NeoSep-ADAPT: Synthesizing Real World Data, systematic reviews, patient and public input, expert consensus and clinical staff perspectives to develop and pilot a master protocol for an adaptive platform trial of neonatal sepsis management.

Sepsis continues to be a major driver of mortality as well as acute and chronic morbidity among neonates requiring hospital-care.

Because of the potentially catastrophic outcomes, management of neonatal sepsis is often very cautious regarding decisions to start and continue antibiotics and administered regimens.

This increases the risk for adverse events, in particular changes to the microbiome with potentially long-term impacts and selection of resistant bacteria in an environment where cross-infections are common.

High quality evidence to inform guidelines on optimal management of neonatal sepsis is largely lacking, in part be due to the complexity of conducting trials in this vulnerable population.

The proposed programme of work for this fellowship will focus on the development work that is needed to implement an embedded platform trial for neonatal sepsis in the UK.

This design is appropriate as there is an urgent need to address multiple research questions in a number of management domains in a timely manner.

The programme makes use of existing networks and collaborative opportunities in the field to inform the design of such a trial and supportive tools.

The key principles will be to ensure generalizability of findings, to minimize the research burden for clinical staff and families, to reflect the multifaceted nature of neonatal sepsis management, to maximise the chances of improved outcomes for participating neonates and to accelerate early translation into clinical practice.

The overarching aim will be achieved through five interrelated objective: 1) To streamline eligibility criteria and core outcome measures for neonatal sepsis trials informed by Real World Data and expert consensus; 2) To propose a modular approach towards risk-based safety assessment in neonatal trials using routinely collected data; 3) To build a roadmap for facilitating family and clinician engagement with neonatal sepsis trials focusing on enrolment models; 4) To develop a master protocol for an adaptive platform trial for investigating management of neonatal sepsis (informed by the findings from objectives 1 to 3); 5) To pilot core elements of the protocol in UK neonatal units.

The methods used are targeted to each objective and include systematic literature reviews, expert workshops, qualitative research involving parents and clinical staff, evaluation of cohort and real-world datasets and mock implementation of trial procedures to identify opportunities for embedding trial procedures in routine care.

Of note, there will not be any patient enrolment.

Instead, it is envisaged that funding for the adaptive platform trial will be sought in the later stages of the proposed project. The programme will be delivered over 40 months according to a pre-defined work plan.

The main output will be a protocol for an adaptive pragmatic platform trial suitable for implementation in the UK and globally.

This protocol will reflect patient and public as well as clinician input, and will be accompanied by relevant family-facing and clinician-facing materials to introduce the trial concept and facilitate engagement. The feasibility of the trial will be ensured by evaluating key trial procedures in up to five UK neonatal units.