An Evaluation of Physiotherapy Assessment; A Mixed Methods Study to Evaluate the Physiotherapy Assessment of Breathing Pattern Disorder
Conditions: Breathing Pattern Disorder, Breathlessness
Sponsor: Royal Brompton & Harefield NHS Foundation Trust

 
Protocol PHAB Version 2 17/5/23 
An Evaluation of Physiotherapy Assessment; A mixed methods study to evaluate the physiotherapy 
assessment of Breathing Pattern Disorder 
 
Short Study Title/Acronym: The Physiotherapy Assessment of Breathing Pattern Disorder (PHAB) 
 
REC Reference: 23/WA/0095 
IRAS ID: 315897 
Document Version and Date: Version 2 17/05/2023 
 
 
CHIEF INVESTIGATOR: 
 
Lizzie Grillo MCSP MSc 
Advanced Physiotherapist 
Physiotherapy Dept 
Royal Brompton Hospital 
Sydney Street 
SW3 6NP 
 
Phone : 07843203979 
Email : l.grillo@imperial.ac.uk 
 
SPONSOR REPRESENTATIVE: 
 
Research Business Manager 
Royal Brompton and Harefield Hospitals 
Guy’s and St Thomas’ NHS Foundation Trust (GSTFT) 
Research Office  
Sydney Street 
London SW3 6NP 
 
Phone: 0207 352 8121 ext. 8736 
Email: research@gstt.nhs.net 
 
 
 
Information in this protocol is confidential and should not be disclosed, other than to those directly involved 
in the execution or the ethical review of the study, without written authorisation from RB&H Research 
Office. 
 
 
 
 
 
Signature Page  

 
 
The undersigned confirm that the following protocol has been agreed and accepted and that the Chief 
Investigator agrees to conduct the study in compliance with the approved protocol and will adhere to the 
principles outlined in the Declaration of Helsinki, the Sponsor’s SOPs, and other regulatory requirement. 
I agree to ensure that the confidential information contained in this document will not be used for any other 
purpose other than the evaluation or conduct of the investigation without the prior written consent of the 
Sponsor 
I also confirm that I will make the findings of the study publicly available through publication or other 
dissemination tools without any unnecessary delay and that an honest accurate and transparent account of the 
study will be given; and that any discrepancies from the study as planned in this protocol will be explained. 
This protocol has been written in accordance with the Sponsor’s guidance for writing non-CTIMP protocols.  
 
 
Chief Investigator (CI)
EJFGrillo 
2/2/23 
Lizzie Grillo
Advanced Physiotherapist 
Royal Brompton & Harefield Hospitals, 
Guy’s, and St Thomas’ NHS Foundation 
Trust (RB&H) 
Signature 
Date 
Principal Investigator (PI) 
(If different from CI) 
 
 
Lizzie Grillo
Advanced Physiotherapist 
EJFGrillo 
2/2/23 
Royal Brompton Hospital
Signature
Date
Sponsor Representative
PPetterson 
2/3/23 
Mr Patrik Pettersson
Research Business Manager 
Royal Brompton & Harefield Hospitals, 
Guy’s, and St Thomas’ NHS Foundation 
Trust (RB&HFT) 
Signature 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
Table of contents 
 
1. 
LIST OF ABBREVIATIONS 
6 
2. 
STUDY PERSONNEL AND FACILITIES 
7 
3. 
STUDY SYNOPSIS 
8 
4. 
INTRODUCTION 
11 
4.1 
BACKGROUND 
11 
4.2 
PRE-CLINICAL DATA/CLINICAL DATA 
12 
4.3 
STUDY RATIONALE AND RISK/BENEFIT ANALYSIS 
12 
4.4 
MANAGEMENT OF POTENTIAL STUDY RISKS 
13 
5. 
STUDY OBJECTIVES 
13 
5.1 
PRIMARY OBJECTIVE 
13 
5.2 
SECONDARY OBJECTIVES 
13 
6.1 
OVERALL DESIGN 
14 
6.2 
TREATMENT AND RATIONALE 
14 
6.3 
SCHEMATIC OF STUDY DESIGN 
15 
7. 
ELIGIBILITY CRITERIA 
15 
7.1 
INCLUSION CRITERIA 
15 
7.2 
EXCLUSION CRITERIA 
16 
7.3 
DISCONTINUATION/WITHDRAWAL OF PARTICIPANTS AND STOPPING RULES 
16 
8. 
SUBJECT/PATIENT RECRUITMENT PROCESS 
16 
9. 
STUDY PROCEDURES 
17 
9.1 
INFORMED CONSENT 
17 
9.2 
RANDOMISATION PROCEDURE 
17 
9.3 
EMERGENCY UN-BLINDING 
18 
10. 
STUDY ASSESSMENTS 
18 
10.1 
SCREENING ASSESSMENTS 
18 
10.2 
BASELINE ASSESSMENTS 
18 
10.3 
TREATMENT PROCEDURE 
18 
10.4 
SUBSEQUENT ASSESSMENTS 
18 
10.5 
SUMMARY CHART OF STUDY ASSESSMENTS 
ERROR! BOOKMARK NOT DEFINED. 
11. 
METHODS 
19 

 
 
11.3 
DEFINITION OF THE END OF STUDY 
20 
12. 
SAFETY REPORTING 
20 
12.1 
DEFINITIONS 
ERROR! BOOKMARK NOT DEFINED. 
12.2 
RECORDING ADVERSE EVENTS (AES) 
ERROR! BOOKMARK NOT DEFINED. 
12.2 
ASSESSMENT OF SAES 
ERROR! BOOKMARK NOT DEFINED. 
12.3 
REPORTING OF SAES TO THE SPONSOR AND THE REC 
ERROR! BOOKMARK NOT DEFINED. 
12.4 
THE TYPE AND DURATION OF THE FOLLOW-UP OF SUBJECTS AFTER AES 
20 
12.5 
PREGNANCY 
ERROR! BOOKMARK NOT DEFINED. 
12.6 
ANNUAL PROGRESS REPORTS (APRS) 
ERROR! BOOKMARK NOT DEFINED. 
12.7 
REPORTING URGENT SAFETY MEASURES 
ERROR! BOOKMARK NOT DEFINED. 
13. 
DATA MANAGEMENT AND QUALITY ASSURANCE 
22 
13.1 
 CONFIDENTIALITY 
22 
13.2 
 DATA COLLECTION TOOL 
22 
13.3 
DATA HANDLING AND ANALYSIS 
23 
13.4 
ARCHIVING ARRANGEMENTS 
23 
14. 
STATISTICAL DESIGN 
23 
14.1 
SAMPLE SIZE AND RECRUITMENT 
23 
14.2 
ENDPOINTS 
24 
14.2.1 
 Primary endpoints 
24 
14.2.2 Secondary endpoints 
24 
14.3 
STATISTICAL ANALYSIS PLAN 
25 
14.3.1 
Primary endpoint analysis 
25 
14.3.2 
Secondary endpoint analysis 
26 
14.4 
RANDOMISATION 
27 
14.5 
INTERIM ANALYSIS (IF APPLICABLE) 
27 
14.6 
OTHER STATISTICAL CONSIDERATIONS 
27 
15. 
COMMITTEES INVOLVED IN THE STUDY 
27 
16. 
MONITORING AND AUDITING 
27 
17. 
DIRECT ACCESS TO SOURCE DATA 
28 
18. 
ETHICS AND REGULATORY REQUIREMENTS 
28 
19. 
FINANCE 
28 
20. 
INSURANCE AND INDEMNITY 
28 
21. 
PUBLICATION POLICY 
28 
22. 
STATEMENT OF COMPLIANCE 
29 

