Delivery of Digital Cognitive Behavioural Therapy Following Concussion: HeadOn Feasibility Study
Phase: NA
Conditions: Concussion, Mild
Sponsor: University of Edinburgh

HeadOn  
Version 4, 8th August 2021 
IRAS no: 279358 
NCT05069948 
 
 
 
          
 
 
Study Protocol 
 
 
Delivery of digital cognitive behavioural therapy following 
concussion: HeadOn Feasibility Study 
 
Sponsor 
The University of Edinburgh and/or Lothian Health 
Board 
The Queen’s Medical Research Institute 
47 Little France Crescent 
Edinburgh 
EH16 4TJ 
Email: resgov@accord.scot 
Tel: 0131 242 3326 
Fax: 0131 242 9447 
Protocol authors 
Aimun Jamjoom, Christine d’Offay, Laura Alexander, 
Matt Reed, David Gillespie, Alan Carson 
Funder 
National Institute of Health Research 
Funding Reference Number 
Grant R46241 
Chief Investigator 
Aimun A.B. Jamjoom 
Sponsor number 
AC20032 
REC Number 
279358 
Version Number and Date 
Version 2 6th April 2021 
Version 3 21st May 2021 
 

HeadOn  
Version 4, 8th August 2021 
IRAS no: 279358 
 
           of 25 
 
 
2 
CONTENTS 
1 
INTRODUCTION .......................................................................................... 5 
1.1 
BACKGROUND ................................................................................... 5 
1.2 
RATIONALE FOR STUDY .................................................................. 6 
2 
STUDY OBJECTIVES .................................................................................. 7 
2.1 
OBJECTIVES ...................................................................................... 7 
2.1.1 
Primary Objective ........................................................................... 7 
2.1.2 
Secondary Objectives .................................................................... 7 
2.2 
ENDPOINTS ........................................................................................ 7 
2.2.1 
Primary Endpoint ............................................................................ 7 
2.2.2 
Secondary Endpoints ..................................................................... 7 
3 
STUDY DESIGN ........................................................................................... 8 
4 
STUDY POPULATION ................................................................................. 9 
4.1 
NUMBER OF PARTICIPANTS ............................................................ 9 
4.2 
INCLUSION CRITERIA ....................................................................... 9 
4.3 
EXCLUSION CRITERIA ...................................................................... 9 
4.4 
Co-enrolment ...................................................................................... 9 
5 
PARTICIPANT SELECTION AND ENROLMENT ........................................ 9 
5.1 
IDENTIFYING PARTICIPANTS ........................................................... 9 
5.2 
CONSENTING PARTICIPANTS .......................................................... 9 
    5.2.1   Withdrawal of study participants ................................................ 10 
 5.2.2   Pathway for patients excluded for severe depression…………10 
6 
DATA COLLECTION ................................................................................. 11 
7 
DATA MANAGEMENT ............................................................................... 14 
7.1 
Personal data ................................................................................... 14 
7.2 
Transfer of data ................................................................................ 15 
7.3 
Data Controller ................................................................................. 15 
7.4 
Data breaches .................................................................................. 16 
8 
STATISTICS AND DATA ANALYSIS ........................................................ 17 
8.1 
SAMPLE SIZE CALCULATION ........................................................ 17 
8.2 
PROPOSED ANALYSES .................................................................. 17 
9 
ADVERSE EVENTS ................................................................................... 18 
10 
OVERSIGHT ARRANGEMENTS ............................................................... 18 
10.1 
INSPECTION OF RECORDS ............................................................ 18 
10.2 
STUDY MONITORING AND AUDIT .................................................. 18 
11 
GOOD CLINICAL PRACTICE .................................................................... 18 
11.1 
ETHICAL CONDUCT ........................................................................ 18 
11.2 
INVESTIGATOR RESPONSIBILITIES .............................................. 18 
11.2.1 Informed Consent ......................................................................... 18 
11.2.2 Study Site Staff .............................................................................. 20 
11.2.3 Data Recording .............................................................................. 20 
11.2.4 Investigator Documentation ......................................................... 20 
11.2.5 GCP Training ................................................................................. 20 

HeadOn  
Version 4, 8th August 2021 
IRAS no: 279358 
 
           of 25 
 
 
3 
11.2.6 Confidentiality ............................................................................... 20 
11.2.7 Data Protection .............................................................................. 20 
12 
STUDY CONDUCT RESPONSIBILITIES .................................................. 21 
12.1 
PROTOCOL AMENDMENTS ............................................................ 21 
12.2 
MANAGEMENT OF PROTOCOL NON COMPLIANCE ................... 21 
12.3 
SERIOUS BREACH REQUIREMENTS ............................................ 21 
12.4 
STUDY RECORD RETENTION ........................................................ 21 
12.5 
END OF STUDY ................................................................................ 21 
12.6 
CONTINUATION OF TREATMENT FOLLOWING THE END OF 
STUDY ............................................................................................... 22 
12.7 
INSURANCE AND INDEMNITY ........................................................ 22 
13 
REPORTING, PUBLICATIONS AND NOTIFICATION OF RESULTS ...... 22 
13.1 
AUTHORSHIP POLICY ..................................................................... 22 
14 
REFERENCES ........................................................................................... 23 
15 
APPENDIX ................................................................................................. 24 
 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
4 
LIST OF ABBREVIATIONS 
 
