Comparison of the Standard 6-Minute Maximal Speed Walk Test Against a 6-Minute Normal Speed Walk Test as an Alternative and More Accurate Assessment for Ambulatory Oxygen Requirement.
Phase: NA
Conditions: Respiratory Disease
Sponsor: Hampshire Hospitals NHS Foundation Trust

Protocol V2.0 February 2023  
 
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Version 2.0 February 2023 – Max_6MWT vs Nor_6MWT 
 
 
 
 
 
Comparison of the standard Maximal 6-Minute Walk Test 
against a Normal-speed 6-Minute Walk Test as an 
alternative and accurate assessment for ambulatory 
oxygen requirement 
 
Version 2.0 
February 2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This protocol has regard for the HRA guidance 
 

 
Version 2.0 February 2023 – Max_6MWT vs Nor_6MWT 
 
TITLE OF THE STUDY 
Comparison of the standard 6-Minute maximal speed Walk Test against a 6-Minute normal speed 
Walk Test as an alternative and more accurate assessment for ambulatory oxygen requirement. 
 
SHORT STUDY TITLE 
Comparing 6-Minute Walk Tests for Ambulatory Oxygen Assessment V1 
 
PROTOCOL VERSION NUMBER AND DATE 
Version Number 
Date 
Summary of changes 
1.0 
19.08.2022 
Initial full study protocol. 
 
1.1 
26.09.2022 
Adjustment of titles and description of maximal 
6MWT to ensure compliance with international 
guidelines. Addition of outline of performing 
6MWT. 
1.2 
02.11.2022 
Revisions based on provisional opinion from the 
REC, including clarification of data protection 
and academic collaborations. 
2.0 
01.02.2023 
Amendment of 6MWT instruction to match most 
recent published guidance. Amendment of 
exclusion criteria 
 
RESEARCH REFERENCE NUMBERS 
 
IRAS Number: 
306758 
 
SPONSORS Number: 
2022 SPON-HG-0922 
 
FUNDERS Number: 
2022 SPON-HG-0922 
 
 

 
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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 Internal Conference on Harmonisation Good 
Clinical Practice (ICH GCP) standards, 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. 
 
For and on behalf of the Study Sponsor: 
Signature:  
Siobhan Laws 
 
Date: 
02/09/2022 
Name (please print): 
Siobhan Laws 
 
 
Position: R&D Director 
 
 
 
Chief Investigator: 
Signature:  
 
 
Date: 
05/09/2022 
Name: (please print): 
Harry Griffin 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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LIST of CONTENTS 
GENERAL INFORMATION 
Page No. 
RESEARCH REFERENCE NUMBERS 
 
i 
SIGNATURE PAGE 
ii 
LIST OF CONTENTS  
iii 
KEY STUDY CONTACTS 
iv 
STUDY SUMMARY 
iv 
FUNDING 
 
v 
ROLE OF SPONSOR AND FUNDER 
v 
PROTOCOL CONTRIBUTORS 
vi 
STUDY FLOW CHART 
 
vii 
STUDY PROTOCOL 
1. BACKGROUND 
 
1 
2. RATIONALE 
 
2 
3. THEORETICAL FRAMEWORK 
3 
4. RESEARCH QUESTION/AIM(S)  
4 
5. STUDY DESIGN/METHODS 
5 
6. STUDY SETTING 
5 
7. SAMPLE AND RECRUITMENT 
6 
8. ETHICAL AND REGULATORY COMPLIANCE 
8 
9. DISSEMINATION  POLICY 
11 
10. REFERENCES 
11 
11. APPENDICES 
12 
 
 

 
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KEY STUDY CONTACTS 
Chief Investigator 
Dr Harry Griffin 
Lead Respiratory Physiologist 
Hampshire Hospitals NHS Foundation Trust 
Basingstoke RG24 9NA 
Email: harry.griffin@hhft.nhs.uk 
Principle Investigator 
Dr Michael Hughes 
Trainee Clinical Scientist 
Hampshire Hospitals NHS Foundation Trust 
Basingstoke RG24 9NA 
Email: michael.hughes@hhft.nhs.uk 
Academic Supervisor (MSc Project 
for Dr Michael Hughes) 
Professor Dilwyn Marple-Horvat  
Professor of Motor Neuroscience 
Faculty of Science and Engineering 
John Dalton Building 
Manchester Metropolitan University 
M15 6BH 
Email: D.E.Marple-Horvat@mmu.ac.uk 
Academic advisor 
Professor James Faulkner 
Faculty Head of Research and Knowledge Exchange, Health 
and Wellbeing  
University of Winchester 
Sparkford Road, SO22 4NR 
Email: James.Faulkner@winchester.ac.uk 
Study Co-ordinator 
Victoria Corner 
Sponsor 
Hampshire Hospitals NHS Foundation Trust 
Basingstoke RG24 9NA 
Funder(s) 
Hampshire Hospitals NHS Foundation Trust 
Basingstoke RG24 9NA 
 
