FLuid Optimisation in Emergency LAparotomy (FLO-ELA) trial

This Data Sharing Agreement permits the retention and processing of the data provided under previous iterations of this Agreement. This is a pragmatic approach to provide an active Agreement whilst enabling University Hospital Southampton NHS Foundation Trust to complete the necessary actions to enable a subsequent application to extend the Agreement meeting all applicable data-sharing standards as published in NHS Digital’s website (see: https://digital.nhs.uk/services/data-access-request-service-dars/dars-guidance).

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.

Queen Mary University London is the sole data processor. The FLO-ELA team at the Pragmatic Clinical Trials Unit (PCTU), Queen Mary University London integrate NELA data with HES and Mortality data for patients recruited into FLO-ELA. Queen Mary University of London is a joint data controller with University of Southampton NHS Foundation Trust (UHSFT). As study Sponsor, UHSFT have overall responsibility for the conduct of the FLO-ELA trial on the clinical side and are involved in making decisions about the outputs and what the data will be used for with QUML and will therefore be a Joint Data Controller. However, they will not process the data under this Agreement as this role has been contracted to PCTU to carry out the data processing.

The Royal College of Anaesthetists (RCoA) are the principal data processors for The National Emergency Laparotomy Audit (NELA) and manage the extraction of the records from the NELA IT system. The Royal College of Anaesthetists (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.

Emergency bowel surgery (laparotomy) is a common major emergency surgical procedure, performed to treat life threatening conditions caused by cancer, infections or previous surgery. Over 30,000 people in England & Wales undergo this surgery annually at a cost of over £650m. Outcomes from emergency bowel surgery are poor; 14% of patients aged over 50 die within a month of surgery, rising to 20% within three months.

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.

FLO-ELA (FLuid Optimisation in Emergency Laparotomy) is a large randomised clinical trial proposal funded by the National Institute for Health Research Health Technology Assessment (HTA) stream.

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. FLO-ELA are using NELA to identify the 100 hospitals which have been invited to participate in FLOELA (~50% of the total NELA group). 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 (~8000 patients) of this proposed 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.

In the future the study will also request HES data. HES data was requested and obtained under Data Sharing Agreement DARS-NIC-60714-M4T1M-V0.29, following consultation with the study health economist, and will be requested in year three of the study subject to an amendment to this agreement. All selected data fields are required for an accurate appraisal of resource-use and cost during the study period. Necessary data minimisation steps are undertaken in order to exclude those fields which are not necessary to answer the research questions: this included fields related to maternal, neonatal (etc.) care.

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 reduce mortality within 90 days of randomisation, when compared with usual care.

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

Primary outcome measure

Days Alive and Out of Hospital within 90 days of randomisation (DAOH-90)

Secondary outcome and process measures

*Mortality within 90 days of randomisation

*Mortality within one year of randomisation

*Duration of hospital stay (number of days from randomisation until hospital discharge)

*Duration of stay in a level 2 or level 3 critical care bed within the primary hospital admission

*Hospital readmission as an inpatient (overnight stay) within 90 days from randomisation

In 2020 recruitment was paused to allow redeployment of central and local trial teams to clinical service during the COVID pandemic. In addition to the recruiting time lost, many centres had reduced non-COVID research delivery capacity. In early 2021, FLO-ELA applied for an extension with NIHR, this was approved, and resulted in a 24-month extension.

The previous Data Sharing Agreements allowed independent closed analysis of mortality rates in both trial groups (standard care and trial intervention) by the Data Monitoring and Ethics Committee (DMEC) in September 2018, September 2019, November 2020 and Feb 2022. A DMEC is a vital part of trial conduct. It is comprised of independent experts including senior clinical trialists/clinicians and a statistician, appointed by the funder. The DMEC’s remit is to analyse outcomes in both trial groups (without reporting this back to the central trial team) in order to monitor the safety of trial participants throughout the trial.

The DMEC make recommendations to the Trial Steering Committee (TSC), which has a composition defined by the funder with a remit to ensure the trial is conducted to accepted standards. TSC members include senior trialists/clinicians, statisticians and lay representatives. At least 75% of TSC members are independent, i.e., not employed by the same organisations as central project team members or by organisations involved in FLO-ELA trial recruitment. If the DMEC observe a major difference in mortality between the two trial groups they may recommend that the trial is terminated early to prevent more patients being exposed to an inferior treatment. In 2018 they recommended that the trial continued recruitment and requested to next analyse the trial data when ~2000 participants have been recruited into the trial, or approximately annually. This is the main purpose of data requested in this Agreement. Please note that the DMEC do not have access to identifiable individual level data, nor do they make decisions about how the NHS England Data will be used.