ACCORD Academic and Clinical Central Office for Research & Development - Joint 
office for The University of Edinburgh and Lothian Health Board 
CI 
Chief Investigator 
CRF 
Case Report Form 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonisation 
PI 
Principal Investigator 
QA 
Quality Assurance 
REC 
Research Ethics Committee 
SOP 
Standard Operating Procedure 
ED 
Emergency department 
CBT 
Cognitive Behavioural Therapy 
EMERGE 
Emergency Medicine Research Group Edinburgh 
USA 
United States of America 
PHQ9 
Patient Health Questionnaire 9 
GOSE 
Glasgow Outcome Scale Extended 
EMA 
Ecological Momentary Assessment 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
5 
INTRODUCTION 
1.1 
BACKGROUND 
Concussion is defined as a traumatically induced physiological disruption of brain function. This 
can occur in a wide range of circumstances from sports and military related injuries, assault, 
road-traffic accidents and falls. Reliable quantification of the public health burden of concussion 
is challenging because many patients do not present to healthcare services after sustaining 
one. However, it is clear that concussion and mild traumatic brain injury is the commonest 
reason for the under 65s to be admitted to hospital (Scottish Intercollegiate Guidelines Network, 
2013). Estimates place the incidence at 300 people per 100 000 seeking medical attention 
however this varies internationally reflecting the availability of emergency medical services 
(Cassidy et al., 2004). This incidence is believed to almost double when patients who do not 
seek medical attention are taken into account. Concussion does not cause the irreversible brain 
damage associated with more severe traumatic injuries but, there is growing evidence that 
patients may suffer from a constellation of physical, emotional and cognitive symptoms after a 
concussion. There is considerable controversy surrounding the natural history, mechanisms, 
causality and prognosis of post-concussion symptoms. A prospective cohort study of patients 
presenting to the emergency department after a concussion found that at 3 months 77% 
reported at least 1 post-concussion symptom (McMahon et al., 2013). The impact of patients 
suffering from these symptoms on healthcare services is highlighted in a study by Hartvigsen 
and colleagues who found that over 90% of patients had sought care from at least one 
healthcare professional related to their symptoms at each of the 5 assessed time-points during 
the 1-year follow-up period (Hartvigsen et al., 2014). Concussions also have been found to 
negatively impact on patients’ quality of life and  return to work (Emanuelson et al., 2003; Graff 
et al., 2019). In the NHS there is no coordinated clinical pathway for patients following a 
concussion.  
Despite disagreement on the exact aetiology of post-concussion symptoms, there is a view that 
a complex interplay between biological, social and psychological factors drive the observed 
clinical phenotype. Therefore psychological interventions have been assessed to determine 
their value as therapies. Cognitive Behavioural Therapy (CBT) is a psychological intervention 
that uses personal coping strategies focusing on the interplay between behaviours, thoughts 
and feelings. There is a strong evidence base on the effectiveness of CBT in a range of mental 
health problems (Hofmann et al., 2012). A systematic review found that CBT has been 
assessed in the context of concussion in 3 randomized controlled trials and concluded that it is 
likely to be effective in the treatment of post-concussion symptoms (Al Sayegh et al., 2010). 
However, providing face-to-face therapy is highly labour intensive and there are considerable 
logistical and economic hurdles in delivering CBT for this patient cohort. Coupled to this, some 
patients do not wish to have face-to-face therapy sessions due to perceived stigma of talking 
therapies. Due to these difficulties, there have been efforts to use technology platforms as a 
means to overcome these barriers. One major success is the company Sleepio which has 
developed an automated CBT programme for patients with chronic insomnia. A clinical trial of 
Sleepio demonstrated that it improved sleep and daytime functioning (Espie et al., 2012). 
Similarly, a systematic review of internet delivered CBT for anxiety and depression concluded 
that it was a promising alternative to face-to-face therapy (Ebert et al., 2015). CBT therefore 
has the potential to be effectively delivered digitally and provide a scalable alternative to 
traditional CBT in the context of concussion.  
 
 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
6 
1.2 
RATIONALE FOR STUDY 
Concussion is common and patients can go on to suffer with a constellation of symptoms which 
impacts their functional outcome and quality of life (McMahon et al., 2013). Patient provision 
with information about their concussion and subsequent follow-up was highly variable in a 
prospective study in the USA (Seabury et al., 2018). This is also the case with psychological 
therapies despite the fact there is evidence that CBT can help patients manage their symptoms 
after a concussion (Al Sayegh et al., 2010).  
We have developed HeadOn - a web application that delivers a CBT programme to patients 
following concussion. The application takes the patient through a 5-stage programme including: 
(i) understanding post-concussion symptoms; (ii) sleep after a concussion; (iii) lifestyle habits 
and exercise; (iv) managing negative thought patterns and (v) returning to baseline. The 
programme is delivered through a combination of weekly tasks (such as completing symptom 
diary, setting exercise goals and setting up a sleep time routine), audio/video media and reading 
material. 
In this study, we would like to examine the feasibility of digitally delivering a course of CBT to 
patients following concussion. We hypothesise that patients will find it an acceptable and useful 
form of treatment. We plan on determining recruitment rates to guide future controlled trials. 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
7 
2 
STUDY OBJECTIVES 
2.1 
OBJECTIVES 
2.1.1 Primary Objective 
Our primary objective is to determine the following regarding the digital delivery of CBT to 
patients following concussion: 
- 
Compliance of participants with a digital CBT program 
- 
Usability of a digital CBT program as a form of therapy 
2.1.2 Secondary Objectives 
Our secondary objectives are: 
- 
Determining functional outcome after the HeadOn program 
- 
Determining the temporal profile of post-concussion symptoms, sleep disturbance and 
mood during the study period 
- 
Identifying return to work rates 
- 
Recruitment rates of patients presenting to a single emergency department 
 
2.2 
ENDPOINTS 
2.2.1 Primary Endpoint 
1) Participant compliance with CBT program 
Data inputted into the digital CBT program will be used as surrogate marker of 
participant compliance. During each stage of the program participants are required to 
input data as part of the CBT tasks. Participants will be divided into the following three 
groups: Fully compliant: participants who input data into the program during all five 
stages; Partially compliant: participants who input data but not during all five stages; 
Non-compliant: participants who do not enter any data into the program 
 
