An Online Lifestyle Modification Course for People With MS: a Randomised Controlled Trial of Course Effectiveness
Phase: NA
Conditions: Multiple Sclerosis
Sponsor: University of Melbourne

 
 
 
PROTOCOL  
An Online Educational Course for People with MS: A randomised 
controlled trial of course effectiveness 
Protocol Number: #1  
Version: #3 
Date: 13/12/2021 
Author/s: 
Dr Sandra Neate  
Dr Jeanette Reece 
Mr Will Bevens 
Ms Maggie Yu 
Dr Steve Simpson-Yap 
 
 
Sponsor/s: 
None 
 
 
CONFIDENTIAL 
 
This document is confidential and the property of The University of Melbourne. No part of it may 
be transmitted, reproduced, published, or used without prior written authorization from the 
institution. 
 
Statement of Compliance 
 
This study will be conducted in compliance with all stipulation of this protocol, the conditions of 
the ethics committee approval, the NHMRC National Statement on ethical Conduct in Human 
Research (2007 updated 2018). Australian Code for the Responsible Conduct of 
Research, 2018 (the Code) and the principles of the Note for Guidance on Good Clinical 
Practice (CPMP/ICH-135/95). 
 
 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
Protocol Number: 1 
Version & date: Version 3, dated 13 December 2021 
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Table of Contents 
 
Study Synopsis ........................................................................................................................ 3-5 
 
Glossary of Abbreviations & Terms ............................................................................................ 6 
 
Study Sites ................................................................................................................................. 7 
3.1 
Study Location/s .............................................................................................................. 7 
 
Introduction/Background Information ......................................................................................... 8 
4.1 
Lay Summary .................................................................................................................. 8 
4.2 
Introduction and key questions ................................................................................... 9-12 
4.3 
Background information ............................................................................................ 12-13 
 
Study Objectives ...................................................................................................................... 13 
5.1 
Hypothesis ..................................................................................................................... 13 
5.2 
Study Aims ............................................................................................................... 13-14 
5.3 
Outcome Measures .................................................................................................. 14-18 
 
Study Design ............................................................................................................................ 18 
6.1 
Study Type & Design & Schedule ............................................................................ 20-26 
6.2 
Standard Care and Additional to Standard Care Procedures ................................... 20-26 
6.3 
Randomisation ............................................................................................................... 29 
6.4 
Study methodology ........................................................................................................ 29 
 
Study Population ...................................................................................................................... 29 
7.1 
Recruitment Procedure .................................................................................................. 30 
7.2 
Inclusion Criteria ............................................................................................................ 31 
7.3 
Exclusion Criteria ........................................................................................................... 31 
7.4 
Consent ......................................................................................................................... 32 
 
Participant Safety and Withdrawal ........................................................................................... 32 
8.1 
Risk Management and Safety ....................................................................................... 31 
8.2 
Handling of Withdrawals ................................................................................................ 31 
8.3 
Replacements ................................................................................................................ 33 
 
Statistical Methods .............................................................................................................. 34-35 
9.1 
Sample Size Estimation & Justification .................................................................... 34-35 
9.2 
Power Calculations ................................................................................................... 34-35 
9.3 
Statistical Methods To Be Undertaken ..................................................................... 34-35 
 Storage of Blood and Tissue Samples ..................................................................................... 35 
10.1 
Details of where samples will be stored, and the type of consent for use of samples ... 35 
 Data Security & Handling ......................................................................................................... 35 
11.1 
Details of where records will be kept & How long will they be stored ............................ 36 
11.2 
Confidentiality and Security ........................................................................................... 37 
11.3 
Ancillary data ................................................................................................................. 37 
 Consumer Involvement ....................................................................................................... 37-39 
 References ............................................................................................................................... 39 
 
 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
Protocol Number: 1 
Version & date: Version 3, dated 13 December 2021 
Page 3 of 51 
 
STUDY SYNOPSIS 
Provide brief information 
Title: 
An Online Educational Course for People with MS: A randomised 
controlled trial of course effectiveness 
Short Title: 
Online Educational Course RCT 
Design: 
Randomised controlled trial (RCT) 
Study Centres: 
The University of Melbourne 
Hospital: 
None 
Study Question: 
This study proposes to conduct a RCT to test the effectiveness of 
an intervention/product providing information on MS-related 
lifestyle behaviour in the form of an online course that was 
developed by researchers from the Neuroepidemiology Unit 
(NEU) at the University of Melbourne in modifying participant’s 
behaviour and improving health outcomes in people with MS. 
The control arm consists of an online course providing general 
MS-related material that was also developed by the NEU.   
 
