FLuid Optimisation in Emergency LAparotomy (FLO-ELA) trial

University Hospital Southampton NHS Foundation Trust (UHSFT) requires access to NHS England data for the purpose of the following research project:

FLuid Optimisation in Emergency LAparotomy (FLO-ELA) trial

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

The National Emergency Laparotomy Audit (NELA) is hosted by the Royal College of Anaesthetists (RCoA) and is part of the National Clinical Audit and Patient Outcomes Programme (NCAPOP), overseen by the Healthcare Quality Improvement Partnership (HQIP). NELA was commissioned following evidence of a high incidence of death, and a wide variation in the provision of care and mortality, for patients undergoing emergency laparotomy in hospitals across England, Wales and Scotland.

NELA is an audit which looks at the improvement of the quality of care for patients undergoing emergency laparotomy (~30,000/yr within the audit) through the provision of high-quality comparative data from all providers of emergency laparotomy surgery. Approximately 50 hospitals that participate in NELA have also been participating in the FLO-ELA trial. Patients who are undergoing the procedures at those hospitals will then be invited to consent to the FLO-ELA trial. Through this consent, patients agree that NELA will share pseudonymised data on aspects of their care while in hospital with the FLO-ELA trial, to allow the trial to describe the clinical characteristics and trial-related care of its participants. The audit and the trial are two separate pieces of work which have a clear link.

The FLO-ELA trial aims to determine whether a discrete medical intervention (perioperative cardiac output-guided haemodynamic therapy) reduces deaths after emergency laparotomy when compared with usual care. Although this intervention may be beneficial for patients undergoing planned major surgery, it has not yet been tested in patients undergoing emergency laparotomy. The FLO-ELA trial is being funded by the NIHR HTA Efficient Study Design stream, for trials able to give robust research output at greater pace and scale and/or lower cost than conventional trial designs. FLO-ELA will do this by linking this trial data to NELA data - recruiting a subset of patients eligible for inclusion in NELA, utilising the existing NELA network of hospitals and the NELA webtool and dataset for trial participant data (with ONS/HES follow up). Due to the large participant pool (~3000 patients) of this trial, it is hoped that this will provide the answer to whether this treatment is effective, in a timely and cost-effective fashion. This represents a unique opportunity to generate practice-changing research in a challenging patient group, with the potential to save hundreds of lives every year.

Trial objectives:

1. To establish whether the use of minimally invasive cardiac output monitoring to guide protocolised administration of intra-venous fluid (goal-directed haemodynamic therapy, GDHT), for patients aged 50 and over undergoing emergency laparotomy will increase the number of days spent alive and out of hospital within 90 days of randomisation, when compared with usual care.

2. To determine whether GDHT reduces mortality 90 days and one year after randomisation and is cost-effective.

The following NHS England Data will be accessed:

• Hospital Episode Statistics Admitted Patient Care (APC), Accident and Emergency (A&E), Critical Care (CC), and Emergency Care Dataset (ECDS) – necessary for an accurate appraisal of resource-use and cost during the study period.

• Civil Registration Mortality – necessary to determine whether GDHT reduces mortality 90 days and one year after randomisation

The level of the Data will be:

• Identifiable: The data will be disseminated to Queen Mary University of London (QMUL) who also hold the identifiers for the trial cohort. Although the clinical data and identifiers will be kept separate, the technical ability remains and therefore the data is classed as identifiable.

The Data will be minimised as follows:

• Limited to a study cohort identified by UHSFT/QMUL – This consists of ~3,000 consenting participants recruited to the FLO-ELA trial who meet the following inclusion criteria:

- Age 50 years and over.

- Scheduled to undergo a surgical procedure which fulfils the criteria for entry into the National Emergency Laparotomy Audit (NELA)

• Limited to data between 2016/17 and 2025/26. For each individual patient, data will only be acccessed from up to 90 days before they joined the trial, and until 1-year after joining the trial.

University Hospital Southampton NHS Foundation Trust (UHSNFT) 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.

The specific public interest in this research project is that the findings will help clinicians to improve the care of all patients undergoing emergency abdominal surgery in the UK. A large number of people need this surgery each year (estimated 30,000 in the UK).

The funding is provided by the National Institute for Health and Care Research (NIHR). The funding is specifically for the trial described. Funding is in place until January 2026.

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

Queen Mary University of London (QMUL) is a processor acting under the instructions of UHSFT. UHSFT’s role is limited to sharing the trial cohort identifiers, to enable linkage with NHS England data, followed by processing and analysing the data returned by NHS England. QMUL will be processing the data under the instructions of UHSFT.

A Trial Steering Committee (TSC) has been formed in accordance with NIHR guidance. It will oversee the trial and conduct meetings at least once a year.

The TSC take responsibility for approving the final trial protocol, monitoring and supervising the progress of the trial, considering recommendations from the Data Monitoring and Ethics Committee (DMEC) and informing and advising on all aspects of the trial.

A Data Monitoring and Ethics Committee (DMEC) has also been formed in accordance with NIHR guidance. It is independent of the trial team and monitors safety data and routinely meets to assess safety analyses. The trial will be terminated early if there is evidence of harm in the intervention group or if recruitment is insufficient.

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 RCoA Patient, Carer and Public Involvement and Engagement in Research Group (RCoA PCPIE) in Research Group, supported the FLO-ELA trial. The PCPIE group, alongside a lay representative, helped develop patient information, and will continue to attend trial meetings and be involved in key decisions throughout the trial. Ongoing public input and support from the RCoA PCPIE group will also be sought for the dissemination of trial outcome findings to a non-medical audience.

