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 clinical and cost-effectiveness of withdrawing long term macrolides in bronchiectasis?
- Intervention: Discontinuation of long-term macrolide plus standard treatment – to be defined and justified by applicants.
- Patient group: Patients diagnosed with bronchiectasis already taking a long-term macrolide for exacerbation prevention for at least 3 months – to be defined and justified by applicants. 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: Continued long term macrolide plus standard treatment – 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. Applicants should stratify by disease severity or other relevant patient characteristics to allow for subgroup analysis to identify clinical subgroups most likely to benefit.
- Important outcomes: Number of bronchiectasis exacerbations; frequency and duration of bronchiectasis-related admissions; health related quality of life; time to next exacerbation.
Other outcomes: health-care resource utilisation; all-cause mortality; adverse effects; cost-effectiveness; antimicrobial resistance; patient acceptability; additional antibiotic usage.
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 from recruitment.
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 bronchiectasis (here on in referred to as bronchiectasis) is a long-term condition where the airways of the lungs become widened, leading to a build-up of excess mucus, which traps bacteria causing inflammation and infection. This results in further damage to the airways, causing more dilation and even more mucus to accumulate, increasing the risk of infection further. As this cycle is repeated, the damage to the lungs gets progressively worse leading to lung function decline, worse quality of life, and mortality.
It has been estimated that as many as 300,000 people have bronchiectasis in the UK and affects both children and adults, although the prevalence increases with age, and is more common in women than men. Complications of bronchiectasis include acute exacerbations, which are defined by an increase in daily respiratory symptoms such as a persistent cough, sputum production, malaise, fatigue, and breathlessness. Mild or moderate exacerbations can be controlled with oral antibiotic treatment, however severe exacerbations require hospitalisation and are a major determinant of healthcare costs within the NHS.
National and international guidelines recommend using long term antibiotics in patients with bronchiectasis who experience three or more exacerbations per year but is based on limited evidence. A specific class of antibiotics known as macrolides are prescribed with the aim of suppressing bacterial infection and inflammation to break the cycle of recurrent infections and exacerbations. Evidence suggests that long-term macrolides reduce exacerbation rates and hospitalisations but increase the risk of antimicrobial resistance and adverse events such as hearing loss, cardiac events, and diarrhoea.
Despite long-term macrolides being widely used in clinical practice to prevent exacerbations, there is no data showing the continued effectiveness or severity of adverse events of macrolide treatment beyond one-year of treatment - it is also unknown how long a patient should be treated. Some centres withdraw long term macrolides, which could result in hospitalisation and mortality if treatment is still required, whereas others continue to keep patients on treatment continuously, which increases the risk of antimicrobial resistance, adverse events, and side effects. The benefits and harms of discontinuation of long-term macrolides in bronchiectasis are unknown and treatment should only be continued if the benefits outweigh the risks. Therefore, the HTA Programme wishes to commission an RCT to determine which subgroups of people benefit from continued treatment and those who do not.
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 on-line no later than 1pm on the 30 November 2022. Applications will be considered by the HTA Funding Committee at its meeting in January 2023.
Guidance notes and supporting information for HTA Programme applications are available.
Important: Shortlisted Stage 1 applicants will be given eight weeks to submit a Stage 2 application. The Stage 2 application will be considered at the Funding Committee in May 2023.
Applications received electronically after 1300 hours 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 one competing team. There may be unusual circumstances where the same person could be included on more than on application eg 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 by email at htacommissioning@nihr.ac.uk.