The research question of the study is: 
Will a Multiple Sclerosis (MS) Online lifestyle modification course 
that delivers evidence-based lifestyle modification 
recommendations to people with MS (the intervention) result in 
sustained lifestyle behaviour change and improved health 
outcomes post-intervention compared with people undertaking 
an MS Online standard-care course (the control)?  
Study Objectives: 
To quantitatively and qualitatively assess the outcomes of 
participants enrolled in the MS Online intervention course 
compared with the MS Online standard-care course in an RCT. 
In particular, we aim to: 
1) To assess the uptake and maintenance of recommended 
lifestyle modifications in a cohort of people with MS after 
undertaking an MS Online intervention course compared with 
people undertaking an MS Online standard-care course.  
2) To assess whether people with MS undertaking and adhering 
to the guidelines of the MS Online intervention course have 
improved health outcomes of depression, fatigue, disability, 
and quality of life over the short-term and medium-term 
compared with people undertaking and adhering to the MS 
Online standard-care course. 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
Protocol Number: 1 
Version & date: Version 3, dated 13 December 2021 
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Primary Objectives: 
To determine whether participants adhering to lifestyle 
modification recommendations outlined in the MS Online 
intervention course have clinically significant increased health-
related quality of life (HRQOL) in both domains of physical and 
mental health compared with participants following 
recommendations of the MS Online standard-care course. These 
outcomes will be examined in the short-term (6 and 12 months) 
and in the medium-term (2.5 years). 
 
That is, we aim to determine whether participants in the Online 
intervention course following recommended lifestyle 
modifications have clinically significant and material increases in 
Physical Health Composite (PHC) and Mental Health Composite 
(MHC) scores, as derived from the validated tool designed to 
measure HRQOL in people with MS (MSQOL-54) compared with 
participants following recommendations of the Online standard-
care course.  
Secondary Objectives 
To determine whether participants following the lifestyle 
modification recommendations in the Online MS intervention 
course have improved depression, anxiety, fatigue, disability and 
self-efficacy in the short-term and medium-term compared with 
people following recommendations of the Online MS standard-
care course. 
Inclusion Criteria: 
Eligible participants must: 
 
1. Be able to read, write, and speak English;  
2. Be 18 years old or over; 
3. Have a confirmed diagnosis of relapsing-remitting MS by 
a neurologist preceding recruitment; 
4. Be able to access the internet and be able to view 
sessions. 
Exclusion Criteria:  
Exclusion criteria of participants include: 
1. Experiencing any serious co-morbid chronic illness or 
neurological illness/injury other than MS that would 
threaten regular participation or significantly affect the 
outcome measures in its own right, such as motor 
neurone disease or stroke, as determined by the study 
investigators;  
2. Currently participating in another study or self-
management program involving modification of lifestyle. 
Number of Planned 
Participants: 
1054 participants, 527 in each arm at 1:1 allocation (intervention 
and standard-care arm) 
Investigational product: 
Not applicable 
Safety considerations: 
Participation in the study poses no physical risk to participants as 
the proposed RCT involves taking part in an Online MS 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
Protocol Number: 1 
Version & date: Version 3, dated 13 December 2021 
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educational course and completing self-reported questionnaires 
and possibly two semi-structured qualitative interviews.  
Any potentially psychological risks from participating in the study 
have been addressed by contingency plans to provide links to 
Online help resources and the contact details of study team 
members to provide further information for participants.  
Statistical Methods: 
Analysis of outcomes: 
Characteristics of quality of life (QoL) will be measured by the 
MSQOL-54, including physical and mental health composite 
scores and multiple subdomains. Linear regression will be used 
to determine cross-sectional and prospective relationships with 
QoL. Characteristics of disability will be assessed using linear 
regression. Characteristics of dichotomous clinically significant 
fatigue and depression will be assessed by log-binomial 
regression. Characteristics of self-efficacy composite scores will 
be assessed by linear and log-binomial regression for continuous 
and dichotomised self-efficacy, respectively. All models will be 
assessed for potential clinical and demographic confounders and 
appropriate adjustments will be made in analyses.  
Subgroups: 
Not applicable 
Consumer Involvement 
Consumers have been involved in the co-design of the MSOC 
RCT. A consumer advisory group comprising of 6-8 people with 
MS in a series of focus groups was involved in the co-design of 
the MS Online intervention and standard-care course. The 
devised course was then tested in a feasibility study (MSOC – 
Feasibility) involving a subgroup of people with MS (n = 31) and 
the quantitative and qualitative outcomes of the MSOC – 
Feasibility study were used to co-design the MS Online 
intervention and standard-care courses in the proposed RCT.  
 
