Evaluation of the Usefulness of Adopting Remote, Mobile-based 6MWT Among Hospital Outpatients (the 6-APPnow), Within the Constraints Imposed by the SARS-COV2 Pandemic
Conditions: Pulmonary Hypertension
Sponsor: Oxford University Hospitals NHS Trust

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Trial Title:  Evaluation of the usefulness of adopting remote, mobile-based 6MWT among hospital 
outpatients (the 6-APP now Study), within the constraints imposed by the SARS-COV2 pandemic 
Internal Reference Number / Short title: 6-APPnow Study 
Ethics Ref: Insert 
IRAS Project ID: Insert  
Date and Version No: 3/5/21 Version number 1 
 
Chief Investigator: 
Dr. Elizabeth Orchard, 
Consultant Cardiologist 
Oxford University Hospitals NHS Foundation Trust 
Investigators:  
Dr. Dario Salvi, Senior Lecturer, University of Malmo, Sweden. 
Dr. Carl Magnus Olsson, Senior Lecturer, University of Malmo, Sweden. 
 
Sponsor:  
Oxford University Hospitals NHS Foundation Trust  
Headley Way 
Oxford 
OX3 9DU 
Funder:  
NIHR BRC and the Swedish Knowledge Foundation 
Chief Investigator Signature:  
 
Statistician Signature: 
 
 
 
No conflicts of Interests 
 
Confidentiality Statement 

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This document contains confidential information that must not be disclosed to anyone other than the 
Sponsor, the Investigator Team, HRA, host organisation, and members of the Research Ethics Committee 
and Regulatory Authorities unless authorised to do so. 
 
 
 

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TABLE OF CONTENTS 
1. 
KEY TRIAL CONTACTS ............................................................................................................................. 6 
2. 
LAY SUMMARY....................................................................................................................................... 6 
3. 
SYNOPSIS ............................................................................................................................................... 6 
4. 
ABBREVIATIONS ..................................................................................................................................... 8 
5. 
BACKGROUND AND RATIONALE ............................................................................................................ 9 
5.1. 
Telemedicine in the context of COVID19 ...................................................................................... 9 
5.2. 
The 6MWT ................................................................................................................................... 10 
5.3. 
Cardiovascular outpatient management during the pandemic .................................................. 10 
5.4. 
Telemedicine services for pulmonary hypertension ................................................................... 11 
6. 
OBJECTIVES AND OUTCOME MEASURES ............................................................................................. 12 
7. 
TRIAL DESIGN ....................................................................................................................................... 13 
8. 
PARTICIPANT IDENTIFICATION ............................................................................................................ 14 
8.1. 
Trial Participants .......................................................................................................................... 14 
8.2. 
Inclusion Criteria .......................................................................................................................... 14 
8.3. 
Exclusion Criteria ......................................................................................................................... 14 
9. 
TRIAL PROCEDURES ............................................................................................................................. 15 
9.1. 
Recruitment ................................................................................................................................. 15 
9.2. 
Screening and Eligibility Assessment ........................................................................................... 15 
9.3. 
Informed Consent ........................................................................................................................ 15 
9.1. 
Enrolment .................................................................................................................................... 16 
9.2. 
Baseline Assessments .................................................................................................................. 16 
9.3. 
Subsequent Visits ........................................................................................................................ 16 
Part 1: logging of events ...................................................................................................................... 16 
Part 2: accuracy, usability and acceptance assessment ...................................................................... 18 
9.4. 
Sample Handling .......................................................................................................................... 19 
9.5. 
Early Discontinuation/Withdrawal of Participants ...................................................................... 19 
9.6. 
Definition of End of Trial ............................................................................................................. 19 
10. 
TRIAL INTERVENTIONS ..................................................................................................................... 20 
10.1. 
Investigational Medicinal Product(s) (IMP) Description .............. Error! Bookmark not defined. 
10.1.1. Blinding of IMPs ........................................................................... Error! Bookmark not defined. 
10.1.2. Storage of IMP ............................................................................. Error! Bookmark not defined. 
10.1.3. Compliance with Trial Treatment ................................................ Error! Bookmark not defined. 

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10.1.4. Accountability of the Trial Treatment ......................................... Error! Bookmark not defined. 
10.1.5. Concomitant Medication ............................................................. Error! Bookmark not defined. 
10.1.6. Post-trial Treatment .................................................................... Error! Bookmark not defined. 
10.2. 
Other Treatments (non-IMPS) ..................................................... Error! Bookmark not defined. 
10.3. 
Other Interventions ..................................................................... Error! Bookmark not defined. 
11. 
SAFETY REPORTING ......................................................................................................................... 20 
11.1. 
Adverse Event Definitions ....................................................................................................... 20 
11.2. 
Assessment results outside of normal parameters as AEs and SAEs ...................................... 21 
11.3. 
Assessment of Causality .......................................................................................................... 21 
11.4. 
Procedures for Reporting Adverse Events ............................................................................... 21 
12. 
STATISTICS ....................................................................................................................................... 22 
12.1. 
Description of Statistical Methods .......................................................................................... 22 
12.2. 
Sample Size Estimation ............................................................................................................ 24 
12.3. 
Analysis Populations ................................................................................................................ 24 
13. 
DATA MANAGEMENT ...................................................................................................................... 24 
13.1. 
Data Recording and Record Keeping ....................................................................................... 24 
13.1. 
Source Data ............................................................................................................................. 25 
13.2. 
Access to Data ......................................................................................................................... 25 
13.3. 
Data Recording and Record Keeping ....................................................................................... 25 
14. 
QUALITY ASSURANCE PROCEDURES ............................................................................................... 26 
14.1. 
Risk assessment ....................................................................................................................... 27 
14.2. 
Monitoring ............................................................................................................................... 27 
14.3. 
Trial committees ...................................................................................................................... 27 
14.4. 
Safety Monitoring Committee ................................................................................................. 27 
15. 
PROTOCOL DEVIATIONS .................................................................................................................. 27 
16. 
ETHICAL AND REGULATORY CONSIDERATIONS ............................................................................... 27 
16.1. 
Regulations .................................................................................. Error! Bookmark not defined. 
16.2. 
6MWT ...................................................................................................................................... 27 
16.3. 
Sars-Cov-2 ................................................................................................................................ 28 
16.4. 
Participant Confidentiality ........................................................... Error! Bookmark not defined. 
16.5. 
Declaration of Helsinki............................................................................................................. 28 
16.6. 
Guidelines for Good Clinical Practice ...................................................................................... 28 
16.7. 
Approvals ................................................................................................................................. 28 

