Introduction
The aim of the Health Technology Assessment (HTA) Programme is to ensure that high quality research information on the clinical effectiveness, cost-effectiveness and broader impact of healthcare treatments and tests are produced in the most efficient way for those who plan, provide or receive care from NHS and social care services. The commissioned workstream invites applications in response to calls for research on specific questions which have been identified and prioritised for their importance to the NHS, patients and social care.
Research question
What is the accuracy of clinical prediction models for early-onset neonatal infection in the UK and what is their effectiveness in guiding management in the baby?
- Intervention: Risk assessment and care based on use of Kaiser Permanente neonatal early-onset sepsis risk calculator (SRC).
- Patient group: Pregnant women and unborn or newborn babies under 72 hours of age (applicants to define and justify).
Applications are encouraged which include recruitment from geographic populations with high disease burden which have been historically underserved by research activity in this field. - Setting: Neonatal care.
- Comparator: Risk assessment and care based on use of NICE guidance.
- Study design: Applicants to define and justify a prospective study design(s) which will sufficiently answer the uncertainties.
- Important outcomes: To be defined and justified by applicants but could include culture-proven infection within 72 hours of birth; antibiotics for suspected bloodstream infection within 72 hours of birth; mortality; admission to neonatal unit; respiratory distress within 72 hours of birth; health-related quality of life; late-onset neonatal infection; length of stay.
Other outcomes: Acceptability; cost-effectiveness.
Existing Core Outcomes should be included amongst the list of outcomes unless a good rationale is provided to do otherwise. Applicants are encouraged to report recruitment and findings disaggregated by sex (and other demographic factors where relevant). - Minimum duration of follow-up: Applicants to define and justify.
Longer-term follow up: If appropriate, researchers should consider obtaining consent to allow potential future follow-up through efficient means (such as routine data) as part of a separately funded study.
Rationale
While thankfully a relatively rare occurrence, neonatal early onset sepsis (EOS), defined as severe infection in the first 72 hours following birth, still impacts a significant number of births resulting in infant deaths, long term morbidity and disability and heartache for affected families.
A range of maternal and neonate factors are associated with increased risk of such infections although predicting who will be affected and who could/should be targeted with preventative or therapeutic antibiotics remains an important clinical challenge. Unnecessary early exposure to antibiotics can increase the risk of side effects in individual babies and children, including the risk of serious infections in the longer term, and increases the risk of bacterial resistance in the wider community.
A NICE guideline for the prevention and treatment of EOS was developed in 2012 (updated in 2021) based on expert consensus, and is still the standard of care in the UK. Since its adoption antibiotic use, investigations for EOS, and hospital stays have all increased raising some concerns.
An alternative risk algorithm, the Kaiser Permanente sepsis risk calculator (SRC) has more recently been developed in the US. While relying on the same maternal risk factors it utilises more neonate clinical indicators which necessitates additional and more frequent clinical observations. Use of the SRC appears to result in potentially significant reductions in antibiotic use without an increase in missed cases of serious infection. Although the SRC tool has not yet been fully validated for use in the NHS, or indeed compared directly with standard care based on the NICE guidance, it is starting to be used already.
The HTA Programme therefore seeks to fund further high-quality evidence which aims to determine the validity of the SRC within the UK NHS setting and to compare it clinical and cost effectiveness against the current NICE guidance-based standard of care in identifying at risk newborns to prevent and reduce the incidence and impact of serious early infection.
Additional commissioning brief background information
A background document is available that provides further information to support applicants for this call. It is intended to summarise what prompted the call and the existing evidence base, including relevant work from the HTA and wider NIHR research portfolio. It was researched and written on the basis of information from a search of relevant sources and databases, and in consultation with a number of experts in the field. If you would like a copy please email htaresearchers@nihr.ac.uk.
Making an application
If you would like to apply for this call, you can begin your application via the funding opportunity page.
Your application must be submitted online no later than 1pm on 22 May 2024. Applications will be considered by the HTA Funding Committee at its meeting in July 2024.
Guidance notes and supporting information for HTA Programme applications are available.
Shortlisted Stage 1 applicants will be given 8 weeks to submit a Stage 2 application. The Stage 2 application will be considered at the Funding Committee in November 2024.
For commissioned topics, the Programme strongly discourages the practice of the same co-applicant joining more than one competing team, other than in unusual circumstances (for example, a lead from a named charity or a unique national expert in a condition).
For such exceptions, each application needs to state the case as to why the same person is included. The shared co-applicant should not divulge application details between teams, and both teams should acknowledge in their application that they are aware of the situation, and that study details have not been shared.
Should you have any queries please contact htagb@nihr.ac.uk.