STUDY SUMMARY 
 
Study Title 
Comparison of the standard Maximal 6-Minute Walk Test 
against a Normal-speed 6-Minute Walk Test as an alternative 
and accurate assessment for ambulatory oxygen 
requirement. 
Internal ref. no. (or short title) 
Maximal-speed vs Normal-speed 6MWT for ambulatory 
oxygen assessment. 
Study Design 
Randomised crossover trial of patients referred for a standard 
Maximal 6-Minute Walk Test (Max_6MWT) where half of 
patients will perform the standard Max_6MWT followed by a 
Normal-speed 6-Minute Walk Test (Nor_6MWT) and the 
other half a Nor_6MWT followed by Max_6MWT. 

 
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Study Participants 
Any patient referred for a Max_6MWT with capacity to 
consent, >18 years of age and able to perform a Max_6MWT. 
Planned Size of Sample (if applicable) 82 
Follow up duration (if applicable) 
N/A 
Planned Study Period 
18 – 24 months 
Research Question/Aim(s) 
 
Does Nor_6MWT provide a better indicator for ambulatory 
oxygen requirement than the standard Max_6MWT 
 
 
FUNDING AND SUPPORT IN KIND 
FUNDER(S) 
(Names and contact details of ALL organisations 
providing funding and/or support in kind for this 
study) 
FINANCIAL AND NON FINANCIALSUPPORT 
GIVEN 
Hampshire Hospitals NHS Foundation Trust 
Use of facilities and personnel for the study 
 
 
 
 
 
 
ROLE OF STUDY SPONSOR AND FUNDER 
The study sponsor and funder is Hampshire Hospitals NHS Foundation Trust (HHFT). As such, HHFT 
will oversee the study and its implementation and will store any patient and study information on site in 
either paper form (within the Respiratory Physiology Department) or electronically on internal NHS 
Trust systems.  
 
 
 

 
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PROTOCOL CONTRIBUTORS 
Harry Griffin as CI for the study has conceptualised and drafted the study protocol, along with its aims 
and primary and secondary outcomes.  
Michael Hughes as PI for the study has reviewed the study protocol and drafted the necessary 
documents for the study. 
Dr Alison Grove advised on the protocol development. 
Professor James Faulkner has reviewed the study protocol. 
Study aims and protocol discussed with Andover Breathe Easy group at their January 2022 meeting 
(14:00 pm, 20/01/2022, Andover). Please see Appendix IV for key points from meeting. 
 
KEY WORDS: 
6MWT, exercise-induced hypoxaemia, ambulatory 
oxygen, oxygen assessment, field exercise test  
 

 
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STUDY FLOW CHART 
 
 

 
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STUDY PROTOCOL 
Comparison of the standard 6-Minute maximal speed Walk Test against a 6-Minute normal speed 
Walk Test as an alternative and more accurate assessment for ambulatory oxygen requirement. 
 
1 
BACKGROUND 
 
Patients with lung disease who report breathlessness on exertion are often referred for a Max_6MWT. 
During this test patients are asked to walk up and down a corridor (or other flat area) for six minutes 
whilst their blood oxygen levels and heart rate are non-invasively measured using a pulse oximeter 
(finger probe) and the distance walked is measured. In addition, a questionnaire that obtains a Borg 
Score measures the patients’ perceived breathlessness and leg muscle fatigue both before and 
immediately following the test. 
 
A Max_6MWT provides clinicians with two primary results. Firstly, they determine whether the 
patient’s blood oxygen levels decline whilst they walk which is used to help determine whether they 
could benefit from ambulatory oxygen therapy. Ambulatory oxygen therapy involves walking with a 
cylinder of compressed oxygen or a portable oxygen concentrator which the patient breathes from via 
a face mask or nasal cannula. Secondly, they provide a total distance walked which provides a 
measurement of functional capacity and physical impairment.  
 
The standardised approach for a Max_6MWT as recommended by international and UK respiratory 
bodies and used by our department is to ask the patient to walk as far as possible during the six 
minutes and thus essentially walk as fast as possible1. A Max_6MWT is therefore appropriate to 
assess the patient’s maximal walking distance and thus functional capacity which is useful for 
assessing the impact of a patient’s lung disease on their quality of life and is also used by surgeons 
and anaesthetics to assess surgical risk. However, it would seem likely that a significant number of 
patients will demonstrate a decline in blood oxygen levels that they may never experience in their daily 
life when they walk at their normal and slower pace. Subsequently they may be incorrectly prescribed 
ambulatory oxygen therapy or prescribed ambulatory oxygen at a flow rate exceeding what is required 
and possibly safe. 
 