 
 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
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GLOSSARY OF ABBREVIATIONS & TERMS 
Insert or delete information as required 
Abbreviation 
Description (using lay language) 
MS 
Multiple Sclerosis 
RCT 
Randomised Controlled Trial 
MSOC 
Multiple Sclerosis Online Course 
MSOC - Feasibility 
Multiple Sclerosis Online Course - Feasibility study 
MSOC - RCT 
Multiple Sclerosis Online Course – Randomised Control Trial 
QoL 
Quality of life  
HRQOL 
Health Related Quality of life  
UoM 
The University of Melbourne 
HREC 
Human Research Ethics Committee 
NHMRC  
National Health and Medical Research Council 
DHQ 
Dietary Habits Questionnaire 
HADS 
Hospital Anxiety and Depression Scale 
MSQOL-54 
Multiple Sclerosis Quality of Life-54 instrument 
IPAQ-SF 
International Physical Activity Questionnaire - Short Form  
FSS 
Fatigue Severity Scale 
MAQ 
Mindfulness Adherence Questionnaire 
PDDS 
Patient-Determined Disease Steps 
PHC 
Physical Health Composite 
MHC 
Mental Health Composite 
MSPSS 
Multidimensional Scale of Perceived Social Support 
UWSE 
University of Washington Self-Efficacy 
 
 
 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
Protocol Number: 1 
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STUDY SITES 
3.1 
STUDY LOCATION/S  
[List all locations, their address & contact details this study or parts of the study will be conducted] 
Site 
Address 
Contact 
Person 
Phone 
Email 
UoM 
Neuroepidemiology Unit, 
Melbourne School of 
Population and Global 
Health, 207 Bouverie 
Street, Carlton 
Dr Sandra 
Neate 
0412877894 
Sandra.neate@unimelb.edu.au  
UoM 
Neuroepidemiology Unit, 
Melbourne School of 
Population and Global 
Health, 207 Bouverie 
Street, Carlton 
Dr 
Jeanette 
Reece 
0402993565 
jreece@unimelb.edu.au  
UoM 
Neuroepidemiology Unit, 
Melbourne School of 
Population and Global 
Health, 207 Bouverie 
Street, Carlton 
Mr William 
Bevens 
0498337231 
William.bevens@unimelb.edu.au  
UoM 
Neuroepidemiology Unit, 
Melbourne School of 
Population and Global 
Health, 207 Bouverie 
Street, Carlton 
Dr Steve 
Simpson-
Yap 
0424409976 
Steve.simpsonyap@unimelb.edu.au  
UoM 
Neuroepidemiology Unit, 
Melbourne School of 
Population and Global 
Health, 207 Bouverie 
Street, Carlton 
Dr Pia 
Jelinek 
0433337112 
Pia.jelinek@gmail.com  
UoM 
Neuroepidemiology Unit, 
Melbourne School of 
Population and Global 
Health, 207 Bouverie 
Street, Carlton 
Ms Maggie 
Yu 
+61383444000 maggie.yu@unimelb.edu.au  
UoM 
Neuroepidemiology Unit, 
Melbourne School of 
Population and Global 
Dr Nupur 
Nag 
+61383444000 nnag@unimelb.edu.au  

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
Protocol Number: 1 
Version & date: Version 3, dated 13 December 2021 
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Health, 207 Bouverie 
Street, Carlton 
UoM 13, VCCC-305 Grattan St, 
Parkville 
Prof 
Kathleen 
Gray 
+61383448936 kgray@unimelb.edu.au 
UoM 
Neuroepidemiology Unit, 
Melbourne School of 
Population and Global 
Health, 207 Bouverie 
Street, Carlton 
Prof 
George 
Jelinek 
+61383444000 g.jelinek@unimelb.edu.au  
UoM 
Neuroepidemiology Unit, 
Melbourne School of 
Population and Global 
Health, 207 Bouverie 
Street, Carlton 
A/Prof 
Tracey 
Weiland 
+61383444000 tweiland@unimelb.edu.au 
 
 
INTRODUCTION/BACKGROUND INFORMATION 
4.1 
LAY SUMMARY 
 
The Multiple Sclerosis Online Course (MSOC), both the intervention and standard-care arms, was 
delivered as part of a feasibility study (MSOC - Feasibility study) in April to June 2021. In the MSOC 
– Feasibility study 31 participants from Australia, New Zealand, and the United States completed the 
MS Online course (n=15 intervention course and n=16 standard-care course). Examination of the 
acceptability and usability in the MSOC – Feasibility study was conducted via quantitative and 
qualitative analyses, with the results of these analyses currently in preparation for publication in a 
peer-reviewed journal.  
In the proposed study, we plan to perform a randomised controlled trial (RCT) utilising the results 
from the MSOC – Feasibility study. That is, the MS Online course has been modified and 
redeveloped to test the effectiveness of the MS Online intervention and standard-care courses in a 
large international RCT (MSOC – RCT). 
This RCT will analyse participant uptake and retention, adoption and adherence to lifestyle 
recommendations and health outcomes at baseline, and 6 months, 12 months, and 2.5 years after 
completing either the MS intervention or standard-care course. The significance of this study is that 
the RCT will test: 
1) whether an MS Online educational intervention course, compared with a standard-care 
course, can change behaviour in people with MS and 
2) whether an MS online educational intervention course, compared with standard-care course, 
leads to superior improved health outcomes in people with MS.  
 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
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4.2 
INTRODUCTION 
 
