after the first date they consented into the study.

For those study participants in phase 2 (group 3) recruited from 21 October 2019 onwards (approximately 3,000 individuals), the consent documents provide for requesting NHS England for a maximum of 10 years** from the date of first consent.

**However, it is noted here that due to trial budget constraints, the EVAREST study is requesting NHS England data only between the periods of 2018 to the latest data available under the consent rules stated above.

The cohort provided to NHS England will only contain participants who consent to data linkage. NHS England will not apply National Data Opt-Out for these participants.

UK GDPR LEGAL BASIS FOR PROCESSING OF PERSONAL DATA

The University of Oxford, as the Data Controller who is also processing the data will process Personal Data under UK GDPR Article 6 (1) (e) - Processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller. As a higher education establishment, the University of Oxford conducts research to improve health care and services, and the data requested is necessary for the performance of a task carried out in the public interest. The University of Oxford hopes that this research study and the dissemination of the results will benefit the health and care of the general public by providing a rich detailed look into Stress Echocardiography practice in the UK and health outcomes following the investigation. This work should enable the study team to identify the accuracy of the investigation as well as areas for improvement. This will allow for corrective action to boost accuracy of Stress Echocardiography and thereby increase the quality of the health of individuals presenting for a Stress Echocardiogram investigation. The dissemination is in the public interest as it should provide evidence for the improvement of patient health and care. The outputs should provide the data needed to identify the accuracy and performance of Stress Echocardiography in across the UK for a large cohort of patients.

Additionally, under UK GDPR Article 9(2)(j) processing of Special Category Personal Data (of which Health data is one) is necessary for archiving for research purposes. Data minimisation processes are being followed and only data that is specifically required for the purposes of this study have been requested, to protect the rights of the data subjects. The data are required for research purposes in the public interest – meeting the conditions in the DPA 2018 Schedule 1 Part 1 (4) – which UK GDPR Recital 52(2) determines is an appropriate derogation from the prohibition on processing special categories of personal data.

TRANSPARENCY ON COMMERCIAL BENEFITS

Whilst Ultromics Ltd and Lantheus Medical Imaging Inc were originally funders of this study but are no longer involved and will have no access to record level NHS England data under this agreement, for the purposes of transparency it is stated here that Ultromics Ltd and Lantheus Medical Imaging Inc may receive indirect benefit from association with the EVAREST study. However, Ultromics Ltd and Lantheus Medical Imaging Inc will have no ability to suppress or otherwise limit the publication of findings from this study.

DATAFLOW

Transfer of linkage file/identifiers from University of Oxford to NHS England:

- University of Oxford will send the list of Patient Identifiable Data (PID) in the form of one file - including participant Study ID, NHS Number, Date of Birth (DoB) and Post Code along with the date that data should flow from for each individual in the cohort. University of Oxford will send this file securely to NHS England via a Secure Electronic File Transfer Service (SEFT) or other secure, NHS England approved file transfer mechanism.

- The NHS England data production teams will link patient identifiers to the datasets requested and extract data either:

a) for phase one study participants originally consented between June 2015 and 21 October 2019 - from 12 months after the date of consent*.

b) for phase two study participants consented from 21 October onwards - from date of participants' first consent date.

(*PLEASE NOTE: The Study team have requested the extraction of data to be for NHS England data for the periods 2018/19 to latest available data only)

- The NHS England production teams will remove patient identifiers from the linked data.

- NHS England transfers the linked data via SEFT or other secure, NHS England approved file transfer mechanism to University of Oxford. This data is pseudonymised (only the participant ID from the linkage transfer is kept and identifiable fields are removed).

- University of Oxford study team downloads the data from SEFT to an encrypted system within the University of Oxford Medical Sciences Division IT Network.

The data will be accessed through this secure network. To remotely access the devices requires a secure 2-factor Medical Sciences Division IT authenticator (VPN) and users are then able to securely access the secure server on the University’s IT framework. All data analysis will be conducted within the confines of the University’s secure server, and will not be downloaded to remote devices for storage or processing.