We are aware that many oxygen services across the UK, including some in Hampshire, will assess 
patients for ambulatory oxygen by having them perform their normal day-to-day activities whilst 
measuring their oxygen levels, rather than performing a Max_6MWT. These include activities such as 
walking up and down the stairs, walking around their house/garden etc. This seems a far more 
appropriate assessment for ambulatory oxygen, but a thorough literature review was unable to find 
any studies that had investigated whether a Max_6MWT caused a greater reduction in blood oxygen 
levels than occurs during these normal day-to-day activities. Until the current guidelines are 
challenged with evidence to show a Max_6MWT may not be an appropriate tool to assess patients for 

 
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Version 2.0 February 2023 – Max_6MWT vs Nor_6MWT 
ambulatory oxygen most departments will continue to follow national and international 
recommendations and use a Max_6MWT. 
In this study, patients who are routinely referred for a Max_6MWT to investigate possible exercise-
induced hypoxaemia will be invited to perform an additional walking test which is performed at their 
normal walking speed, referred here on in as a Nor_6MWT. This additional test will utilise the exact 
same medical equipment to record their blood oxygen levels as that of the Max_6MWT and be 
performed at the same location (i.e. flat hospital corridor). The order of performing these tests will be 
randomised with half performing the Max_6MWT first and the other half performing the Nor_6MWT 
first. Patients will be given 20 minutes to rest between each test in line with the British Thoracic 
Society guidelines, or a minimum of 10 minutes with a return to baseline of SpO2, HR and Borg 
Scores. 
2 
RATIONALE  
 
• 
The routinely used and internationally recognised diagnostic test for assessing the 
requirement of ambulatory oxygen, Max_6MWT may not correspond to the degree of 
exercise that patients actually perform when they would use their prescribed ambulatory 
oxygen (i.e. normal walking speed). 
 
• 
It is possible that a significant proportion of patients prescribed ambulatory oxygen cannot 
physiologically benefit from using it as they do not experience a decline in oxygen levels 
during their normal physical exercise. 
 
• 
Prescribing of ambulatory oxygen to patients that cannot benefit from it carries additional 
burdens for the patient, and costs for the NHS, without improving the patient's quality of life.  
 
• 
If this study shows that a normal walking speed test is a more appropriate assessment for 
ambulatory oxygen, a higher proportion of patients prescribed ambulatory oxygen will benefit 
from the therapy and reduce incorrect prescribing of ambulatory oxygen. 
 
• 
Max_6MWT is a maximal exercise test for most patients with notable respiratory disease and 
is not always well tolerated (e.g. becoming very breathless). Furthermore, it carries a small 
but not insignificant risk of acute heart issues and falls. A 6 minute or shorter test at normal 
walking speed would be safer and easier for a patient to perform. 
 
• 
Patients’ wellbeing could be harmed by misdiagnosing exercise-induced hypoxaemia. 
Anecdotal evidence suggests some patients become less active after being prescribed 
ambulatory oxygen for a variety of reasons, including feeling self-conscious or struggling to 
carry the oxygen cylinder.  
 
• 
Furthermore, patients may be worried about exercising without ambulatory oxygen if 
prescribed this therapy due to the perception of risk due to exercise-induced hypoxaemia and 
potentially incorrect requirement for supplemental oxygen. 
 
• 
Patients who demonstrate exercise-induced hypoxaemia during a Max_6MWT are required 
to repeat the Max_6MWT at least once in order to identify the required flow rate of 
ambulatory oxygen. Titrating the flow of ambulatory oxygen is required to ensure it is 
sufficient to prevent the exercise-induced hypoxaemia but not too high that could induce 
hypoventilation and subsequent CO2 retention. It is plausible that prescribing a flow rate 
shown to prevent hypoxaemia during a Max_6MWT could far exceed that required to prevent 

 
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Version 2.0 February 2023 – Max_6MWT vs Nor_6MWT 
hypoxaemia during a patients' normal day to day exercise activities and lead to CO2 
retention. Furthermore, prescribing at a higher than required flow rate will lead to reduced 
cylinder duration or reduced battery life of portable concentrators which in turn could lead to 
restraints in the duration patients could exercise for. 
 
• 
In some cases, sub-maximal 6MWT are reported to be performed 2 without rationale or 
comparison with the internationally recognised guidelines for a maximal-effort 6MWT 3. There 
is no published literature adapting the Max_6MWT to improve the suitability for ambulatory 
oxygen assessment. 
3 
THEORETICAL FRAMEWORK 
Due to the nature of the Max_6MWT, patients are required to walk as far as they can in 6 minutes. 
This may lead to an inaccurate assessment of their requirement for ambulatory oxygen as this form of 
exercise may not correspond to their normal daily activities (such as walking to the shops, walking up 
the stairs, gardening). It may also not accurately measure the normal changes in oxygen saturation (or 
desaturation) that occurs in these patients during their normal daily activities. 
These two problems could lead to the prescribing of ambulatory oxygen that does not assist patients 
in their normal daily activities and, therefore, is a burdensome and ineffective therapy for some 
individuals 4. Several studies have also shown that ambulatory oxygen is often prescribed with no 
measurable benefit to patients due to a variety of factors, including potentially inaccurate indications 
from investigations like 6MWTs. This appears to be exaggerated in patients with milder symptoms in 
diseases such as COPD, and potential benefits were negated when patients had to carry their 
supplemental oxygen supply 4,5. 
 
