Follow-up of clinical outcomes, healthcare episodes and prescriptions in individuals with microvascular angina: The PRIZE Registry

University of Glasgow requires access to NHS England data for the purpose of the following research project:

Follow-up of clinical outcomes, healthcare episodes and prescriptions in individuals with microvascular angina: The PRIZE Registry.

Microvascular angina is caused by abnormalities of the small blood vessels in the heart. It may cause anginal chest symptoms during exercise and at other times such as cold weather, emotional stress. The medicines that doctors currently prescribe for patients with microvascular angina were not developed for treatment of this condition and are given on a trial and error basis.

Endothelin is a chemical that circulates in the blood and can accumulate in the blood and blood vessel walls in patients with microvascular angina. Endothelin works by acting on one of two pathways (A or B) and it is the ‘A’ pathway that causes the blood vessel problems in the heart. Endothelin is therefore implicated in causing microvascular angina.

Patients with microvascular angina were initially (first) invited to give informed consent to participate in a follow-up registry. The registry involved collection of information on medical history, etc at baseline and participants gave informed consent for follow-up. The purpose of this data request is the follow-up of the registry population.

222 individuals in the UK entered the registry, including 139 individuals residing in England, who consented for University of Glasgow to access their health records. University of Glasgow now require follow-up information on health outcomes for the 139 participants residing in England.

From within the registry, a subset of individuals were eligible for participation in a clinical trial. The Precision Medicine With Zibotentan in Microvascular Angina (PRIZE) study is a registry-based clinical trial. A subset of individuals who participated in the clinical trial participated in an optional MRI sub-study which investigated the effect of zibotentan on heart muscle blood flow using cardiovascular magnetic resonance imaging (MRI). MRI was performed at five sites using 1.5 and 3.0 Tesla scanners with a standardized protocol including adenosine stress and rest perfusion imaging, parametric mapping, and late gadolinium enhancement. In the end, 18 participants underwent MRI at baseline and after 12 weeks of each treatment arm corresponding to Visits 3, 4 and 5 of the main trial. Overall, zibotentan did not improve blood flow or heart function as revealed by MRI. The trial took place between 2019 – 2023 and is now closed.

The following is a summary of the aims of the research project provided by University of Glasgow:

• Understand the natural history of Microvascular angina

• Assess whether the effects of zibotentan during the study might associate with the clinical outcomes in the longer term.

The following NHS England Data will be accessed:

• Hospital Episode Statistics - Admitted Patient Care

• Hospital Episode Statistics - Outpatients

• Emergency Care Data Set (ECDS)

• Civil Registration Mortality

Access to these data is necessary to check longer-term clinical outcome data and estimate NHS costs of healthcare.

The level of the Data will be identifiable.

The Data will be minimised as follows:

• Limited to a cohort identified by University of Glasgow. The cohort consists of 139 individuals in the registry who reside in England, and consented to participate.

• Limited to data from the date of consent for each participant to latest available periods available (no data will flow for participants who has withdrawn their consent).

University of Glasgow is a research sponsor and is the sole controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above.

NHS Greater Glasgow and Clyde (NHS GG&C) is a co-sponsor but are not involved as a controller or processor.

The lawful basis for processing personal data under the UK GDPR is:

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.

The lawful basis for processing special category data under the UK GDPR is:

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.

The funding is provided by The Medical Research Council (MRC). The funding is specifically for the project described.

The funder will have no ability to suppress or otherwise limit the publication of findings.

Iron Mountain is a processor acting under the instructions of University of Glasgow. The role of Iron Mountain is limited to data back-up services only.

NHS Greater Glasgow & Clyde are a co-sponsor of the research but are not involved in decisions about the manner and means of conducting the research. A co-sponsorship agreement between University of Glasgow and NHS Greater Glasgow & Clyde describes University of Glasgow as the sole Data Controller for the purposes of the research.

Data will be accessed by substantive employees of University of Glasgow only.

A Public and Patient Involvement and Engagement group of the NHS Golden Jubilee hospital helped refine the purpose of the research. The group strongly supported the collection of the data for the purposes described above. Further, the Chief Investigator serves as a voluntary advisor to patient forums, including INOCA International and the International Heart Spasms Alliance. One of the drivers for change in these forums is the lack of clinical information on the natural history of microvascular angina – this condition has historically been under-recognised, with a lack of funded research into this condition and the related evidence gap on the burden of illness, NHS healthcare utilisation, polypharmacy and prognosis.

Microvascular angina is one of the conditions included under the umbrella term Ischaemia with Non-Obstructive Coronary Arteries (INOCA). The Chief Investigator was involved in qualitative research involving interviews with patients with a confirmed or presumed diagnosis of INOCA: https://bmjopen.bmj.com/content/14/12/e086770. The research concluded that the patient group have specific concerns about the need for improved professional knowledge and evidence-based guidance regarding the management of INOCA.

The clinical trial sub-study benefitted from 'in-kind' support from Astrazeneca (AZ). AZ support was limited to provision of the medicine zibotentan free of charge. AZ receives a non-exclusive licence to use study results that relate to the study drug (zibotentan) for internal R&D purposes. AZ had a time-limited option to negotiate an exclusive licence for such results, but this option was not exercised. Astrazeneca have not provided funding to support the clinical trial or long-term follow up study.

