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 positive airway pressure therapy in the treatment of patients with chronic obstructive pulmonary disease-obstructive sleep apnoea (COPD-OSA) overlap syndrome?
- Intervention: Positive airway pressure therapy (continuous positive airway pressure therapy in non-hypercapnic non-acidotic patients and non-invasive ventilation in hypercapnic non-acidotic patients) – to be defined and justified by applicants.
- Patient group: Patients with COPD who are screened for and subsequently diagnosed with obstructive sleep apnoea (OSA) – the severity of COPD and OSA to be defined and justified by applicants. Patients must not currently use or have previously used home positive airway pressure therapy. Applicants should define and justify if the patient population is those with stable COPD or those who have been discharged following an exacerbation.
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: Any appropriate setting.
- Comparator: 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: To be defined and justified by applicants, for example Quality of life; Epworth Sleepiness score; COPD exacerbation frequency; Hospital admission rates.
- Other outcomes: Patient acceptability; Time to first COPD exacerbation; Major adverse cardiovascular events; All-cause mortality; Cost-effectiveness; Health Care Utilisation; Adherence to treatment; Cognitive outcome measures.
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: 12 months after 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
Obstructive sleep apnoea (OSA) is a condition whereby a person’s breathing stops for short spells when they are asleep because of a full airway obstruction. OSA is classified as mild, moderate or severe depending on the frequency of respiratory events during one night. Chronic obstructive pulmonary disease (COPD) refers to a group of diseases that cause airflow blockage and breathing-related problems. Overlap syndrome occurs in people who have both COPD and OSA, and the combined effect of these conditions may be associate with greater morbidity and mortality than either condition alone. Overlap syndrome is estimated to affect 1% of the adult UK population, but the true prevalence is thought to be much higher. Overlap syndrome detrimentally impacts on people’s quality of life, increases their risk of hospitalisation from COPD exacerbations and increases the risk of developing serious health problems, particularly cardiovascular disease.
Positive airway pressure (PAP) therapy delivered by a mask is a non-invasive, externally applied pressure on the patient’s airway. This positive airflow helps keep the airway open, preventing the collapse that occurs during apnoea, thus allowing normal breathing, improving quality of sleep, reducing tiredness and the risk of related conditions such as hypertension. Two common modes of PAP therapy are continuous positive airway pressure (CPAP) and non-invasive ventilation (NIV). In CPAP, a constant pressure is applied which splints open the upper airway and thereby prevents its collapse. NIV provides two different pressures: a higher-level during inspiration, and a lower level during expiration, which actively supports the respiratory muscles to assist ventilation.
Whilst observational studies have shown an association between CPAP therapy and reduced COPD exacerbations, cardiovascular events and mortality, there are no randomised trials that have examined its clinical effects in patients with overlap syndrome. There are even fewer data on the use of NIV in this population. NICE recommend CPAP therapy for the treatment of overlap syndrome without severe hypercapnia (excessive carbon dioxide in the bloodstream) and NIV for patients with severe daytime hypercapnia. However, these recommendations are based on extrapolation of data from a different patient population and the committees’ own experiences. There is no evidence from randomised trials that determine which type of PAP therapy should be given to patients with overlap syndrome, which lead to NICE making a research recommendation to identify the optimal treatment for people with overlap syndrome: CPAP or NIV?
There is lack of evidence for the role of CPAP in patients diagnosed with milder sleep apnoea symptoms and a recent hospital admission following an exacerbation of COPD. In addition, the role of CPAP compared to NIV in those with stable COPD but recently diagnosed OSA with borderline hypercapnia is also unclear. Therefore, the HTA programme would like to commission a large scale RCT to determine the effectiveness of PAP therapy in patients with overlap syndrome and is potentially interested in funding more than one application. The patient group is to be defined and justified by applicants and can be either those with stable COPD and/or those being discharged from hospital following an exacerbation.
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.