 
 

 
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4 
RESEARCH QUESTION/AIM(S) 
To compare the nadir in oxygen saturation reached whilst performing a standard Max_6MWT 
compared with a Nor_6MWT. 
To compare the average oxygen saturation and average drop in oxygen saturation from baseline to 
the nadir whilst performing a standard Max_6MWT compared with a Nor_6MWT. 
To measure when the nadir in oxygen saturation occurs during a Nor_6MWT. 
To assess in patients prescribed ambulatory oxygen, what benefit in their symptoms do they report 
and how does this compare to their Max_6MWT and Nor_6MWT results. 
 
4.1 
Objectives 
 
Primary objective: 
1. 
Average drop in SpO2 from baseline to nadir  
 
Secondary objectives: 
1. 
Average SpO2 during the 6 minutes walking 
2. 
Nadir in oxygen saturation (SpO2)   
3.  
At what time does the nadir in SpO2 occur during a Nor_6MWT 
 
Other objectives: 
1. 
Walking speed: Distance walked divided by 6 minutes  
2. 
Average HR during the 6 minutes walking 
3. 
Peak HR 
5. 
Borg Scores 
6. 
Results from questionnaires (for patient’s prescribed ambulatory oxygen) 
 
4.2 
Outcome 
A greater drop in oxygen saturation during a Max_6MWT compared with Nor_6MWT may indicate 
over-prescribing of ambulatory oxygen as during normal activity, patients’ requirement for oxygen may 
be lower than indicated by a Max_6MWT. Whilst ambulatory oxygen can improve patients’ quality of 
life, it is not without drawbacks and, therefore, prescribing only to patients that will benefit is important. 
 
 
 
 
 

 
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5 
STUDY DESIGN and METHODS of DATA COLLECTION AND 
DATA ANALYSIS 
 
Patients attending a routine appointment for a Max_6MWT will be identified and approached to be 
invited to participate in the research study. 
Along with a basic clinical history, the patient’s blood pressure, Borg score for dyspnoea and leg 
fatigue, oxygen saturation and heart rate will be recorded before the walk tests – their baseline 
measurement. 
The order of the tests will be randomised using a random number generator on the day where odd 
numbers will perform a Max_6MWT followed by a Nor_6MWT and even numbers the reverse. For 
each test, clear instructions will be provided along with continuous monitoring of their oxygen 
saturation heart rate and distance walked for the 6 minutes of the test using a using a Bluetooth 
enabled device that transmits this data to a medically approved monitoring device with manual lap 
counting. Should this equipment fail, manual readings will be taken every minute during the test. 
Between each test, ample time (usually 20 minutes) will be provided for a patient’s degree of 
dyspnoea and leg fatigue, and objective measurements of heart rate and oxygen saturation to return 
to baseline. 
From these tests it is possible to determine the distance walked, the degree of dyspnoea and leg 
fatigue, the time to nadir in oxygen saturation, the average drop in oxygen saturation and the average 
and peak heart rate. These data can be compared using paired tests to determine differences 
between Max_6MWT and Nor_6MWT. 
Only the results of the clinical standard Max_6MWT will be relayed back to the referring member of 
the clinical care team – they will not see the outcome of the Nor_6MWT. A copy of the IPAQ Elderly 
Short questionnaire will be provided to fill out during the appointment – this forms the baseline 
assessment. If they decide to prescribe ambulatory oxygen, questionnaires will be provided to 
complete either in physical form, or over the phone with a member of the research team. These 
patients will be identified from the hospital digital patient record. These will include two identical copies 
of the IPAQ Elderly Short questionnaire – one before they begin ambulatory oxygen and one to 
complete after four weeks of using ambulatory oxygen – and an Ambulatory Oxygen Questionnaire 
four weeks after starting ambulatory oxygen. These will provide a surrogate for clinical benefit 
achieved by the use of ambulatory oxygen. The questionnaires will contain patient identifiable 
information to enable linking of the data to their test results and, therefore, will be stored securely on a 
NHS shared drive within HHFT. A secure nhs.net email will be used to receive the completed 
questionnaires if physical copies are not returned. These data, as a metric of clinical improvement, 
can then be compared with the outcomes of both the Max_6MWT and Nor_6MWT to determine if 
these tests can predict patients that will benefit from ambulatory oxygen.  
The data from these tests will be stored on the clinical software used in routine testing (SentrySuite, 
Vyaire) and this may be exported to numerical handling software such as Excel (Microsoft) and stored 
internally on an NHS shared drive. Follow up will be limited to questionnaire data for those prescribed 
ambulatory oxygen and this will be arranged either by the physiology team or by the consultants 
prescribing ambulatory oxygen. 
In the event a patient be randomised to the Nor_6MWT and declines to proceed to the Max_6MWT, 
the results from the Nor_6MWT will be passed on to the medical team and the patient will be 
withdrawn from the study. 
 