Outputs from the final FLO-ELA trial analysis will only include aggregated data. No individual level data received from NHS England will ever leave the safe haven where the analysis is taking place. The following outputs are planned:

1st Report to Funder (90 day outcomes) - Spring 2024

Final FLO-ELA Investigators Meeting - Autumn 2024

Peer-Reviewed Publications - Autumn 2024 2nd Report to Funder (12 month outcomes) - Spring 2025

Conferences, meetings and wider dissemination work - 2024/2025/2026 ongoing but with particular focus for on the 12 months after trial result publication.

In accordance with current practice, appropriately pseudonymised record-level data may be shared with researchers in the future to support further studies in this area such as meta-analysis. This will be subject to the strict data sharing policy in place at the Pragmatic Clinical Trials Unit. Patient consent will be requested for such future data sharing at the time of recruitment into the trial. Appropriate approvals from NHS England will also be sought prior to any data sharing. Data will not be shared with other researchers under this version of the Data Sharing Agreement.

Details of expected outputs: The main scientific report (aggregated / summary data only) will be sent to a high level journal such as the Lancet for their consideration first. Second choices would include the British Medical Journal, the New England Journal of Medicine, and the Journal of the American Medical Association. These are all general interest journals read by a wide range of healthcare workers worldwide.

The study plan to invite all the clinicians and research teams from hospitals that have been involved in the trial to a final FLO-ELA meeting where they will disseminate and discuss the findings. Only aggregated outputs will be shared in the findings. The study will also present the work at scientific meetings and congresses. For example, the ͚Annual Congress of Enhanced Recovery and Perioperative Medicine͛ and the ͚Evidence-Based Peri-Operative Medicine͛ conferences. They will also disseminate the aggregated findings through the mainstream media and also through social media (e.g., Twitter) with the support of their patient representatives. The main target audience will be surgeons, anaesthetists and intensive care doctors but also patients and their carer’s.

A plain English summary of the trial results and any important trial information will be presented here http://www.floela.org/

More broadly, work will be carried out with patient partners and the Patient, Carer and Public Involvement and Engagement group (PCPIE) at the Royal College of Anaesthetists (RCoA) to plan lay-orientated dissemination of the trial results to a non-medical audience. The RCoA PCPIE group was formed to provide high quality guidance on research proposals in the field of perioperative medicine. It is supported by the RCoA department of education and research. The FLO-ELA trial has been supported by the RCoA PCPIE group from the early stages of trial design. During all of the active communication activities outlined above, the study team will ensure that information reaches interested groups in society and that they will engage with them in knowledge-sharing and dialogue.

The Study Team will produce specific reports for healthcare policy makers and advise on the implications of findings and optimal implementation. This will include the Department of Health, Royal Colleges, Commissioners, NICE, NHS Trusts and other stakeholder groups. The dissemination of this information to front line NHS staff will include manuscripts in high impact journals, and through regional, national and international meetings. This process will be assisted by the extensive network support for FLO-ELA, including the UK Perioperative Medicine Clinical Trials Network and trainee research networks. The reach is further extended by engagement of both the anaesthetic and surgical communities.

More specifically, the trial findings will feed rapidly into guidance and audit standard setting by the National Emergency Laparotomy Audit (NELA) and the Royal College of Anaesthetists / Royal College of Surgeons. NELA, a core partner of the FLO-ELA proposal, maintains close communication with a very large community of contributing clinicians and has been highly effective at disseminating the results of its national reports. 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). This is backed up by strong engagement through social media (@NELANews Twitter account has >1000 followers, @FLOELAtrial has ~700). 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.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide

Data have been used to prepare DMEC reports on three occasions. The 4th report is currently being prepared. 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 most recent DMEC. 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.

This Data Sharing Agreement permits the retention of the data provided under previous iterations of this Agreement for an interim period. This is a pragmatic approach to provide an active Agreement whilst enabling University Hospital Southampton NHS Foundation Trust to complete the necessary actions to enable a subsequent application to extend the Agreement meeting all applicable data sharing standards as published in NHS Digital’s website (see: https://digital.nhs.uk/services/data-access-request-service-dars/dars-guidance).

This request for data is justified under Article 6 of the General Data Protection Regulation as the data processed is necessary for the performance of a task carried out in the public interest (6.1.e.). The aim of FLO-ELA is to reduce the mortality rate of patients who undergo an emergency laparotomy by comparing two different methods of fluid administration during this surgery. The data requested is necessary to determine whether there is a difference between these two groups and therefore whether the aim has been achieved.

As this request is considered special category data, the request is also covered under Article 9 of the General Data Protection Regulation. The processing of this data is necessary for scientific research purposes and is proportionate to the aim pursued, respects the essence of the right to data protection and provides for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject (9.2.j.). A Research Ethics Committee has approved the FLO-ELA Trial.