Although genetic factors are responsible for roughly 25% of the risk of multiple sclerosis (MS) onset, 
they play less of a part in disease progression. By contrast, disease progression and disability are 
associated or influenced by environmental factors including modifiable lifestyle behaviours. These 
risk factors include smoking, a diet high in saturated fat and low in omega-3 polyunsaturated fatty 
acids, lack of physical activity, inadequate vitamin D level, and stress. The amelioration of these 
risks is associated with a reduction in the chronic inflammatory state associated with MS(Fragoso, 
2014), and subsequent improved health outcomes including improved mental and physical health 
quality of life(Hadgkiss, Jelinek, Weiland, et al., 2015; Jelinek et al., 2013; Marck et al., 2014), 
reduced relapse rate(D'Hooghe M, Nagels, Bissay, & De Keyser, 2010), depression risk(K. L. Taylor 
et al., 2014), clinically significant fatigue(T.J. Weiland et al., 2015; T. J. Weiland et al., 2015), and 
less disability and symptom burden(Fitzgerald et al., 2018; Jelinek et al., 2016). Lifestyle modification 
of these risk factors represents an effective, low cost and low risk intervention in MS. 
Studies of a lifestyle modification programs for MS including evidence-based recommendations 
regarding diet, exercise, stress management, sun exposure, and vitamin D delivered via intensive 
face-to-face residential workshops. These workshops have demonstrated 11.3% and 19.5% 
improvement in overall quality of life at one and 5-year time-points post workshop, respectively, 
compared to baseline measures (Hadgkiss et al., 2013), and that behaviour change was feasible 
and sustainable (Marck et al., 2018). However face-to-face interventions are resource intensive and 
present potential barriers to participation for people with MS, including geographical, financial and 
disease specific factors such as fatigue and mobility. The COVID-19 pandemic has highlighted the 
highly unpredictable ability to travel and presented further MS specific challenges relating to potential 
immunosuppression and subsequent vulnerability of participants in face-to-face education. 
Web-based interventions have shown great efficacy at promoting positive lifestyle changes in a 
range of populations for a variety of medical conditions (Bardus, Smith, Samaha, & Abraham, 2016; 
Bossen, Veenhof, Dekker, & de Bakker, 2014; Knittle et al., 2018; Kohl, Crutzen, & de Vries, 2013; 
Neve, Morgan, Jones, & Collins, 2010; Olson, 2016), including MS (Fischer et al., 2015; Hind et al., 
2014; Kirsten van, Trecia, & Rona, 2015; Moss-Morris et al., 2012). However, there is a paucity of 
studies that incorporate multiple lifestyle recommendations into one program. To date, no evidence-
based lifestyle modification program for people with MS has been translated into a web-based Online 
intervention that has been tested in a randomised controlled trial (RCT) with long-term follow-up.  
People with MS are a highly motivated population that show modest levels of engagement and 
retention in lifestyle management programs, and previous Online self-assessments have found 
favourable levels of engagement and retention in the short- and long-term (Jongen et al., 2017). An 
Online educational intervention for people with MS would potentially alleviate resource issues, 
ameliorate barriers of geography and mobility and meet all the requirements post pandemic of 
reaching an already potentially vulnerable population.  
Our research team, together with a community advisory group of people with MS, has developed the 
Multiple Sclerosis Online Course (MSOC) in two arms: the MS online intervention course and the 
MS online standard-care course. Each course delivers educational modules regarding the biological 
basis of MS and preventing MS in family members through lifestyle modification in diet, exercise, 
stress reducing activities, sunlight and vitamin D, omega 3 and smoking and alcohol intake. The 
intervention course provides evidence-based recommendations for lifestyle modification across 
these modules, delivered via a mixture of videos, presentations, and reading components. The 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
Protocol Number: 1 
Version & date: Version 3, dated 13 December 2021 
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standard-care course is similar in structure and functionality but contains standard MS health 
recommendations from a range of international MS websites. Results from the MSOC – Feasibility 
study (The University of Melbourne HREC 1851781.1) comprising the MS Online intervention course 
versus the MS Online standard-care course demonstrated that people with MS completed both the 
intervention and standard-care course at satisfactory rates, believed the course was readily 
accessible and enjoyable, and participated in follow-up evaluation (quantitative and qualitative 
manuscripts currently in preparation).   
Our research question is: Will a Multiple Sclerosis Online Course that delivers evidence-based 
lifestyle modification recommendations to people with MS (the intervention) result in greater post-
intervention sustained lifestyle behaviour change and improved health outcomes compared with a 
standard-care course (the control)?  
Results of the RCT will be disseminated through international conference presentations and in peer-
review international journals with open access to ensure research findings are readily available for 
people with MS, clinicians and the general public. 
Following completion of the RCT, the MS Online Course will be made available free of charge to 
people with MS worldwide via the Overcoming MS Charity to empower people with MS to adopt a 
program of positive lifestyle change to improve their health and well-being. 
 