2) mHealth App Usability Questionnaire  
2.2.2 Secondary Endpoints 
1) Post-concussion symptom burden measured using the Rivermead post-concussion 
questionnaire 
2) Mood measured using the PHQ9 questionnaire 
3) Quality of sleep measured using the Pittsburgh Sleep Quality Index  
4) Functional status measured by Glasgow Outcome Score Extended 
5) Healthcare utility questionnaire 
6) Time to return to work  
7) Willingness to be randomised in future randomised trials  
8) Patient recruitment rates 
 
 
 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
8 
3 
STUDY DESIGN 
The HeadOn feasibility study is a prospective feasibility study of patients presenting to the 
Edinburgh Royal Infirmary and St John’s Hospital Emergency Departments (ED) (Figure 1). 
Patients will be identified from the ED. Potentially eligible patients will be contacted by a 
member of the Emergency Medicine Research Group Edinburgh (EMERGE) research team 
and their consent will be sought for participation. Those not recruited at presentation to the ED 
will be contacted by telephone, text or email within two weeks of their concussion date to seek 
their participation in the study, again by a member of the EMERGE research team. After 
consenting, the participant will be taken through the registration process for the HeadOn 
program. For patients who are contacted after discharge they will be taken through registration 
process over the telephone or if preferable will be able to return to the ED to go over the 
process.  
 
At registration the participant will be invited to complete a series of patient reported measures 
including the Rivermead post-concussion questionnaire, Pittsburgh Sleep Quality Index, PHQ9 
questionnaire and FAST alcohol questionnaire within the HeadOn program. Alongside this, a 
series of researcher-led anonymised data points will be collected in a separate specially 
designed database including demographics, date of concussion, neurological and imaging 
findings which will all be collected from the medical notes and imaging reports. The HeadOn 
program runs for five weeks following which the participant will be invited to complete the same 
set of outcome measures. Alongside this, all the participant will be contacted (via telephone, 
text or email) by a member of the research team at week 5 to complete a further five 
measurements: Glasgow Outcome Score Extended, mHealth App Usability questionnaire, time 
to return to work and a healthcare utility questionnaire. Interested participants will be invited 
back within two months of enrolling in the study for a more detailed qualitative interviews about 
HeadOn. The study will recruit for a period of 6-months or up to 100 participants.  
 
  
Figure 1: Schematic of HeadOn study design 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
9 
4 
STUDY POPULATION 
4.1 
NUMBER OF PARTICIPANTS 
The study aims to recruit over a 6-month period at the Royal Infirmary of Edinburgh and St 
John’s Hospital ED with the aim to recruit 100 participants.  
4.2 
INCLUSION CRITERIA 
- 
Patients aged 16 years and older (no upper age limit) 
- 
Presenting to the ED with a concussion  
- 
Concussion defined as a traumatically induced alteration of mental status (either 
defined as loss of consciousness and/or amnesia) 
- 
Patient is Glasgow Coma Scale score of 13-15 on initial presentation to the ED  
- 
Patient needs to be able to start using HeadOn within 14 days of their head injury 
4.3 
EXCLUSION CRITERIA 
- 
Patients aged under 16 years old  
- 
Patients requiring surgical management of their cranial injury 
- 
Significant other associated injuries requiring hospitalisation (spinal injury, fractures, 
abdominal, cardiothoracic or vascular injuries) 
- 
Does not have capacity to give consent 
- 
Non-English speakers 
- 
Patient in police custody or in prison  
 
4.4 
CO-ENROLMENT 
Co-enrolment will be permitted with any other study provided it is not expected to place an 
undue burden upon participants and their families, and will not compromise the primary end-
point of either trial. Co-enrolment will only be permitted with agreement of the Chief 
Investigators of both studies. A written co-enrolment agreement will not be sought for co-
enrolment with this study. 
 
5.  
PARTICIPANT SELECTION AND ENROLMENT 
5.1  
IDENTIFYING PARTICIPANTS 
Patients will be identified in the ED. The EMERGE team, where it is locally agreed that they are 
part of the clinical care team, will identify patients using triage information and clinical or 
electronic records in the ED at presentation or through screening of admission logs. In this 
case, it is anticipated they would identify patients and make the first approach. Any member of 
the clinical team who has received general and trial specific training and is on the delegation 
log may also identify patients in this way.  
 
Patients with concussion do not typically have long stays in ED and can be discharged after a 
few hours. Those patients that are not approached at admission or not recruited at presentation 
to the ED will be identified through ED admission logs by a member of the EMERGE team and 
will be contacted within two week from the date of their concussion to seek their participation in 
the study by a suitably trained member of the research team. 
5.2  
CONSENTING PARTICIPANTS 
Potentially eligible patients within the ED will be screened by the EMERGE team and 
approached and verbal consent gained on whether they would be interested to participate by a 
suitably trained member of the research team. Following this, the patient will be provided with 
a participant information leaflet (paper or digital). Potential participants will be recruited to the 
study within the four hour management window in ED. If the patient requires more time to decide 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
10 
they can express an interest to participate after discharge from ED up to 14 days from the date 
of their concussion. Those interested to take part in the study will be consented by a member 
of the research team using the RedCap e-consent function which will be linked through the 
HeadOn website (www.headon-health.com/research).  
 
Patients that are discharged before they agree to participate in the study or are identified post-
discharge can be enrolled in the study by a suitably trained member of the research team up to 
14 days from the date of their concussion. Initially patients will be contacted to see if they are 
interested in receiving information about the study. Those that are will be directed to the 
HeadOn website or sent the material by their preferred means (email/post). If they are 
interested in participating, the patients will be directed to the HeadOn website to be consented 
using the RedCap e-consent function.  
 
5.2.1 Withdrawal of Study Participants 
Participants are free to withdraw from the study at any point or a participant can be withdrawn 
by the Investigator. If withdrawal occurs, the primary reason for withdrawal will be documented 
in the participant’s case report form, if possible. The participant will have the option of 
withdrawal from all aspects of the study but continued use of data collected up to that point. To 
safeguard rights, the minimum personally identifiable information possible will be collected.  

