Health Technology Assessment

Selective decontamination of the digestive tract in children and young people receiving mechanical ventilation

Overview

  • Opportunity status:
    Open
  • Type:
    Programme
  • Opening date:
  • Closing date:
  • Reference ID:
    2024/208

Ready to apply?

Our Health Technology Assessment (HTA) Programme is looking to fund research into selective decontamination of the digestive tract in children and young people receiving mechanical ventilation.

This is a two-stage, commissioned funding opportunity. To apply for the first stage you should submit an Outline Application. If invited to the second stage, you will then need to complete a Full Application.

Eligibility

See our HTA Programme page for eligibility on what we will fund.

Key dates

28 November 2024

Outline Application opening date

2 April 2025, 1pm

Outline Application closing date

Mid May 2025

Outline Application funding committee meeting

Late May

Outline Application decisions notified

Late May

Full Application opening date

17 July 2025

Full Application closing date

Mid September 2025

Full Application funding committee meeting

Mid October 2025

Full Application decisions notified

Studies within a trial or review

This funding opportunity is eligible for a SWAT/SWAR (study within a trial or study within a review), which can help significantly improve methodology of future research as well as the host study. Find out about the benefits of SWATs/SWARs and how to include one in your application.

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Research specification

The aim of the 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 clinical and cost effectiveness of enteral non-absorbable antibiotics to induce selective digestive tract decontamination in children and young people receiving mechanical ventilation who are expected to be invasively ventilated for a prolonged period?

  1. Patient group: Critically ill children and young people (>37 weeks corrected gestational age to <16 years) receiving mechanical ventilation who are expected to be invasively ventilated for a prolonged period (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.
  2. Intervention: Enteral non-absorbable antibiotics to induce selective digestive tractdecontamination (SDD) in addition to standard infection control strategy (formulation and timings to be defined and justified by applicants).
  3. Control: Standard infection control strategy.
  4. Important outcomes: Days free of mechanical ventilation.
  5. Other outcomes: Measure of organ recovery; development of complications during PICU stay (related to SDD administration) subset microbiome pattern and antimicrobial resistance monitoring; antimicrobial usage; ventilator-acquired pneumonia rate; mortality; health complications/adverse events/associated infections; Quality of Life; recovery/readmission; 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).
  6. Setting: Paediatric intensive care units (PICU).
  7. Study design: An efficient and focused randomised controlled trial with an internal pilot phase to test key trial processes such as recruitment and adherence. Clear stop/go criteria should be provided to inform progression from pilot to full trial. Applicants should clearly define and justify.
    Applicants should consider how the study can provide a cost-efficient analysis of antimicrobial resistance, including the necessary samples to demonstrate antimicrobial outcomes and consider efficient use of routinely collected data and readily available resistance data.
        Co-production, which ensures that the research demonstrates an equal partnership with service commissioners, providers and service users (or their advocates), should be embedded throughout the project's life cycle from application to completion. Applicants may wish to consult the NIHR Learning for Involvement guidance on co-producing research.
  8. Minimum duration of follow-up: Until hospital discharge.
    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

Hospital-acquired infections, particularly respiratory tract infections like pneumonia, pose a significant risk to vulnerable patients in intensive care units (ICUs) and are associated with an increased likelihood of adverse outcomes. These infections can be caused by potentially harmful microorganisms found in the throat and gut, either upon admission to the ICU or acquired during a hospital stay. One approach to reducing mortality from such infections in adults is selective decontamination of the digestive tract (SDD) in addition to standard infection control procedures. SDD involves using specific non-absorbable antibiotics applied to the mouth and stomach to reduce or eliminate potentially pathogenic microorganisms instead of using broad-spectrum antibiotics that can disrupt the natural gut microbiome. It is important to consider the impact of SDD on antimicrobial resistance in treated patients and the ecology of ICUs. However, various studies have shown that routine use of SDD does not negatively impact resistance. A recent study in adults found that continuous use of SDD was linked to reduced antibiotic resistance rates.

Paediatric Intensive Care Units (PICU) provide critical care for children, especially those who are medically unstable and require intubation, ventilation, and continuous medical or nursing supervision. In the UK, around 17,000 children were admitted to PICUs in 2022. Ventilator-acquired pneumonia (VAP) is a particular concern for this population, as sedated, intubated patients are at higher risk of lower respiratory tract infection. VAP is linked to prolonged mechanical ventilation, extended hospital stays, increased admission costs, and higher morbidity and mortality. There is limited evidence regarding the use of SDD in children admitted to PICUs. As PICU mortality rates are typically very low, previous studies have not indicated a benefit in terms of mortality but have shown that SDD may be effective in reducing VAP.