All data analysis will be conducted by EVAREST study team members who are substantive employees of the University of Oxford or authorised study team members with an appropriate contract which has been reviewed and approved by NHS England.

The Patient identifiers provided to NHS England were originally collected by the local study teams at each participating site in the study and were then provided to the University of Oxford study team. These identifiers are only held at the University of Oxford for the purposes of providing to the NHS England team for linkage purposes. Once the identifiers are provided to the NHS England team, they will be destroyed by the University of Oxford study team prior to receiving record-level NHS England data.

The University of Oxford will not be sharing record-level NHS England data outside of the University of Oxford. All record-level NHS England data will be maintained and analysed within the University of Oxford.

Those handling the data for the Data Controller will have been authorised to do so internally and will have logged information security training.

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 (see below)

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, data processors must make sure that:

• National-level figures only may be presented unrounded, without small number suppression

• cell values from 1 to 7 (inclusive) are suppressed at a sub-national 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.

The study team at University of Oxford aim to publish this work in a peer-reviewed journal. During the course of analysis there may be conferences and presentations that are conducted that include mention of EVAREST either in part or fully. All data included in presentations or publications will be anonymised meaning only high-level aggregate data with small numbers supressed (as per the HES analysis guide) will be presented.

The University of Oxford will aim to facilitate the dissemination of the research and scientific work to stakeholders during the project and after completion. The study team will aim to disseminate this research to the scientific public through presentations, publications and discussions. The study team will also aim to disseminate this research to the general public through publications. The study team are also planning to disseminate this work for potential policy change such as with National Institute for Health and Care Excellence (NICE) or European Society of Cardiology (ESC). This should all be accomplished through conferences, publications, presentations, webinars, engagement using professional and established relationships.

The study team aim to analyse the data and public preliminary work in 2023/2024 contingent upon when the data is received from NHS England. There may be various presentations, conferences, public events within that time that the data will also be presented at.

The research study and the dissemination of the results hopes to benefit the health and care of the general public by providing a detailed look into Stress Echocardiography practice in the UK and health outcomes following the investigation. This work hopes to enable the study team to identify the accuracy of the investigation as well as areas for improvement. This should allow for corrective action to boost accuracy of Stress Echocardiography and thereby increase the quality of the health of individuals presenting for a Stress Echocardiogram investigation.

The dissemination is in the public interest as it hopes to provide evidence for the improvement of patient health and care. The outputs aim to provide the data needed to identify the accuracy and performance of Stress Echocardiography in across the UK for a large cohort of patients. Once the purpose is achieved, the benefits discussed hope to be realised.

The study team hope that the details of the work and dissemination will look to identify room for improvement in the practice of Stress Echocardiography. This could potentially impact all centres in the UK who routinely perform stress echocardiograms (around 120 as of 2014). If areas for improvement are noted and actioned, this could potentially lead to an increase in overall diagnostic accuracy of stress echocardiography, thereby reducing the need for potentially unnecessary further procedures and investigations in the patient care pathway. A reduction in unnecessary procedures and interventions could potentially decrease the burden on the NHS and allow resources to be utilised elsewhere. Individual patients could receive the benefit in having a more experienced and accurate stress echocardiogram investigation. This benefit in the individual level could be identified through further downstream research studies assessing stress echocardiography and patient health outcomes. It could take time to achieve these benefits as implementing trainings and affirmative action plans for increasing centre performance can take time. Policy change and cost savings can also require sufficient time to enact. The University of Oxford would expect that within the next 10 years they could see evidence of change in the patient care pathway, burden to NHS resources, and potentially national/international policy due to this dissemination.

There have been two manuscripts published that make use of the NHS Digital data by the University of Oxford EVAREST study team:

https://doi.org/10.1093/ehjci/jeaf099

https://doi.org/10.1093/ehjci/jeae291

Further analysis and subsequent publications will be expected during the DSA extension period.