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
11 
6. 
DATA COLLECTION 
Data will be collected at four points during the study period: at baseline, during the HeadOn 
program, at the final 5-week follow-up and during a voluntary qualitative interview. Two forms 
of data will be collected: patient-reported and researcher collected.  
 
At baseline, participants will complete four patient questionnaires within the HeadOn program 
(Rivermead postconcussion, PHQ9, Pittsburgh Sleep Quality and the FAST alcohol screen). 
Researchers will also capture demographic, clinical and imaging findings data taken from 
participants notes and investigation finding reports. During the HeadOn program, participants 
will undergo a series of ecological momentary assessments (EMAs) aimed at capturing 
information about their symptoms, mood, thoughts about their concussion and behaviour 
(Appendix). This includes a symptom and mood diary which will be delivered daily. Alongside 
this, a series of other EMAs are delivered to the participant at different stages of the program 
(Figure 2): Stage 3 (Alcohol tracker), Stage 4 (Thought diary) and Stage 5 (Goal setting). 
HeadOn generates automated reminders (by email or notification) to help keep participants 
engaged. In the final 5-week follow-up of the study, both participant-reported and researcher 
collected outcome measures will be captured. Participants will complete the following 
questionnaires digitally through the HeadOn program: Rivermead postconcussion, PHQ9, 
Pittsburgh Sleep Quality and FAST alcohol screen. The participant will also be contacted by a 
trained member of the HeadOn research team to complete four questionnaires: the mHealth 
app usability questionnaire, healthcare utility, return to work questionnaire and the Glasgow 
Outcome Score Extended (GOSE). The participant will also be reminded to complete the week 
5 patient-reported questionnaires if they had not already done so. If the participant has not 
completed these questionnaires by week 6, then they will be contacted again by a member of 
the research team to complete these questionnaires. 
 
Patients who have consented to take part in qualitative interviews will be contacted (by phone 
or email) and invited to participate in an in-depth interview with a member of the research team. 
Any participant who declines to be interviewed will also be offered to provide their feedback in 
an online survey. Interviews will be conducted over the telephone or videoconference and will 
last approximately 40-60 minutes (Appendix). Participants will be asked for their views and 
experiences on the following topics: (1) about their experience of using the intervention (2) 
when and how they used the intervention (3) how easy or not easy they found the intervention 
to use (4) likes and dislikes about the intervention (5) the functions were most useful and least 
useful (6) what changes they would make within the intervention. 
 
The data captured will be kept in two different databases based upon whether it is participant-
reported or researcher collected. Researcher collected data will be entered into a specially 
designed password protected online accessed secure database (RedCap). REDCap is run by 
the Surgical Informatics research group (The University of Edinburgh) under licence from 
Vanderbilt University. REDCap was developed specifically around HIPAA-Security guidelines. 
It is hosted within the University of Edinburgh Virtual Machine architecture which is physically 
secured. Linux web servers running apache2/php5 host the application. Web browser 
communication to the server is SSL-encrypted by default. All other ports are firewall protected. 
Data is stored in MySQL databases on a separate server. This server is behind a firewall and 
can only be accessed from the IP address of the web server. An SSL tunnel encrypts 
communication between the web and databases servers. File upload is secured between 
servers using the WebDAV protocol with SSL. "At rest" encryption is in place on the database 
server. Daily back-ups are made of both servers and stored for four weeks prior to being 
deleted. Operating security updates are installed automatically. Antivirus software runs to a 
scheduled protocol on the web server. User passwords are managed directly. Accounts are 
disabled after 5 failed login attempts. Users are auto logged out after 30 mins of no activity. 
Users are forced to change password after 42 days. Password strength: AT LEAST 9 
CHARACTERS IN LENGTH and must consist of AT LEAST one lower-case letter, one upper-
case letter, and one number. Daily audit tracking of users is in place with removal of unused 
user accounts. Participants who consent using the RedCap e-consent function will enter their 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
12 
name and signature into the system as part of the consent process. Identifiable electronic 
information will be kept in a separate database on an NHS server, which will not be accessible 
outside the immediate research team. These data will be linked by study number to the 
anonymised research database and will be stored on a secure, password protected location on 
the local hospital computer drive and only accessible to relevant staff. Researcher collected 
data will be entered directly into the database using the participant’s unique study number.  
 
Patient-reported data will be captured through the HeadOn digital platform (www.headon-
health.com) which is hosted on the Microsoft Azure cloud computing service which meets 
industry standard data protection protocols. As part of the registration process, the patient will 
input their email address, name and study number into the system. Qualitative interviews will 
be conducted over the telephone and recorded using a digital voice recorder that generates 
encrypted audio files. These files will be transcribed by Christine d’Offay (Edinburgh University 
MSc student) and kept on the Edinburgh University network. They will be pseudo-annonymised 
and linked to participant through their research number. 
 
 
 
 
Figure 2: Flow chart demonstrating patient reported and researched collected data collected 
at different time points.  
 
 
 
 
 
 
 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
13 
 
 
 
 
 
Enrolment 
Allocation 
Post-allocation 
Close-
out 
TIMEPOINT** 
-t1 
0 
w1 
w2 
w3 
w4 
w5 
tx 
ENROLMENT: 
 
 
 
 
 
 
 
 
Eligibility screen 
X 
 
 
 
 
 
 
 
Informed consent  
X 
 
 
 
 
 
 
 
Allocation 
 
X 
 
 
 
 
 
 
INTERVENTION: 
 
 
 
 
 
 
 
 
HeadOn program 
 
 
 
 
 
 
 
 
ASSESSMENTS: 
 
 
 
 
 
 
 
 
Baseline variables 
X 
X 
 
 
 
 
 
 
Researcher 
collected data 
 
X 
 
 
 
 
 
X 
Patient reported 
data 
 
X 
X 
X 
X 
X 
X 
X 
Qualitative 
interview 
 
 
 
 
 
 
 
X 
Table 1: SPIRIT figure for HeadOn feasibility study 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
14 
7 
DATA MANAGEMENT 
7.1  
Personal Data 
Researcher captured anonymised data will be entered into a specially designed password 
protected online accessed secure database (RedCap). As detailed above, RedCap complies 
with stringent data security standards and is hosted within the University of Edinburgh Virtual 
Machine architecture which is physically secured. Participants will be identified on RedCap by 
study number alone. Patients who consent using the e-consent RedCap function will enter their 
name and signature into the system as part of the consent process. 
 