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16.8. 
Other Ethical Considerations ................................................................................................... 28 
16.9. 
Reporting ................................................................................................................................. 28 
16.10. 
Participant Confidentiality ....................................................................................................... 28 
16.11. 
Expenses and Benefits ............................................................................................................. 29 
17. 
FINANCE AND INSURANCE .............................................................................................................. 29 
17.1. 
Funding .................................................................................................................................... 29 
17.2. 
Insurance ................................................................................................................................. 29 
17.3. 
Contractual arrangements ...................................................................................................... 29 
18. 
PUBLICATION POLICY ....................................................................................................................... 29 
19. 
DEVELOPMENT OF A NEW PRODUCT/ PROCESS OR THE GENERATION OF INTELLECTUAL 
PROPERTY .................................................................................................................................................... 30 
20. 
ARCHIVING....................................................................................................................................... 30 
21. 
REFERENCES .................................................................................................................................... 30 
22. 
APPENDIX B:  SCHEDULE OF PROCEDURES ..................................................................................... 32 
23. 
APPENDIX C:  SAE REPORTING FLOW CHART ...................................... Error! Bookmark not defined. 
24. 
APPENDIX D:  AMENDMENT HISTORY ............................................................................................. 34 
 
 

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1. KEY TRIAL CONTACTS 
 
Chief Investigator 
Dr Elizabeth Orchard 
Department of Cardiology 
Oxford University Hospitals 
Elizabeth.orchard@ouh.nhs.uk 
Sponsor 
Oxford University Hospitals NHS Foundation Trust  
Headley Way 
Oxford OX3 9DU 
ouh.sponsorship@ouh.nhs.uk 
Funder(s) 
The Swedish Knowledge Foundation 
Statistician 
Dario Salvi 
Senior Lecturer, Malmo University, Sweden 
dario.salvi@mau.se 
 
2. LAY SUMMARY  
The six-minute walk test (6MWT) is a standard method for measuring exercise capacity in patients with 
cardiopulmonary disease such as pulmonary hypertension (PAH) and measures how far a patient can 
walk in 6 minutes. The test is usually performed in the hospital, by walking along a hospital corridor. 
Since the outbreak of SARS-CoV-2, there has been a need to minimise patient contact with hospitals and 
their staff to reduce transmission of the virus. In a previous research project called 6APP, we designed, 
developed and evaluated a mobile phone app, to allow them to perform the 6MWT in the community. 
Given the current circumstances, cardiovascular outpatients including patients in the PHT clinic in Oxford 
are being recommended to use an app derived from that project to provide their 6MWT distance to the 
clinical team for assessment, in addition to their symptoms and general well-being. This is felt to be more 
appealing to the patients, and would reduce the time spent in hospital on the day of their outpatient 
appointment. 
We would like to measure the usefulness of adopting remote, mobile-based 6MWT among hospital 
outpatients, within the constraints imposed by the SARS-COV2 pandemic. 
3. SYNOPSIS 

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The Trial will review the use of a mobile-based 6MWT by hospital outpatients during the coronavirus 
pandemic and evaluate its use 
Trial Title 
Evaluation of the usefulness of adopting remote, mobile-based 6MWT 
among hospital outpatients (the 6-APP now Study), within the 
constraints imposed by the SARS-COV2 pandemic. 
Internal ref. no. (or 
short title) 
6-APPnow Study 
Trial registration 
Clinical Trials. gov 
Sponsor  
Oxford University Hospitals NHS Foundation Trust 
 Headley Way, Oxford, OX3 9DU 
Funder  
NIHR BRC and the Swedish Knowledge Foundation 
Trial Design 
Patient survey to evaluate their use of the 6 minute walk test 
smartphone app as a surrogate for regular clinic 6MWT. 
Trial Participants 
Patients using 6 minute walk tests for managing cardiopulmonary 
function or disease management 
Sample Size 
250-500 patients attending the outpatient clinics 
Planned Trial Period  
Q2 2021 – Q2 2022 
Planned Recruitment 
period  
Q2 2021 – Q2 2022 
 
Objectives 
Outcome Measures 
Timepoint(s)  
Primary 
 
To 
assess 
whether 
patients are able and 
willing 
to 
use 
a 
smartphone app for the 
6MWT  
 
 
 
Percentage of participants 
who perform at least one 
app-based 6MWT before 
patient consultation. 
 
 
 
At 3, 6, 9 
and 
12 
months 
after 
the 
start of the 
study. 
Secondary 
 
To assess the accuracy of 
the 
app-based 
measurement. 
  
  
To 
assess 
whether 
differences 
in 
distance 
walked 
altered 
management of patients. 
 
Measurement of walked 
distance 
(6MWD) 
measured 
by 
the 
app 
compared with a trundle 
wheel reference. 
  
Number 
of 
clinical 
investigations 
and 
multidisciplinary 
team 
discussion 
triggered 
by 
variations 
in 
app-based 
6MWD. 
 
12 months 
 
 
 
 
 
 
 
At 3, 6, 9 
and 
12 
months 
after 
the 
start of the 
study. 
 

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To assess the usability and 
acceptance of the app. 
 
 
To collect raw data from 
phones’ sensors to allow 
the 
development 
of 
future algorithms for app-
guided 6MWT. 
 
To determine whether the 
use of the 6MWT reduces 
time spent and number in 
hospital visits. 
 
 
 
To compare the use of 
6MWT during pandemic 
with pre-pandemic use. 
 
 
 
 
Standard 
usability 
and 
acceptance questionnaires, 
semi-structured interviews. 
 
Localisation position (GPS), 
speed, acceleration, step 
count, gyroscope samples 
collected during 6MWT. 
 
 
Time spent in hospital 
attendances and number 
of hospital visits made 
during 
use 
of 
the 
6MWTapp compared with 
previous periods. 
 
Total number of 6MWTs 
performed 
during 
2020 
pandemic period compared 
with pre-pandemic period. 
 
 
 
12 months 
 
 
 
12 months 
 
 
 
 
 
 
12 months 
 
 
 
 
 
 
 
12 months 
 
4. ABBREVIATIONS 
 
AE 
Adverse event 
AR  
Adverse reaction 
CI 
Chief Investigator 
CRA 
Clinical Research Associate (Monitor) 
CRF 
Case Report Form 
CRO  
Contract Research Organisation 
CT 
Clinical Trials 
CTA 
Clinical Trials Authorisation 
CTRG 
Clinical Trials and Research Governance 
DMC/DMSC 
Data Monitoring Committee / Data Monitoring and Safety Committee 
FC 
Functional capacity 
GCP 
Good Clinical Practice 

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GP 
General Practitioner 
ICF 
Informed Consent Form 
NHS 
National Health Service 
NRES 
National Research Ethics Service 
NYHA 
New York Heart Association 
OUH 
Oxford University Hospitals 
PAH 
Pulmonary arterial hypertension 
PH 
Pulmonary hypertension 
PI 
Principal Investigator 
PIL 
Participant/ Patient Information Leaflet 
R&D 
NHS Trust R&D Department 
REC 
Research Ethics Committee 
SOP 
Standard Operating Procedure 
VO2 Max 
Maximal oxygen consumption on exercise test 
6MWD 
Six minute walk distance 
6MWT 
Six minute walk test 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TMF 
Trial Master File 
TSG 
Oxford University Hospitals NHS Foundation Trust / University of Oxford Trials Safety 
Group 
 
