PARAMEDIC-3 (Pre-hospitAl RAndomised trial of MEDICation route in out-of-hospital cardiac arrest) - Consenting Subset of the Cohort

The University of Warwick requires access to NHS England data for the purpose of the following research project: PARAMEDIC-3 (Pre-hospitAl RAndomised trial of MEDICation route in out-of-hospital cardiac arrest).

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

PARAMEDIC-3 is a follow-on trial from PARAMEDIC-2 which indicated that the route of administration of adrenaline could influence how fast adrenaline is delivered to patients thus influencing the participant outcome in patients experiencing an Out of Hospital Cardiac Arrest (OHCA). It is a stand-alone project and not part of a larger programme.

The PARAMEDIC-3 trial is a pragmatic, allocation concealed, open-label, multi-centre, superiority randomised controlled trial aiming to evaluate the clinical-effectiveness of the intraosseous (IO) and intravenous (IV) drug routes for administration of adrenaline for out of hospital cardiac arrests. The objective for processing NHS England data is to collect data on survival, and patient's length of stay in Intensive Care Unit (ICU) and hospital (trial secondary outcomes) to complement data collected during the course of the trial. Hospital Episode Statistics (HES) data will also be used in health economics analysis, alongside other data collected in patient questionnaires, to determine which route of adrenaline administration gives the best patient outcomes and is the most is cost-effective.

The following NHS England Data will be accessed:

• Hospital Episode Statistics Admitted Patient Care, Critical Care, Outpatients and Emergency Care Dataset – necessary to determine if there is a difference in survival, required hospital based healthcare activity and associated NHS cost between trial arms.

• Civil Registration Mortality – necessary to verify data reported by participating ambulance services

ETHNIC_CATEGORY: Found in the Emergency Care Dataset (ECDS) – Ethnicity is an important field for us to ensure that results are representative of the population in England. Having the ethnicity available will help the University of Warwick interpret the results, and ensure inclusivity in the reporting of the results on the diverse population in England.

date_of_death: Found in the Civil Registration Deaths Dataset – Date of Death is one of the secondary outcomes of the PARAMEDIC-3 study. These data will enable the University of Warwick to determine survival up to 6-months and undertake time-to event analyses. These data will also inform health economic analysis which will provide key additional information for healthcare policy makers.

The level of the Data will be:

• Pseudonymised

The Data will be minimised as follows:

• Limited to a trial cohort identified by the University of Warwick for patients who were randomised into the PARAMEDIC-3 Trial and survived to admission to hospital following an Out of Hospital Cardiac Arrest (OHCA). This subset of the cohort consists of 151 individuals who survived and regained capacity in order to provide informed patient consent to participate in the study.

• Limited to data between the 2020/21 financial year and December 2024. For each individual patient, data will only be provided from the time of the OCHA until 6 months afterwards.

The University of Warwick is the research sponsor and 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

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.

This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care.

The funding is provided by the National Institute for Health Research (NIHR). The funding is specifically for the trial described. Funding is in place until April 2025.

There are multiple clinical collaborators and PPI representatives involved in the management of the trial. They will not be involved with, or advise on data processing, but are likely to help interpret the aggregated results (with small numbers suppressed) for the purpose of the report.

The trial has four oversight groups: The Trial Management Group (TMG), the independent Trial Steering Committee (TSC), the independent data Monitoring Committee (DMC) and the independent Patient and Public Involvement (PPI) group.

The main responsibilities of the TSC are as follows: 1) Providing advice, through its Chair, to the Trial Funder, the Trial Sponsor, the Chief Investigator, the Host Institution and the Contractor on all appropriate aspects of the project 2) Focusing on progress of the trial/project, adherence to the protocol, patient safety and the consideration of new information of relevance to the research question 3) The rights, safety and well-being of the participants are the most important considerations and should prevail over the interests of science and society 4) Ensure appropriate ethical and other approvals are obtained in line with the project plan 4) Agree proposals for substantial protocol amendments and provide advice to the sponsor and funder regarding approvals of such amendments 5) Provide advice to the investigators on all aspects of the trial/project.

The DMC consist of independent experts with relevant clinical research, and statistical experience. The DMC met prior to the start of the trial and at intervals not less than annually thereafter. Confidential reports containing recruitment, protocol compliance, safety data and interim assessments of outcomes are reviewed by the DMC. The DMC advise the TSC as to whether there is evidence or reason why the trial should be amended or terminated.