Queen Mary University London is the sole data processor. The FLO-ELA team at the Pragmatic Clinical Trials Unit (PCTU), Queen Mary University London integrate NELA data with HES and Mortality data for patients recruited into FLO-ELA. Queen Mary University of London is a joint data controller with University of Southampton NHS Foundation Trust (UHSFT). As study Sponsor, UHSFT have overall responsibility for the conduct of the FLO-ELA trial on the clinical side and are involved in making decisions about the outputs and what the data will be used for with QUML and will therefore be a Joint Data Controller. However, they will not process the data under this Agreement as this role has been contracted to PCTU to carry out the data processing.

The Royal College of Anaesthetists (RCoA) are the principal data processors for NELA and manage the extraction of the records from the NELA IT system. The Royal College of Anaesthetists (RCoA) cannot access and is not permitted to access FLO-ELA data, including any of the data disseminated under this Agreement by NHS Digital. The Royal College of Anaesthetists role is to act as a data processor for NELA on behalf of HQIP.

Emergency bowel surgery (laparotomy) is a common major emergency surgical procedure, performed to treat life threatening conditions caused by cancer, infections or previous surgery. Over 30,000 people in England & Wales undergo this surgery annually at a cost of over £650m. Outcomes from emergency bowel surgery are poor; 14% of patients aged over 50 die within a month of surgery, rising to 20% within three months.

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.

FLO-ELA (FLuid Optimisation in Emergency LAparotomy) is a large randomised clinical trial proposal funded by the National Institute for Health Research Health Technology Assessment (HTA) stream.

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. FLO-ELA are using NELA to identify the 100 hospitals which have been invited to participate in FLOELA (~50% of the total NELA group). 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 (~8000 patients) of this proposed 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.

In the future the study will also request HES data. HES data was requested and obtained under Data Sharing Agreement DARS-NIC-60714-M4T1M-V0.29, following consultation with the study health economist, and will be requested in year three of the study subject to an amendment to this agreement. All selected data fields are required for an accurate appraisal of resource-use and cost during the study period. Necessary data minimisation steps are undertaken in order to exclude those fields which are not necessary to answer the research questions: this included fields related to maternal, neonatal (etc.) care.

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 reduce mortality within 90 days of randomisation, when compared with usual care.

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

Primary outcome measure

*Mortality within 90 days of randomisation

Secondary outcome and process measures

*Mortality within one year of randomisation

*Duration of hospital stay (number of days from randomisation until hospital discharge)

*Duration of stay in a level 2 or level 3 critical care bed within the primary hospital admission

*Hospital readmission as an inpatient (overnight stay) within 90 days from randomisation

The main purpose for this extension is to account for the extended timeline of the trial. In 2020 recruitment was paused to allow redeployment of central and local trial teams to clinical service during the COVID pandemic. In addition to the recruiting time lost, many centres had reduced non-COVID research delivery capacity. In early 2021, FLO-ELA applied for an extension with NIHR, this was approved, and resulted in a 24-month extension.

The previous Data Sharing Agreements allowed independent closed analysis of mortality rates in both trial groups (standard care and trial intervention) by the Data Monitoring and Ethics Committee (DMEC) in September 2018, September 2019, November 2020 and Feb 2022. A DMEC is a vital part of trial conduct. It is comprised of independent experts including senior clinical trialists/clinicians and a statistician, appointed by the funder. The DMEC’s remit is to analyse outcomes in both trial groups (without reporting this back to the central trial team) in order to monitor the safety of trial participants throughout the trial.

The DMEC make recommendations to the Trial Steering Committee (TSC), which has a composition defined by the funder with a remit to ensure the trial is conducted to accepted standards. TSC members include senior trialists/clinicians, statisticians and lay representatives. At least 75% of TSC members are independent, i.e., not employed by the same organisations as central project team members or by organisations involved in FLO-ELA trial recruitment. If the DMEC observe a major difference in mortality between the two trial groups they may recommend that the trial is terminated early to prevent more patients being exposed to an inferior treatment. In 2018 they recommended that the trial continued recruitment and requested to next analyse the trial data when ~2000 participants have been recruited into the trial, or approximately annually. This is the main purpose of data requested in this Agreement. Please note that the DMEC do not have access to identifiable individual level data, nor do they make decisions about how the NHS Digital Data will be used.

Outputs from the final FLO-ELA trial analysis will only include aggregated data. No individual level data received from NHS Digital will ever leave the safe haven where the analysis is taking place. The following outputs are planned:

Final Report to Funder - Jan 2024

Final FLO-ELA Investigators Meeting - summer 2024

Peer Reviewed Publications - summer 2024

Conferences, meetings and wider dissemination work - 2024 ongoing but with particular focus for on the 12 months after trial result publication.