In 2016, the HTA Programme commissioned a study to evaluate the feasibility of SDD in mechanically ventilated children in paediatric intensive care. The study has now been completed and has concluded that a definitive trial incorporating the protocol adaptations and outcomes arising from the feasibility is viable and acceptable. Therefore, the HTA Programme is now interested in commissioning a substantive trial to evaluate the intervention fully.  

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.

Application guidance

Please read our Domestic Outline Application guidance to help you complete all aspects of your application. You must read this alongside the information below, which details specific requirements our HTA programme looks for in applications. You can also check our HTA Programme page for details about the Programme's scope.

Research Plan

Please include the following information when writing your Research Plan.

Methodology/plan

Include the below detail in your methodology/plan:

The research question

Please provide a concise statement of your proposed research including how it fits our HTA Programme remit.

You should include a clear explanation of the main (single) research question phrased in PICO terms where applicable to your study type:

  • population: NHS (or social care) target population i.e. real patients
  • intervention: A technology that is or could be used now in the NHS or social care. You may wish to refer to the Template for Intervention Description and Replication (TIDieR) guidance
  • comparator: Usually the next best treatment, but could be placebo
  • outcome: Patient/service user centred, leading to effectiveness and cost-effectiveness 

For some funding opportunities, much of this information will be detailed in the research specification. In this case, you should only provide any relevant additional information not already captured in the research specification. If you wish to propose a study that does not meet one or more of the requirements set out in the research specification, please use this section to explain the reasons for your approach.

Summarise your project plan plus any additional points required to support statements made in previous sections of your application. Include any key references required to justify them (for example in the use of particular outcome measures or methods of analysis).

Why is this research important in terms of improving the health and/or wellbeing of the public and/or to patients and health care services?

It is essential that you clearly identify the health and care need your research meets or contributes to. Please outline the anticipated value or contribution your study will provide. You must justify that this unmet need is a high priority to the NHS, social care or those who use these services. Your justification should be proportionate to the level of funding you are asking for. In some cases, substantive justification will be needed to prove your research is in an area of major importance. This includes detailing what support there is for this work from relevant clinical and patient communities.

Design

Give a brief statement on the type of study design you will be using.

  • for primary research, state the health or care service setting(s) in which the study will occur. For example general practice, hospital outpatients, ambulance service users, social care  
  • for secondary research or modelling, please explain the criteria applied to assess the quality and relevance of studies identified by the search strategy. Explain  how these will be decided if these are not yet known

We welcome innovative methods that offer substantial benefits. If you have a complex design, for example it is Bayesian and model-based, you should justify the use of these designs over a more standard approach. For example, by showing the statistical properties are superior, or that resources required are lower. You  should also demonstrate that you have appropriate expertise within the research team to implement the approach. 

What is the evidence that the intervention is ready for HTA evaluation?

For some funding opportunities, the review of the existing evidence will have already been undertaken by the NIHR HTA Programme to inform the research specification. In this case please ensure you meet the requirements in the research specification.

For researcher-led applications and commissioned funding opportunities with a broader scope, we require evidence that the intervention is ready for HTA evaluation.

You should present and reference relevant high-quality evidence synthesis including systematic reviews, modelling studies and meta-analyses. Where no such published evidence synthesis exists, you are expected to undertake an appropriate review of the currently available evidence. You would do this using a predetermined and described methodology that systematically identifies, critically appraises and then synthesises the available evidence, and then present a summary of these findings in your proposal.

You should propose valid and reliable methods for identifying and selecting relevant material, assessing its quality and synthesising the results. See the NHS centre for Reviews and Dissemination guidance for guidance on choosing appropriate methods.     

If you are undertaking systematic reviews, we will register them in the PROSPERO database for you. PROSPERO was developed by our NIHR’s Centre for Reviews and Dissemination (CRD). It is the first online facility to register systematic reviews for research about health and social care from all around the world. Access is completely free and open to the public. PROSPERO registration is a condition of NIHR funding for eligible systematic reviews.

If your proposed  study builds on previous work then the results of the previous study must be available to the Funding Committee before an application will be considered. Please reference the published results. If not yet published, the committee may ask to see the results. They may also ask for evidence that a previous study has been accepted for publication, to demonstrate that peer review has taken place.

