SurfON: Multicentre, open-label, randomised controlled trial of early surfactant therapy versus expectant management in late preterm and early term infants with respiratory distress

University of Oxford (National Perinatal Epidemiology Unit) and University of Leicester requires access to NHS England data for the purpose of the following study trial: SurfON: Multicentre, open-label, randomised controlled trial of early surfactant therapy versus expectant management in late preterm and early term infants with respiratory distress

The following is a summary of the aims of the trial provided by the University of Oxford:

The Surfactant or Not (SurfON) trial began in September 2020 to determine whether, in late preterm and early term infants with respiratory distress, the early use of surfactant, versus expectant management, results in shorter duration of hospital stay and fewer babies who fail to respond to treatment.

There are around 35,000 late preterm and 130,000 early term live births per year in the UK. For the majority of late preterm and early term babies, neonatal care can be managed alongside their mother on a normal postnatal ward, but a substantial minority (up to around 30-40%) require admission to a neonatal unit (NNU). Respiratory disease is the commonest reason for late preterm and early term babies to need NNU admission. Respiratory distress syndrome (RDS) is due to lung immaturity and the associated deficiency of surfactant, a phospholipid and protein substance produced in the lungs to reduce alveolar surface tension and improve lung compliance. The treatment for RDS is exogenous surfactant, administered via an endo-tracheal tube or small catheter into the lungs. Surfactant is most effective if given early in the course of the respiratory disease. RDS is most prominent in very preterm babies (born before 32 weeks), but is also common in late preterm and early term babies. To date, no evidence-based guidance exists, and there is no consensus among clinicians about optimum strategies for the early care of late preterm and early term babies with respiratory distress and consequently, management varies considerably. Therefore, there is a need to define the most clinically-effective, and cost effective approach to early respiratory management in this population.

The SurfON trial, funded by the National Institute for Health and Care Research (NIHR) is a multi-centre trial randomising 1,522 neonates to either receive early use of surfactant (n=761) or expectant management (n=761) across 43 UK NHS Trusts (38 in England), with follow-up to one year of age. A multicentre trial allows the results to be generalisable to NHS practice and therefore requires data from participants across England. As of 23/04/2024 SurfON has recruited 1,030 babies (of which 898 are in England). SurfON is the first trial ever to assess the effectiveness and cost-effectiveness of early use of surfactant in late preterm or early term live births.

The following NHS England Data will be accessed:

• Hospital Episode Statistics

o Admitted Patient Care, Critical Care, Outpatients and Emergency Care Dataset (ECDS) – necessary to accurately assess the costs to the NHS that babies incurred during their first year of life.

• Civil Registration Mortality – necessary in order to estimate one-year survival of trial participants

The level of the Data will be:

• Identifiable

The data shared with University of Oxford will be pseudonymised, however date of death has been requested and in combination with other data held by University of Oxford this may result in individuals being identified within the dataset.

Full Date of death is required for statistical analysis and to avoid including biases into the study, if only month/year were provided the University of Oxford and University of Leicester could overestimate/underestimate one-year survival by up to 30 days.

The Data will be minimised as follows:

• Limited to a study cohort of 1,522 identified by University of Oxford and the University of Leicester– This consists of newborn infants recruited under parental consent, who were born 2-6 weeks prior to their due data, who require help with their breathing.

• Limited to data between 2020/21 and 2025/26. For each individual patient, data will only be provided from Date of Birth and up to 1-year after Date of Birth plus the additional weeks of prematurity

The University of Leicester as the research sponsor, and the University of Oxford as the main collaborator, are joint controllers as the organisations 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.

There is public interest for patients, healthcare staff and the NHS, as this research will decrease uncertainty and allow standardisation of care for more efficient and cost-effective 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 31/08/2025.