5. BACKGROUND AND RATIONALE 
5.1. Telemedicine in the context of COVID19 
Since the outbreak of SARS-CoV-2, health care systems have been subject to increased pressures. This is 
mainly due to infected patients being admitted to the medical wards and intensive care units, but also  
due to the requirement to reduce exposure of both healthcare professionals and patients to COVID by 
minimising contact.  
There are indications that reduced access to healthcare services during the pandemic is responsible for 
more than half of excess deaths in the United States1. In response to this, the CDC is advocating the use 
of telemedicine to keep providing a remote version of healthcare services2. A study of telemedicine 
 
1 https://jamanetwork.com/journals/jama/fullarticle/2768086 
2 https://www.cdc.gov/coronavirus/2019-ncov/hcp/telehealth.html 

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services in China used during COVID-19 pandemic showed that they reduced burden on hospitals, 
prevented overcrowding, reduced the risk of cross-infection, and relieved patients' anxiety3. The use of 
telemedicine is also being developed in Europe, where many patients are being denied the use of clinical 
services, like cardiac rehabilitation4, because of centres being closed. In the context of the NHS, an 
increased use of telemedicine services is being observed5. The NHS long-term plans do, in fact, include 
tele-consultations as a pillar for its sustainability6. Healthwatch have produced useful advice for 
outpatient clinicians to consider avoiding asking patients to attend physical outpatient appointments 
where a clinically-appropriate and accessible alternative exists.  Where an appointment is clinically 
necessary, the national benchmark is that at least 25% could be conducted by telephone or video 
including 60% of all follow-up appointments. Initial promising results are being seen in the context of 
diabetes, where virtual clinics are recommended as mitigation to the pandemic7. 
5.2. The 6MWT 
To assess patient’s exercise capacity, the six-minute walk test (6MWT) is a standard method used in 
patients with cardiopulmonary disease such as Heart Failure (HF) or Pulmonary arterial Hypertension8 
(PAH). The 6MWT measures how far a patient can walk in 6 minutes. Walking is an activity performed 
every day, by most patients except for those most severely limited. By assessing patients’ ability to 
exercise, the 6MWT provides a global assessment of respiratory, cardiovascular, neuromuscular and 
cognitive function. The 6MWT does not differentiate what limits the patient, nor does it assess maximal 
exercise capacity. Instead, the 6MWT allows the patient to exercise at a daily functional level, and is a 
useful tool for assessing changes after a therapeutic intervention, and correlates with a subjective 
improvement in dyspnoea9. 
In PAH the 6MWT is used to evaluate patients’ response to treatment, with an increase in 6MWT 
distance of greater than 42 m being considered a clinically significant improvement10. Furthermore, 
change in 6MWT distance correlates with VO2 max, NYHA class and mortality in those patients, providing 
an objective assessment of disease progression, prognosis and response to treatment. It is a universally 
accepted test as it is safe and easily performed by the patient. 
5.3. Cardiovascular outpatient management during the pandemic 
 
3 https://mhealth.jmir.org/2020/7/e19417/ 
4
 https://clinowl.com/the-future-is-now-a-call-for-action-for-cardiac-telerehabilitation-in-the-covid-19-pandemic-
from-the-secondary-prevention-and-rehabilitation-section-of-the-european-association-of-preventive-cardiolo/ 
5 https://digital.nhs.uk/coronavirus/nhs-digital-tech-analytics 
6 https://www.bmj.com/content/364/bmj.l84.long 
7 https://www.jmir.org/2020/8/e21609/ 
8 https://pubmed.ncbi.nlm.nih.gov/12890299/ 
9 https://www.ahajournals.org/doi/full/10.1161/circulationaha.112.105890 
10 https://www.atsjournals.org/doi/full/10.1164/rccm.201203-0480oc 

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Since the outbreak of SARS-CoV-2, the standard regime of care for outpatients with cardiovascular 
disease has been affected.  
For example, in PAH patients, the normal regime of a 6MWT, echocardiogram and face to face 
consultation was abandoned as those patients were felt to be extremely clinically vulnerable, and 
therefore were recommended to shield at home. Therefore patients needed to be assessed without 
having any face to face contact, unless in an emergency. This situation continued for five months until 
August, when shielding was initially withdrawn, however we are now back in this situation with a highly 
transmissible variant SARS-CoV-2. Therefore the need to reduce time spent in hospital continues as the 
virus continues within the community. 
In cardiovascular outpatient clinics in Oxford, patients are now being regularly contacted by phone to 
replace face to face visits. During these phone calls, questions about the general status of the patient are 
asked, i.e. how far they think they can walk and whether they have noticed a change in their exercise 
capacity or functional capacity, but currently no objective data, like the results of the 6MWT, are 
available for assessment. 
5.4. Telemedicine services for pulmonary hypertension 
In a previous research project called 6APP, we designed, developed and evaluated a mobile-health “app” 
(a type of telemedicine where patients use their mobile phones), to allow them to perform the 6MWT in 
the community. We hypothesized that a test conducted by patients, in their environment, would reflect 
more the patient’s functional status, would free up healthcare resources and would be less stressful and 
costly for the patients themselves. 
The app allowed patients to perform the test both indoors, by walking back and forth along a corridor of 
fixed length, and outdoors, using the localization system (like the GPS). In our study with 30 PAH 
patients, we proved that the app is accurate when used outdoors, the measurements are reliable and 
repeatable and the method is well-accepted by patients11. 
After these encouraging results, the app has been simplified and made available for free for both 
Android and iPhones under the name of “Timed Walk”. The original app was developed by Dario Salvi at 
the Institute of Biomedical Engineering of the Oxford University. The current app, which uses the same 
validated outdoors test approach, is instead maintained by the University of Malmo, Sweden, where Dr. 
Salvi is currently employed. 
Given the current circumstances, the PH clinic in Oxford and other cardiovascular outpatient clinics are 
recommending patients to use the Timed Walk app, the results of which are being used by the clinical 
team to assess patients in addition to their symptoms and general well-being. This is felt to be more 
appealing to the patients, and would reduce the time spent in hospital on the day of their outpatient 
appointment. The app only allows outdoor tests (as these proved to be more reliable and practical) and 
to share 6MWT data via email if patients want to. 
 
11 https://mhealth.jmir.org/2020/1/e13756/ and https://preprints.jmir.org/preprint/22748 

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It has to be noted that the app is only used to identify trends and, when deterioration is detected, for 
example reduction in 6MWT distance walked or change in Borg score, patients are invited to the clinic 
for further assessment. 
 
6. OBJECTIVES AND OUTCOME MEASURES 
The population to be studied is composed of hospital outpatients who have conditions where the 6MWT 
is routinely used in clinical care, and/or are using the 6APP as an alternative. 
The objective is:  To evaluate the usefulness of adopting remote, mobile-based 6MWT among hospital 
outpatients, within the constraints imposed by the SARS-COV2 pandemic. 
 