 
 
23. 
LIST OF PROTOCOL APPENDICES 
29 
24. 
REFERENCES 
ERROR! BOOKMARK NOT DEFINED. 
 
 
 
 
 
 
 

 
 
1. LIST OF ABBREVIATIONS  
 
 
AE 
Adverse Event 
AR 
Adverse Reaction 
ASR 
Annual Safety Report 
Ax 
Assessment 
BH 
Breath Hold 
BORG 
Borg rating of perceive exertion 
BPD 
Breathing Pattern Disorder 
BPAT 
Breathing Pattern Assessment Tool 
CI 
Chief Investigator 
CRF 
Case Report Form 
DMC 
Data Monitoring Committee 
D12 
Dyspnoea 12 questionnaire 
EQ5D 
EQ-Quol Questionnaire 
EXACT 
Exacerbations of Chronic Pulmonary Disease Tool 
GAfREC 
Governance Arrangements for NHS Research Ethics 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
HRA 
Health Research Authority  
ICF 
Informed Consent Form 
ISF 
Investigator Site File 
ISRCTN 
International Standard Randomised   
MUST 
Malnutrition Universal Screening Tool 
MARM 
Manual Assessment of Respiratory Motion 
NHS R&D 
National Health Service Research & Development   
NIMP 
Non- Investigational Medicinal Product 
NQ 
Nijmegen Questionnaire 
PI 
Principal Investigator 
PIS 
Participant Information Sheet 
PAG 
Project Advisory Group 
QA 
Quality Assurance 
QC 
Quality Control 
REC 
Research Ethics Committee 
SAR 
Serious Adverse Reaction 
SAE 
Serious Adverse Event 
SAG 
Study Advisory Group 
SDV 
Source Document Verification 
SEBQ 
Short Evaluation of Breathing Questionnaire 
SOP 
Standard Operating Procedure  
SmPC 
Summary of Product Characteristics  
6MWT 
Six Minute Walk Test 
 
 
 

 
 
 
 
 
2. STUDY PERSONNEL AND FACILITIE 
 
Principal Investigator (PI): Lizzie Grillo, Advanced Physiotherapist 
 
 
 
 
 
 
 
 E-mail:  l.grillo@imperial.ac.uk 
Phone:  07843203979  
 
 Fax: [fax no.] 
 
Statistician:                        Winston Banya 
 
 
 E-mail:  w.banya@rbht.nhs.uk 
 
 
 Fax : [fax no.] 
 

 
 
3. STUDY SYNOPSIS 
 
 
Full study title: 
An Evaluation of Physiotherapy Assessment; A mixed methods study to 
evaluate the physiotherapy assessment of Breathing Pattern Disorder 
 
Short study title:  
Physiotherapy Assessment of Breathing Pattern Disorder (PHAB) 
Chief Investigator: 
Lizzie Grillo 
Medical 
condition/disease 
under investigation: 
Breathing Pattern Disorder 
Primary Objective: 
To evaluate the measurement properties of the BPAT and its utility in the 
assessment of BPD 
• To determine the inter-observer and inter-occasion reliability of 
the BPAT   
• To determine the associations of the BPAT with other routine 
assessment tools used in BPD assessment   
• To determine the responsiveness of the BPAT to physiotherapy 
intervention for BPD  
• To determine the change over time in BPAT and other 
assessments (3 months)   
 
Secondary  
Objective:  
• To evaluate other measurements of BPD and their usefulness in 
monitoring the effects of treatment for BPD 
• To determine the feasibility of recruitment, follow up and 
retention of patients, and recording completed assessments (to 
inform future trial design)  
• To evaluate the acceptability, to patients and clinicians, of 
assessments for BPD  
 
Study population:  
Stage One
A convenience sample of patients referred to physiotherapy outpatient 
from the asthma or unexplained breathlessness services for BPD  
 
Stage Two  
Participants from stage 2 who completed the assessment and treatments 
of their BPD. Physiotherapists who have delivered the assessment and/or 
treatment aspects of BPD management 
Recruitment Target: 
Stage One
100 patients, 25 healthy controls and 25 patients with asthma and no 
BPD 
 
Stage Two  
5 patients and 5 clinicians 

 
 
Recruitment Window 
(Months): 
21 months 
Methodology:  
Stage One and Two
Mixed methods, questionnaire  
Eligibility criteria: 
Inclusion criteria:
 
Patients with BPD 
Adults aged above 18 years 
Outpatient referrals for ‘unexplained breathlessness’ or possible 
breathing pattern disorder 
Primary BPD (no other respiratory or cardiology diagnosis)  
Secondary BPD (patients with a diagnosis of another respiratory 
diagnosis including asthma or UA diagnosis) 
Able to complete up to four sessions of outpatient physiotherapy 
intervention  
Healthy Control 
Recruited from relative/significant other accompanying the study 
participant 
Hospital staff 
No respiratory or cardiac diagnosis 
Patients with Asthma 
Attending SARA Clinic 
Diagnosis of Asthma 
No Diagnosis of BPD 
  
Stage Two  
Participants from stage 2 who completed the assessment and treatments 
of their BPD. Physiotherapists who have delivered the assessment and/or 
treatment aspects of BPD management 
Eligibility criteria: 
Study treatment: (i.e., 
dose and mode of the 
study drug 
administration if 
applicable): 
Exclusion Criteria
 
Patients 
Patients with a respiratory diagnosis including COPD, ILD, Bronchiectasis 
and Cystic Fibrosis 
Pregnancy 
Unable to give informed consent 
Anyone currently participating in pulmonary/cardiac rehabilitation  
Anyone currently receiving treatment from a speech and language 
therapist for an upper airway’s diagnosis (e.g., Inducible Laryngeal 
Obstruction ILO or Laryngeal hypersensitivity syndrome (LHS) 
 
Healthy Control and patients with asthma 
Not meeting inclusion criteria 
Stage One
 

 
 
BPAT: Breathing Pattern Assessment Tool
A Clinician completed tool to look at components of breathing pattern assessment. The BPAT is a 
tabulated means of collating data obtained at respiratory physiotherapy assessment. Assessment 
components include (i) evaluation of chest/abdominal wall movement, noise of (ii) inspiratory and 
(iii) expiratory flow, (iv) channel of inspiration and expiration, (v) signs of air hunger (yawning, 
sighing and deeper breaths), (vi) RR and (vii) rhythm. Each component is given a score from 0 to 2, 
based on features consistent with expected normal (0) versus that present in severe DB (2), giving a 
total score of between 0 and 14. The BPAT is completed with a patient positioned, as per the 
standard assessment of resting breathing pattern (i.e., sat comfortably in a supported seat for at 
least 5 min) and takes approximately 1 min to collate. 
 
Visit 1: Research Visit for administration of BPAT 
Participants (including both patients and healthy controls) will attend for an initial research visit. 
Two physiotherapists (physio-1 and physio-2) separately and simultaneously complete a BPAT score. 
The patient will be asked to sit quietly in the chair while this is being completed. To reduce the 
patient’s conscious awareness of their breathing being checked, physio-1 will ‘take their pulse’ whilst 
completing the BPAT score at the same time as physio-2, by observing their breathing for two 
minutes. This section of the assessment will be video recorded to enable a third physiotherapist 
(physio-3) to complete a BPAT score from this recording. This will be the only visit completed by the 
Healthy Control patients 
 
NB: Data for asthma controls will be collected from the Systematic Assessment of Asthma Clinic 
(SARA) where, as part of usual care, patients get a physiotherapy assessment alongside a Nijmegen 
Questionnaire, Short Evaluation of Breathing Questionnaire (SEBQ), Dyspnea-12 (D-12) and BPAT. No 
additional visit will be required for this group. 
 