QMUL will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number, Date of Birth, 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, ECDS and Civil Registration Deaths datasets to QMUL. The Data will

• contain directly identifying data items including: NHS Number, Date of Birth, Postcode, Gender which will be held in a separate location at QMUL to the NHS England data, which 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 secure servers at QMUL.

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).

Remote processing will be from secure locations within England/Wales. The data will not leave: England/Wales at any time.

Access is restricted to employees of PCTU (Queen Mary University of London) 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 data from the National Emergency Laparotomy Audit (NELA) data obtained from the Royal College of Anaesthetists (RCoA). The FLO-ELA pseudonymised trial ID will be used as a link between both pseudonymised datasets. The NELA data provides information on baseline participant characteristics, trial intervention and wider perioperative care. The RCoA are the principal data processors for NELA and manage the extraction of the records from the NELA IT system. RCoA cannot access and is not permitted to access FLO-ELA data, including any of the data disseminated under this Agreement by NHS England. The Royal College of Anaesthetists role is to act as a data processor for NELA on behalf of HQIP.

The aggregated information derived from the Data will be combined with aggregated data from other sources. The NELA data and the HES-Mortality data, will be mapped to a Health Economics (HE) dataset containing aggregated quality of life data (EQ-5D-3L questionnaire scores) from participants in the preceding Enhanced Peri-Operative Care for High-risk patients (EPOCH) laparotomy trial. The EPOCH HE dataset represents a different group of patients from another study. Therefore, this mapping does not involve onward linkage of individuals͛ record-level data to other datasets containing their data. Instead, it will use broad patient characteristics to estimate EQ-5D-3L scores for FLO-ELA participants.

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.

Analysts from the PCTU at QMUL will analyse the Data for the purposes described above.

The expected outputs of the processing will be:

• A report of findings to the funder – Targeted for February 2026, with a follow-up report to the funder expected in February 2027.

• Submissions to peer reviewed journals, which may include the Lancet, the British Medical Journal, the New England Journal of Medicine, and the Journal of the American Medical Association – Targeted for summer 2026 and Q1 2027.

• Presentations to scientific meetings and congresses. For example, the ͚Annual Congress of Enhanced Recovery and Perioperative Medicine͛ and the ͚Evidence-Based Peri-Operative Medicine͛ conferences.

• Presentations at specific conferences or appropriate conferences

• A plain English summary of the trial results and any important trial information presented on the FLO-ELA trial webpage (http://www.floela.org/).

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 datasets from which the information was derived.

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

• Journals

• Final trial meeting open to clinicians and research teams from hospitals that have been involved in the trial where they will disseminate and discuss the findings.

• Social media

• Briefing documents provided to the management board of the National Emergency Laparotomy Audit, its commissioner (HQIP) and hosting organisation (The Royal College of Anaesthetists).

• Press/media engagement

• Public promotion of the research - Comprehensive coverage in mainstream media has previously included newspaper articles (e.g., The Times, The Guardian in print and online), television coverage (BBC Breakfast), radio interviews (BBC Radio 4 Inside Health) and high-profile online news sources (BBC News). The study team will build on this previous success and plan on a similar level of engagement through these outlets with the findings of FLO-ELA.

• Reports aimed at members of the public.

• Reports aimed at healthcare policy makers, including the Department of Health, Royal Colleges, Commissioners, NICE, NHS Trusts and other stakeholder groups

• Report to the research funder (National Institute of Health and Care Research)

• Presentation and discussion of trial results at international conferences of anaesthesia and perioperative care

Report to Funder - February 2026

Follow-Up Report to Funder - Feb 2027

Peer Reviewed Publications - Summer 2026 and Q1 2027

Conferences, meetings and wider dissemination work - ongoing, but with particular focus for on the 12 months after trial result publication

The FLO-ELA trial will provide the highest level of evidence for this intervention, informing the decision to widely implement on a national level by confirming the extent of any clinical benefit or harm, healthcare costs and cost effectiveness. A positive outcome from this trial could change practice across the

developed world. NELA would expect rapid translation of this intervention into routine clinical practice within 12-24 months of trial report. This is supported in the UK by the ongoing National Emergency Laparotomy Audit and its parent organisation the Healthcare Quality Improvement Partnership. This quality improvement vehicle will maintain long term engagement and sustained interest in this area with the large number of clinicians involved in the FLO-ELA trial and the wider clinical community after trial completion.

Further, the study will provide specific reports on the findings of the FLO-ELA trial for healthcare policy makers. Through the support of the advisory group, findings will be disseminated appropriately to NHS England and devolved nations, NHS trusts and other stakeholder groups. The research study will advise on the implications of findings and optimal implementation.

As a definitive pragmatic effectiveness trial, with an intervention delivered by clinicians in a large number of NHS sites and in a patient group highly representative of the ultimate target population, rapid and widespread uptake of the trial findings into routine practice is expected. This has the potential to rapidly change care for over 30,000 patients across the UK each year. If shown to be beneficial, this could equate to several hundred lives being saved each year. Conversely, if no benefit is found, this treatment can be discarded, allowing clinicians to focus on other areas of care for this challenging patient group

With the use of Data Disseminated under the previous Data Sharing Agreement (DARS-NIC-60714-M4T1M), the following benefits were realised:

Data has been used to prepare DMEC reports on four occasions. The first report (2018) did not raise concerns with the DMEC. Data from the second report (2019) highlighted a drop in primary outcome (within 90-day mortality) event rate in aggregated data over the course of the trial that led to a re-evaluation of primary outcome, since a reduced event rate in the Control arm would have rendered the study underpowered in relation to the original sample size calculation (where power set at 90%). No additional concerns were raised at the following DMECs. The mortality data have therefore been valuable in enabling the DMEC/trial team to monitor trial safety and in highlighting the above issue of a non-treatment related drop in mortality necessitating the switch to a new primary outcome.