In accordance with current practice, appropriately pseudonymised record-level data may be shared with researchers in the future to support further studies in this area such as meta-analysis. This will be subject to the strict data sharing policy in place at the Pragmatic Clinical Trials Unit. Patient consent will be requested for such future data sharing at the time of recruitment into the trial. Appropriate approvals from NHS Digital will also be sought prior to any data sharing. Data will not be shared with other researchers under this version of the Data Sharing Agreement.

Details of expected outputs: The main scientific report (aggregated / summary data only) will be sent to a high level journal such as the Lancet for their consideration first. Second choices would include the British Medical Journal, the New England Journal of Medicine, and the Journal of the American Medical Association. These are all general interest journals read by a wide range of healthcare workers worldwide.

The study plan to invite all the clinicians and research teams from hospitals that have been involved in the trial to a final FLO-ELA meeting where they will disseminate and discuss the findings. Only aggregated outputs will be shared in the findings.

The study will also present the work at scientific meetings and congresses. For example, the ͚Annual Congress of Enhanced Recovery and Perioperative Medicine͛ and the ͚Evidence-Based Peri-Operative Medicine͛ conferences. They will also disseminate the aggregated findings through the mainstream media and also through social media (e.g., Twitter) with the support of their patient representatives. The main target audience will be surgeons, anaesthetists and intensive care doctors but also patients and their carer’s.

A plain English summary of the trial results and any important trial information will be presented here http://www.floela.org/

More broadly, work will be carried out with patient partners and the Patient, Carer and Public Involvement and Engagement group (PCPIE) at the Royal College of Anaesthetists (RCoA) to plan lay-orientated dissemination of the trial results to a non-medical audience. The RCoA PCPIE group was formed to provide high quality guidance on research proposals in the field of perioperative medicine. It is supported by the RCoA department of education and research. The FLO-ELA trial has been supported by the RCoA PCPIE group from the early stages of trial design. During all of the active communication activities outlined above, the study team will ensure that information reaches interested groups in society and that they will engage with them in knowledge-sharing and dialogue.

The Study Team will produce specific reports for healthcare policy makers and advise on the implications of findings and optimal implementation. This will include the Department of Health, Royal Colleges, Commissioners, NICE, NHS Trusts and other stakeholder groups. The dissemination of this information to front line NHS staff will include manuscripts in high impact journals, and through regional, national and international meetings. This process will be assisted by the extensive network support for FLO-ELA, including the UK Perioperative Medicine Clinical Trials Network and trainee research networks. The reach is further extended by engagement of both the anaesthetic and surgical communities.

More specifically, the trial findings will feed rapidly into guidance and audit standard setting by the National Emergency Laparotomy Audit (NELA) and the Royal College of Anaesthetists / Royal College of Surgeons. NELA, a core partner of the FLO-ELA proposal, maintains close communication with a very large community of contributing clinicians and has been highly effective at disseminating the results of its national reports. 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). This is backed up by strong engagement through social media (@NELANews Twitter account has >1000 followers, @FLOELAtrial has ~700). 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.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide

Data have been used to prepare DMEC reports on three occasions. The 4th report is currently being prepared. 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 most recent DMEC (2020). 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.

This request for data is justified under Article 6 of the General Data Protection Regulation as the data processed is necessary for the performance of a task carried out in the public interest (6.1.e.). The aim of FLO-ELA is to reduce the mortality rate of patients who undergo an emergency laparotomy by comparing two different methods of fluid administration during this surgery. The data requested is necessary to determine whether there is a difference between these two groups and therefore whether the aim has been achieved.

As this request is considered special category data, the request is also covered under Article 9 of the General Data Protection Regulation. The processing of this data is necessary for scientific research purposes and is proportionate to the aim pursued, respects the essence of the right to data protection and provides for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject (9.2.j.). A Research Ethics Committee has approved the FLO-ELA Trial, with no moral or ethical issues raised by the proposed dissemination of this data, nor harm to the public.

Emergency bowel surgery (laparotomy) is a common major emergency surgical procedure, performed to treat life threatening conditions caused by cancer, infections or previous surgery. Over 30,000 people in England & Wales undergo this surgery annually at a cost of over £650m. Outcomes from emergency bowel surgery are poor; 14% of patients aged over 50 die within a month of surgery, rising to 20% within three months.

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.

FLO-ELA (FLuid Optimisation in Emergency LAparotomy) is a large randomised clinical trial proposal funded by the National Institute for Health Research Health Technology Assessment (HTA) stream.

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. FLO-ELA are using NELA to identify the 100 hospitals which have been invited to participate in FLOELA (~50% of the total NELA group). 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). The study have a trial proposal which will be large enough (~8000 patients) to give a definitive answer on 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 reduce mortality within 90 days of randomisation, when compared with usual care.