Visit 2 (usual care): All patients will attend for a second appointment between one and three weeks 
later (in line with usual care) where physio-2 will complete a second BPAT within their standard 
physiotherapy assessment and will confirm the presence/absence of BPD, through both objective 
and subjective observation. The physiotherapist will be asked to record their decision by completing 
“Outcome Questions” which ask them to rate on a visual analogue scale how likely it is that the 
individual has BPD.  
 
Visit 2-5 (usual care): All patients with physiotherapy-confirmed BPD will complete a course of four 
sessions of outpatient physiotherapy intervention in line with usual care.  
 
Visit 5 End of Treatment (usual care): Patients will complete their final session and completion of 
outcomes as per usual care. Patients will be asked to rate their change in breathlessness following 
intervention using a using a seven point Global Rating of Change Questionnaire (GRCQ) according to 
the following responses: “:1: Much better”; “2: Better”; “3: A little better”; “4: The same”; “5: A little 
worse”; “6: Worse” and “7: Much worse”. The physiotherapist (physio 2) will record their own 
evaluation of the patient’s response to the treatment using the same scale. Additionally, the patient 
will be invited to explain the reason for their answer in a free text box; this text will be recorded 
anonymously. 
 
Visit 6 Follow up: Patients will be followed-up (remotely or in person as per patient request) at three 

 
 
months and physio-1 will complete a BPAT score.
 
Stage Two B 
Convenience sampling of participants from study who have completed the assessment and all 
treatment sessions, and a convenience sample of physiotherapists who delivered the assessment 
and/or treatment aspects will be invited to take part after completion of the study data collection.  
 
The experiences of physiotherapists’ (n=5) and patients’ (n=5) participation in the study will be 
explored by in-depth, semi-structured interviews lasting 30-60 minutes, conducted face-to-face or 
via digital platform according to national guidance and individual preference. All interviews will be 
audio/visual recorded, specifically, experiences of the BPAT assessment and outcome measures will 
be explored.  
 
4. INTRODUCTION 
4.1 
BACKGROUND 
In health, and at rest, human respiration is achieved through the largely subconscious rhythm of breathing at a 
comfortable tidal volume. Increases in both the rate and depth of breathing are triggered by temporary, 
physiological responses to stimuli such as exertion or anxiety1. In respiratory disease where there is loss of 
function or reserve, these patterns may be disturbed resulting in the familiar, if complex, sensation of 
‘breathlessness’. Non-physiological disorders in breathing pattern are known collectively as Breathing Pattern 
Disorder (BPD) or Dysfunctional Breathing (DB); however, there is inconsistency in the is nomenclature which 
clinicians describe as frustrating (Focus group paper), For this application we will use the term BPD. Individuals 
with BPD tend to breathe in a manner that is disconnected from their respiratory or metabolic requirements2, 
in some cases leading to a decreased arterial partial pressure of carbon dioxide through hyperventilation3.  
 
The condition may be present in the absence of respiratory disease (‘primary’ BPD), or it may accompany 
another respiratory disorder, commonly asthma2 (‘secondary’ BPD). However, there is limited knowledge on 
whether these presentations differ in clinically important ways.  Individuals with BPD experience non-
physiological breathlessness, air hunger and limitation in function5. Its pathogenesis is incompletely understood 
but probably comprises an interplay between biomechanical and biochemical stimuli and psychopathological, 
cognitive factors2,3,4. Various assessments can be used to assess BPD; however many do not capture the core 
components across all types of presentation. 
 
Whether primary or secondary, BPD is not uncommon. The Nijmegen Questionnaire (NQ) is a self-completed 
questionnaire of 16 items, developed to assess hyperventilation but commonly used to evaluate the presence 
of BPD7. Among patients registered with a UK general practice, positive responses to the NQ were received 
from 8% of 208 adults without respiratory disease8, and from 29% of 227 adults being treated for asthma9; the 
overall prevalence of BPD measured in this way was 9.5%8. This figure is likely to be an underestimate of the 
true prevalence, as the NQ may not capture all types of BPD, it being an assessment of hyperventilation which 
may only be one form of BPD10; further, it can be scored higher in patients with physiological breathlessness 
and higher levels of anxiety11. 

 
 
 
BPD is a complex and burdensome condition; those with the condition report worse physical functioning scores 
than those with severe asthma12, and are more anxious, with a poorer health related quality-of-life13. BPD is 
likely to be a key consequence of COVID-19 due to the disease’s impacts on (cardio-)respiratory physiology, de-
conditioning, and anxiety over prolonged recovery. The British Thoracic Society recommends that patients 
hospitalised with COVID-19 should, after discharge, have their breathing pattern assessed by a 
physiotherapist14. 
 
4.2 
PRE-CLINICAL DATA/CLINICAL DATA 
In 2016, I led the development of a straightforward, practical instrument to improve the consistency of BPD 
assessment15. The Breathing Pattern Assessment Tool (BPAT) is a tabulated means of collating data from a 
physiotherapy assessment. The tool was developed within our specialist centre by expert physiotherapists and 
was piloted in assessment clinics to support the diagnosis of BPD in a ‘severe asthma’ population. In 
preliminary testing, patients with BPD (with or without asthma) had a higher BPAT score compared with those 
with no BPD (as assessed by a physiotherapist)1. More specifically, it is suggested that the BPAT has clinical 
utility in patients with severe asthma or unexplained breathlessness, with a score of >4 indicative of BPD15. The 
BPAT appears to demonstrate face validity by its uptake nationally and internationally within asthma services, 
and more recently within post-Covid clinics to help with screening of patients for treatment of BPD16,17. Data 
from the UCLH Covid clinic (n=280), for example, show that 20% of patients had a BPAT score >4 with 90 of 
them being referred for (virtual) specialist physiotherapy treatment, and improvements in BPAT scores 
following four sessions of care18. Unpublished data from a private clinic in London showed that in 172 patients 
referred for post Covid management, average BPAT scores were 6.3 and NQ was 31 (Julie Moore, personal 
communication). Eighty three percent of patients showed improvements in these scores after eight weeks of a 
multidisciplinary intervention.  Additional data have shown further validity of the BPAT compared to alternative 
objective assessments of BPD19 and reliability between clinicians20 including over a virtual platform21 which will 
be important within an environment of social distancing and ‘virtual’ delivery of therapies.  
 
4.3 
STUDY RATIONALE AND RISK/BENEFIT ANALYSIS 
The manifestations of BPD are readily misinterpreted – by both patients and clinicians – as those of asthma or 
similar respiratory diseases2. This leads to prescriptions of medications that are neither required nor effective, 
including inhaled or oral steroids1. Furthermore, BPD frequently amplifies other respiratory conditions, 
increasing the likelihood of excess prescriptions and the misuse of prescribing budgets*. In Covid-19 follow-up 
clinics, a high proportion of patients complain of disproportionate breathlessness, alongside symptoms of 
fatigue and decreased exercise tolerance18.  While most post-Covid clinics are requesting a physiotherapy 
assessment of BPD as a key management step, diagnosis is hampered by there being no universally accepted 
terminology or method of assessment1 since most tools do not capture the core components of BPD. 
Moreover, BPD does not always present in the same way, a heterogeneity that may further lead to inconsistent 
assessment*. 
 
