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 clinical and cost-effectiveness of Pseudomonas aeruginosa eradication treatment in bronchiectasis?
- Intervention: Pseudomonas aeruginosa eradication treatment as recommended by the British Thoracic Society Guidelines, consisting of a combination of systemic antibiotics for 2 weeks followed by inhaled antibiotics for 3 months – to be defined and justified by applicants.
- Patient group: Patients with confirmed non-cystic fibrosis bronchiectasis and isolation of P. aeruginosa in sputum or another respiratory tract sample - either the first ever isolate or a new isolate after at least 12 months free of infection – to be defined and justified by applicants. Patients should not be currently receiving long-term inhaled antibiotic treatment. 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: Primary and secondary care.
- Comparator: Symptomatic management only – to be defined and justified by applicants.
- Study design: A 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.
- Important outcomes: Number of bronchiectasis exacerbations; Cost-effectiveness.
Other outcomes: Eradication of P. aeruginosa; Time to reinfection; Chronic P. aeruginosa infection; Antibiotic resistance; Bronchiectasis-related hospital admissions; Respiratory symptoms measured using validated questionnaires; Quality of life; Adherence; Health-care contacts; All-cause mortality; Adverse Effects. 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: 2 years after completion of eradication treatment.
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
Non-cystic fibrosis (NCF) bronchiectasis is a long-term condition where the airways of the lungs become widened, leading to a build-up of excess mucus that can make the lungs more vulnerable to infection. The most common symptoms include a persistent cough that usually brings up phlegm, shortness of breath, exacerbations, and recurrent respiratory tract infections, and is associated with a poor quality of life. It has been estimated that as many as 300,000 people have NCF bronchiectasis (here on in referred to as bronchiectasis) in the UK and affects both children and adults, although the prevalence increases with age, and is more common in women than men.
The vicious cycle of bronchiectasis refers to a process whereby bacteria trapped in the excess mucus leads to inflammation and infection, which further damages the airways causing more dilation and even more mucus accumulating, increasing the risk of infection further. As this cycle is repeated, the damage to the lungs gets progressively worse leading to recurrent exacerbations, lung function decline, worse quality of life, and mortality.
Patients are frequently infected with Pseudomonas aeruginosa, which, if left untreated can lead to chronic infection, which requires long-term antibiotic therapy, increasing the likelihood of the pathogen developing antibiotic resistance. Chronic infection also increases exacerbations, hospitalisation, and mortality, and is associated with a worse quality of life. There is some evidence to suggest that identifying and treating patients who have isolated P. aeruginosa infection can eradicate the organism from the lung, preventing chronic colonisation, and improving outcomes for patients.
National and international guidelines recommend the eradication of P. aeruginosa with systemic and inhaled antibiotics, however, these guidelines are based on very low-quality evidence from only a few small studies (only one of which is an RCT) and expert opinion. As a result, these guidelines and research priorities from Delphi exercises with expert physicians have highlighted the need for an RCT of P. aeruginosa eradication therapy to determine the clinical outcomes and cost-effectiveness in patients with bronchiectasis. Therefore, the HTA Programme wishes to commission a large scale RCT to determine if eradication of P. aeruginosa is clinically and cost-effective at preventing chronic infection, and reducing the frequency of exacerbations, hospitalisation, and respiratory symptoms.
Applications should be co-produced, demonstrating an equal partnership with service commissioners, providers and service users (or their advocates) in order to provide evidence and actionable findings of immediate utility to decision-makers and service users. Applicants may wish to consult the NIHR guidance on co-producing research.
To support the ambitions of NIHR’s Best Research for Best Health: the next chapter, NIHR strongly encourages the inclusion of nurses, midwives and allied health professionals within well-developed research teams responding to this call, to increase the building of nurse, midwife and allied health professional-related research activity, capacity and capability across the professions. Depending on the level of experience, this could be through the role of lead applicant, as joint co-applicant (supported by detailed mentoring plans submitted with the application), or as a co-applicant member of the research team. Through this activity, NIHR aims to support nurses, midwives and allied health professionals to become future research leaders and release the potential to lead, use, deliver and participate in research as a part of their job.
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 wish to submit a Stage 1 application for this call, the online application form can be found on the funding opportunities page. To select this call, use the filters on the right of the screen or search using the call name and/or number.
Your application must be submitted online no later than 1pm, 29 November 2023. Applications will be considered by the HTA Funding Committee at its meeting in January 2024.
Guidance notes and supporting information for HTA Programme applications are available.
Important: 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 May 2024. Applications received electronically after 1pm on the due date will not be considered.
For commissioned topics, the Programme strongly discourages the practice of the same Co-Applicant joining more than 1 competing team. There may be unusual circumstances where the same person could be included on more than 1 application, e.g. a Lead from a named charity or a unique national expert in a condition.
For such exceptions, (i) each application needs to state the case as to why the same person is included, (ii) the shared Co-Applicant should not divulge application details between teams and (iii) both teams should acknowledge in their application that they are aware that one of their Co-Applicants is part of a competing application and that study details have not been shared.
Should you have any queries please contact us: htacommissioning@nihr.ac.uk.