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

Primary outcome measure

*Mortality within 90 days of randomisation

Secondary outcome and process measures

*Mortality within one year of randomisation

*Duration of hospital stay (number of days from randomisation until hospital discharge)

*Duration of stay in a level 2 or level 3 critical care bed within the primary hospital admission

*Hospital readmission as an inpatient (overnight stay) within 90 days from randomisation

The previous Data Sharing Agreement allowed independent closed analysis of mortality rates in both trial groups (standard care and trial intervention) by the Data Monitoring and Ethics Committee (DMEC) in September 2018. A DMEC is a vital part of trial conduct. It is comprised of independent experts including senior clinical trialists/clinicians and a statistician, appointed by the funder. The DMEC’s remit is to analyse outcomes in both trial groups (without reporting this back to the central trial team) in order to monitor the safety of trial participants throughout the trial.

The DMEC make recommendations to the Trial Steering Committee (TSC), which has a composition defined by the funder with a remit to ensure the trial is conducted to accepted standards. . TSC members include senior trialists/clinicians, statisticians and lay representatives. At least 75% of TSC members are independent, i.e. not employed by the same organisations as central project team members or by organisations involved in FLO-ELA trial recruitment. If the DMEC observe a major difference in mortality between the two trial groups they may recommend that the trial is terminated early to prevent more patients being exposed to an inferior treatment. In 2018 they recommended that the trial continued recruitment, and requested to next analyse the trial data when ~2000 participants have been recruited into the trial, or approximately annually. This is the main purpose of data requested in this renewal. Please note that the DMEC do not have access to identifiable individual level data, nor do they make decisions about how the NHS Digital Data will be used.

Outputs from the final FLO-ELA trial analysis will only include aggregated data. No individual level data received from NHS Digital will ever leave the safe haven where the analysis is taking place. The following outputs are planned:

Final Report to Funder - March 2022

Final FLO-ELA Investigators Meeting - summer 2022

Peer Reviewed Publications - summer 2022

Conferences, meetings and wider dissemination work - 2022 ongoing but with particular focus for the 12 months after trial result publication.

In accordance with current practice, appropriately pseudonymised record-level data may be shared with researchers in the future to support further studies in this area such as meta-analysis. This will be subject to the strict data sharing policy in place at the Pragmatic Clinical Trials Unit. Patient consent will be requested for such future data sharing at the time of recruitment into the trial. Appropriate approvals from NHS Digital will also be sought prior to any data sharing. Data will not be shared with other researchers under this version of the Data Sharing Agreement.

Details of expected outputs: The main scientific report (aggregated / summary data only) will be sent to a high level journal such as the Lancet for their consideration first. Second choices would include the British Medical Journal, the New England Journal of Medicine, and the Journal of the American Medical Association. These are all general interest journals read by a wide range of healthcare workers worldwide.

The study plan to invite all the clinicians and research teams from hospitals that have been involved in the trial to a final FLO-ELA meeting where they will disseminate and discuss the findings. Only aggregated outputs will be shared in the findings.

The study will also present the work at scientific meetings and congresses. For example the ͚Annual Congress of Enhanced Recovery and Perioperative Medicine͛ and the ͚Evidence-Based Peri-Operative Medicine͛ conferences. They will also disseminate the aggregated findings through the mainstream media and also through social media (e.g. Twitter) with the support of their patient representatives. The main target audience will be surgeons, anaesthetists and intensive care doctors but also patients and their carer’s.

A plain English summary of the trial results and any important trial information will be presented here http://www.floela.org/

More broadly, work will be carried out with patient partners and the Patient, Carer and Public Involvement and Engagement group (PCPIE) at the Royal College of Anaesthetists (RCoA) to plan lay-orientated dissemination of the trial results to a non-medical audience. The RCoA PCPIE group was formed to provide high quality guidance on research proposals in the field of perioperative medicine. It is supported by the RCoA department of education and research. The FLO-ELA trial has been supported by the RCoA PCPIE group from the early stages of trial design During all of the active communication activities outlined above, the study team will ensure that information reaches interested groups in society and that they will engage with them in knowledge-sharing and dialogue.

The Study Team will produce specific reports for healthcare policy makers and advise on the implications of findings and optimal implementation. This will include the Department of Health, Royal Colleges, Commissioners, NICE, NHS Trusts and other stakeholder groups. The dissemination of this information to front line NHS staff will include manuscripts in high impact journals, and through regional, national and international meetings. This process will be assisted by the extensive network support for FLO-ELA, including the UK Perioperative Medicine Clinical Trials Network and trainee research networks. The reach is further extended by engagement of both the anaesthetic and surgical communities.