Objectives 
Outcome Measures 
Timepoint(s) of evaluation 
of this outcome measure (if 
applicable) 
Primary Objective 
To assess whether patients are 
able and willing to use a 
smartphone app for the 6MWT 
  
Percentage 
of 
participants 
who perform at least one app-
based 6MWT before patient 
consultation. 
 
At 3, 6, 9 and 12 months 
after the start of the study. 
Secondary Objectives 
To assess the accuracy of the 
app-based measurement. 
 
To assess whether differences 
in distance walked according to 
the app altered management of 
patients. 
 
 
 
Comparison 
of 
walked 
distance (6MWD) measured by 
the app versus a trundle wheel 
reference. 
Number 
of 
clinical 
investigations 
and 
multidisciplinary 
team 
discussion 
triggered 
by 
variations 
in 
app-based 
6MWD. 
 
 
12 months. 
 
 
At 3, 6, 9 and 12 months 
after the start of the study. 
 
 

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To assess the usability and 
acceptance of the app. 
 
 
To collect raw data from 
phones’ sensors to allow the 
development 
of 
future 
algorithms 
for 
app-guided 
6MWT. 
 
To determine whether the use 
of the 6MWT reduces time 
spent and number in hospital 
visits. 
 
 
To compare the use of 6MWT 
during pandemic with pre-
pandemic use. 
 
 
Standard 
usability 
and 
acceptance 
questionnaires, 
semi-structured interviews. 
 
 
Localisation 
position 
(GPS), 
speed, 
acceleration, 
step 
count, 
gyroscope 
samples 
collected during 6MWT. 
 
Time 
spent 
in 
hospital 
attendances and number of 
hospital visits made during use 
of the 6MWT compared with 
previous periods. 
 
 
 
Total 
number 
of 
6MWTs 
performed 
during 
2020 
pandemic period compared 
with pre-pandemic period. 
12 months. 
 
 
 
 
12 months. 
 
 
12 months. 
 
 
 
 
12 months. 
 
7. TRIAL DESIGN 
The study consists of 2 parts. The first consists of collecting data about the use of an app for phone-
based 6MWT, the “Timed Walk” app, during the outpatient consultations (via phone or in clinic). These 
data will be used to understand if patients are using the app and if the measurements produced by the 
app are being used for clinical decisions. The data will be collected on an electronic spreadsheet, using a 
coding schema, which will be analysed every 3 months for quality assurance and at the end of the study 
for the final statistics. 
The second part of the study will involve a sample of 15 patients who will be sent a trundle wheel and 
will be invited to perform 10 6MWT using the app and the trundle wheel simultaneously. The data 
collected in this way will be used to A) assess the accuracy of the app measurement and B) create a 
public anonymised dataset for the development of future algorithms for the 6MWT. The same group of 
patients will also be invited to answer a questionnaire about the usability and acceptance of the app and 
will be interviewed about the same topics. 

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This study is a collaboration between the Oxford University Hospital (OUH) Trust and Malmo University, 
Sweden. Malmo University is the main developer and maintainer of the Timed Walk app, and their 
interest focuses on the accuracy and usability of the app. The OUH Trust is, on the other hand, interested 
in using the app to remotely monitor their cardiac patients and assessing its impact on the management 
of those patients. Malmo University will therefore offer engineering work both in terms of the app and 
data analysis and OUH will recruit patients and collect data. 
8. PARTICIPANT IDENTIFICATION 
8.1. Trial Participants 
All patients under the care of the cardiovascular clinics in Oxford, who are able to walk and use a 
smartphone. 
8.2. Inclusion Criteria 
 
• 
Participant is willing and able to give informed consent for participation in the study. 
• 
Male or Female, aged 18 years or above. 
• 
Under the care of the cardiovascular clinic at OUH Owning or having access to a smartphone with 
either Android or iOS 
• 
Being able to use a smartphone app 
• 
Being able to walk 
 
A subgroup of 15 patients will be identified among those who are more willing to use the app to perform 
the additional measurements with the trundle wheel and to answer the questionnaire. This group should 
include a balanced representation of age groups and sexes. 
8.3. Exclusion Criteria 
The participant may not enter the study if ANY of the following apply: 
• 
Long term oxygen therapy 
• 
Cognitive impairments 
• 
Cannot use a smartphone 
• 
Pregnancy 
• 
Not able to complete a 6MW 

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• 
Any other significant disease or disorder which, in the opinion of the Investigator, may either put 
the participants at risk because of participation in the trial, or may influence the result of the 
trial, or the participant’s ability to participate in the trial. 
9. TRIAL PROCEDURES 
9.1. Recruitment 
Outpatients undergoing follow up in the cardiovascular outpatient clinics in Oxford will be eligible for 
participation. Some of these patients are already using the app, regardless of the study, for example in 
the case of the pulmonary hypertension clinic. They will be approached by a member of the clinical team 
for consideration and recruited during a regular consultation either via phone call or during a visit in the 
clinic. They will be asked to download the app over the Internet. 
9.2. Screening and Eligibility Assessment 
Patients will be screened every week according to the scheduled clinic phone calls or visits. A list of 
candidates who match inclusion and exclusion criteria (except use of smartphone) will be prepared 
before consultation. 
During the consultation, patients will be asked about their access and fluency with smartphones to 
further verify compliance with the criteria. 
The subgroup of 15 patients will be chosen among those using the app depending on the frequency of 
their use of the app and general willingness to participate in the study. 
9.3. Informed Consent 
Patients to be recruited will be sent a study information sheet and consent form by post before being 
recruited. The information sheet will explain how to download and use the app and will introduce the 
study. Informed consent forms will have to be signed and sent by post (a pre-stamped folder will be 
prepared). For those patients attending the clinic physically, the information sheet and the informed 
consent will be given and signed during the day of the clinic. 
Signed informed consents will be collected by the research team, either on the day of their appointment 
or if a tele-medicine appointment, it will be sent back to the research team. If any patient denies consent 
or withdraws, the reason will be recorded on the spreadsheet. 
The subgroup of 15 patients selected for part 2 of the study will be sent an additional leaflet with 
instructions and further consent will be sought with a different consent form. 
The participant must personally sign and date the latest approved version of the Informed Consent form 
before any trial specific procedures are performed. 