Potential benefits of participants enrolling in the RCT: 
Increasing evidence in the scientific literature suggests that lifestyle modification could be a point of 
intervention for improving quality of life and clinical outcomes in people with MS. In the NEU at the 
University of Melbourne we have developed an online course that will deliver the relevant information 
to people with MS that has the potential to improve their health outcomes. While we have developed 
an intervention course and a standard-care course, both online courses have the potential to improve 
health outcomes in people with MS. Topics included in the online courses that have been associated 
with improved health outcomes which may prove to be beneficial to RCT participants are outlined 
below. However, findings in the literature are conflicted and emphases there is need for a RCT to 
directly identify any causal associations between lifestyle factors and health outcomes (our proposed 
MSOC – RCT study): 
 
Diet 
Topics covered in the MS-online related course include a module on diet quality. Several  studies 
have found better quality-of-the-diet is associated with reduced relapses,(Simpson-Yap et al., 2020) 
and disability.(Fitzgerald et al., 2018; Jelinek et al., 2016; Simpson-Yap, Nag, Probst, Jelinek, & 
Neate, 2021) Other studies have found diet is associated with improved QoL.(Evers, Heerings, de 
Roos, Jongen, & Visser, 2021; Hadgkiss, Jelinek, Weiland, et al., 2015; Marck, Probst, Chen, Taylor, 
& van der Mei, 2021) In particular, a study from our group of a large international cohort found a 10% 
improvement in diet quality as assessed by the Diet Habits Questionnaire was associated with 6% 
and 5% higher physical and mental-QoL at baseline, respectively, and this was most evident for 
fruit/vegetable and fat.(Hadgkiss, Jelinek, Weiland, et al., 2015) 
 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
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Vitamin D 
In a cross-sectional study, Vitamin D supplementation was found to be associated with improved 
health outcomes in people with MS.(Jelinek et al., 2015) A further study by Simpson-Yap et al. found 
vitamin D supplementation was associated with higher physical and mental QoL in a cross-sectional 
analysis but only associated with higher physical QoL in a prospective analysis.(Simpson-Yap, 
Jelinek, et al., 2021) Other observational studies have found lower vitamin D levels are associated 
with increased risk of MS and progression.(Duan et al., 2014; Martinez-Lapiscina, Mahatanan, Lee, 
Charoenpong, & Hong, 2020) 
 
Omega-3 
Studies have found increased Omega-3 intake or oily fish consumption is associated with improved 
health outcomes in people with MS. In particular, Jelinek et al. found Omega-3 intake improved QoL 
and reduced relapses,(Jelinek et al., 2013) and Coe et al. found consuming fish decreased 
fatigue.(Coe et al., 2021) 
 
Stress relief 
Observational studies have found stress reduction can reduce exacerbations in people with MS and 
improve QoL and emotional wellbeing in people with MS.(Mohr et al., 2012; Senders et al., 2019; P. 
Taylor, Dorstyn, & Prior, 2020) In particular, the randomised controlled trial by Mohr et al. 
demonstrated stress management training reduced disease activity by reducing the presence of new 
lesions in the brain of people with relapsing-remitting MS.(Mohr et al., 2012) However, other studies 
found stress reduction did not improve QoL.(Agland et al., 2018) 
 
Physical activity 
Observational studies have found physical activity is associated with increased energy and social 
functioning and improved physical and mental health outcomes.(Marck et al., 2014; Marck, 
Learmonth, Chen, & van der Mei, 2020; Motl & Gosney, 2008) 
 
Key questions: 
Does participation of people with MS in the MS Online intervention course change lifestyle 
behaviours compared with participants in an MS Online standard care course in the: 
1) Short-term 
2) Medium-term 
What is the effect on participant health outcomes from different levels of adoption and adherence to 
lifestyle recommendations in the MS Online intervention course compared with MS Online standard-
care course with respect to: 
1) Quality of life 

 
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2) Fatigue 
3) Depression 
4) Anxiety 
5) Disability 
6) Self-efficacy 
4.3 
BACKGROUND INFORMATION 
 