More specifically the trial findings will feed rapidly into guidance and audit standard setting by the National Emergency Laparotomy Audit (NELA) and the Royal College of Anaesthetists / Royal College of Surgeons. NELA, a core partner of the FLO-ELA proposal, maintains close communication

with a very large community of contributing clinicians and has been highly effective at disseminating the results of its national reports. 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). This is backed up by strong engagement through social media (@NELANews Twitter account has >1000 followers, @FLOELAtrial has ~700). 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.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide

With the data received so far, a DMEC report has been produced to evaluate patient safety. The researchers have been able to validate the pre-trial assumptions on mortality rates, giving reassurance that the planned number of participants will be enough to address the main question of the trial.

This request for data is justified under Article 6 of the General Data Protection Regulation as the data processed is necessary for the performance of a task carried out in the public interest (6.1.e.). The aim of FLO-ELA is to reduce the mortality rate of patients who undergo an emergency laparotomy by comparing two different methods of fluid administration during this surgery. The data requested is necessary to determine whether there is a difference between these two groups and therefore whether the aim has been achieved.

As this request is considered special category data, the request is also covered under Article 9 of the General Data Protection Regulation. The processing of this data is necessary for scientific research purposes and is proportionate to the aim pursued, respects the essence of the right to data protection and provides for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject (9.2.j.). A Research Ethics Committee has approved the FLO-ELA Trial, with no moral or ethical issues raised by the proposed dissemination of this data, nor harm to the public.

Emergency bowel surgery (laparotomy) is a common major emergency surgical procedure, performed to treat life threatening conditions caused by cancer, infections or previous surgery. Over 30,000 people in England & Wales undergo this surgery annually at a cost of over £650m. Outcomes from emergency bowel surgery are poor; 14% of patients aged over 50 die within a month of surgery, rising to 20% within three months.

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.

FLO-ELA (FLuid Optimisation in Emergency LAparotomy) is a large randomised clinical trial proposal funded by the National Institute for Health Research Health Technology Assessment (HTA) stream.

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. FLO-ELA are using NELA to identify the 100 hospitals which have been invited to participate in FLOELA (~50% of the total NELA group). 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). The study have a trial proposal which will be large enough (~8000 patients) to give a definitive answer on 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 reduce mortality within 90 days of randomisation, when compared with usual care.

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

Primary outcome measure

*Mortality within 90 days of randomisation

Secondary outcome and process measures

*Mortality within one year of randomisation

*Duration of hospital stay (number of days from randomisation until hospital discharge)

*Duration of stay in a level 2 or level 3 critical care bed within the primary hospital admission

*Hospital readmission as an inpatient (overnight stay) within 90 days from randomisation

The previous Data Sharing Agreement allowed independent closed analysis of mortality rates in both trial groups (standard care and trial intervention) by the Data Monitoring and Ethics Committee (DMEC) in September 2018. A DMEC is a vital part of trial conduct. It is comprised of independent experts including senior clinical trialists/clinicians and a statistician, appointed by the funder. The DMEC’s remit is to analyse outcomes in both trial groups (without reporting this back to the central trial team) in order to monitor the safety of trial participants throughout the trial.

The DMEC make recommendations to the Trial Steering Committee (TSC), which has a composition defined by the funder with a remit to ensure the trial is conducted to accepted standards. . TSC members include senior trialists/clinicians, statisticians and lay representatives. At least 75% of TSC members are independent, i.e. not employed by the same organisations as central project team members or by organisations involved in FLO-ELA trial recruitment. If the DMEC observe a major difference in mortality between the two trial groups they may recommend that the trial is terminated early to prevent more patients being exposed to an inferior treatment. In 2018 they recommended that the trial continued recruitment, and requested to next analyse the trial data when ~2000 participants have been recruited into the trial, or approximately annually. This is the main purpose of data requested in this renewal. Please note that the DMEC do not have access to identifiable individual level data, nor do they make decisions about how the NHS Digital Data will be used.

Outputs from the final FLO-ELA trial analysis will only include aggregated data. No individual level data received from NHS Digital will ever leave the safe haven where the analysis is taking place. The following outputs are planned:

Final Report to Funder - March 2022

Final FLO-ELA Investigators Meeting - summer 2022

Peer Reviewed Publications - summer 2022

Conferences, meetings and wider dissemination work - 2022 ongoing but with particular focus for the 12 months after trial result publication.

In accordance with current practice, appropriately pseudonymised record-level data may be shared with researchers in the future to support further studies in this area such as meta-analysis. This will be subject to the strict data sharing policy in place at the Pragmatic Clinical Trials Unit. Patient consent will be requested for such future data sharing at the time of recruitment into the trial. Appropriate approvals from NHS Digital will also be sought prior to any data sharing. Data will not be shared with other researchers under this version of the Data Sharing Agreement.

Details of expected outputs: The main scientific report (aggregated / summary data only) will be sent to a high level journal such as the Lancet for their consideration first. Second choices would include the British Medical Journal, the New England Journal of Medicine, and the Journal of the American Medical Association. These are all general interest journals read by a wide range of healthcare workers worldwide.