Identifiable electronic information will be kept in a separate database, which will not be 
accessible outside the immediate research team. These data will be linked by study number to 
the anonymised research database and will be stored on a secure, password protected location 
on the local hospital (NHS Lothian) computer drive and only accessible to relevant staff. 
 
Identifiable non-electronic data of the participant will be kept in a locked filing cabinet in a locked 
local research study office. Computers used to collate the data will have limited access 
measures via usernames and passwords. A fully anonymised version of the data will be shared 
on the Edinburgh University DataShare service and made available for 5 years after completion 
of the study. 
 
Published results will not contain any personal data that could allow identification of individual 
participants. 
 
 
 
Figure 3: Data flow diagram 
 
 
 
 
 
 
 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
15 
 
Data stream 
Data type 
Where is 
database 
kept? 
Who inputs 
data? 
Who has access 
to data? 
Is data 
anonymous? 
HeadOn app 
 
www.headon-
health.com 
 
Email 
(mandatory) 
Name (optional) 
HeadOn ID 
Research ID 
Symptom 
type/severity 
Mood 
Sleep quality 
Alcohol 
consumption 
 
 
 
Microsoft 
Azure cloud 
service 
Study 
participant 
Routine clinical care 
team (EMERGE 
research nurses) 
Aimun Jamjoom 
(PI) 
Christine d’Offay 
(MSc student) 
Pogo Studio Ltd 
(only if technical 
issue requiring 
support) 
No. Email and 
name are 
identifiable.  
However, 
exported data is 
anonymised with 
HeadOn / 
Research ID and 
file is encrypted 
 
RedCap 
database 
 
Demographic  
Clinical 
examination 
Imaging findings 
Outcome data 
e-consent (name 
and signature) 
Redcap is a 
medical 
database 
platform 
hosted by 
Edinburgh 
University 
Routine 
clinical care 
team 
(EMERGE 
research 
nurses) 
Routine clinical care 
team (EMERGE 
research nurses) 
Aimun Jamjoom 
(PI) 
Christine d’Offay 
(MSc student) 
Yes, linked to 
identifiable 
patient data 
through research 
ID number 
Study key 
(excel sheet) 
Patient name, 
CHI; contact 
details; research 
number; 
recruitment data 
Dataform 
containing 
patient name, 
CHI; contact 
details and 
research 
number which 
is kept on 
NHS Lothian 
computer 
network  
Routine 
clinical care 
team 
(EMERGE 
research 
nurses) 
Routine clinical care 
team (EMERGE 
research nurses) 
Aimun Jamjoom 
(PI) 
Christine d’Offay 
(MSc student) 
No 
Qualitative 
interview data 
Audio recordings 
of qualitative 
interviews 
Edinburgh 
university 
network 
Christine 
d’Offay  
Aimun Jamjoom 
(PI), Christine 
d’Offay (MSc 
student) 
 
Yes, only 
research ID used  
Table 2: Data stream details 
 
7.2 
Transfer of Data 
Data entry will be completed by the local research team and data analysis by the study 
statistician. Participants enter identifiable data (name/email address) outwith the local NHS 
region as part of the HeadOn registration process and RedCap e-consent function. Participant 
identifiable data will be removed from any electronic data being sent for analysis. 
 
7.3 
Data Controller 
The University of Edinburgh and NHS Lothian are joint data controllers along with any other 
entities involved in delivering the study that may be a data controller in accordance with 
applicable laws. 
 
The Chief Investigator will be responsible for the quality of the data recorded in the electronic 
CRF on the research database. 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
16 
All Investigators and study site staff involved with this study will comply with the requirements 
of the Data Protection Act 2018 with regard to the collection, storage, processing and disclosure 
of personal information and will uphold the Act’s core principles. Access to collated participant 
data will be restricted to those clinicians treating the participants, representatives of the sponsor 
and representatives of regulatory authorities. 
7.4 
Data Breaches 
Any data breaches will be reported to the University of Edinburgh and NHS Lothian Data 
Protection Officers who will onward report to the relevant authority according to the appropriate 
timelines if required. 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
17 
8 
STATISTICS AND DATA ANALYSIS 
8.1 
SAMPLE SIZE CALCULATION 
From admission data from the Royal Infirmary of Infirmary and St John’s Hospital ED, 
approximately 1000 patients that meet our inclusion criteria present to the hospital every year. 
Over a 6-month period, there would be approximately 500 eligible patients. Assuming a 
recruitment rate of ~30% we are aiming to recruit 100 participant during the study period.  
8.2 
PROPOSED ANALYSES 
We plan on conducting the following analyses. The study PI will be performing the analysis: 
 
8.2.1 Patient demographics 
We plan on conducting descriptive analyses of patient demographics, clinical findings 
and imaging reports.  
 
8.2.2 Recruitment rates 
In this analysis, we will be calculating the recruitment rate as determined by the number 
of patients consenting to participate compared to those screened and eligible for 
recruitment. 
 
8.2.3 Patient compliance 
During each stage of the program participants are required to input data as part of the 
CBT tasks. Participants will be divided into the following three groups: 
a) Fully compliant: participants who input data into the program during all five 
stages 
b) Partially compliant: participants who input data but not during all five stages 
c) Non-compliant: participants who do not enter any data into the program 
We plan to conduct simple descriptive analysis to better understand trends in patient 
interaction with HeadOn. 
 