Further to the guidance in the Background and Rationale section of the Research Plan, please justify the clinical importance of your proposed study to patients and the public, and outline the anticipated value or contribution the study will provide to clinical practice now and in future. You must justify that this unmet need is a high priority to the NHS, social care or those who use these services. Your justification should be proportionate to the level of funding you are asking for. In some cases, substantive justification will be needed to prove your research is in an area of major importance. This includes detailing what support there is for this work from relevant clinical and patient communities. In addition, please consider how your proposed study could be implemented across the wider NHS or social care settings. 

Target population and inclusion/exclusion criteria      

Clearly define the population from which the study sample receives the health technology concerned (or the control intervention where appropriate). For example, women over 60, people with a learning disability, people with advanced cancer. Please provide an explanation of the inclusion/exclusion criteria.

Health technologies being assessed      

Give a clear definition of the health technology to be assessed. The purpose of HTA is to assess the value of a health technology compared to best alternatives or where none exists, against no intervention. Where there are established alternative technologies, these should also be defined. Where the technology is subject to rapid change, you should include details of how this will be dealt with in your project.

Measurement of costs and outcomes      

Not all HTA studies require full economic evaluations. When considering including      a cost-effectiveness analysis, you should carefully describe what this will add to the study. Where an economic component is proposed, you should aim to use the simplest approach, or fully justify where more complex methodologies are needed. You should justify the use of outcome measures where a legitimate choice exists between alternatives. If your study includes a health economic component, state from what perspective costs and benefits will be considered, and (briefly) how these will be collected. Where established Core Outcomes exist you should include these in the list of outcomes unless there is good reason to do otherwise. Please see the COMET Initiative website to identify whether Core Outcomes have been established. COMET stands for Core Outcome Measures in Effectiveness Trials.

Longer-term follow-up      

You should consider getting consent from participants to allow you to follow-up with them in the future. This would be through efficient means (such as routine data) as part of a separately funded study. Getting consent may be useful after your main study is completed, to undertake longer-term follow-up -  either because of what is currently known about the possible long-term effects of the intervention, or because subsequent research suggests long-term follow-up of this cohort would be useful. You should therefore consider building in provision for a mechanism to facilitate longer-term follow-up beyond the life of the main study, including obtaining consent for this from participants at study entry.

Sample size      

State the required sample size, giving details of the estimated effect size, power and/or precision employed in the calculation. You must provide this information so the Funding  Committee can replicate the calculation and understand the assumptions made.

Difference between current and planned care pathways      

Please define the current standard care pathway and how this differs from the trial arms.

Diagnostics and imaging     

You should justify where you consider improvements in diagnostic accuracy to be relevant. Where there is poor evidence to link diagnostic improvements to patient benefits, part of the primary research may be to assess the effects of such changes on patient management and outcomes. You should also assess changes in other resources (particularly other subsequent therapies) used as a result of changes in diagnostic methods.

Dissemination      

Our key concern is to ensure that projects funded by the HTA Programme are designed from the outset to produce useful, timely and relevant research findings which impact practice.

Studies within a trial or review (SWATs/SWARs)      

You may apply for up to £30,000 funding to evaluate alternative ways of managing studies and how researchers can effectively engage with key stakeholders to promote the uptake and use of the evidence generated. This may be completed as part of your main study. Any methodological sub-study proposed should represent a very minor element of a larger study and must not undermine the delivery of the main study.

There are some examples on the Northern Ireland Hubs for Trials Methodology Research web page. You are also encouraged to review the work of Trial Forge. Where there is already a number of SWATs answering the same or similar question, substantial additional justification would be needed. You may want to consider collaborations with groups able to carry out methodological work, for example around such issues as evaluating sustainability outcomes for trials. SWATs/SWARs may not all be powered to provide meaningful outcomes but will be useful for meta-analysis and applicants should consider using protocols published on the Northern Ireland MRC Trials Hub for Methodology Research SWAT registry. Applicants who wish to include a SWAT/SWAR in your study, you should indicate that you intend to do so in Outline Application. There is no need to provide a detailed description of the SWAT/SWAR at this stage.

