24/11 Nebulised therapy in patients with stable Chronic Obstructive Pulmonary Disease and disabling breathlessness commissioning brief

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 Nebulised therapy in patients with stable Chronic Obstructive Pulmonary Disease (COPD) and disabling breathlessness?

1. Patient group: Patients with stable COPD and disabling breathlessness – 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.
2. Intervention(s): Nebulised therapy arms, applicants to define and justify dose and whether regular or as needed:
   Nebulised salbutamol plus usual care.
   Nebulised saline plus usual care.
   Consideration should be given to the use of sham (saline via modified upper airway nebuliser) plus usual care. To be defined and justified by applicants.
3. Comparator: Usual care – inhaled salbutamol as required and optimised inhaler use. To be defined and justified by applicants.
4. Important outcomes: Patient-reported measure of respiratory symptoms (to be defined and justified by applicants), Quality of life.
   Other outcomes: Patient preference, Change in FEV1, Change in exercise capacity, COPD assessment test, Cost-effectiveness, Adverse events, Patient acceptability.
   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).
5. Setting: Primary and secondary care. Consideration may be given to including pre-hospital/ambulance services.
6. Study design: A multi-arm 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 to define and justify if a parallel or crossover study design should be used.
7. Minimum duration of follow-up: To be defined and justified by applicants.
   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

COPD is a common chronic inflammatory lung disease that causes obstructed airflow in the lungs and affects more than 1 million people in the UK. COPD accounts for approximately 30,000 deaths each year in the UK and is the second largest cause of emergency admissions. People with COPD experience a high burden of symptoms, most notably breathlessness, which affects all aspects of patients’ lives.

Inhaled bronchodilators are the mainstay of COPD symptom management, and work by relaxing the smooth muscle in the airways, thereby widening the airways, making breathing easier. Salbutamol is an example of a bronchodilator that is predominately taken via a hand-held inhaler due to its convenience, portability, and lack of maintenance. However, poor inhaler technique is known to compromise symptom relief in more than half of patients, which increases the risk of hospitalisation and negatively impacts quality of life.

Salbutamol can also be given using a nebuliser, a machine that turns liquid medicine into a fine mist, which the patient can breathe in through a mask or mouthpiece. Because the medicine is delivered to the lungs over many breaths, poor inhalation technique is less of an issue.

The use of nebulised therapy is ill-defined and there is variation in practice both within and between hospitals. Previous systematic reviews have concluded that there is no difference in lung function between inhalers and nebulisers, however the trials assessed are small, include patients with asthma, do not use a placebo, and do not include patient-reported outcomes. More recent patient surveys have shown a preference for nebulisers and greater feelings of symptom relief (particularly breathlessness), quality of life, and satisfaction with treatment, compared to therapy administered by inhalers.

There is a lack of evidence on inhalation device effectiveness in patients with stable COPD. Therefore, the HTA Programme wishes to commission research in this area to determine if nebulised therapy is more clinically and cost-effective than inhaler therapy at controlling disabling breathlessness and improving quality of life for patients with stable COPD.

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 funding opportunity, you can begin your application via the Funding opportunities page.

Your application must be submitted online no later than 1pm, 24 July 2024. Applications will be considered by the HTA Funding Committee at its meeting in September 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 January 2025.

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 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, 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 us via email: htacommissioning@nihr.ac.uk.