8.2.4 Temporal change in secondary outcome measures 
A number of secondary outcome measures are examined at both recruitment and at 
the 5-week follow-up (Rivermead post-concussion questionnaire, PHQ9 questionnaire, 
Pittsburgh Sleep Quality Index). We plan a descriptive analysis of the temporal 
changes in the aggregate scores of these measures. 
 
8.2.5 Functional outcome 
The Glasgow Outcome Scale extended is being used to determine functional outcome 
in this study. It is an 8-level scale with 8 representing a complete recovery down to 1 
which is death. We plan on dichotomising participants to complete recovery (score 8) 
versus incomplete recovery (<8). Logistic regression will then be used to examine the 
predictive role of a range of admission data points (demographics, clinical findings 
(LOC vs no LOC, amnesia vs no amnesia) and admission patient reported measures 
(Rivermead, PHQ9). 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
18 
8.2.6 HeadOn symptom diary data 
As part of our analysis, we aim to examine the association between data collected in 
the HeadOn symptom diary and functional outcome. Participants will be dichotomised 
based on their aggregate scores of the symptom diary. Logistic repression will then be 
used to examine its predictive relationship with GOSE outcome.  
 
 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
19 
9 ADVERSE EVENTS 
This is a low-risk study. Participants found to have a PHQ9 score of >20 will be told of the 
result and asked if their GP can be informed of the finding to arrange appropriate follow-up 
and management. 
 
10 
OVERSIGHT ARRANGEMENTS 
10.1 INSPECTION OF RECORDS 
Investigators and institutions involved in the study will permit trial related monitoring and audits 
on behalf of the sponsor, REC review, and regulatory inspection(s).  In the event of audit or 
monitoring, the Investigator agrees to allow the representatives of the sponsor direct access to 
all study records and source documentation. In the event of regulatory inspection, the 
Investigator agrees to allow inspectors direct access to all study records and source 
documentation. 
10.2 STUDY MONITORING AND AUDIT 
The ACCORD Sponsor Representative will assess the study to determine if an independent 
risk assessment is required.  If required, the independent risk assessment will be carried out 
by the ACCORD Quality Assurance Group to determine if an audit should be performed 
before/during/after the study and, if so, at what frequency. 
 
Risk assessment, if required, will determine if audit by the ACCORD QA group is required. 
Should audit be required, details will be captured in an audit plan. Audit of Investigator sites, 
study management activities and study collaborative units, facilities and 3rd parties may be 
performed. 
11 
GOOD CLINICAL PRACTICE 
11.1 ETHICAL CONDUCT 
The study will be conducted in accordance with the principles of the International Conference 
on Harmonisation Tripartite Guideline for Good Clinical Practice (ICH GCP). 
Before the study can commence, all required approvals will be obtained and any conditions of 
approvals will be met. 
11.2 INVESTIGATOR RESPONSIBILITIES 
The Investigator is responsible for the overall conduct of the study at the site and compliance 
with the protocol and any protocol amendments.  In accordance with the principles of ICH GCP, 
the following areas listed in this section are also the responsibility of the Investigator.  
Responsibilities may be delegated to an appropriate member of study site staff.   
11.2.1 Informed Consent 
The Investigator is responsible for ensuring informed consent is obtained before any protocol 
specific procedures are carried out. The decision of a participant to participate in clinical 
research is voluntary and should be based on a clear understanding of what is involved. 
Participants must receive adequate oral and written/electronic information – appropriate 
Participant Information and Informed Consent Forms will be provided. The oral explanation to 
the participant will be performed by the Investigator or qualified delegated person, and must 
cover all the elements specified in the Participant Information Sheet and Consent Form. 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
20 
The participant must be given every opportunity to clarify any points they do not understand 
and, if necessary, ask for more information. The participant must be given sufficient time to 
consider the information provided.  It should be emphasised that the participant may withdraw 
their consent to participate at any time without loss of benefits to which they otherwise would 
be entitled. 
The participant will be informed and agree to their medical records being inspected by 
regulatory authorities and representatives of the sponsor(s). 
The Investigator or delegated member of the trial team and the participant will sign and date 
the Informed Consent Form(s) to confirm that consent has been obtained. The participant will 
receive a copy of this document and a copy filed in the Investigator Site File (ISF) and 
participant’s medical notes (if applicable). 
11.2.2 Study Site Staff 
The Investigator must be familiar with the protocol and the study requirements.  It is the 
Investigator’s responsibility to ensure that all staff assisting with the study are adequately 
informed about the protocol and their trial related duties. 
11.2.3 Data Recording 
The Principal Investigator is responsible for the quality of the data recorded in the CRF at each 
Investigator Site.  
11.2.4  Investigator Documentation 
• 
The Principal Investigator will ensure that the required documentation is available in 
local Investigator Site files ISFs.  
11.2.5 GCP Training 
For non-CTIMP (i.e. non-drug) studies all researchers are encouraged to undertake GCP 
training in order to understand the principles of GCP. However, this is not a mandatory 
requirement unless deemed so by the sponsor.  GCP training status for all investigators 
should be indicated in their respective CVs.  
11.2.6 Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records must be identified in a 
manner designed to maintain participant confidentiality.  All records must be kept in a secure 
storage area with limited access.  Clinical information will not be released without the written 
permission of the participant.  The Investigator and study site staff involved with this study may 
not disclose or use for any purpose other than performance of the study, any data, record, or 
other unpublished information, which is confidential or identifiable, and has been disclosed to 
those individuals for the purpose of the study..  Prior written agreement from the sponsor or its 
designee must be obtained for the disclosure of any said confidential information to other 
parties. 
11.2.7 Data Protection 
All Investigators and study site staff involved with this study must comply with the requirements 
of the appropriate data protection legislation (including the General Data Protection Regulation 
and Data Protection Act) with regard to the collection, storage, processing and disclosure of 
personal information.  
Computers used to collate the data will have limited access measures via user names and 
passwords. 
 