Lifestyle factors are known to affect the progression of multiple sclerosis (MS). Studies of participants 
with MS attending an evidence-based lifestyle modification program, delivered via face-to-face 
workshops in Australia, have demonstrated improved mental and physical health, reduced relapse 
rate and improved quality of life over three years follow-up, and that behaviour change has been 
found to be feasible and sustainable. However, the face-to-face modality of this educational 
intervention is resource-intensive and accessibility may be impeded by geography, cost, and MS-
specific factors such as illness, fatigue, and disability. Furthermore, the COVID-19 pandemic has 
highlighted the unpredictable ability to travel and the importance of flexibility of health-related 
education.  
The Neuroepidemiology Unit, Melbourne School of Population and Global Health, has developed 
the Multiple Sclerosis Online Course (MSOC) to deliver a widely accessible and user-friendly 
educational tool for people with MS. The course aims to deliver the best available evidence regarding 
lifestyle-related risk factors in the development and progression of MS and behaviour modification 
to improve health outcomes.  
Two forms of the course were developed:  
1. an MS Online intervention course based delivering evidence-based information regarding 
modifiable lifestyle related risk factors implicated in disease progression; and  
2. an MS Online standard-care course, similar in format and presentation, but containing general 
information sourced from standard MS websites. Both courses have seven modules delivered over 
six weeks.  
A feasibility study involving the delivery of the intervention and standard-care course was conducted 
from April to June 2021 (MSOC – Feasibility). This study assessed the primary outcomes of attrition 
in both the intervention and standard-care arm. Secondary outcomes assessed the completion of 
the baselines survey, and quantitatively assessed learnability, accessibility, and desirability via a 
Likert scale follow-up survey. A qualitative analysis examining motivation, expectations and 
outcomes was also conducted. Based on the MSOC – Feasibility study, we have modified 
recruitment, functionality, and the community forum aspects of the course. We now aim to test the 
effectiveness of the intervention arm of the course compared with the standard-care arm in a larger 
randomised controlled trial (MSOC - RCT). 
 
Choice of comparators in RCT: 
The proposed study aims to prospectively determine whether an Online MS Lifestyle Modification 
Course (the intervention arm) can deliver an evidence-based educational intervention that results in 
behaviour change which is sustained and is translated into improved health outcomes for people 

 
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with MS, and whether these effects are superior to the Online standard-care course (the control 
arm). 
In this RCT, we will be comparing two interventions/products that were developed by researchers at 
the Neuroepidemiology Unit (NEU) at the University of Melbourne: 
1. the MS Online intervention course that delivers information on diet, exercise, Vitamin D and 
omega-3 supplementation and stress relief/meditation 
2. the MS Online standard-care course that delivers standard MS-related information that can 
be obtained through publicly-available Websites. 
 
In people with MS, we aim to compare health outcomes of people enrolled in the intervention (the 
MS Online intervention course) with the control arm (the MS Online standard-care course) by 
assessing: 
 
o 
assess the uptake and maintenance of recommended lifestyle modifications in a cohort of 
people with MS after undertaking an MS online educational lifestyle course compared with 
people undertaking an online standard-care course. 
 
o 
assess whether people with MS undertaking an MS online educational lifestyle intervention 
course results in improved clinical outcomes and health outcomes of depression, fatigue, 
disability, and quality of life over the short-term and medium-term compared with people 
undertaking an online standard-care course. 
 
 
STUDY OBJECTIVES 
5.1 
HYPOTHESIS  
 
People with MS who undertake the MS Online intervention course (the intervention arm) delivering 
evidence-based lifestyle modification education will have sustained behaviour change and improved 
health outcomes that are superior to the health outcomes in people with MS undertaking the MS 
Online standard-care course (the control arm). 
 
5.2 
STUDY AIMS 
 
To quantitatively and qualitatively assess the arms of the Multiple Sclerosis Online Course in an RCT 
(the MS Online intervention course and MS Online standard-care course). We aim to measure:  
 
1) The degree of engagement with and participation in the course 
2) Adoption of lifestyle behaviours change following course completion 
3) Adherence to lifestyle behaviour change over time 
4) Short-term and medium-term health outcomes and 
5) To compare all these outcomes between both arms. 
 

 
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Overall, the proposed RCT will enable a causal relationship between lifestyle factors and clinical and 
health outcomes to be examined. 
 