 
 

 
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5.1  
6-minute walk test protocol 
Steps for carrying out the walk test are outlined below: 
 
Group 1: Maximal speed walking test (Max_6MWT) followed by normal speed walking test 
(Nor_6MWT). 
Step 1: Wait at least 10 minutes in a seated position from any previous breathing tests. Baseline blood 
pressure, heart rate and oxygen saturation obtained. Borg score completed. 
Step 2: Instructions provided: " 
The aim of this test is to walk as far as possible for 6 minutes. You will walk along this hallway 
between the markers, as many times as you can in 6 minutes. 
I will let you know as each minute goes past, and then at 6 minutes I will ask you to stop where you 
are. 6 minutes is a long time to walk, so you will be exerting yourself. You are permitted to slow down, 
to stop, and to rest as necessary, but please resume walking as soon as you are able. 
Remember that the objective is to walk as far as possible for 6 minutes, but don't run or jog. " 
Step 3: Very slow walk to the start line and then perform the walk test. 
Step 4: Perform post-test Borg score immediately after the test. Twenty minutes of rest, or a minimum 
of 10 minutes sitting rest/recovery with a return to baseline of SpO2, HR and Borg Score 
Step 5: Proceed to perform Nor_6MWT as above but with the following instructions: “ 
The aim of this test is to walk at your normal walking speed for 6 minutes. This could be the speed that 
you walk a dog if you have one, or the speed you would walk around town shopping. You will walk 
along this hallway between the markers for 6 minutes. 
I will let you know as each minute goes past, and then at 6 minutes I will ask you to stop where you 
are. 6 minutes is a long time to walk, so you will be exerting yourself. You are permitted to slow down, 
to stop, and to rest as necessary, but please resume walking as soon as you are able. 
Remember that the objective is to walk at your normal walking speed for 6 minutes, but don't run or 
jog.” 
Step 6: Perform post-test Borg score immediately after the test. Allow the patient to rest for at least 10 
minutes or until SpO2 and HR back to baseline.  
…………………………………………………………………………………………  
Group 2: Nor_6MWT followed by Max_6MWT. 
Step 1: Wait at least 10 minutes in a seated position from any previous breathing tests. Baseline blood 
pressure, heart rate and oxygen saturation obtained. Borg score completed. 
Step 2: Instructions provided: “ 
The aim of this test is to walk at your normal walking speed for 6 minutes. This could be the speed that 
you walk a dog if you have one, or the speed you would walk around town shopping. You will walk 
along this hallway between the markers for 6 minutes. 
I will let you know as each minute goes past, and then at 6 minutes I will ask you to stop where you 
are. 6 minutes is a long time to walk, so you will be exerting yourself. You are permitted to slow down, 
to stop, and to rest as necessary, but please resume walking as soon as you are able. 
Remember that the objective is to walk at your normal walking speed for 6 minutes, but don't run or 
jog." 
Step 3: Very slow walk to the start line and then perform the walk test. 

 
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Step 4: Perform post-test Borg score immediately after the test. Twenty minutes of rest, or a minimum 
of 10 minutes sitting rest/recovery with a return to baseline of SpO2, HR and Borg Score 
Step 5: Proceed to perform Max_6MWT with the following instructions: “ 
The aim of this test is to walk as far as possible for 6 minutes. You will walk along this hallway 
between the markers, as many times as you can in 6 minutes. 
I will let you know as each minute goes past, and then at 6 minutes I will ask you to stop where you 
are. 6 minutes is a long time to walk, so you will be exerting yourself. You are permitted to slow down, 
to stop, and to rest as necessary, but please resume walking as soon as you are able. 
Remember that the objective is to walk as far as possible for 6 minutes, but don't run or jog.” 
Step 6: Perform post-test Borg score immediately after the test. Allow the patient to rest for at least 10 
minutes or until SpO2 and HR back to baseline.  
 
6 
STUDY SETTING 
This is a single centre study, taking place at two locations within HHFT: the Royal Hampshire County 
Hospital, Cardiac Measurement Department and at Basingstoke and North Hampshire Hospital, 
Cardiac Investigations. These locations are current sites for standard Max_6MWT and are suitable for 
carrying out the additional Nor_6MWT with access to the required space and equipment for this 
research.  
Patients will be assessed during a routine clinic appointment and the tests performed in a corridor 
within the respective departments.  
Each location will perform the same activity. 
 