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

The University of Oxford and the University of Leicester are working with other NHS and research organisations to deliver this study including:

1) NHS Lothian;

2) Belfast Health and Social Care Trust;

3) University Hospitals of Leicester NHS Trust;

4) University of Nottingham; and

5) Bliss

Only University of Oxford substantive employees who are members of the SurfON team will be allowed access to data from NHS England. The Chief Investigator (University of Leicester) will have input on reviewing the HEAP (Health Economic Analysis Plan) and will interpret the aggregated (small numbers suppressed) results of the analysis. Members of the study team outside of the University of Oxford will only have access to aggregated data for the purposes of contributing to the oversight, analysis and reporting of the study. The trial steering committee (TSC), which includes independent members, provides overall supervision of the trial on behalf of the funder. The data safety and monitoring committee (DSMC) is a group of independent experts external to the trial who assess the progress, conduct, participant safety and, if required critical endpoints of a clinical trial. TSC and DSMC will not have access to NHS England data.

TSC are all independent members who will not have access to the NHS England data – they will only access aggregated small numbers suppressed data in the form of reports during formal oversight meetings.

This study was developed through collaboration with several stakeholders including: neonatologists, statisticians, trialists, health economists, research nurses, and patient representatives. The study was designed with the support of Bliss, the charity for sick and newborn babies. Bliss were instrumental in the development of the funding application and ensuring patient views were incorporated into the trial design. Bliss also worked on the Plain English Summary to ensure that the terminology was acceptable and understandable for non-medical readers. The dissemination of the trial results to parents and carers will be guided by PPI representatives who site on the Trial Steering Committee and also by Bliss who represent the parents of premature babies. All results will be communicated using lay language to ensure accessibility for all.

The University of Oxford will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number, Date of Birth, Surname, First Name 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 the University of Oxford.

• 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.

To complete the intended analysis, the dataset will be linked via an pseudonymised study ID to the clinical data collected during study. No subset of the data will be made available or shared with anyone within or outside of NDPH.

The Data will be stored on servers within the Nuffield Department of Population Health (NDPH), at the University of Oxford

Backups are stored in a NDPH private S3 cloud system spread over three sites, the configuration of which allows full access even if connectivity is lost to one location. Backed up data are kept on encrypted media. The locations of the cloud systems are secure server rooms with access granted to the NDPH Infrastructure Team.

The Data will be accessed onsite at the premises of NDPH.

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

The Controllers 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) i

- 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.

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 or agents of the University of Oxford who have authorisation from the Chief Investigator.

Only NDPH staff with an operational requirement will have access to the data. All other members of staff and any external organisation will not be permitted to access the data.

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

The Data will be linked at person record level with the SurfON trial dataset using SurfON trial anonymised identifiers (i.e. participant ID).

Analysts from the University of Oxford will process the Data for the purposes described above.

The expected outputs of the processing will be:

• A report of findings to NIHR covering the background, aims, methods, results and discussion of the SurfON trial

• A report of findings to the Scientific Advisory Committee of the Royal College of Paediatrics and Child Health (RCPCH), the Royal College of Midwives (RCM) and the Royal College of Obstetricians and Gynaecologists (RCOG).

• Submissions to peer reviewed journals

• Presentations at UK conferences including the BAPM, BMFMS, RCPCH and RCM scientific meetings and to key international conferences including the North American Pediatric Academic Societies Annual Conference and the European Society for Paediatric Research

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 – there will be a publication of the main trial results and a separate publication is planned for the health economic outcomes.

• Webinars – parents/ participants online results webinar

• Social media – results will be promoted on the SurfON, NPEU CTU and NPEU Twitter and Bluesky accounts.

• Conferences – it is planned that the results will be presented at an international conference.

• Posters prepared with the Patient and Public Involvement (PPI) team which will be presented at any workshop or conference where relevant PPI is being discussed.

• Press/media engagement

• Public promotion of the research by producing a plain language summary for patients and the public.

• Participant results leaflet will be produced and sent to those that took part, this will also be available on the NPEU CTU website.

Dissemination plan dates are proposed dates and may be subject to change due to impacts from health economics.

- March 2025: Submit protocol summary for publication

- July 2025: Presentation of main results to oversight committees.