5.3 
OUTCOME MEASURES 
 
QUANTATIVE OUTCOMES 
Lifestyle behaviour of participants will be assessed at baseline and 6 months, 12 months and 
2.5 years after completion of the Online MS course (intervention or standard-care). 
Lifestyle/behaviour outcomes to be measured include: 
a. 
Exercise 
To assess physical activity we will use The International Physical Activity Questionnaire - 
Short Form (IPAQ-SF), a 7-item 7-day recall of frequency and duration of vigorous and 
moderate physical activity, walking, and sitting assessed in nine items(Craig et al., 2003). 
The IPAQ and its short form have been validated in several studies and populations globally, 
and the long form has been used previously for people with MS(Stroud, Minahan, & 
Sabapathy, 2009; Weikert et al., 2012).   
 
b. 
Diet 
Since we aim to assess diet broadly with a particular consideration for fats, we will modify 
the Diet Habits Questionnaire (DHQ)(McKellar et al., 2008). The original 24-item DHQ has 
eight dietary sub-scores, and assesses saturated and unsaturated fat intake, fruit and 
vegetable, fibre, takeaway, snack habits, and omega-3 consumption, among other estimates. 
In our modified version, we removed three items regarding sodium intake, and one item on 
alcohol was replaced with an alternate alcohol assessment measure. We added a 
researcher-devised item regarding oily fish consumption that was separate from the DHQ: 
“How often do you eat oily fish such as sardines, mackerel, herring, salmon, tune or trout? 
(Never; Less than once a week; About 1 - 2 times a week; About 3 - 4 times a week; At least 
5 times a week) and options regarding “I don’t eat meat” and “I don’t eat dairy”.   
 
c. 
Alcohol consumption 
Volume and frequency of alcohol consumed will queried. In Australia a standard drink is 
considered to be 10 grams of ethanol.  Frequency of binge drinking, defined by the Australian 
Bureau of Statistics as more than 7 drinks a week for men, and more than 5 for women, will 
be queried.  
 
d. 
Smoking 

 
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Smoking status (never/ex-smoker/current smoker) will be queried. For current smokers, 
typical number of cigarettes per week will be queried along with the total years they have 
been smoking. For ex-smokers, their typical number of cigarettes per week when they 
smoked will be queried, as well as the total years they smoked and the duration since they 
quit smoking.  
 
e. 
Omega-3 uptake 
We will assess both the type and daily dosage of omega-3 supplementation used on average 
in the last 12 months. Types of omega-3 will include fish oil, high potency fish oil, and flaxseed 
oil. 
 
f. 
Vitamin D uptake 
We will assess vitamin D supplementation by measuring dosage and frequency of vitamin D 
intake. 
 
g. 
Sun exposure 
To assess sun exposure we will modify the Ausimmune Longitudinal Study in people with 
MS (Lucas et al, Neurology, 2011). For each of summer and winter, participants will be asked 
to report number of days per week they were out in the sun; average duration spent in the 
sun on days they were out in the sun (none, 1-15 minutes to >60 minutes). We will also query 
whether participants deliberately increased their sun exposure to increase their vitamin D 
levels. 
 
h. 
Stress management 
We will use 2 questions of the Mindfulness Adherence Questionnaire (MAQ)(Hassed et al., 
2021), a 6-item subset of main questionnaire, to measure the type and frequency of the 
participant’s experience of meditation. 
 
 
Other measures: 
a. 
Sociodemographics 
Data will be collected for date of birth, sex, current location of residence, country of birth, 
cultural 
background 
(Australian 
Standard 
Classification 
of 
Cultural 
and 
Ethnic 
Groups(Statistics, 2012)) and highest education level completed at baseline only, whereas 
marital status and employment status will be queried at all timepoints.  
 
 

 
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b. 
Medication use 
Participants will also be asked to indicate whether they take prescription antidepressant, 
anxiolytic/sedative, or antifatigue medications. 
 
c. 
Comorbidities 
The Self-administered Comorbidity Questionnaire (SCQ) will be used to assess the presence 
of comorbidities in the absence of medical record review(Sangha, Stucki, Liang, Fossel, & 
Katz, 2003). It has demonstrated criterion validity when assessed against medical 
records(Stolwijk et al., 2014), and has been used in studies of participants with MS 
(Giovannetti et al., 2016; Holper et al., 2010). The clinically meaningful difference in the 
number of comorbidities for MS assessed using the self-administered comorbidity 
questionnaire has not been determined.  
 
d. 
BMI  
Body Mass Index (weight/height)2 will be calculated from data collected on self-reported 
participant 
weight 
and 
height 
and 
classified 
using 
the 
WHO 
classification 
system(Organization, 2017). A meaningful change in BMI is difficult to will be defined by 
comparing to BMI at baseline.  
 
e. 
Perceived Social Support 
The 12-item multidimensional Scale of Perceived Social Support (MSPSS) will be used to 
measures participants' social interaction and satisfaction with social support(Zimet, Dahlem, 
Zimet, & Farley, 1988). Higher score of MSPSS indicates higher quality of social support. 
 