The study plan to invite all the clinicians and research teams from hospitals that have been involved in the trial to a final FLO-ELA meeting where they will disseminate and discuss the findings. Only aggregated outputs will be shared in the findings.

The study will also present the work at scientific meetings and congresses. For example the ͚Annual Congress of Enhanced Recovery and Perioperative Medicine͛ and the ͚Evidence-Based Peri-Operative Medicine͛ conferences. They will also disseminate the aggregated findings through the mainstream media and also through social media (e.g. Twitter) with the support of their patient representatives. The main target audience will be surgeons, anaesthetists and intensive care doctors but also patients and their carer’s.

A plain English summary of the trial results and any important trial information will be presented here http://www.floela.org/

More broadly, work will be carried out with patient partners and the Patient, Carer and Public Involvement and Engagement group (PCPIE) at the Royal College of Anaesthetists (RCoA) to plan lay-orientated dissemination of the trial results to a non-medical audience. The RCoA PCPIE group was formed to provide high quality guidance on research proposals in the field of perioperative medicine. It is supported by the RCoA department of education and research. The FLO-ELA trial has been supported by the RCoA PCPIE group from the early stages of trial design During all of the active communication activities outlined above, the study team will ensure that information reaches interested groups in society and that they will engage with them in knowledge-sharing and dialogue.

The Study Team will produce specific reports for healthcare policy makers and advise on the implications of findings and optimal implementation. This will include the Department of Health, Royal Colleges, Commissioners, NICE, NHS Trusts and other stakeholder groups. The dissemination of this information to front line NHS staff will include manuscripts in high impact journals, and through regional, national and international meetings. This process will be assisted by the extensive network support for FLO-ELA, including the UK Perioperative Medicine Clinical Trials Network and trainee research networks. The reach is further extended by engagement of both the anaesthetic and surgical communities.

More specifically the trial findings will feed rapidly into guidance and audit standard setting by the National Emergency Laparotomy Audit (NELA) and the Royal College of Anaesthetists / Royal College of Surgeons. NELA, a core partner of the FLO-ELA proposal, maintains close communication

with a very large community of contributing clinicians and has been highly effective at disseminating the results of its national reports. 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). This is backed up by strong engagement through social media (@NELANews Twitter account has >1000 followers, @FLOELAtrial has ~700). 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.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide

With the data received so far, a DMEC report has been produced to evaluate patient safety. The researchers have been able to validate the pre-trial assumptions on mortality rates, giving reassurance that the planned number of participants will be enough to address the main question of the trial.

This request for data is justified under Article 6 of the General Data Protection Regulation as the data processed is necessary for the performance of a task carried out in the public interest (6.1.e.). The aim of FLO-ELA is to reduce the mortality rate of patients who undergo an emergency laparotomy by comparing two different methods of fluid administration during this surgery. The data requested is necessary to determine whether there is a difference between these two groups and therefore whether the aim has been achieved.

As this request is considered special category data, the request is also covered under Article 9 of the General Data Protection Regulation. The processing of this data is necessary for scientific research purposes and is proportionate to the aim pursued, respects the essence of the right to data protection and provides for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject (9.2.j.). A Research Ethics Committee has approved the FLO-ELA Trial, with no moral or ethical issues raised by the proposed dissemination of this data, nor harm to the public.

Emergency bowel surgery (laparotomy) is a common major emergency surgical procedure, performed to treat life threatening conditions caused by cancer, infections or previous surgery. Over 30,000 people in England & Wales undergo this surgery annually at a cost of over £650m. Outcomes from emergency bowel surgery are poor; 14% of patients aged over 50 die within a month of surgery, rising to 20% within three months.

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.

FLO-ELA (FLuid Optimisation in Emergency LAparotomy) is a large randomised clinical trial proposal funded by the National Institute for Health Research Health Technology Assessment (HTA) stream.

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. FLO-ELA are using NELA to identify the 100 hospitals which have been invited to participate in FLOELA (~50% of the total NELA group). 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). The study have a trial proposal which will be large enough (~8000 patients) to give a definitive answer on 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 reduce mortality within 90 days of randomisation, when compared with usual care.

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

Primary outcome measure

*Mortality within 90 days of randomisation

Secondary outcome and process measures

*Mortality within one year of randomisation

*Duration of hospital stay (number of days from randomisation until hospital discharge)

*Duration of stay in a level 2 or level 3 critical care bed within the primary hospital admission

*Hospital readmission as an inpatient (overnight stay) within 90 days from randomisation

The previous Data Sharing Agreement allowed independent closed analysis of mortality rates in both trial groups (standard care and trial intervention) by the Data Monitoring and Ethics Committee (DMEC) in September 2018. A DMEC is a vital part of trial conduct. It is comprised of independent experts including senior clinical trialists/clinicians and a statistician, appointed by the funder. The DMEC’s remit is to analyse outcomes in both trial groups (without reporting this back to the central trial team) in order to monitor the safety of trial participants throughout the trial.