Breathing exercises, delivered by physiotherapists, are first line treatments for BPD22 although with limited 
evidence of their efficacy from high quality trials23. In the UK, current physiotherapy approaches are multi-
component, advising modification of breathing pattern through manipulation of tidal and minute volumes, and 
encouragement of nasal and lower rib cage/abdominal respiration24. Clinical experience repeatedly shows the 
impact on, and relief to, individuals of a diagnosis of BPD by a physiotherapist, even before functional 

 
 
improvements are seen with therapy. A Cochrane review on breathing exercises in asthma23 suggested 
interventions from physiotherapy breathing re-education impact positively on QoL – although with low quality 
evidence. Interest has recently increased following an NIHR HTA-funded RCT in patients with asthma showing a 
trend for a reduction in healthcare costs and improvements in quality of life24. The data did not include the 
prevalence of patients with BPD, in whom it is probable that there would have been the greatest 
improvements. 
 
Breathing Pattern Disorder (BPD) is an important condition. It is associated with significant morbidity and can 
be treated with physiotherapy. Limited evidence exists regarding how best to assess and recognise BPD, which 
may limit the opportunity for patients to be referred promptly to services to receive the care they need. 
Additionally, the terminology used for this condition and its different presentations has limited consistency 
which hampers both its referral and assessment. There are promising reports of the validity and utility of the 
BPAT, there is a need for further examination of its measurement properties which this protocol aims to 
evaluate.  
 
 
4.4 
MANAGEMENT OF POTENTIAL STUDY RISKS 
This study does not raise significant risk management issues as the assessments and treatments are part of 
usual care. Careful consideration has been given to management of data which will be stored and managed 
exclusively on a password protected server at the Royal Brompton Hospital which is backed up every 24 hours. 
There is a Serious Adverse Event (SAE) protocol in situ to deal with adverse events that may occur during the 
duration of this research. Additionally careful thought has been given to the numbers of outcome measures the 
patients are required to complete and have minimised this where possible. Discussion with lay representatives 
have suggested that if the questionnaires/assessments are justified they are happy to complete them. 
5. STUDY OBJECTIVES 
5.1 
PRIMARY OBJECTIVE 
Objectives of the Study 
 
 
To determine the reliability of the BPAT between visits and between clinicians 
 
To determine the associations of the BPAT with other routine assessment tools used in BPD 
assessment   
 
To determine the responsiveness of the BPAT to physiotherapy intervention  
 
To determine the change over time in BPAT and other assessments (3 months)   
 
5.2 
SECONDARY OBJECTIVES 
 
To evaluate other measurements of BPD and their usefulness in monitoring the effects of treatment for 
BPD 
 
To determine the feasibility of recruitment, follow up and retention of patients, and recording 
completed assessments (to inform future trial design)  
 
To evaluate the validity and acceptability, to patients and clinicians, of assessments for BPD  
 

 
 
6. STUDY DESIGN 
 
6.1 
OVERALL DESIGN 
This study is a non-commercial study completed as part of a NIHR Doctoral fellowship.  
 
Stage One 
A mixed methods questionnaire study where patients will be recruited directly from physiotherapy referrals 
and will receive the usual care as part of the physiotherapy service for BPD in the trust. Assessments at 
baseline, end of treatment and at follow-up will be utilised to answer the study questions. The physiotherapist 
completing the baseline, end of treatment and follow up assessments will be blinded to both the physiotherapy 
assessment and intervention. Additionally, physiotherapist one, two and three (who will separately complete a 
BPAT assessment on the same patient) will be blinded to each other’s BPAT score. All visits will be in line with 
usual care for this cohort of patients with the exemption of visit one which will be additional to collect inter-
visit reliability data. The healthy controls will also be required to complete assessments, however these will all 
be in line with assessments usually completed in standard physiotherapy assessments. 
 
A subsequent qualitative study with in-depth interviews will run directly after study 1, with a sample of patients 
who completed the assessment and treatments within the study protocol. Additionally, a convenience sample 
of physiotherapists who delivered the assessment or treatment aspects will be invited to take part. The 
experiences of physiotherapists’ (n=5) and patients’ (n=5) participation in the study will be explored in indepth, 
semi-structured interviews. Specifically, experiences of the BPAT assessment and outcome measures will be 
explored.  
 
6.2 
TREATMENT AND RATIONALE 
 
Stage One 
This is a study evaluating the BPAT which is used as part of usual care. Patients will not be receiving additionally 
interventions or treatment. Data will be collected as part of usual care for the assessment and treatment of 
BPD. 
 
All patients recruited to the study will complete usual care as currently delivered within the service at the Royal 
Brompton Hospital. All sessions will be completed by physiotherapist at Band 6 and above (2-5 years of 
experience within respiratory physiotherapy), who will have completed departmental competencies in the 
assessment treatment of BPD. There will be an assessment and treatment guide for the physiotherapy staff to 
follow at each stage based on current clinical practice. This will aim to guide the assessment and treatment 
content but will not be a prescription of specific components. Therefore, the clinicians will be able to include an 
individually tailored programme of treatment as they do in usual care. This study is not investigating the 
treatment intervention, merely the response of the outcome measures after this intervention.  
 
Patients will only be considered for final assessment and follow-up once they have completed 4 treatment 
sessions of physiotherapy. The patients who drop out of the study will still be included in the results and where 
able, the reason for dropping out/incomplete treatment will be collected in line with current service reporting. 
 

 
 
Stage Two  
Patients will be participating in the focus group only and not receiving any additional treatment. 
 
6.3 
SCHEMATIC OF STAGE 1 DESIGN  
 
Referred for OP Physiotherapy
Baseline Data
N=100 patients
BPAT Ax: Physio 1 and Physio 2 complete independently
Physio3 completes: BPAT via video recording
2nd Visit
Repeat BPAT Score Physio2
Full Physiotherapy Ax as per usual care
Physio completes outcome questions
Participants complete sessions 2, 3, 4, 5 as per usual care
1-hour sessions of standard physiotherapy intervention for BPD
Final Data collection on last visit (session 5)
Physio2 completes: BPAT and final 
assessments (usual care)
Physio and Clinician complete Global rating 
change scale 
No of patients not appropriate
No of patients declined
Qualitative study
N=5 patients and n=5 physiotherapists
In depth interviews completed
3-month review
Patient completes usual care questionnaire
Physiotherapist completes: BPAT (virtual or 
F2F)
Healthy controls
N=50
Participant complete: NQ, D-12, SEBQ,  
Physio completes:  BPAT
 
 
 
7. ELIGIBILITY CRITERIA 
7.1 
INCLUSION CRITERIA 
Patients with BPD 
Adults aged above 18 years 
Outpatient referrals for ‘unexplained breathlessness’ or possible breathing pattern disorder 
Primary BPD (no other respiratory or cardiology diagnosis)  
Secondary BPD (patients with a diagnosis of another respiratory diagnosis including asthma or UA diagnosis) 
Able to complete up to four sessions of outpatient physiotherapy intervention  
 
Healthy Control 
Recruited from relative/significant other accompanying the study participant 
Hospital staff 
No respiratory or cardiac diagnosis 
 
Patients with Asthma 
Attending SARA Clinic 

 
 