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Written and verbal versions of the Participant Information and Informed Consent will be presented to 
the participants detailing no less than: the exact nature of the trial; what it will involve for the 
participant; the implications and constraints of the protocol; the known side effects and any risks 
involved in taking part. It will be clearly stated that the participant is free to withdraw from the trial at 
any time for any reason without prejudice to future care, without affecting their legal rights and with no 
obligation to give the reason for withdrawal. 
The participant will be allowed as much time as wished to consider the information, and the opportunity 
to question the Investigator, their GP or other independent parties to decide whether they will 
participate in the trial. Written Informed Consent will then be obtained by means of participant dated 
signature and dated signature of the person who presented and obtained the Informed Consent. This 
consent will be obtained at the time of either their clinic appointment, either face to face or by 
telephone and the consent form returned by post. The person who obtained the consent must be 
suitably qualified and experienced, and have been authorised to do so by the Chief/Principal 
Investigator. A copy of the signed Informed Consent will be given to the participant. The original signed 
form will be retained at the trial site, and a copy to be filed in medical records. 
9.1.  Enrolment 
All eligible patients will be enrolled from outpatient clinics. They will be recruited to the trial and not 
randomised . 
9.2. Baseline Assessments 
There is no baseline assessment of each patient, however, we will request baseline statistics about 
6MWT performed during 5 years previous to the pandemic. These data will be pulled from the electronic 
health record. Only the patient ID and the date of the 6MWT are needed for this analysis. 
9.3. Subsequent Visits 
Part 1: logging of events 
At each consultation, either through phone or face to face visit, the clinician who contacts the patient 
will log on the spreadsheet the distance walked and a series of study-related events, marked with a code. 
Coding is needed to simplify and automate later analysis. The following is an example of the structure of 
the spreadsheet: 
Patient 
hospital 
number 
Date 
Event 
Comments 
 
 
 
 
 
Events codes are explained in the following table: 

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Event 
Code 
Example comments 
The patient accepts to join the 
study and provides consent. 
RECRUIT-ACCEPT 
Patient has accepted to join the 
study. 
The patient denies consent and 
does not join the study. 
RECRUIT-DENY 
Patient denies consent because 
of lack of time. 
The patient has decided to 
withdraw from the study. 
RECRUIT-WITHDRAW 
Patient’s 
conditions 
have 
worsened and she cannot walk 
6 minutes any more. 
The patient declares to have 
the app installed on a phone 
he/she can use. 
APP-OK 
Patient has downloaded the 
app, 
everything 
works 
as 
expected.  
The 
patient 
declares 
that 
he/she is having technical 
issues with the app. 
APP-ISSUE 
The app crashes when started 
on iPhone 11. 
The patient shares a 6MWT not 
older than 2 weeks either 
through email or by telephone. 
APP-6MWT 
Date: 3/5/2021, distance: 420 m 
The 
patient 
needs 
further 
evaluation because of changed 
medical conditions. The role of 
the app-based 6MWT is also 
coded depending on whether it 
was irrelevant to the decision, 
partially 
involved 
or 
fundamental for the decision. 
The event is logged once per 
decision (further contacts with 
the patient resulting from the 
decision should not include the 
tag). 
NEW-EVAL-NO-6MWT 
NEW-EVAL-PART-6MWT 
NEW-EVAL-FULL-6MWT 
The patient shows a general 
deterioration, last 6MWT was 
below 
300m. 
An 
MDT 
is 
required. 
The patient needs a change in 
the treatment. The role of the 
app-based 6MWT is specified 
as above. 
NEW-TREAT-NO-6MWT 
NEW-TREAT-PART-6MWT 
NEW-TREAT-FULL-6MWT 
Medication regime increased 
because of a lower 6MWD in 
the last 4 weeks. 

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Regular clinic 6MWT 
CLINIC-6MWT 
Date: 
23/4/2021, 
distance: 
450m 
Additional observations 
EXTRA-OBS 
Because of reduced risk of 
corona infection, patient is 
invited to the clinic. 
 
A list of possible codes with their explanation will be included in a tab of the spreadsheet. 
Part 2: accuracy, usability and acceptance assessment 
Fifteen patients will be selected based on their ability and engagement and invited to perform 10 
additional 6MWT using the app and a trundle wheel simultaneously. An additional informed consent 
form will be sent to these patients. To those who accept, the research team will send a pre-packaged 
trundle wheel. 
At the end of each of these tests, patients will need to share the raw data collected by the phone during 
the test through the app’s “share” button. When prompted, users will choose to share the data through 
email and send them to a special address that will be set up for the purpose in Malmo. The app will 
automatically attach to these emails the data it used to compute the distance including the patient’s 
geographical position (longitude, latitude, altitude, speed) and inertial sensors data (acceleration, 
inclination, detected steps). Patients will be instructed to also add the distance measured by the trundle 
wheel to the message for reference. 
In order to study the accuracy under different conditions, patients will be instructed to perform 5 tests 
walking along paths the shape of which is known to obtain the best distance estimation (straight or 
gently curved paths). Patients will also perform 5 more tests walking over paths that may be more 
“challenging” for the app, for example those including narrow curves, U-turns or in confined spaces. 
If less than 15 trundle wheels are purchased for the study, patients will be asked to send the meters back 
to the clinical centre once the 10 tests are completed. Trundle wheels will be then cleaned and 
disinfected and sent to another batch of patients until covering 15 subjects. 
 
Towards the end of the study, patients of the subgroup will be sent an online questionnaire related to 
usability and acceptance to be filled in electronically.  The questionnaire will be based on the validated 
and widely used uMARS questionnaire 12 and the Mobile Health Technology Acceptance Model 
(MoHTAM) questionnaire13. 
Five to ten patients will be selected for an additional phone-based short interview. Notes from the 
interview will be taken and voice will be recorded if technically possible. The interview will aim at 
 
12 https://mhealth.jmir.org/2016/2/e72/ 
13 https://ieeexplore.ieee.org/abstract/document/6149947 

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understanding causes and motivations for use or non-use of the app, based on a technology acceptance 
model. Patients will have to sign an authorization to allow the registration of their voice. This will be sent 
together with the informed consent. 
9.4. Sample Handling 
No samples will be taken. 
9.5. Early Discontinuation/Withdrawal of Participants  
During the course of the trial a participant may choose to withdraw early from the trial treatment at any 
time.  This may happen for a number of reasons, including but not limited to:   
• 
The occurrence of what the participant perceives as an intolerable AE.   
• 
Inability to comply with trial procedures  
• 
Participant decision  
 
Participants may choose to stop study assessments but may remain on study follow-up.  
Participants may also withdraw their consent, meaning that they wish to withdraw from the study 
completely. Patients are allowed to withdraw at any time. In case of withdrawal, they will communicate 
it to the staff who will log the withdrawal on the spreadsheet together with the reason. The patients will 
remain under regular active follow up 
 
1) Participants can withdraw from the study but permit data obtained up until the point of 
withdrawal to be retained for use in the study analysis.  No further data would be collected after 
withdrawal.  
2) Participants can withdraw completely from the study and withdraw the data collected up until 
the point of withdrawal. The data already collected would not be used in the final study analysis.  
 
In addition, the Investigator may discontinue a participant from the trial treatment at any time if the 
Investigator considers it necessary for any reason including, but not limited to: 
• 
Pregnancy 
 
The type of withdrawal and reason for withdrawal will be recorded in the CRF. 
If the participant is withdrawn due to an adverse event, the Investigator will arrange for follow-up visits 
or telephone calls until the adverse event has resolved or stabilised. 
 
9.6. Definition of End of Trial 

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The study ends 12 months after the first patient has been recruited or when restrictions to clinical 
practice due to the pandemic are lifted. 
 