- September 2025: Collaborators final results meeting

- October 2025 and onwards: Presentation of results at international conference (JENs Conference mid-October).

- December 2025: Submit main paper to journal TBC

- Following main journal publication:

a) SurfON (NPEU) website announcements, to include summary results video and results infographic and X (formally Twitter) announcement.

b) Press office release for Oxford, University of Leicester, HTA

c) Send summary results to SurfON participants (email/ post)

d) Online results event for parents

- October 26: Obtaining health economic data from national databases.

- Nov/ Dec 2026: Results of long term outcomes and health economic analysis presented to oversight committees

- January 2027 : Submit NIHR HTA Publication

- January 2027: Submit long term outcomes/ health economic analysis paper to journal

- Following publication: SurfON (NPEU) website and X (formally Twitter) announcement of long-term results.

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

This research on early surfactant therapy for late preterm and early term infants with respiratory distress promises significant patient benefits. Key outcomes include:

• Decreased severity of neonatal respiratory disease: Reducing the need for neonatal unit admission, intensive care interventions and complications.

• Improved long-term respiratory health: Reducing the risk of chronic respiratory issues.

• Enhanced breastfeeding: Facilitating successful breastfeeding through minimising mother-baby separation, shorter neonatal unit stays and improved infant health.

• Cost-effectiveness: Potentially reducing healthcare costs by minimizing intensive care needs and length of hospital stay for both mother and baby.

• Improved parental well-being: Reducing stress associated with neonatal intensive care and prolonged hospital stay.

Ultimately, the study aims to deliver improved clinical outcomes, enhance long-term health, and optimize resource utilisation, leading to more effective and compassionate care

It is envisaged that through the dissemination of the study results to parents, healthcare professionals, and key health organisations, the findings of this research will add to the body of evidence considered by professional bodies, organisations, and individual care practitioners responsible for making policy decisions within the NHS or treatment decisions for specific patients.

By presenting the results at major conferences and publishing in high-impact journals, the research aims to reach a broad audience, facilitating the adoption of early surfactant therapy if proven effective. This will lead to public benefits by improving clinical outcomes, reducing healthcare costs, and enhancing the quality of care for late preterm and early term infants with respiratory distress and their families.

To optimise the potential public benefits from the use of the data, several actions will be taken:

• Dissemination to key stakeholders: The results of the study will be disseminated to parents, healthcare professionals, and key health organisations. This includes reporting to the Scientific Advisory Committee of the Royal College of Paediatrics and Child Health (RCPCH), the British Association of Perinatal Medicine (BAPM), the Royal College of Midwives (RCM), and the Royal College of Obstetricians and Gynaecologists (RCOG).

• Presentations at conferences: The findings will be presented at major professional conferences in the UK, such as the BAPM, BMFMS, RCPCH, and RCM scientific meetings, as well as key international conferences including the joint European Neonatal Societies meeting, and North American conferences Hot Topics in Neonatology and the Pediatric Academic Societies Annual Conference.

• Publication in peer-reviewed journals: The trial protocol and results will be published in high-impact peer-reviewed international journals to ensure wide visibility and credibility within the scientific and clinical community.

• Engagement with charities and societies: Bliss, the charity for sick and preterm newborn babies, has been instrumental in the development of this funding application and is a member of the co-applicant group. Bliss will help recruit a parent advisory panel to guide and support the research team, ensuring that trial methods and conduct are acceptable to parents and families. This collaboration will also assist in disseminating the results to relevant stakeholders and the public.

• Direct communication with participants: It is the policy of the NPEU to send trial results to parents of all participants unless they have opted out, ensuring that those directly involved are informed of the outcomes.

• Media and public engagement: Efforts will be made to advertise the findings to a wider audience through various media channels, ensuring that the public and healthcare providers are aware of the research outcomes and their implications for clinical practice.

By taking these actions, the research aims to maximise its impact on clinical practice, policy-making, and public awareness, ultimately leading to improved care and outcomes for late preterm and early term infants with respiratory distress.

Yielded Benefits is not a requirement for new applications.