Novel methods within a randomised controlled trial in respiratory disease

Abstract

Introduction:
A well designed randomised controlled trial is the best-known process to assess if a healthcare intervention works. The number of clinical trials registered and open for recruitment is increasing every year, through the global cumulative effort of many researchers and the large numbers of participants who volunteer their time. However, trials can be methodologically poor, ultimately leading to research waste whilst leaving important clinical questions unanswered. This thesis aimed to explore a series of novel methods as solutions in respiratory medicine.

Methods:
A number of studies were embedded within the CLEAR bronchiectasis trial. Studies investigated remote data collection in lung function using patient-led technology, the use of remote patient reported outcomes within the new standardised EMBARC framework for exacerbations and novel Studies Within A Trial (SWAT) to increase patient recruitment and retention. A systematic review was also completed for the use of mucoactives in acute respiratory failure, which together with the other methods explored in the CLEAR trial, informed the conditional design of a new trial in respiratory medicine.

Results:
Remote spirometry was completed by patients at home with moderate adherence and was not significantly different to supervised spirometry performed at clinic visits for a number of lung function tests (FEV1, FVC, FEF25-75 and PEF). The EMBARC definition was found to be equivalent to the Fuchs criteria for classifying exacerbations and it was feasible to assess key symptoms using remote patient reported outcomes. In addition, the symptoms contained within EMBARC corresponded to those that deteriorated most at the start of exacerbations. For the SWAT, modifications to the invitation letters had no significant effect on recruitment and giving patients enrolled in the trial a thank you card had no effect on retention, albeit both SWAT had small sample sizes. The systematic review found limited evidence for mucoactives in critically ill patients and justified the design of a large robust clinical trial.

Conclusion:
A comprehensive programme of important methodological research can be undertaken within a large clinical trial with aims that are distinct from those of the main trial. Remote spirometry and using the EMBARC definition with patient reported outcomes can be implemented in further bronchiectasis trials to increase pragmatism and quality. Further research is needed to identify methods to increase recruitment and retention. A large, randomised trial for common mucoactives in the critically ill is needed.

Date of Award	Dec 2021
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Northern Ireland Department for the Economy & Professor John Glover Memorial Fund
Supervisor	Judy Bradley (Supervisor), Mike Clarke (Supervisor), Danny McAuley (Supervisor) & Brenda O'Neill (Supervisor)