10. TRIAL INTERVENTIONS  
Not applicable 
 
 
11. SAFETY REPORTING 
The study is low risk however, in the event of an adverse event (AE) or serious adverse event (SAE) 
occurring to a participant this would be reported as per the below. 
11.1. 
Adverse Event Definitions 
Adverse Event (AE) 
Any untoward medical occurrence in a participant to whom a medicinal 
product has been administered, including occurrences which are not 
necessarily caused by or related to that product. 
Device deficiency 
Inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance.  Device deficiencies 
include malfunctions, use errors and inadequate labelling. 
Device deficiencies that did not lead to an adverse event, but could 
have led to a medical occurrence if suitable action had not been taken, 
or intervention had not been made or if circumstances had been less 
fortunate 
User error 
Act or omission of an act that results in a different medical device 
response than intended by the manufacturer or expected by the user.  
Use error includes slips, lapses and mistakes.  An unexpected 
physiological response of the subject does not itself constitute a use 
error. 
 
NB: to avoid confusion or misunderstanding of the difference between the terms “serious” and “severe”, 
the following note of clarification is provided: “Severe” is often used to describe intensity of a specific 
event, which may be of relatively minor medical significance. “Seriousness” is the regulatory definition 
supplied above. 
The following definitions will be used to determine the severity rating for all adverse events: 

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● Mild: awareness of signs or symptoms that does not interfere with the subject’s usual activity or 
is transient that resolved without treatment and with no sequelae. 
● Moderate: a sign or symptom, which interferes with the subject’s usual activity. 
● Severe: incapacity with inability to do work or perform usual activities. 
  
11.2. 
Assessment results outside of normal parameters as AEs and SAEs 
All adverse events (including ADEs) and device deficiencies occurring during the course of the study will 
be recorded on the CRF whether or not attributed to the trial device. The information recorded will 
include but not be limited to: 
● A description of the event 
● The dates of the onset and resolution 
● Action taken 
● Outcome 
● Assessment of relatedness to the device 
● Whether the AE is serious or not 
● Whether the AE arises from device deficiency 
● Whether the AE arises from user error 
 
The severity of events will be assessed on the following scale:  1 = mild, 2 = moderate, 3 = severe. 
Issues with the device will also be logged on the study spreadsheet using the APP-ISSUE code. 
AEs/ADEs considered related to the device as judged by a medically qualified investigator or the Sponsor 
will be followed either until resolution, or the event is considered stable. 
It will be left to the Investigator’s clinical judgment to decide whether or not an AE/ADE is of sufficient 
severity to require the participant’s removal from the study.  A participant may also voluntarily withdraw 
from the study due to what he or she perceives as an intolerable AE/ADE.  If either of these occurs, the 
participant must undergo an end of trial assessment and be given appropriate care under medical 
supervision until symptoms cease, or the condition becomes stable. 
11.3. 
Assessment of Causality 
The relationship of each adverse event to the trial must be determined by a medically qualified individual 
according to the following definitions: 
Related: The adverse event follows a reasonable temporal sequence from trial. It cannot reasonably be 
attributed to any other cause.   
Not Related: The adverse event is probably produced by the participant’s clinical state or by other 
modes of therapy administered to the participant. 
11.4. 
Procedures for Reporting Adverse Events  

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All AEs occurring during the safety window for the trial as defined above that are observed by the 
Investigator or reported by the participant, will be reported on the trial CRF,  
The following information will be reported on the CRF: description, date of onset and end date, severity, 
assessment of relatedness to trial device and action taken.  Follow-up information should be provided as 
necessary. 
The severity of events will be assessed on the following scale:  1 = mild, 2 = moderate, 3 = severe. 
Non-serious AEs considered related to the trial as judged by a medically qualified investigator or the 
Sponsor will be followed up until the event is stable. 
11.5. 
Definition of Serious Adverse Events 
A serious adverse event is any untoward medical occurrence that: 
• 
results in death 
• 
is life-threatening 
• 
requires inpatient hospitalisation or prolongation of existing hospitalisation 
• 
results in persistent or significant disability/incapacity 
• 
consists of a congenital anomaly or birth defect. 
Other ‘important medical events’ may also be considered a serious adverse event when, based upon 
appropriate medical judgement, the event may jeopardise the participant and may require medical or 
surgical intervention to prevent one of the outcomes listed above. 
NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the 
participant was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more severe. 
11.6. 
Reporting Procedures for Serious Adverse Events 
A serious adverse event (SAE) occurring to a participant should be reported to the REC that gave a 
favourable opinion of the study where in the opinion of the Chief Investigator the event was ‘related’ 
(resulted from administration of any of the research procedures) and ‘unexpected’ in relation to those 
procedures. Reports of related and unexpected SAEs should be submitted within 15 working days of the 
Chief Investigator becoming aware of the event, using the HRA report of serious adverse event form (see 
HRA website). 
 
12. STATISTICS 
12.1. 
Description of Statistical Methods 
The analysis of the data involves reviewing the spreadsheet. The use of the labels will simplify analysis 
and will avoid manual coding. The R programming environment will be used to compute statistics. 

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To assess whether patients are able and willing to use a smartphone app for the 6MWT. 
For each recruited patient, we will compute the number of app-based 6MWT results available since they 
confirmed that they have downloaded the app. From this number, we will compute a histogram of the 
number of available app-based 6MWT per patient and the percentage of participants who perform at 
least one app-based 6MWT prior to every consultation. 
To assess the accuracy of the app-based measurement. 
We will compare the walked distance measured by the app with the distance measured by the trundle 
wheel for those tests that provide both information. We will compute descriptive statistics (mean, 
standard deviation, percentiles) of the difference and BlandAltman plots. 
To assess whether differences in distance walked according to the app altered management of 
patients. 
We will use the codes related to clinical evaluations to compute descriptive statistics about the 
frequency of those evaluations and about how many of them were triggered by observed changes of the 
6MWD. 
To assess the usability and acceptance of the app. 
We will compute descriptive statistics of the results of the usability and acceptance questionnaires. We 
will use thematic content analysis to analyse the interview transcripts. 
To collect raw data from phones’ sensors to allow the development of future algorithms for app-
guided 6MWT. 
We will also use the sensors data sent from patients involved in part 2 of the study to identify strategies 
to improve the algorithm that computes the distance. The availability of this type of data would be 
unique and would open interesting research in computer science and biomedical engineering. The 
University of Malmo is planning to experiment signal processing (Kalman filters, FIR filters) and machine 
learning (LSTM RNN) techniques to improve the accuracy of the current GPS-based algorithm and to 
explore the possibility to develop an indoor version of the algorithm based purely on the inertial sensors 
(acceleration). 
To determine whether the use of the 6MWT reduces time spent and number in hospital visits. 
We will estimate the time spent in hospital attendances and the number of hospital visits made during 
the study period and compare it with previous 5 years. 
Compare the use of 6MWT during pandemic with standard care. 
We will compute statistics regarding the number of 6MWT available per patient over the last 5 years and 
compare them with the number of available 6MWT results within the study period. This will help identify 
the difference between the number of 6MWT per patient per year before the pandemic (standard 
6MWT in clinic) and after the pandemic (using the app). 
 