A Public and Patient Involvement and Engagement group helped refine the purpose of the research. The group supported the collection of the data for the purposes described above. The group support the development of patient and public facing information, advise on the strategy for approaching / informing patients about their participation in the trial, and advise on how information collected is used.

The group will support development of a communication strategy (including social media), and support the dissemination of information to the public both during and at the end of the trial. The team will identify at least two PPI members to become independent members of the TSC.

The University of Warwick will transfer data to NHS England. The data will consist of identifying details, specifically Participant name, Date of Birth, Post Code and NHS Number for the cohort to be linked with NHS England data.

NHS England will provide the relevant data records from the HES and Civil Registration Deaths datasets to the University of Warwick. 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 the University of Warwick.

The Data will be accessed onsite at the premises of the University of Warwick and the Data will be accessed by Authorised personnel via remote access.

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

The Controller(s) 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).

Remote processing will be from secure locations within England. The Data will not leave England at any time.

Access is restricted to employees of the University of Warwick who have authorisation from the chief investigator.

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

The Data will not be linked with any other data.

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 University of Warwick will analyse the Data for the purposes described above.

The expected outputs of the processing will be:

• A report of findings to trial collaborators, including the funding body (NIHR Health Technology Assessment (HTA) Monograph), an NIHR journal publication and a lay summary of the trial results to public and patient involvement partners that include the trials management group (monthly meeting), the independent trial steering committee and the Patient and Public Involvement (PPI) Group that both meet on a biannual basis.

• Submissions to peer reviewed journals such as The New England Journal of Medicine and The Lancet [indicate the expected milestone(s) of frequency of expected submissions]

• Presentations to ambulance services (National Ambulance Service Medical Directors and Joint Royal College Ambulance Liaison Committee (JRCALC).

• Presentations at scientific and international conferences.

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

• Public reports

• Direct bilateral engagement with the international and national resuscitation guideline writing organisations to ensure the results will be incorporated into national and international resuscitation guidelines via existing guideline development groups, which include several of the trial co-investigators.

• Public events such as international conferences

• Press/media engagement

• Public promotion of the research by working with the University of Warwick's Marketing and Communication team to develop a strategy for communication with the media (television, radio, newspaper etc) to enhance communication of the trial results to patients / participants.

• Participant newsletters

• Reports aimed at participants

Each year over 30,000 people in the UK receive treatment from National Health Service (NHS) Ambulance Services for an out-of-hospital cardiac arrest. Following arrival of the ambulance service, treatment transitions from bystander-delivered basic life support (where provided) to paramedic-led advanced life support, including airway management, ventilation, and drug therapy. Previous trials have shown that parenteral adrenaline, compared with placebo, in adult out-of-hospital cardiac arrest is highly effective at achieving return of spontaneous circulation, but had a much smaller effect on long-term survival and favourable neurological function. Results show recovery to be highly time-dependent, such that each one-minute reduction in time to drug administration was associated with an absolute increase in 30-day survival of 0.7%. PARAMEDIC-3 could further medical knowledge in the area of OHCA.

The University expects the output from this trial will impact international resuscitation guidelines. There are established pathways through which advances in resuscitation science can be rapidly implemented into practice. The University expect that the Trial Findings will be published in the first half of 2025.

The applicant will ensure that the results of this trial are fed into the International Liaison Committee on Resuscitation (ILCOR) evidence assessment and guideline process. ILCOR run a 5 yearly review of resuscitation science from which international CPR guidelines are created. There is good evidence of penetration of these guidelines into clinical practice within 1-2 years of their publication. In addition, ILCOR run an on-going evidence evaluation process whereby new studies are identified and incorporated into systematic reviews. The outputs from these reviews are shared with national resuscitation councils such as Resuscitation Council (UK) and form the basis for the development and revision of national guidelines.

Guidelines used by the NHS are based on recommendations from the Resuscitation Council UK (RCUK) and are implemented within NHS Ambulance Trusts through the JRCALC. Key investigators on the trial also hold senior positions within the Resuscitation Council so they will be aware of the work and the results. It is likely that the trial findings will be presented at a RCUK national conference.

The University of Warwick anticipate that the impact of this trial will be sufficient to determine future policy in this area.

Yielded Benefits is not a requirement for new applications.