Diagnosis of Asthma 
No Diagnosis of BPD 
  
Stage Two  
 
Participants from stage 2 who completed the assessment and treatments of their BPD. Physiotherapists who 
have delivered the assessment and/or treatment aspects of BPD management 
 
7.2 
EXCLUSION CRITERIA 
Stage One 
 
Patients 
Patients with a respiratory diagnosis including COPD, ILD, Bronchiectasis and Cystic Fibrosis 
Pregnancy 
Unable to give informed consent 
Anyone currently participating in pulmonary/cardiac rehabilitation  
Anyone currently receiving treatment from a speech and language therapist for an upper airway’s diagnosis 
(e.g., Inducible Laryngeal Obstruction ILO or Laryngeal hypersensitivity syndrome (LHS) 
 
Healthy Control and patients with asthma 
Not meeting inclusion criteria 
 
 
7.3 
DISCONTINUATION/WITHDRAWAL OF PARTICIPANTS AND STOPPING RULES 
All information collected in the process of this study will be retained for data analysis, including information 
about those not completing treatment and where possible the reason why they have withdrawn. Subjects will 
only be withdrawn from the study if they have expressed not wanting to continue or if another diagnosis or 
symptoms prevents them from completing and the clinician feels this will limit their response (e.g. A diagnosis 
of an acute illness). 
8. SUBJECT/PATIENT RECRUITMENT PROCESS 
Patient recruitment at a site will only commence once the study team has ensured that the following 
approvals/essential documents are in place:  
 
1. Health Research Authority (HRA) approval,  
2. Local Site Delegation of Duties and Signature Log is completed (if applicable). 
 
Stage One 
 
A convenience sample of patients referred to physiotherapy outpatient services of Royal Brompton Hospitals 
for BPD or unexplained breathlessness, over a 22-month recruitment period will be recruited. This sample will 
include 100 participants to ensure there are adequate numbers within any subgroup analyses.  
 

 
 
Healthy control patients will be recruited from a convenience sample of a relative/significant other 
accompanying the study participant and will attend for one visit to complete a BPAT and other measurements. 
Permission will be requested from the participant to approach them prior to consenting. 
 
Asthma control patients will be recruited from the Systematic Assessment of Asthma Clinic and data used from 
their completed usual care assessment. These patients will not be required to attend for any additional visits. 
 
The medical staff referring to physiotherapy will be made aware of the study so they can inform the patients 
they may be contacted about it once the referral is received by the physiotherapy department.  
 
The chief investigator will contact the patient whilst they are on the waiting list for physiotherapy to check if 
they are suitable and to ask them if they are happy to take part in the study. If they are then the CI will 
email/post them information about the study for them to consider prior to booking in of sessions. 
 
If the patients are willing to take part, their session of physiotherapy (assessment sessions and treatment [visit 
1-5]) will be block booked into the physiotherapy diary. 
 
Study Two  
Convenience sampling of participants from study 2 who completed the assessment and treatments within the 
study protocol. Additionally, a convenience sample of physiotherapists who have delivered the assessment 
and/or treatment aspects will be invited to take part. Demographic data for the physiotherapists (age, gender, 
current NHS band, years of experience in BPD) and participants (age, gender, respiratory diagnosis, BPAT score, 
employment) will be recorded.   
 
9. STUDY PROCEDURES  
9.1 
INFORMED CONSENT 
All stages 
Consent to enter either studies will be obtained after a full account has been provided of its nature, purpose, 
risks, burdens and potential benefits, and the patient has had the opportunity to deliberate. The patient will be 
allowed to specify the time they wish to spend deliberating, usually up to 24 hours.  
 
A copy of the signed Informed Consent Form along with a copy of the most recent approved Participant 
Information Sheet (PIS) will be given to the study participant. The original signed consent form will be retained 
at the study site (one filed in the medical notes and one field in the Study Master File (SMF)). A copy of the 
consent form will also be given to the participant. 
  
Once a patient is referred to physiotherapy their data is kept on hospital systems including Anglia Ice and excel 
databases. The CI will review the individual’s data against the inclusion and exclusion criteria. If they are eligible 
for inclusion in the study the CI will make, contact with the individuals and ask if they are interested in taking 
part. 
 
9.2 
RANDOMISATION PROCEDURE 

 
 
This section does not apply  
 
9.3 
EMERGENCY UN-BLINDING 
This section does not apply  
10. STUDY ASSESSMENTS 
10.1 SCREENING ASSESSMENTS 
No formal assessments will be included, however information from the referral and collected within the 
electronic record will be utilised to screen the patient for inclusion and exclusion criteria. 
 
10.2 BASELINE ASSESSMENTS 
 
Stage One 
 
Physiotherapist will complete a BPAT score in addition to the assessments completed in usual care. The BPAT is 
a Clinician completed tool to look at components of breathing pattern assessment. It is a tabulated means of 
collating data obtained at respiratory physiotherapy assessment. Assessment components include (i) 
evaluation of chest/abdominal wall movement, noise of (ii) inspiratory and (iii) expiratory flow, (iv) channel of 
inspiration and expiration, (v) signs of air hunger (yawning, sighing and deeper breaths), (vi) RR and (vii) 
rhythm. Each component is given a score from 0 to 2, based on features consistent with expected normal (0) 
versus that present in severe DB (2), giving a total score of between 0 and 14. The BPAT is completed with a 
patient positioned, as per the standard assessment of resting breathing pattern (i.e., sat comfortably in a 
supported seat for at least 5 min) and takes approximately 1 min to collate. 
 
 
Stage Two  
 
No measurements will be taken from individuals in this study 
 
 
10.3 TREATMENT PROCEDURE 
Stage One 
 
Visit 1: Research Visit for administration of BPAT 
 
Participants (including both patients and healthy controls) will attend for an initial research visit. At the 
beginning of the assessment, two physiotherapists (physio-1 and physio-2) separately and simultaneously 
complete a BPAT score. The patient will be asked to sit quietly in the chair while this is being completed. To 
reduce the patient’s conscious awareness of their breathing being checked, physio-1 will ‘take their pulse’ 
whilst completing the BPAT score at the same time as physio-2, by observing their breathing for two minutes. 
This section of the assessment will be video recorded to enable a third physiotherapist (physio 3) to complete a 
BPAT score from this recording. This will be the only visit completed by the Healthy Control patients 

 
 
 
NB: Data for asthma controls will be collected from the Systematic Assessment of Asthma Clinic (SARA) where, 
as part of usual care, patients get a physiotherapy assessment alongside a NQ, SEBQ, D-12 and BPAT. No 
additional visit will be required for this group. 
 
Visit 2: Usual Care 
All patients will attend for a second appointment between one and three weeks later (in line with usual care) 
where physio-2 will complete a second BPAT within their standard physiotherapy assessment and will confirm 
the presence/absence of BPD, through both objective and subjective observation. The physiotherapist will be 
asked to record their decision by completing “Outcome Questions” which ask them to rate on a visual analogue 
scale how likely it is that the individual has BPD.  
 
10.4 SUBSEQUENT ASSESSMENTS 
Stage One 
 
Visits 2-5: Usual Care 
All patients with physiotherapy-confirmed BPD will complete a course of four sessions outpatient 
physiotherapy intervention as part of usual care for this treatment pathway.  
 