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12.2. 
Sample Size Estimation 
For part 1, we will not use sampling as we aim to involve all patients in the cardiovascular clinics who 
require a 6MWT and are able to use the app. 
With regards to part 2, our 15 patients cohort is in agreement with typical usability studies. 
12.3. 
Analysis Populations  
All participants. 
13. DATA MANAGEMENT 
13.1. 
Data Recording and Record Keeping 
Part1 
The data will be collected using an electronic spreadsheet shared by the team at OUH. Patients will be 
asked about their recent app-based 6MWTs during visits or phone calls and will be invited to share the 
log of their app-based 6MWTs by email or telephone with the clinician. If patients have technical 
problems and need assistance, they can contact the team in Sweden, who are responsible for the 
development of the Timed Walk app. In this case, the patient can disclose their identity to the team in 
Sweden if they wish. 
Every 3 months, the spreadsheet will be anonymised by substituting the patient hospital number with an 
internal ID and sent to Malmo University for analysis in an encrypted email. 
 
Part 2 
Results of the additional 6MWTs performed by the subgroup of 15 patients will be shared by email with 
the team in Malmo. We will seek explicit consent to share these data, both as identifiable information 
for the researchers in Sweden and in an anonymous format publicly.  
In order to anonymise the data before publication, the following strategy will be used: 
● Email addresses will be removed and an internal patient ID will be used to group tests belonging 
to the same user. 
● Timestamps will be formatted only in relation to the start of the test. 
● Location data will be anonymised using a random offset on both longitude and latitude (resulting 
in the trace to keep its original shape, but the position to be placed in a random place). 
● Any unique identifier of the phone will be removed, but the make and model may be kept in 
order to compare different phones characteristics. 
 
Electronic questionnaires for usability and acceptance will be set up using Microsoft Forms. Malmo 
University has an agreement with Microsoft to use the product for research purposes and guarantees 

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that data is protected according to the GDPR. The questionnaire will not require personal information to 
be collected and will be deleted after analysis. 
Audio recording of the interviews will be collected by OUH and sent electronically to Malmo University 
for analysis. These files will not be linked to the identity of the patient, they will be transcribed and 
deleted immediately after. All files containing patients’ anonymised data exchanged between Malmo 
and OUH will be encrypted using a password which will be communicated verbally during a phone call. 
Paper forms will be kept by the Principal Investigator at OUH. 
Identifiable patients data will be kept by OUH for up to 10 years after study completion or until ethical 
approval terminates, whichever is sooner. 
13.1. 
Source Data 
Source documents are where data are first recorded, and from which participants’ CRF data are 
obtained. These include, but are not limited to, hospital records (from which medical history and 
previous and concurrent medication may be summarised into the CRF), clinical and office charts, 
laboratory and pharmacy records, diaries, microfiches, radiographs, and correspondence. 
CRF entries will be considered source data if the CRF is the site of the original recording (e.g. there is no 
other written or electronic record of data).  All documents will be stored safely in confidential conditions. 
On all trial-specific documents, other than the signed consent, the participant will be referred to by the 
trial participant number/code, not by name. 
13.2. 
Access to Data 
Direct access will be granted to authorised representatives from the Sponsor and host institution for 
monitoring and/or audit of the study to ensure compliance with regulations. 
All authorised representatives will be employed by the Oxford University Hospitals Trusts (OUH), hold 
honorary contracts with OUH, or hold a valid NHS Research Passport 
Malmo University will access data collected in part 1 of the study only in an anonymised format, while 
data collected in phase 2 will be sent using patients’ emails, and therefore will be identifiable. Direct 
contact with patients may be allowed, with patients consent, for solving technical issues, via email or 
phone. 
After anonymisation, data collected in phase 2 will be made public through websites used for the sharing 
of research data like Physionet. Anonymised data will be made available with a permissive license like 
Creative Commons BY-SA 4.014. 
13.3. 
Data Recording and Record Keeping 
 
14 https://creativecommons.org/licenses/by-sa/4.0/ 

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On all trial-specific documents, other than the signed consent, the participant will be referred to by the 
trial participant number/code, not by name. 
Spreadsheets with logs of part 1 will be stored on computers at the John Radcliffe Hospital, in offices 
normally locked when not in use and on computers that require authorised personnel login to be used. 
Before being sent to Malmo, spreadsheets will be pseudonymised with a study-specific participant and 
encrypted using a password shared verbally during a call.  
Data collected during the 6MWT (acceleration, distance, location) in part 2 will be sent by participants, 
using their emails, to a specific email account setup by Malmo University and accessible only by 
researchers involved in the study. The files in attachment will be anonymised and made public. 
Data sent to Malmo in both parts 1 and 2 will be kept on Malmo’s researcher’s computers. These are 
encrypted and only accessible by authorised personnel. The data will be kept by Malmo until the 
publication of the results and no longer than 5 years after the end of the project. 
Data 
Identifiable? 
Transmission 
Storage 
Retention 
OUH 
Malmo 
OUH 
Malmo 
OUH 
Malmo 
Part 1 logs 
Yes 
Study IDs 
Encrypted 
emails from 
OUH to 
Malmo 
Computers 
in locked 
rooms 
Encrypted 
computers 
10 
years 
Until 
publication or 
5 years 
Part 2 6MWT 
raw data 
NA 
Temporarily, 
until 
anonymised 
Email from 
participants 
to Malmo 
NA 
Encrypted 
computers 
NA 
Forever after 
anonymization 
Part 2 
interviews 
audio files 
Yes 
Study IDs 
Encrypted 
emails from 
OUH to 
Malmo 
Computers 
in locked 
rooms 
Encrypted 
computers 
10 
years 
Until 
publication or 
5 years 
Part 2 
questionnaires 
NA 
No 
Participants  
fill web 
forms 
NA 
Microsoft 
forms 
managed 
by Malmo  
NA 
Until 
publication or 
5 years 
 
14. QUALITY ASSURANCE PROCEDURES 
Data produced on the electronic health record will be analysed every 3 months to assess their quality by 
the research team. Assessment will focus on the presence of the keywords, their correct spelling and the 
consistency of the data. 
Upon suspicion of the app not being able to produce accurate data, or of misuse of the app, the clinical 
team may request patients to share the details of a test. These data can then be used on a web tool to 
visualise the path walked, altitude and statistics that may help the clinician to identify the problem. The 
web tool retains the data locally in the browser and does not share them with any server or third party 
over the Internet. 