Multiple long-term conditions - studies within a project

We encourage you to consider multiple long-term conditions (MLTC) - studies within your project. This is to further understanding of MLTC, and improve knowledge on the best methods and processes for incorporating MLTC research questions into complex projects (including clinical trials) in health, social care and public health. You  can propose an embedded study within a project (SWAP) which would support this. The study would be short and efficient, with findings put into the public domain as soon as they are available, as an interim output. A SWAP will be a small part of the overall application and should be costed at no more than £30,000 to include all dissemination and publication associated with the SWAP. You are not required to give a detailed description of the SWAP this stage.

Mechanistic research      

We will support the collection of samples and data, where the HTA study provides an opportunity for valuable, hypothesis-testing research into the ‘mechanism of action’ of the intervention. The cost of sample collection and storage must be made clear in your application and must be modest in scale. Unless otherwise specified, any mechanistic work must be funded separately. You should note where there are plans to apply for and undertake the associated mechanistic study, for example via application to the MRC-NIHR Efficacy and Mechanism Evaluation (EME) programme. Any mechanistic work must not have a detrimental effect on the main study.

Project timetables including recruitment rate      

Indicate the anticipated duration of the study. Pay particular attention to the expected recruitment rate and a justify your estimate. Outline the main stages of your proposed project including regulatory steps, team recruitment, patient recruitment, and the expected duration of each.

Expertise in your team 

The team should be multidisciplinary and include relevant expertise in the clinical area concerned. They should have expertise in performing evidence synthesis and (where appropriate) other areas. For example, experience in operational research, being a patient and public involvement (PPI) Lead, being a public voice with lived experience, a health economist or statistician. 

For commissioned topics, we strongly discourage 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.

Clinical Trials Unit involvement 

We advise that studies involving a clinical trial have engaged with an accredited Clinical Trials Unit (CTU) listed on the UKCRC CTU Network. Note that you must provide a letter of CTU support with all Full Applications involving a clinical trial. If you are designing or undertaking clinical trials, we encourage you to consult the Clinical Trials Toolkit.

Ethics/regulatory approvals

See the HRA website for guidance on the application process for ethical and other approvals. This process may vary depending where you are based in the UK. The HRA approval page provides more information. 

If you are using patient information from an existing database, please ensure you have consent or that appropriate exemptions are in place. Approval to use confidential patient information without consent must be requested from the HRA who make decisions with advice from the Confidentiality Advisory Group (CAG).

To take advantage of the growing utility of routine data, we encourage you to consider asking participants to consent to long-term follow-up. That is, beyond the outcomes of the HTA study where appropriate.

See the UK policy framework for health and social care research for a summary of the responsibilities of key research stakeholders.

Medicines and Healthcare products Regulatory Agency (MHRA) considerations

The MHRA can provide guidance on the regulations that apply to your study. If you are planning a study on a medicine used outside its licensed indication, dose, or formulation, we encourage you to contact the Medicines Repurposing Programme for support and advice before submitting your application.

Application process

Find out how to apply for this funding opportunity and what you need to do to get your application ready.

How to apply 

When you are ready to apply, you will need to log in to our application system to apply. This funding opportunity is on our new Awards Management System and you will need to create a new account to apply.

The closing date is 2 April 2025 at 1pm. Applications received after 1pm on the closing date will not be considered. 

Please read the following guidance before submitting an application:  

  • all the application guidance detailed in the 'Application guidance' section in this funding opportunity

Download application form template

You can download a Word document template of the application form below. Please use this template as a guide only, to help you prepare your application. For example, to see how many characters are accepted in each section and to see how information in the form is laid out. Please do not try to use this as an application form; it cannot be submitted as an application. You must submit your application online via our Awards Management System.

Domestic Outline Application form template

Research inclusion and reasonable adjustments

At NIHR we are committed to creating a diverse and inclusive culture. We encourage applications from people from all backgrounds and communities bringing diverse skills and experiences. If you need any reasonable adjustments throughout the application process, please contact the programme team via the information in the Contact Details tab.

Research Support Service

Got a research idea and not sure how to turn it into a funding application? The free NIHR Research Support Service (RSS) supports researchers in England to apply for funding. It can help you develop and deliver clinical and applied health, social care and public health research post award.

Contact Details 

  • For help with your application contact htacommissioning@nihr.ac.uk
  • For more information about the funding Programme, visit the HTA Page
  • Got a research idea and not sure how to turn it into a funding application? The free NIHR Research Support Service (RSS) supports researchers in England to apply for funding, and to develop and deliver clinical and applied health, social care and public health research post award. Find out how the RSS can help you.