Visit 5: End of Treatment  
Patients will complete their final session and completion of outcomes as per usual care. Patients will be asked 
to rate their change in breathlessness following intervention using a using a seven point Global Rating of 
Change Questionnaire (GRCQ) according to the following responses: “:1: Much better”; “2: Better”; “3: A little 
better”; “4: The same”; “5: A little worse”; “6: Worse” and “7: Much worse”. The physiotherapist (physio 2) will 
record their own evaluation of the patient’s response to the treatment using the same scale. Additionally, the 
patient will be invited to explain the reason for their answer in a free text box; this text will be recorded 
anonymously. 
 
Visit 6: Follow up 
Patients will be followed-up (remotely or in person as per patient request) at three months and physio-1 will 
complete a BPAT score. This is an additional visit to usual care. 
 
Study Two  (visit 7 for those recruited) 
The experiences of physiotherapists’ (n=5) and patients’ (n=5) participation in the study will be explored in in-
depth, semi-structured interviews lasting 30-60 minutes, conducted face-to-face or via digital platform 
according to national guidance and individual preference. All interviews will be audio/visual recorded, 
Specifically, experiences of the BPAT assessment and outcome measures will be explored. A framework of 
questions informed by literature will be developed with oversight from the Study Advisory Group who will 
review the interview guide created.  
11. METHODS 
11.1 Laboratory Procedures 
This is not appropriate for this study design 

 
 
 
 
11.2 Radiology or any other procedure(s)  
Not required in this study 
Techniques and Interventions 
 
Tools 
Not required in this study 
 Study Drugs  
 
Not in this study 
 
11.3 DEFINITION OF THE END OF STUDY 
Stage One 
The end of the study will be when the individual has completed all assessments at baseline, end of treatment.  
 
Stage Two  
When the participant(s) recruited have completed the in-depth interviews 
12. SAFETY REPORTING 
12.1 DEFINITION 
Adverse Event (AE) — any untoward medical occurrence in a patient or clinical study subject who is 
administered a treatment, and which does not necessarily have a causal relationship with this treatment (i.e. 
any unfavourable or unintended change in the structure (signs), function (symptoms), or chemistry (lab data) in 
a subject to whom a treatment/study procedure has been administered, including occurrences unrelated to 
that product/procedure/device). 
Serious Adverse Event (SAE) – is defined as an untoward occurrence that: 
 
Results in death; or  
 
Is life-threatening (places the subject, in the view of the Investigator, at immediate risk of 
death) 
 
Requires hospitalization or prolongation of existing hospitalization (hospitalisation is defined 
as an inpatient admission, regardless of length of stay; even if it is a precautionary measure for 
observation; including hospitalisation for an elective procedure, for a pre-existing condition) 
 
Results in persistent or significant disability or incapacity (substantial disruption of one’s ability 
to conduct normal life functions) 
 
Consists of a congenital anomaly or birth defect (in offspring of subjects or their parents taking 
the study drug regardless of time of diagnosis) 
 
Is otherwise considered medically significant by the investigator. 
 

 
 
Important medical events that may not be immediately life-threatening or result in death or hospitalisation but 
may jeopardise the subject or may require intervention to prevent one of the outcomes listed in the definition 
of serious will also be considered serious. 
 
12.2 RECORDING ADVERSE EVENTS (AES) 
 
All Adverse Events (AEs) will be recorded in the hospital notes and Case Report Form (CRF).   
If the Investigator suspects that the disease has progressed faster due to the administration of the study 
treatment/procedure, then he/she will report this as an unexpected adverse event to the Sponsor and the REC 
as detailed in Section 12.6.  
 
12.3 ASSESSMENT OF SAES 
Classification and causality of Adverse Events (AEs) will be conducted by local PIs and reviewed by CI. The CI 
cannot downgrade the site PI’s classification and if there is disagreement which cannot be resolved during 
formal discussion then the assessment of the site PI will be accepted. The CI, can however, upgrade the 
seriousness of an event without consultation with the site PI. 
12.4 EXPECTED AES  
REPORTING OF SAES TO THE SPONSOR AND THE REC 
The CI and their research team at RBHT are responsible for reporting SAEs to the Research Office immediately 
and/or within 24 hours of becoming aware of the event in accordance with the process outlined below.  
 
An SAE occurring to a research participant will be reported to the Research Ethics Committee (REC) that 
gave a favorable opinion of the study, the study Sponsor (RB&HFT Research Office) and the local R&D 
Office where in the opinion of the CI/PI the event was:   
 
 
‘Related’: that is, it resulted from administration of any of the research procedures; and  
 
‘Unexpected’: that is, the type of event is not listed in the protocol as an expected occurrence.  
 
Reports of related and unexpected SAEs will be submitted to the REC within 15 days of the CI/PI becoming 
aware of the event; using the SAE reporting form for non-CTIMPs published on the HRA website and entitled 
non-CTIMP safety report to REC. The form should be completed in typescript and signed by the Chief 
Investigator (CI) prior to submission to the REC.  
 
Reports of SAEs in double-blind studies should be un-blinded.All SAEs that are to be reported to the REC should 
also be forwarded to the Research Office in parallel and must be recorded, signed and dated by the 
Investigator at site. Research Office accepts study specific SAE forms, HRA SAE Form or RB&HFT template SAE 
Reporting Form available here.  
 
Information can be submitted to the Research Office in electronic format: 
 
E-mail: research.reporting@rbht.nhs.uk. 
 
Following submission by the CI, the coordinator of the main REC will acknowledge receipt of safety reports 
within 30 days. It is the responsibility of the CI and his/her research team to send a copy of the SAE notification 
and acknowledgement receipt to the Research Office.    

 
 
 
The research team also has the responsibility to report SAEs occurring in a certain period (28 days) after a 
patient completes the study. Any SAEs reported to the Investigators during this phase must be documented in 
the patient’s medical notes and submitted via an SAE reporting form. 
 
12.5 THE TYPE AND DURATION OF FOLLOW UP 
12.6 PREGNANCY 
Not applicable to this study 
12.7 ANNUAL PROGRESS REPORTS (APRS) 
The Chief Investigator will prepare the APR for the study. It will be reviewed by the RO and sent to the REC by 
the CI within 30 days of the anniversary date on which the favourable opinion was given by the REC, and 
annually until the study is declared ended. 
12.8 REPORTING URGENT SAFETY MEASURES 
The Sponsor and/or the Investigator may take appropriate urgent safety measures to protect the subjects of a 
clinical study against any immediate hazard to their health or safety. If safety measures are taken, REC approval 
is not required before the measure is taken.  
The Investigator will immediately and in any event no later than 3 days from the date the measures are taken, 
give written notice to the REC and the study Sponsor of the measures taken and the circumstances giving rise 
to those measures. 
In order to prevent any delays in the reporting timelines the Sponsor has delegated this responsibility to the 
CI/PI. Therefore, the CI/PI must report any urgent safety measures to the REC directly, and in parallel to the 
Sponsor. The REC coordinator will acknowledge receipt of urgent safety measures within 30 days.  
13. DATA MANAGEMENT AND QUALITY ASSURANCE 
13.1  CONFIDENTIALITY  
All data will be handled in accordance with the Data Protection Act (2018), NHS Caldecott Principles, The UK 
Policy Framework for Health and Social Care Research, and the condition of the REC approval. 
 
The Case Report Forms (CRFs) will not bear the subject’s name or other personal identifiable data. The 
subject’s study Identification Number (ID) will be used for identification. 
 
No data will be shared with any external organisation without appropriate consent and data sharing agreement 
in place, as applicable. 
 