Published results will not contain any personal data and be of a form where individuals are 
not identified and re-identification is not likely to take place 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
21 
12 
STUDY CONDUCT RESPONSIBILITIES 
12.1 PROTOCOL AMENDMENTS 
Any changes in research activity, except those necessary to remove an apparent, immediate 
hazard to the participant in the case of an urgent safety measure, must be reviewed and 
approved by the Chief Investigator.   
Amendments will be submitted to a sponsor representative for review and authorisation before 
being submitted in writing to the appropriate REC, and local R&D for approval prior to 
participants being enrolled into an amended protocol. 
12.2 MANAGEMENT OF PROTOCOL NON-COMPLIANCE 
Prospective protocol deviations, i.e. protocol waivers, will not be approved by the sponsors and 
therefore will not be implemented, except where necessary to eliminate an immediate hazard 
to study participants. If this necessitates a subsequent protocol amendment, this should be 
submitted to the REC, and local R&D for review and approval if appropriate. 
Protocol deviations will be recorded in a protocol deviation log and logs will be submitted to the 
sponsors every 3 months. Each protocol violation will be reported to the sponsor within 3 days 
of becoming aware of the violation.  All protocol deviation logs and violation forms should be 
emailed to QA@accord.scot 
Deviations and violations are non-compliance events discovered after the event has occurred.  
Deviation logs will be maintained for each site in multi-centre studies.  An alternative frequency 
of deviation log submission to the sponsors may be agreed in writing with the sponsors. 
 
12.3 SERIOUS BREACH REQUIREMENTS 
A serious breach is a breach which is likely to effect to a significant degree: 
(a) the safety or physical or mental integrity of the participants of the trial; or 
(b) the scientific value of the trial. 
If a potential serious breach is identified by the Chief investigator, Principal Investigator or 
delegates, the co-sponsors (seriousbreach@accord.scot) must be notified within 24 hours.  It 
is the responsibility of the co-sponsors to assess the impact of the breach on the scientific value 
of the trial, to determine whether the incident constitutes a serious breach and report to research 
ethics committees as necessary.  
12.4 STUDY RECORD RETENTION 
All study documentation will be kept for a minimum of 3 years from the protocol defined end of 
study point. When the minimum retention period has elapsed, study documentation will not be 
destroyed without permission from the sponsor. 
12.5  END OF STUDY 
The end of study is defined as the last participant’s last visit.   
The Investigators or the co-sponsor(s) have the right at any time to terminate the study for 
clinical or administrative reasons.  
The end of the study will be reported to the REC, and R+D Office(s) and co-sponsors within 90 
days, or 15 days if the study is terminated prematurely. The Investigators will inform participants 
of the premature study closure and ensure that the appropriate follow up is arranged for all 
participants involved. End of study notification will be reported to the co-sponsors via email to 
resgov@accord.scot 
A summary report of the study will be provided to the REC within 1 year of the end of the study. 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
22 
 
12.6  CONTINUATION OF TREATMENT FOLLOWING THE END OF 
STUDY 
Once the study is completed, patient access to the HeadOn site will be restricted to allow 
analysis of the data and the integration of any development changes to the program.  
 
12.7  INSURANCE AND INDEMNITY 
The co-sponsors are responsible for ensuring proper provision has been made for insurance or 
indemnity to cover their liability and the liability of the Chief Investigator and staff. 
The following arrangements are in place to fulfil the co-sponsors' responsibilities: 
• 
The Protocol has been designed by the Chief Investigator and researchers employed 
by the University and collaborators.  The University has insurance in place (which 
includes no-fault compensation) for negligent harm caused by poor protocol design 
by the Chief Investigator and researchers employed by the University. 
• 
Sites participating in the study will be liable for clinical negligence and other negligent 
harm to individuals taking part in the study and covered by the duty of care owed to 
them by the sites concerned.  The co-sponsors require individual sites participating 
in the study to arrange for their own insurance or indemnity in respect of these 
liabilities. 
• 
Sites which are part of the United Kingdom's National Health Service will have the 
benefit of NHS Indemnity. 
• 
Sites out with the United Kingdom will be responsible for arranging their own 
indemnity or insurance for their participation in the study, as well as for compliance 
with local law applicable to their participation in the study. 
13 
REPORTING, PUBLICATIONS AND NOTIFICATION OF 
RESULTS 
13.1 AUTHORSHIP POLICY 
Ownership of the data arising from this study resides with the study team. Authorship in any 
ensuing publications will be conducted as per the International Committee of Medical Journal 
Editors standards.  

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
23 
14 
REFERENCES 
Cassidy JD, Carroll LJ, Peloso PM, Borg J, von Holst H, Holm L, et al. Incidence, risk factors 
and prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task 
Force on Mild Traumatic Brain Injury. J Rehabil Med 2004: 28–60. 
 
Ebert DD, Zarski A-C, Christensen H, Stikkelbroek Y, Cuijpers P, Berking M, et al. Internet 
and computer-based cognitive behavioral therapy for anxiety and depression in youth: a 
meta-analysis of randomized controlled outcome trials. PLoS One 2015; 10: e0119895. 
 
Emanuelson I, Andersson Holmkvist E, Bjorklund R, Stalhammar D. Quality of life and post-
concussion symptoms in adults after mild traumatic brain injury: a population-based study in 
western Sweden. Acta Neurol Scand 2003; 108: 332–338. 
 
Espie CA, Kyle SD, Williams C, Ong JC, Douglas NJ, Hames P, et al. A Randomized, 
Placebo-Controlled Trial of Online Cognitive Behavioral Therapy for Chronic Insomnia 
Disorder Delivered via an Automated Media-Rich Web Application. Sleep 2012; 35: 769–781. 
 