7 
SAMPLE AND RECRUITMENT 
 
7.1  
Eligibility Criteria 
Patients must be attending a respiratory outpatient clinic at Hampshire Hospitals NHS Foundation 
Trust to be eligible for the study and meet the following criteria: 
7.1.1 Inclusion criteria  
1. Referred for a Max_6MWT 
2. Provision of informed written consent 
3. Aged 18 years or over 
 
7.1.2 Exclusion criteria  
1. Lack of capacity to provide informed consent 
2. Poor peripheral perfusion that prevents an accurate measurement of SpO2 
3. Contraindicated to perform a Max_6MWT as indicated in the standard HHFT 6MWT SOP 
4. Already prescribed ambulatory oxygen 
7.2  
Sampling 
 
All patients referred for a diagnostic 6MWT will be informed of the study and asked if they wish to 
participate following reading and understanding the patient information leaflet and providing informed 
consent. 

 
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7.2.1  Size of sample 
A sufficient number of patients will be recruited in order to assess any differences between the 
Max_6MWT and Nor_6MWT. The study is to establish whether there is any significant difference of the 
continuous variable, SpO2, at rest and at end of 6 minute-walk.  Prior data, from the HHFT pilot study, 
yielded an effect size of 0.30 and this study will need 82 subjects to be able to reject the null hypothesis 
that this response difference is null with a power of 80%. The Type I error probability associated with this 
test for null hypothesis is 0.05. 
 
 
7.2.2  Sampling technique 
As the proposed study will assess a novel test against standard of care, convenience sampling will be 
utilised to capture any patient referred for the standard of care test. 
 
7.3 
 Recruitment 
Once patients are referred for a standard Max_6MWT by a doctor at HHFT, patients will be made 
aware of the study by a covering letter and Patient Information Leaflet (PIL) alongside their routine 
appointment letter. At their outpatient appointment, the patient will again have the opportunity to 
review the PIL and ask any questions to the researcher(s) conducting the study. If they are willing to 
participate, informed consent will be taken during their appointment prior to testing. Accepting or 
refusing to participate in the study will have no impact on the care provided to the patient, or their 
ongoing clinical investigations and treatment. 
If a patient is unable to complete both the Max_6MWT and Nor_6MWT, they will be subsequently 
removed from the study. 
 
7.3.1 Sample identification 
The CI or named individuals on the delegation log will screen for patients who meet the eligibility 
criteria based on the referral information provided on the digital bookings system. Patients will not be 
actively recruited by either Patient Identification Centres or by public advertising.  
Any person identifying patients will already have access to this information as part of the patient’s 
ongoing clinical care. As such, no arrangements are required to pass this information on to anyone 
outside the patients’ existing clinical care team. Additionally, as the study will be conducted within a 
patients’ existing outpatient appointment, there is no reimbursements for travel or time to participate in 
this research. 
 
7.3.2 Consent 
Informed consent will be taken on the day of the outpatient appointment after the patient has had time 
to review the supporting information in the Patient Information Leaflet, either prior to the appointment 
or at the beginning of the appointment if the patient has not done so prior. The researcher taking 
informed consent will outline the nature of the study; confirm the patient has capacity to provide 
consent (using the below criteria) and has had an opportunity to ask any questions. A patient will be 
told they may abort the study at any point without reason and that this will not affect the care provided 
by the clinical care team. 
Assessing capacity to provide informed consent - a patient must: 
• understand the purpose and nature of the research  

 
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• understand what the research involves, its benefits (or lack of benefits), risks and burdens  
• understand the alternatives to taking part  
• be able to retain the information long enough to make an effective decision 
• be able to make a free choice  
• be capable of making this particular decision at the time it needs to be made (though their 
capacity may fluctuate, and they may be capable of making some decisions but not others 
depending on their complexity) 
• where participants are capable of consenting for themselves but are particularly 
susceptible to coercion, it is important to explain how their interests will be protected 
 
 
 
 
 
 
8 
ETHICAL AND REGULATORY CONSIDERATIONS 
This research aligns with both ethical and regulatory framework, aiming to improve the quality of care 
for patients and providing better diagnostic tools. The research poses very low risk to patients 
participating as they are only required to walk at their normal walking pace on a flat surface and whilst 
there may be no immediate direct benefit, there is a direct implication for future clinical decision 
making based on the outcomes of this study. 
Collection of physiological data is done with non-invasive methods and respects the dignity of patients 
participating in the study. These collection techniques are internationally recognised and conform to all 
local and national legislation. 
 
8.1 
Assessment and management of risk 
The study will be conducted according to the principles of the Declaration of Helsinki (9.10.2008) and 
Good Clinical Practice and in accordance with the Medical Research Involving Human Participants Act 
(WMO) and other guidelines, regulations and acts. All members of the research team will have up to 
date safeguarding training provided by HHFT and be aware of dealing with safeguarding concerns in 
line with local Trust policies. 
There is minimal additional risk to patients involved in this study. Walking for 6 minutes in a controlled 
environment has a small risk of falls and syncope. These risks are managed by visually monitoring 
patients continuously, ensuring a seat is available by the testing site and assessing baseline blood 
pressure and SpO2. 
 