13.2  DATA COLLECTION TOOL  
Case Report Forms (CRF) will be designed by the CI and the final version will be reviewed and discussed with 
the study Sponsor. All data will be entered legibly in black ink with a ball-point pen.  If the Investigator makes 
an error, it will be crossed through with a single line in such a way to ensure that the original entry can still be 
read. The correct entry will then be clearly inserted. The amendment will be initialled and dated by the person 
making the correction immediately. Overwriting or use of correction fluid will not be permitted. 

 
 
 
It is the Investigator’s responsibility to ensure the accuracy of all data entered and recorded in the CRFs. The 
Delegation of Responsibilities Log will identify all study personnel responsible for data collection, entry, 
handling and managing the database. 
 
 
13.3 DATA HANDLING AND ANALYSIS 
All data will be handled in accordance with the Data Protection Act (2018), NHS Caldecott Principles, The UK 
Policy Framework for Health and Social Care Research, and the condition of the REC approval. Case report files 
will be completed digitally. They will be accessed, completed, and stored on the network drive at the Royal 
Brompton Hospital and Imperial College which is backed up every 24 hours. Access to the NHS and university 
computers requires usernames and passwords. Further access to particular network drives requires permission 
from senior line managers. Files within the limited access network drive will be password protected.  
All data will be anonymised, and patient information removed. The focus group, nominal group and in-depth 
interview audio recordings will be immediately saved to the chief investigators personal drive on the NHS or 
Imperial College network. The transcription of these recordings will also be anonymised and saved in a 
password protected file 
Files transferred electronically will be anonymised/encrypted and password protected and emailed through 
secure email addresses. No data will be shared with any external organisation without appropriate consent and 
data sharing agreement in place, as applicable. This is explained in the information sheet and consent form. 
13.4 ARCHIVING ARRANGEMENTS 
The study documents (including the Study Master File (SMF), Case Report Forms (CRFs), Informed Consent 
Forms along with the study database) will be kept for a minimum of five years. They will be stored in locked 
offices within the Royal Brompton and Harefield Hospitals. The CI is responsible for the secure archiving of 
study documents. The study database will also be kept electronically on the RB&HFT computer network, for a 
minimum of five years.  
 
The approved repository for longer retention of local materials for studies that involve RB&H patients is Box-It 
Storage UK. The study documentation will be prepared for archiving by the research team in line with the 
Research Office Archiving SOP and the transfer will be arranged by the Research Office.  
14. STATISTICAL DESIGN 
14.1 SAMPLE SIZE AND RECRUITMENT 
 
A convenience sample of patients referred to physiotherapy outpatient services of Royal Brompton Hospitals 
over a 20-month recruitment period for BPD or unexplained breathlessness. This sample will include 100 
participants to ensure there are adequate numbers within any subgroup analyses. Recruitment will occur over 
a 22-month period; we anticipate recruiting 6-8 participants each month. I am in a strong position to achieve 
this as I sit within a renowned, specialist institution with a high patient throughput of approximately 40 
patients referred per month at Royal Brompton alone. 

 
 
  
Participants will be approached by members of their clinical team initially, asked if they are interested in taking 
part and if so, given the PIS to read. At this point their details can be passed to the research team if they wish 
to participate. 
 
Sample size calculations: 
Inter rater reliability 
This calculation assumed a single-measure ICC framework with two ratings per participant (Physio 1 is always 
the same, physio 2 pool of 4), 80% power, alpha 0.05, and a minimum acceptable ICC of 0.85, resulting in a 
required sample of 25 participants.  
 
Intra visit relaibility 
The same physiotherapist assesses participants on both occasions; therefore, this analysis plans to use a two-
way mixed-effects, single-measure ICC model, ICC(3,1). As no prior estimate was available for between-visit 
reliability, a more conservative expected ICC of 0.90 was assumed. Using a minimum acceptable ICC of 0.80, 
80% power, and alpha 0.05, the required sample was 58 participants. 
 
Construct validity (associations with other measures) 
To detect moderate correlations between symptom and breathlessness scores (r = 0.30 to 0.40) requires 47-85 
participants. 
 
Construct validity (distinguish between groups) 
Using a standard one-way ANOVA with 3 groups (BPD n=100/Asthma n=25 /HC n=25), alpha 0.05, and power 
0.80, the required total sample is approximately 63 total (21 per group) assuming a large effect size (f=0.4) 
 
Stage Two  
 
Participants who have completed stage Two will be invited to take part in the qualitative study 
 
 
14.2 ENDPOINTS 
14.2.1 Primary endpoints 
Stage One 
 
The primary end points will be baseline assessment data for the outcome measures previously described for 
100 participants. This includes BPAT data from visit 1 and visit 2, between clinician data and BPAT data 
compared to other completed outcome measures including NQ, D-12, SEBQ, BH, 6MWT, & MARM. Additionally 
change in BPAT, post physiotherapy intervention will also be collected.  
 
Study Two  
Acceptability of the BPAT to clinicians, measured by qualitative analysis 
 
14.3.1 Secondary endpoints 
 

 
 
Study One 
 
 
Change in NQ, SEBQ, D-12, EQ5D5L, BH, exercise test, MARM post physiotherapy intervention. 
 
No of patients recruited, number of patients completing follow up, number of outcome measures 
completed 
 
14.3 STATISTICAL ANALYSIS PLAN 
 
Analysis will be carried out according to a statistical analysis plan developed by Winston Banya, Trust 
Statistician at Royal Brompton Hospital, using STATA. Analysis will be on an intention to treat basis. A p value of 
<0.05 will be taken to be significant. 
 
14.3.1 Primary endpoint analysis 
 
Study One 
 
Reliability 
Reliability will be assessed using the single measure, intra-class correlation co-efficient (ICC) of consistency. 
Measurement variability will be determined by calculating the standard error of measurement (SEM) and 
percentages of standard errors of the measurements (SEM%). This will be completed from data collected for 
intra-visit and inter-visit BPAT scores for all participants Cronbach’s alpha will be used to assess internal 
consistency of the BPAT tool, and Cohen’s kappa to further evaluate the qualitative agreement between 
physiotherapists completing the BPAT. Time between the two BPAT assessments will be recorded and included 
in the analysis. 
 
Validity 
Validity will be evaluated for all group data, with several factors including intercorrelation between BPAT 
scores, and convergent and discriminate validities by examining relationships with other measures to assess 
BPD (NQ, SEBQ, D-12, MARM and BH). The ability of BPAT to detect BPD will be assessed in a receiver operating 
characteristic analysis with estimates of sensitivity and specificity at relevant cut-off points, determined by the 
Youden Index. Regression analysis will assess the determinants associated with high/low BPAT scores. If 
normally distributed data multiple linear regressions will be completed from the raw scores. If non normal 
data, then logistics regression will be performed on a categorised variables with a BPAT of >4 being counted as 
high and BPAT< as low.   
 