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The study may be monitored, or audited in accordance with the current approved protocol, GCP, 
relevant regulations and standard operating procedures.  
14.1. 
Risk assessment  
 A risk assessment has not been undertaken. 
14.2. 
Monitoring  
Monitoring will not be undertaken for this study. 
14.3. 
Trial committees 
Not applicable 
14.4. 
Safety Monitoring Committee 
Not applicable 
15. PROTOCOL DEVIATIONS  
A study related deviation is a departure from the ethically approved study protocol or other study 
document or process (e.g. consent process or administration of study intervention) or from Good Clinical 
Practice (GCP) or any applicable regulatory requirements. Any deviations from the protocol will be 
documented in a protocol deviation form and filed in the study master file. 
16. SERIOUS BREACHES 
A “serious breach” is a breach of the protocol or of the conditions or principles of Good Clinical Practice 
which is likely to affect to a significant degree – 
 (a) the safety or physical or mental integrity of the trial subjects; or 
(b) the scientific value of the research. 
In the event that a serious breach is suspected the Sponsor must be contacted within 1 working day. In 
collaboration with the C.I., the serious breach will be reviewed by the Sponsor and, if appropriate, the 
Sponsor will report it to the approving REC committee and the relevant NHS host organisation within 
seven calendar days.  
 
17. ETHICAL AND REGULATORY CONSIDERATIONS 
 
17.1. 
6MWT 

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6MWT testing is very safe and is used in many conditions including in people with heart failure. However, 
as can occur with all forms of exercise, very occasionally some people have significant changes in their 
heart rate and rhythm that require medical attention. The participants undergoing the app-based 6MWT 
will be provided with a checklist for them to assess themselves with, and would not undertake a test if 
they fail this. 
17.2. 
Sars-Cov-2 
The study will follow the general recommendations of the NHS, particularly the advice from Healthwatch 
to consider avoiding asking patients to attend physical outpatient appointments where a clinically-
appropriate and accessible alternative exists. In this regard, the study aims to significantly lower the 
number of patients needing visits to the PH clinic and in itself does not require patients to do so. 
 
17.3. 
Declaration of Helsinki 
The Investigator will ensure that this trial is conducted in accordance with the principles of the 
Declaration of Helsinki.  
17.4. 
Guidelines for Good Clinical Practice 
The Investigator will ensure that this trial is conducted in accordance with relevant regulations and with 
Good Clinical Practice. 
17.5. 
Approvals 
Following Sponsor approval the protocol, informed consent form, participant information will be 
submitted to an appropriate Research Ethics Committee (REC), HRA (where required), regulatory 
authorities (MHRA in the UK), and host institution(s) for written approval. 
The Investigator will submit and, where necessary, obtain approval from the above parties for all 
substantial amendments to the original approved documents. 
17.6. 
Other Ethical Considerations 
Not applicable 
17.7. 
Reporting 
The CI shall submit once a year throughout the clinical trial, or on request, an Annual Progress Report to 
the REC, HRA (where required), host organisation, funder (where required) and Sponsor.  In addition, an 
End of Trial notification and final report will be submitted to the MHRA, the REC, host organisation and 
Sponsor. 
17.8. 
Participant Confidentiality 

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The study will comply with the General Data Protection Regulation (GDPR) and Data Protection Act 2018, 
which require data to be de-identified as soon as it is practical to do so. The processing of the personal 
data of participants will be minimised by making use of a unique participant study number only on all 
study documents and any electronic database(s), . All documents will be stored securely and only 
accessible by study staff and authorised personnel. The study staff will safeguard the privacy of 
participants’ personal data. 
17.9. 
Expenses and Benefits 
Not applicable 
18. FINANCE AND INSURANCE 
18.1. 
Funding 
The study will be partially funded by: the Swedish Knowledge Foundation, KK stiftelsen, through the 
Internet of Things and People research profile. Their contribution will support the involvement of the 
research team at Malmo University. 
18.2. 
Insurance 
NHS bodies are legally liable for the negligent acts and omissions of their employees. If any patient is 
harmed whilst taking part in a clinical research study as a result of negligence on the part of a member of 
the study team this liability cover would apply. 
Non-negligent harm is not covered by the NHS indemnity scheme. The Oxford University NHS Trust, 
therefore, cannot agree in advance to pay compensation in these circumstances. In exceptional 
circumstances an ex-gratia payment may be offered. 
 
18.3. 
Contractual arrangements  
 A collaboration or data sharing agreement will be required between the trust and The University in 
Sweden. 
19. PUBLICATION POLICY 
The research team will be involved in editing and reviewing manuscripts, abstracts, press releases and 
any other publications arising from the study. All involved researchers and clinical staff will be invited to 
co-author the papers. 
Authorship will be determined in accordance with the ICMJE guidelines and other contributors will be 
acknowledged. 

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20. DEVELOPMENT OF A NEW PRODUCT/ PROCESS OR THE GENERATION OF INTELLECTUAL 
PROPERTY  
Not applicable 
 
21. ARCHIVING 
22. Anonymous Data will be kept for up to 10 years after study completion or until ethical 
approval terminates, whichever is sooner.REFERENCES 
1 https://jamanetwork.com/journals/jama/fullarticle/2768086 
2 https://www.cdc.gov/coronavirus/2019-ncov/hcp/telehealth.html 
3 https://mhealth.jmir.org/2020/7/e19417/ 
4 https://clinowl.com/the-future-is-now-a-call-for-action-for-cardiac-telerehabilitation-in-the-covid-19-
pandemic-from-the-secondary-prevention-and-rehabilitation-section-of-the-european-association-of-
preventive-cardiolo/ 
5 https://digital.nhs.uk/coronavirus/nhs-digital-tech-analytics 
6https://www.bmj.com/content/364/bmj.l84.long 
7 https://www.jmir.org/2020/8/e21609/ 
8 https://pubmed.ncbi.nlm.nih.gov/12890299/ 
9 https://www.ahajournals.org/doi/full/10.1161/circulationaha.112.105890 
10 https://www.atsjournals.org/doi/full/10.1164/rccm.201203-0480oc 
11 https://mhealth.jmir.org/2020/1/e13756/ and https://preprints.jmir.org/preprint/22748 
12 https://mhealth.jmir.org/2016/2/e72/ 
13 https://ieeexplore.ieee.org/abstract/document/6149947 
14 https://creativecommons.org/licenses/by-sa/4.0/ 
15 https://creativecommons.org/licenses/by-sa/4.0/ 
 
 
 

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23. APPENDIX B:  SCHEDULE OF PROCEDURES 
 
Procedures 
Visit timing 
Day 1 
Phase 1 
Phase 2 
End of 
study 
Informed consent 
X 
 
 
 
6MWT using app 
 
X 
X 
 
6MWT using app + raw 
data 
 
 
X 
 
Questionnaire 
 
 
 
X 
Interview 
 
 
 
X 
 
 
 

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24. APPENDIX D:  AMENDMENT HISTORY 
 
Amendment 
No. 
Protocol 
Version 
No. 
Date issued 
Author(s) 
of 
changes 
Details of Changes made 
 
 
 
 
 
 
List details of all protocol amendments here whenever a new version of the protocol is produced.  
Protocol amendments must be submitted to the Sponsor for approval prior to submission to the REC 
committee, or HRA (where required).