8.1.1 Adverse and Serious Adverse Events 
As the study only involves walking down a corridor, it is not envisaged any adverse and serious adverse 
events are not expected, however procedures will be place in case of an event. 
Adverse events (AE) are defined as any untoward medical occurrence in a study participant, which does 
not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavourable 
and unintended sign, symptom, or disease. Occurrence of possible AEs will be registered by the principal 
investigator.  

 
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All adverse events reported spontaneously by the participant or observed by the principal investigator or 
their staff will be recorded. On a study day, Adverse Events (AEs) may be established by asking the 
participants: “How are you feeling?” before and after the experimental procedures.  
 
A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose: 
 
• 
results in death;  
• 
is life threatening (at the time of the event);  
• 
requires hospitalisation or prolongation of existing in patients’ hospitalisation;  
• 
results in persistent or significant disability or incapacity;  
• 
is a new event of the trial likely to affect the safety of the participants, such as an unexpected 
outcome of an adverse reaction, lack of efficacy of an IMP used for the treatment of a life-
threatening disease or a major safety finding from a newly completed animal study. 
 
Any Serious Adverse Event, with a possible relation to the study will be reported by the medical 
investigator upon hearing (within 24 hrs) to the sponsor, and the general practitioner and the study 
participant will be informed. Any SAE not or unlikely to be related to the study will be reported to the 
sponsor and ethical committee by the Chief Investigator within three working days. 
 
As this is a single-day study with no lasting intervention or therapy, reporting and recording of AEs and 
SAEs will only happen if they occur during the study visit itself. It is not deemed that completing a 
questionnaire carries any risk and will not be monitored under the AE/SAE criteria.  
 
8.2  
 Research Ethics Committee (REC) and other Regulatory review & reports 
Appropriate ethical approval from both local R&D and REC will be sought prior to the study commencing. 
Any amendments to the protocol or related documents will also receive appropriate approvals prior to 
implementation. The CI along with the sponsor will determine if an amendment is substantial or non-
substantial and amendments will then be drafted and then reviewed by the CI before submission to the 
sponsor and the REC where required. All amendments will be noted at the beginning of the protocol in 
the relevant section and relevant parties notified by email, including when these changes can be 
implemented following approval from the relevant bodies and or committees.  
These approvals and correspondences will be stored in the site file and appropriate annual reports such 
as the annual progress review will be submitted by the named CI. The REC will be notified at the end of 
the study and a subsequent final report will be submitted within 12 months, along with any publications 
from the study. 
 
8.3  
Peer review 
This protocol has been peer reviewed externally by three independent external reviewers, each of 
whom has experience of working directly with the standard 6-minute walk test or with research 
projects that use similar measurements and patient groups to those described within this protocol. 
Each reviewer was provided a copy of the protocol, information leaflet and associated questionnaires 
for review using a standard reviewers form supplied by the R&D department at HHFT.  
 
8.4 
Protocol compliance  
Accidental protocol deviations can happen at any time. If a protocol deviation is identified, the CI and 
sponsor will be made aware immediately and the exact deviation documented and stored in the site 
file. Appropriate action will be taken to avoid repeating the protocol deviation. If frequent recurring 

 
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deviations are identified, the protocol will be reviewed by the CI and amended to prevent future 
deviations. Recurring deviations may be classed as a serious breach and may be treated as such. 
 
8.5 
Data protection and patient confidentiality  
All (personal) data will be handled confidentially in accordance with the Data Protection Act 1998 and 
General Data Protection Regulation (GDPR). Personal data are stored on the HHFT secure digital 
electronic patient records (EPR) on an internal network, which is protected by usernames and 
passwords.  All personal data will remain within HHFT and there will be no transmission of this data to 
third parties.   
All personal source data will be kept on the NHS clinical server and in medical records as part of 
normal medical care.  A copy of the consent form and patient information sheet will also be stored in 
the medical records where possible and within the site file. In case of withdrawal from the study, the 
participant can decide whether the data already acquired shall be destroyed or can be used.   
In the event of a data protection breach or serious breach of GCP, all HHFT protocols will be followed 
to ensure proper reporting and management of such an incident. 
Participants will be given a study ID upon consenting to the study allowing for pseudo-anonymisation 
of any data collected. The link connecting patient names to the pseudo-anonymised research data will 
be kept in an encrypted file held on NHS servers to which only the CI and those delegated by the PI 
will have access to (all paper documents will be stored in a specific site file within HHFT). Clinical 
information collected and any test results that may be useful to a patients’ ongoing clinical care may 
be stored alongside routine test results and treated as confidential patient information as part of their 
healthcare record and exempt from the archiving and deletion policies as part of this research. 
Any information shared with academic collaborators at the University of Winchester and Manchester 
Metropolitan University (for the purposes of completion of a part-time MSc by the study PI) will only 
use the study ID and no personal identifiable information.  
Questionnaires returned by email will be sent to a secure NHS account 
(respphysresearch@hhft.nhs.uk) accessible by researchers involved in the study and on the study 
delegation log. 
 