Graff HJ, Siersma V, Møller A, Kragstrup J, Andersen LL, Egerod I, et al. Labour market 
attachment after mild traumatic brain injury : nationwide cohort study with 5-year register 
follow- up in Denmark. 2019: 1–10. 
 
Hartvigsen J, Boyle E, Cassidy JD, Carroll LJ. Mild traumatic brain injury after motor vehicle 
collisions: What are the symptoms and who treats them? A population-based 1-year inception 
cohort study. Arch Phys Med Rehabil 2014; 95: S286–S294. 
 
Hofmann SG, Asnaani A, Vonk IJJ, Sawyer AT, Fang A. The Efficacy of Cognitive Behavioral 
Therapy: A Review of Meta-analyses. Cognit Ther Res 2012; 36: 427–440. 
 
McMahon P, Hricik A, Yue JK, Puccio AM, Inoue T, Lingsma HF, et al. Symptomatology and 
Functional Outcome in Mild Traumatic Brain Injury: Results from the Prospective TRACK-TBI 
Study. J Neurotrauma 2013; 8: 1–8. 
 
Al Sayegh A, Sandford D, Carson AJ. Psychological approaches to treatment of 
postconcussion syndrome: a systematic review. J Neurol Neurosurg Psychiatry 2010; 81: 
1128–1134. 
 
Scottish Intercollegiate Guidelines Network. SIGN 130 • Brain injury rehabilitation in adults. 
2013 
 
Seabury SA, Gaudette É, Goldman DP, Markowitz AJ, Brooks J, McCrea MA, et al. 
Assessment of Follow-up Care After Emergency Department Presentation for Mild Traumatic 
Brain Injury and Concussion. JAMA Netw Open 2018; 1: e180210. 
 
Thompson HJ, Vavilala MS, Rivara FP. Chapter 1 Common Data Elements and Federal 
Interagency Traumatic Brain Injury Research Informatics System for TBI Research. Annu Rev 
Nurs Res 2015; 33: 1–11. 
 
Zhou L, Bao J, Setiawan IMA, Saptono A, Parmanto B. The mHealth app usability 
questionnaire (MAUQ): Development and validation study. J Med Internet Res 2019; 21 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
24 
15 
APPENDIX 
Appendix I: Rivermead Post-concussion Questionnaire 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
25 
 
Appendix II: PHQ-9 Questionnaire 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
26 
 
 
Appendix III: Pittsburgh Sleep Quality Index  
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
27 
 
Appendix IV: FAST alcohol screening test  
 
  
 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
28 
 
 
mHealth App Usability Questionnaire 
 
 
 
 
 
 
 
 
Strongly 
agree 
 
 
 
 
 
Strongly 
disagree 
The app was easy to use 
1 
2 
3 
4 
5 
6 
7 
It was easy for me to learn to use the app 
1 
2 
3 
4 
5 
6 
7 
I like the interface of the app 
1 
2 
3 
4 
5 
6 
7 
The information in the app was well 
organised, so I could easily find the 
information I needed 
1 
2 
3 
4 
5 
6 
7 
I feel comfortable using this app in social 
settings 
1 
2 
3 
4 
5 
6 
7 
The amount of time involved in using this 
app has been fitting for me 
1 
2 
3 
4 
5 
6 
7 
I would use this app again 
1 
2 
3 
4 
5 
6 
7 
Overall, I am satisfied with this app 
1 
2 
3 
4 
5 
6 
7 
Whenever I made a mistake using the app, 
I could recover easily and quickly 
1 
2 
3 
4 
5 
6 
7 
This mHealth app provided an acceptable 
way to receive healthcare services 
1 
2 
3 
4 
5 
6 
7 
The app adequately acknowledged and 
provided information to let me know the 
progress of my actions 
1 
2 
3 
4 
5 
6 
7 
The navigation was consistent when 
moving between screens 
1 
2 
3 
4 
5 
6 
7 
The interface of the app allowed me to use 
all the functions (such as entering 
information, responding to reminder, 
viewing information) offered by the app 
1 
2 
3 
4 
5 
6 
7 
This app has all the functions and 
capabilities I expect it to have 
1 
2 
3 
4 
5 
6 
7 
The app would be useful for my health and 
well-being 
1 
2 
3 
4 
5 
6 
7 
The app improved my access to healthcare 
services 
1 
2 
3 
4 
5 
6 
7 
The app helped me manage my health 
effectively 
1 
2 
3 
4 
5 
6 
7 
The app made it convenient for me to 
communicate with my healthcare provider 
1 
2 
3 
4 
5 
6 
7 
Using the app, I had many more 
opportunities to interact with my health care 
provider 
1 
2 
3 
4 
5 
6 
7 
I felt confident that any information I sent to 
my provider using this app would be 
received 
1 
2 
3 
4 
5 
6 
7 
I felt comfortable communicating with my 
healthcare provider using the app 
1 
2 
3 
4 
5 
6 
7 
Appendix VI: mHealth App Usability Questionnaire (Zhou et al., 2019) 
 
 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
29 
 
 
Appendix VII: HeadOn homepage showing reminder/task sections alongside the weekly 
audio which introduces the stage.  
 
 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
30 
 
 
Appendix VIII: HeadOn Symptom diary 
 
 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
31 
 
 
Appendix IX: HeadOn thought monitor 
 
 
 

HeadOn                                    
Version 4, 8th August 2021 
IRAS no: 279358 
  
 
           of 25 
 
 
32 
 
Appendix X: Qualitative interview schedule overview 
 
 
Interview Guide  
 
Participants will be initially asked about their concussion and or/use of health apps. The list 
of topics asked to participants include; 
 
1. About their experience of using the HeadOn  
2. When and how they used the intervention 
3. How easy or not easy they found the intervention to use 
4. Likes and dislikes about the intervention  
5. The functions which were most useful and least useful 
6. What changes they would make to improve HeadOn