CHARIOT Study

University Hospitals Southampton NHS Foundation Trust requires access to NHS England data for the purpose of the following research project:

Is the [C]urrent T[h]reshold for Diagnosis of “[A]bnormality”, including Non ST Elevation Myocardial Infarction, using [R]aised H[i]ghly Sensitive Tr[o]ponin Appropriate for a Hospi[t]al Population? (CHARIOT) - 5 Year Outcomes

The following is a summary of the aims of the research project provided by University Hospitals Southampton NHS Foundation Trust.

The original CHARIOT study was intended to demonstrate the frequency with which elevated troponin concentrations (a blood test which was designed to test for heart attacks) are seen in patients presenting with symptoms not traditionally associated with a heart attack. Whilst the 1- and 2.5-year follow up data demonstrated that the troponin concentrations were associated with short-medium term outcomes, the aim of the 5 and 10 year analysis is to see whether these troponin concentrations are associated with longer term outcomes. This is important because longer term relationship can be demonstrated then it will not only help clinicians with the interpretation of these assays but also encourage future research to assess whether this risk could be altered by any intervention.

The following NHS England Data will be accessed:

• Hospital Episode Statistics

o Admitted Patient Care – necessary in order to assess whether the High-sensitivity troponin blood test can predict future cardiovascular events, by assessing whether these patients presented with heart attacks, strokes or heart failure events.

• Civil Registration Mortality – necessary in order to assess the prognostic utility of high sensitivity troponin concentrations, specifically by determining whether the patient is alive and if applicable the date of death. Also necessary to assess whether there is a relationship with cardiovascular and/or non-cardiovascular mortality.

The level of the Data will be:

• Identifiable – necessary because although the data provided by NHS England will contain pseudonymised fields, University Hospital Southampton NHS Foundation Trust retain access to the corresponding identifiers. While no efforts will be made to reidentify participants, the technical capability to do so remains

The Data will be minimised as follows:

• Limited to a study cohort identified by University Hospital Southampton – Consisting of 20,000 patients whom UHS performed biochemistry testing on as part of their routine care between the 29th of June 2017 and 24th August 2017.

• Limited to data between 2017/18 and 2022/23. For each individual patient, data will only be provided from the date they joined the study and until 5-years after the biochemistry testing was performed.

University Hospital Southampton NHS Foundation Trust is the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above.

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

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.

Data will be accessed by:

• Substantive employees of University Hospital Southampton NHS Foundation Trust and;

• Individuals holding an honorary contract under the supervision of a substantive employee of University Hospital Southampton NHS Foundation Trust for the purposes described in this DSA only. University Hospitals Southampton NHS Foundation Trust must maintain records in a single location that cover the following details of each individual given access under an honorary contract:

o Their substantive employer;

o Their role in respect of the purpose for the processing specified in the DSA;

o The start date and end date of the duration in which the Data will be accessed by the individual under an honorary contract;

o The necessity for the Data to be accessed by the person(s) holding an honorary contract, instead of a substantive employee of an organisation named as controller or a processor in this DSA;

o Confirmation that an appropriate contract is in place which follows the relevant guidance and is countersigned by the substantive employer of the honorary contract holder.

A Public and Patient Involvement and Engagement group helped refine the purpose of the research. The British Cardiac Patients Association group supported the collection of the data for the purposes described above

University Hospital Southampton NHS Foundation Trust will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number, Date of Birth, Name, Postcode, Gender 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 and Civil Registrations of Death datasets to University Hospital Southampton NHS Foundation Trust. 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 record level data already held by the recipient

The Data will not be transferred to any other location.

The Data will be stored on servers at University Hospital Southampton NHS Foundation Trust.

The Data will not leave: England and Wales at any time.

Data will be accessed by an individual with an honorary contract with University Hospital Southampton NHS Foundation Trust. The individual will act as an agent of University Hospital Southampton NHS Foundation Trust at all times under supervision from employees of University Hospital Southampton NHS Foundation Trust. Aside from this individual, access is restricted to employees or agents of University Hospital Southampton NHS Foundation Trust who have authorisation from the Chief Investigator.

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

The Data will be linked at person record level with the data from the original CHARIOT study using the unique study identifier.

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 based at University Hospital Southampton NHS Foundation Trust will process the Data for the purposes described above.

The expected outputs of the processing will be:

• Submissions to high impact academic journal relating to cardiovascular medicine. This is expected to be published within one year of receiving the data

• Presentations for wider audiences than just cardiology, for example acute and general medicine (previous results have been presented nationally through the Royal College of Physicians and locally at medical training events).

• Presentations at a major international cardiovascular conference (such as the European Society of Cardiology Congress).

• Presentation of results in a plain language summary on the research section of the University Hospital Southampton’s website.

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 promotion of the research through a presentation of results on UHS’ website.

We expect to submit the manuscript for publication within a year of receiving the data from NHS England. We also expect to present these data at international conferences within a year of receiving the data.

There are two main potential areas of public benefit that are likely to be derived from this analysis. First these data will help clinicians in the day-to-day interpretation of troponin assays which are regularly performed outside their original indication. The interpretation of these tests outside their original purpose often causes significant challenges and concerns amongst clinicians. Therefore, our data will help inform clinicians as to how best to interpret these tests which is likely to result in benefits to individual patients. The second likely benefit from this analysis is the stimulation of future research. It is probable that future work will look at both further refining the prognostic role of these assays but also how the risk information provided by these assays can be utilised in clinical practice. For example, if a patient is identified as being at higher risk based on their troponin concentration at the moment clinicians do not have a strategy to adapt this risk. If our analysis demonstrates that troponin concentrations are associated with long term risk, then this is likely to result in studies seeking to adapt this risk. The exciting potential here is that with a simple blood test an individual’s risk of future events can be assessed and then steps taken to adjust this risk. This has important implications for individuals but also significant implications for healthcare systems who could save significant resources by risk profiling patients with a simple blood test to allow targeted treatments.

It is expected that these data will have two specific benefits to patients. First, these data will help improve clinician understanding of how to interpret these assays in clinical practice. Our data have already demonstrated that up to 25% of patients presenting to emergency services have these tests performed, the majority without evidence of a heart attack. It is very likely that the data from this study will provide further insights into the role of these assays in practice, more as a marker of risk rather than a binary marker of a heart attack. The second benefit is these data are likely to encourage further research that could pave the way for a single blood test to act as a marker of risk that can then be adjusted with specific medical strategies.

It is expected that these data will be published in a respected peer review journal and presented at international conferences. It is likely that this will lead to significant medical media interest, much like the previous CHARIOT publications. This means that the findings of this study will be shared widely and so will rapidly have an impact on clinical practice and drive subsequent research.

These data will be published and presented to medical professionals. It is however expected that the results will lead to media interest (as with previous publications) which will help share the data to the public. Further we will plan to make the results available in a plain language version on the University Hospital Southampton website and on social media. We believe that these steps will help to highlight these data to a broader audience beyond just medical professionals.

From the original CHARIOT DSA DARS-NIC-287601-K4P2V:

Use of NHS England data demonstrated that the assay is closely associated with mortality. These data are likely to lead to further studies to assess whether any medical interventions can alter this increased risk which may well lead to new treatments for these patients

These data support the concept that high sensitivity troponin is associated with adverse outcomes and as such these data are likely to stimulate further research to ascertain whether these adverse outcomes could be adjusted.

The study will allow clinicians a better understanding of how to interpret the high sensitivity troponin assays tests.