8.6 
Indemnity 
The study will be conducted within an NHS Trust and by NHS employees and, therefore, the NHS 
indemnity scheme will cover all activities under this study. As the study will be carried out during a 
normal procedure referred for by a medical professional, it is not expected any compensation would 
be required as a result of this study. 
 
8.7 
Access to the final study dataset 
The CI and individuals involved in the routine care for patients participating in the study will have 
access to the final dataset, including physiologists and clinical scientists. In addition, any medical 
professionals involved in the routine care of the patients involved in the study will also have access to 
the final dataset – although their access to the full dataset during the study will be restricted as 
outlined in the study design and methods. 
A final report, that does not allow identification of individuals’ participating in the research, will also be 
published on a public domain and freely available to participants and members of the public. 
 
 

 
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9 
DISSEMINIATION POLICY 
 
9.1  
Dissemination policy 
The data arising from the study remains the ownership of HHFT. Upon completion, anonymised data will 
be formulated into a written report with the aim of publication either as a journal article or conference 
proceedings. These data may also be presented at conferences verbally and/or a poster. 
The full dataset will also be made available to the medical team involved in the routine care of the study 
participants once the study has completed or for an individual participant once their involvement in the 
study is complete (they have reached the end of the study protocol). 
A final report will also be generated for study participants to inform them of any findings from the study in 
the form of a leaflet, poster or patient feedback session. The required information will be submitted to the 
public-facing database where the clinical trial is registered. The CI and PI will aim to share this with 
participants via email where this information is accessible. 
 
9.2  
Authorship eligibility guidelines and any intended use of professional writers 
Authorship will be reserved for those directly involved in the collection of study data and the 
presentation of these data in written form or presented at conferences. 
 
10 
REFERENCES 
 
1. 
Crapo, R. O. et al. ATS statement: Guidelines for the six-minute walk test. Am. J. Respir. Crit. 
Care Med. 166, 111–117 (2002). 
2. 
Lewko, A., Marshall, J. & Garrod, R. Ambulatory oxygen therapy assessment: A comparative 
study of incremental shuttle and six-minute walking tests. Kingst. Univ. Res. Repos. 
3. 
ATS. ATS Statement: Guidelines for the Six-Minute walk test. Am. J. Respir. Crit. Care Med. 
166, 111–117 (2002). 
4. 
Whitty, J. A. et al. Cost-effectiveness of ambulatory oxygen in improving quality of life in fibrotic 
lung disease: preliminary evidence from the AmbOx Trial. Eur. Respir. J. 55, 1901157 (2020). 
5. 
Criner, G. J. Ambulatory Home Oxygen: What Is the Evidence for Benefit, and Who Does It 
Help? Respir. Care 58, 48–64 (2013). 
 
 
 

 
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11 
APPENDICIES 
 
11.1 
Appendix 1- Required documentation  
 
Researchers involved in the study: 
➢ CV 
➢ GCP Certificate 
➢ Present on the delegation log 
 
At the study site: 
➢ Copy of PIL 
➢ Consent forms 
➢ Site file containing study protocol 
➢ Approvals and correspondence relating to the study 
➢ Delegation Log 
➢ All correspondence with relevant regulatory bodies 
 
11.2  Appendix 2 – Schedule of Procedures 
 
All procedures will be performed in a single visit during a routine outpatient appointment. Collection of 
questionnaire data will occur after this appointment if subsequently a patient is prescribed ambulatory 
oxygen either by posting the physical questionnaire to the research team, or by email. In addition, a 
separate Schedule of Events document has been attached for convenience. 
 
11.3 
Appendix 3 – Amendment History 
Amendment 
No. 
Protocol 
version no. 
Date issued 
Author(s) of 
changes 
Details of changes made 
1 
2.0 
Pending 
Michael 
Hughes 
Amendment of 6MWT instruction to 
match most recent published guidance. 
Amendment of exclusion criteria. 
 
11.4 
Appendix 4 – Meeting notes from the Breathe Easy group 
Attendees at the Breathe Easy group (Andover) discussed the research study. Attendees all agreed 
that “a six-minute walk test is not the normal thing that any one of them would do, in their own 
situations, so not a good test as to whether they need oxygen in their day to day lives.” 
Attendees highlighted the need for adequate rest between the two walk tests, which we will 
encompass into the study design. Attendees that had previously performed six-minute walk tests 
commented on the varying protocols depending on who asked them to do the tests (including 
physiotherapists, nurses, rehabilitation practitioners, pre-op assessments): sometimes they were 
asked to walk at normal speed, sometimes at maximal speed and there was quite a lot of confusion 
over the purpose of the tests. They were very happy with the idea of the study and felt if it could 
reduce the need for them to do these maximal tests which they found very hard then they would 
appreciate it.