Responsiveness 
To analyse the responsiveness to the intervention, the primary outcome will be the change before and after 
treatment in the BPAT score. Secondary outcomes including a change before and after treatment in NQ, D-12, 
SEBQ, EQ5D5L and GRCQ will also be reviewed. All outcomes will be analysed as both continuous and 
categorical (in this case binary). When considering the outcomes as continuous, linear regression will be used 
to assess the effectiveness of the intervention. When considering the outcomes as categorical, they will be 
categorised as either ‘improvement’ or ‘no improvement’. Improvement will be defined for all variables as an 
increase in the score of 1 or more, and no improvement will be defined as either no change in the score or a 
decrease in the score. For the binary outcomes, logistic regression will be used to assess the effectiveness of 

 
 
the intervention. Finally, all regression models will be conducted as both univariable analysis and multivariable 
analysis, adjusting for gender, age and asthma 
 
Effect Size 
Effect sizes (ES) are the most used method for interpreting and comparing changes in questionnaire scores and 
are calculated by measuring the difference between the mean scores pre- and post-intervention and dividing 
this value by the standard deviation of the pre-intervention score. A standard unit of measurement is then 
assigned to change in health status which helps with interpretation and comparison with other measures. The 
standardized response mean (SRM) is similar to the ES and is calculated by dividing the mean change in scores 
by the standard deviation of change in score. E and SRMs for the BPAT and other validated scores for all 
patients who completed measures at timepoint 1 and timepoint 2 will be reported on. 
 
Feasibility 
Feasibility outcomes will be collected, including number of patients eligible for inclusion, recruitment rate, 
adherence, retention rate and data completeness. 
 
Qualitative analysis 
 
Patient explanation for global rating of change will be explored with thematic analysis and presented 
descriptively.  
 
14.3.2 Secondary endpoint analysis 
 
Stage One 
 
Validity, Responsiveness and Effect Size 
All statistics (except for reliability) will be completed for the other standard outcome measures including NQ, 
SEBQ, D-12, exercise test, BH, MARM and EQ5D5L. 
 
Feasibility 
Feasibility outcomes will be collected, including number of patients eligible for inclusion, recruitment rate, 
adherence, retention rate and data completeness. 
 
Stage Two  
 
Interview recordings will be transcribed verbatim, checked for accuracy and pseudonymised. Scripts will be 
read and re-read, and a codebook developed. Thematic analysis will be applied and NVivo 10 software used to 
support code development and analysis.  
 
Taking a deductive approach codes and themes will be grouped into higher-order codes and domains. To 
increase rigour, a second researcher will independently conduct this process of analysis in a subset of 
transcripts; coding will be compared and discussed, and the codebook updated. Research reflexivity to alleviate 
bias pre- and post-interviews will be adhered to. An iterative process of data reduction, comparison, 
organisation and understanding through thematic analysis will be used to analyse each data source.  
 

 
 
 
14.4 RANDOMISATION 
Not applicable for this study design 
 
14.5 INTERIM ANALYSIS (IF APPLICABLE) 
Not applicable for this study design 
 
14.6 OTHER STATISTICAL CONSIDERATIONS 
Not applicable 
 
15. COMMITTEES INVOLVED IN THE STUDY 
My research timetable will be regularly reviewed with my supervisory team, who I will meet regularly either in 
person or via virtual calls. We will meet independently but also quarterly with all supervisors together. A Study 
Advisory Group (SAG) including the Principal Investigator (PI), supervisor(s), PPI representative(s) and PPI 
support from RBH, alongside relevant stakeholders will meet 2-3 times a year to monitor progress and 
performance throughout. A Professional Advisory Group (PAG) will additionally be created and used at various 
stages along the project when stakeholder engagement is required, including the dissemination plans.  
I will take the role of PI, with responsibility for the day-to-day running of the project including 1. Maintaining 
frequent communication with stakeholders, recruitment and consenting of all participants, leading the data 
collection and analysis with the support of the statistician, ensuring all stakeholders are regularly updated at 
key milestones (R&D, REC, NIHR, PPI groups), including financial departments Study Advisory Group (SAG)  
Study Advisory Group 
This group includes myself, my supervisors, two patients with BPD and a physiotherapist not involved in the 
study. The patient representatives have been approached and have agreed in principle. This group will meet 
regularly at time points set out in the study timetable (virtual and/or in person). They will have a key role in 
guiding, reviewing, and informing each step in the research process (see below).  
Professional advisory group (PAG)  
This group includes clinical expertise through representation from the Physiotherapy for BPD group in the UK 
and international representation from the Bradcliff breathing group. In addition, there will be representation 
from Asthma UK due to the impact of BPD in asthma.  
16. MONITORING AND AUDITING 

 
 
The requirement for study monitoring or audit will be based on the internal Research Office risk assessment 
procedure and applicable Standard Operating Procedures (SOPs). It is the responsibility of the RO to determine 
the monitoring risk assessment and explain the rationale to the study research team. 
 
Study monitoring and/or audit will be discussed with the CI before arrangements are made to conduct the visit.  
17. DIRECT ACCESS TO SOURCE DATA 
The Investigator(s)/institution(s) will permit study-related monitoring, audits, REC review, and regulatory 
inspection(s), providing direct access to source data/documents. Study participants are informed of this during 
the informed consent discussion. Participants will consent to provide access to their medical notes. 
18. ETHICS AND REGULATORY REQUIREMENTS 
The Sponsor will ensure that the study protocol, Patient Information Sheet (PIS), Informed Consent Form (ICF), 
GP letter and submitted supporting documents have been approved by the Health Research Authority (HRA) 
which includes Research Ethics Committee (REC) approval if applicable, prior to any patient recruitment taking 
place. The protocol and all agreed substantial protocol amendments, will be documented, and submitted for 
HRA approval prior to implementation. 
 
Before site(s) can enrol patients into the study confirmation of capacity and capability must be issued by the 
institution hosting the trial (unless HRA specifically has confirmed in the HRA approval letter that this is not 
required). It is the responsibility of the PI at each site to ensure that all subsequent amendments gain the 
necessary approvals by the participating site. This does not affect the individual clinician’s responsibility to take 
immediate action if thought necessary to protect the health and interest of individual patients. 
 
Within 90 days after the end of the study, the CI will ensure that the REC is notified that the study has finished. 
If the study is terminated prematurely, those reports will be made within 15 days after the end of the study. 
 
The CI will supply a final summary report of the clinical study to the REC and the Sponsor in parallel within 
one year after the end of the study.  
19. FINANCE 
This study is funded by the NIHR.  
20. INSURANCE AND INDEMNITY 
NHS bodies are liable for clinical negligence and other negligent harm to individuals covered by their duty of 
care. NHS Institutions employing researchers are liable for negligent harm caused by the design of studies they 
initiate.  
21. PUBLICATION POLICY 

 
 
Data ownership rights will lie with the institution sponsoring the study. 
 
 
22. STATEMENT OF COMPLIANCE 
The trial will be conducted in compliance with the protocol, Sponsor’s Standard Operating Procedures (SOPs), 
GCP and the applicable regulatory requirement(s). 
 
The study conduct shall comply with all relevant laws of the  UK country in which the study site is located 
including but not limited to, the Human Rights Act 1998, the Data Protection Act 2018, and with all relevant 
guidance relating to medicines and clinical studies from time to time in force including, but not limited to, the 
ICH GCP, the World Medical Association Declaration of Helsinki entitled 'Ethical Principles for Medical Research 
Involving Human Subjects' (2008 Version), the UK Policy Framework for Health and Social Care Research.    
 
This study will be conducted in compliance with the protocol approved by HRA and according to RGF standards. 
No deviation from the protocol will be implemented without the prior review and approval of the Sponsor and 
HRA except where it may be necessary to eliminate an immediate hazard to a research subject. In such case, 
the deviation will be reported to the Sponsor and the REC as soon as possible. 
 
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3. Courtney R. Breathing training for dysfunctional breathing in asthma: taking a multidimensional 
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in the community with and without asthma. Primary Care Respiratory Journal. 2005; 14:78-82. doi: 
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8. Thomas M. Prevalence of dysfunctional breathing in patients treated for asthma in primary care: cross 
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