The DMEC make recommendations to the Trial Steering Committee (TSC), which has a composition defined by the funder with a remit to ensure the trial is conducted to accepted standards. . TSC members include senior trialists/clinicians, statisticians and lay representatives. At least 75% of TSC members are independent, i.e. not employed by the same organisations as central project team members or by organisations involved in FLO-ELA trial recruitment. If the DMEC observe a major difference in mortality between the two trial groups they may recommend that the trial is terminated early to prevent more patients being exposed to an inferior treatment. In 2018 they recommended that the trial continued recruitment, and requested to next analyse the trial data when ~2000 participants have been recruited into the trial, or approximately annually. This is the main purpose of data requested in this renewal. Please note that the DMEC do not have access to identifiable individual level data, nor do they make decisions about how the NHS Digital Data will be used.

Outputs from the final FLO-ELA trial analysis will only include aggregated data. No individual level data received from NHS Digital will ever leave the safe haven where the analysis is taking place. The following outputs are planned:

Final Report to Funder - March 2022

Final FLO-ELA Investigators Meeting - summer 2022

Peer Reviewed Publications - summer 2022

Conferences, meetings and wider dissemination work - 2022 ongoing but with particular focus for the 12 months after trial result publication.

In accordance with current practice, appropriately pseudonymised record-level data may be shared with researchers in the future to support further studies in this area such as meta-analysis. This will be subject to the strict data sharing policy in place at the Pragmatic Clinical Trials Unit. Patient consent will be requested for such future data sharing at the time of recruitment into the trial. Appropriate approvals from NHS Digital will also be sought prior to any data sharing. Data will not be shared with other researchers under this version of the Data Sharing Agreement.

Details of expected outputs: The main scientific report (aggregated / summary data only) will be sent to a high level journal such as the Lancet for their consideration first. Second choices would include the British Medical Journal, the New England Journal of Medicine, and the Journal of the American Medical Association. These are all general interest journals read by a wide range of healthcare workers worldwide.

The study plan to invite all the clinicians and research teams from hospitals that have been involved in the trial to a final FLO-ELA meeting where they will disseminate and discuss the findings. Only aggregated outputs will be shared in the findings.

The study will also present the work at scientific meetings and congresses. For example the ͚Annual Congress of Enhanced Recovery and Perioperative Medicine͛ and the ͚Evidence-Based Peri-Operative Medicine͛ conferences. They will also disseminate the aggregated findings through the mainstream media and also through social media (e.g. Twitter) with the support of their patient representatives. The main target audience will be surgeons, anaesthetists and intensive care doctors but also patients and their carer’s.

A plain English summary of the trial results and any important trial information will be presented here http://www.floela.org/

More broadly, work will be carried out with patient partners and the Patient, Carer and Public Involvement and Engagement group (PCPIE) at the Royal College of Anaesthetists (RCoA) to plan lay-orientated dissemination of the trial results to a non-medical audience. The RCoA PCPIE group was formed to provide high quality guidance on research proposals in the field of perioperative medicine. It is supported by the RCoA department of education and research. The FLO-ELA trial has been supported by the RCoA PCPIE group from the early stages of trial design During all of the active communication activities outlined above, the study team will ensure that information reaches interested groups in society and that they will engage with them in knowledge-sharing and dialogue.

The Study Team will produce specific reports for healthcare policy makers and advise on the implications of findings and optimal implementation. This will include the Department of Health, Royal Colleges, Commissioners, NICE, NHS Trusts and other stakeholder groups. The dissemination of this information to front line NHS staff will include manuscripts in high impact journals, and through regional, national and international meetings. This process will be assisted by the extensive network support for FLO-ELA, including the UK Perioperative Medicine Clinical Trials Network and trainee research networks. The reach is further extended by engagement of both the anaesthetic and surgical communities.

More specifically the trial findings will feed rapidly into guidance and audit standard setting by the National Emergency Laparotomy Audit (NELA) and the Royal College of Anaesthetists / Royal College of Surgeons. NELA, a core partner of the FLO-ELA proposal, maintains close communication

with a very large community of contributing clinicians and has been highly effective at disseminating the results of its national reports. 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). This is backed up by strong engagement through social media (@NELANews Twitter account has >1000 followers, @FLOELAtrial has ~700). 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.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide

With the data received so far, a DMEC report has been produced to evaluate patient safety. The researchers have been able to validate the pre-trial assumptions on mortality rates, giving reassurance that the planned number of participants will be enough to address the main question of the trial.