The MRI sub-study benefitted from software developed and provided by Siemens Healthcare. Support from Siemens was limited to provision of the software and personnel time only. Siemens receives a non-exclusive licence to use study results that relate to Siemens’ software for MBF analysis for internal R&D purposes. Siemens had a time limited option to negotiate an exclusive licence for such results, but this option was not exercised. Siemens have not provided MRI sub-study, or long-term follow up study.

University of Glasgow will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number, Date of Birth, Postcode, and a unique person ID) for the cohort to be linked with NHS England data.

NHS England will provide the relevant records from the HES Admitted Patient Care, HES Outpatients, Emergency Care, and Civil Registrations of Death datasets. The data will contain no direct identifying data items but will contain a unique person ID which can be used to link the Data with other pseudonymised record level data already held by University of Glasgow.

The Data will not be transferred to any other location.

The Data will be stored in the Robertson Centre Safe Haven on servers at the University of Glasgow.

University of Glasgow uses offsite back-up services provided by Iron Mountain.

The Data will be accessed by authorised personnel via remote access.

The Controller must confirm and provide evidence upon audit by NHS England that access via any remote device complies with the data security obligations within this DSA and the Data Sharing Framework Contract.

For remote access:

• Remote access will only be from secure locations situated within the territory of use (as further restricted elsewhere within the DSA if so done) stated within this DSA;

• Access controls granting users the minimum level of access required are in place;

• Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data;

• Multifactor authentication (MFA) is required for remote access;

• Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access;

• All remote access is undertaken within the scope of the organisation’s DSPT (or other security arrangements as per this DSA) and complies with the organisation’s remote access policy.

The above applies in addition to any condition set out elsewhere within the DSA (e.g. who may carry out processing, and for what purpose).

The Data will not leave the UK at any time.

Data will be accessed by employees or agents of University of Glasgow who have authorisation from the Principal Investigator.

NHS Greater Glasgow & Clyde are not permitted to access the Data.

All personnel accessing the Data have been appropriately trained in data protection and confidentiality.

The Data will be linked at person record level with study data collected by University of Glasgow.

The identifying details will be stored in a separate database to the linked dataset used for analysis. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset.

Researchers from the Robertson Centre for Biostatistics (RCB) at the University of Glasgow will process the Data for the purposes described above.

The expected outputs of the processing will be:

• A final report of findings to the funder (Medical Research Council)

• Submissions to peer reviewed journals in the field of cardiology

• Publication of results on the University of Glasgow’s website: https://www.gla.ac.uk/research/az/bhfglasgow/

• Publication of results through a press release and social media.

The main report is envisaged to be published two years after the release of the NHS England data. University of Glasgow anticipate additional, related (secondary) analyses which would extend into years 3-5 with all final revisions/publications being achieved and completed within 5 years of receiving the Data.

The outputs will not contain NHS England Data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Social media

• Public reports

• Briefing documents provided to the Medical Research Council.

• Press/media engagement

The target date for dissemination of the main publication is mid-2027. Secondary publications are expected throughout 2028-2030.

The findings of this research study are expected to contribute to evidence-based decision-making for policy-makers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of health care users relevant to the subject matter of the study.

The use of the data could:

• help the system to better understand the health and care needs of populations.

• lead to the identification or improvement of treatments or interventions, or health and care system design to improve health and care outcomes or experience.

• advance understanding of the need for, or effectiveness of, preventative health and care measures for patients diagnosed with microvascular angina.

• support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work).

The PRIZE registry is unique worldwide in the potential for long-term follow-up of individuals with microvascular angina involving episodes of healthcare, vital status and medication.

The information from this study should be sufficiently impactful to support prioritisation in clinical guidelines e.g. NICE, NHS etc. and also to support the case with pharmaceutical companies to invest funding into R&D for the development of new medicines that could improve health outcomes for patients with microvascular angina.

It is hoped that through publication of findings in appropriate media, the findings of this research will add to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients with microvascular angina. The information will therefore be empowering to patients with lived experience (including in their discussions with their doctor) and within NHS healthcare organisations (primary and secondary care networks) to provide systems of care for patients with lived experience (including to reduce their dependency on primary and secondary care services).

The British Heart Foundation is the major charity for cardiovascular disease in the UK. The Chief Investigator (CI) has close links with the charity. The CI has contributed to their public-facing information for this condition and will continue to do so following the publication of the main results from this record linkage analysis. These future results will greatly enhance the patient agenda in this area, extending current work as outlined below:

https://www.bhf.org.uk/informationsupport/heart-matters-magazine/medical/ask-the-experts/microvascular-angina

https://www.bhf.org.uk/women-scotland

The future reports from this data will be made available to the British Heart Foundation and other relevant stakeholder organisations such as:

https://inocainternational.com/professor-colin-berry/

https://inocainternational.com/2022/09/04/episode-2-professor-colin-berry/

https://www.internationalheartspasmsalliance.org/professionals/healthcare-professionals/professor-colin-berry/

Yielded Benefits is not a requirement for new applications.