 
 
Health outcomes of participants will be assessed at baseline and 6, 12 and 30 months after 
completion of the respective Online MS course. Health outcomes measured include: 
 
f. 
Mental and physical quality of life (qol) 
The MSQOL-54 will be used to assess a spectrum of HRQOL outcomes. In particular, the 
two primary outcome measures for this study will be change in Physical Health Composite 
(PHC) and Mental Health Composite (MHC) derived from the MSQOL-54. PHC and MCH are 
derived by combining scores of relevant subscales (Vickrey, Hays, Harooni, Myers, & Ellison, 
1995). Although minimal clinically important differences have not been established for the 
MSQOL-54 composite scores, differences of at least five points have previously been 
determined as the minimum clinically meaningful change in an HRQOL measure (Osoba et 
al., 1998; Taphoorn, et al., 2005). This is based on recommendations that a difference 

 
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equivalent to half the standard deviation be universally considered an important magnitude 
for all HRQOL tools (Norman, Sloan, & Wyrwich, 2003). The MSQOL-54 has been 
psychometrically validated since 1995, used online and also translated into many different 
languages. 
 
g. 
Fatigue 
Clinically significant fatigue will be measured by the 9-item Fatigue Severity Scale (FSS) 
(Krupp, LaRocca, Muir-Nash, & Steinberg, 1989). The FSS has good internal consistency, 
stability, and sensitivity to change over time(Amato et al., 2001; Smedal et al., 2011).  A mean 
score ≥4 has been suggested as a cut-off to indicate clinically significant fatigue and is widely 
used for people with MS (Lerdal, Celius, & Moum, 2003; Marrie et al., 2005; Smedal et al., 
2011). A meaningful change on the FSS has been reported demonstrated to be a change of 
≥1.9 points in people with MS (Learmonth et al., 2013) and so here a change in mean score 
of 1.9 points or more will be considered clinically meaningful. 
 
h. 
Anxiety and depression 
The Hospital Anxiety and Depression Scale (HADS) for the presence of and severity of 
anxiety and depressive symptoms. The HADS is commonly used for screening for anxiety 
and depression, as well as selecting and monitoring treatment and has been used to measure 
depression in MS (Zigmond & Snaith, 1983).  
 
i. 
Patient-reported disability 
The Patient-Determined Disease Steps (PDDS) is a self-reported measure of ambulatory 
disability. The PDDS is scored ordinally from 0 (normal) to 8 (bed bound) with detailed 
descriptors and definitions. It correlates well with the EDSS and moderately with the widely 
used Multiple Sclerosis Functional Composite and has excellent test-retest reliability. PDDS 
is considered a practical tool to use to assess changes in disability over time (Hohol, Orav, & 
Weiner, 1999). One step will be considered a clinically meaningful change in the PDDS. 
 
j. 
Self-efficacy 
Self-efficacy (the belief in one’s ability to produce the effects or outcomes one wants) will be 
measured using the University of Washington Self-Efficacy (UWSE) survey, a 
psychometrically sound instrument that includes 6 items for measuring self-efficacy, validated 
in MS (Amtmann et al., 2012). 
 
 
Primary intervention quantitative outcomes/endpoints: 

 
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The two primary outcome measures for this study are changes (improvements) from baseline in 1. 
Physical Health Composite (PHC) and 2. Mental Health Composite (MHC) derived from the MSQOL-
54 in the short-term and medium-term. Differences of at least five points have previously been 
determined as the minimum clinically meaningful change in an HRQOL measure (Osoba, Rodrigues, 
Myles, Zee, & Pater, 1998; Taphoorn & Bottomley, 2005). Previous data suggests a difference of 
five points is achievable in a sample of people with MS (Hadgkiss, Jelinek, Taylor, et al., 2015). 
 
Secondary intervention quantitative outcomes/endpoints: 
 
Secondary outcomes include clinically relevant changes (improvements) in depression, anxiety 
fatigue, disability and self-efficacy in the short-term and medium-term. 
 
QUALITATIVE OUTCOMES 
A qualitative study using semi-structured interviews will be conducted within one month and 12 
months after completing the MS Online course (the same group of people with MS will be interviewed 
at both time points).  
 
A randomly selected sample of approximately 15 participants from each the standard-care course 
arm and intervention course arm will receive an email or phone call requesting their participation in 
30 to 60 minutes qualitative interview. Interviews will be conducted by telephone or via the internet 
by 3 trained interviewers. All interviewers will be involved in the first three interviews to ensure 
consistency in the format and content of qualitative interviews.   
 
Semi-structured interviews have been developed based on an iterative process by researchers. 
Schedules of qualitative interviews are described in the attached file, MSOC RCT qualitative 
interviews schedule.docx 
 
The 1-month interview guide will cover the following domains:  
1) Participants’ views regarding motivation to undertake the course 
2) Views of the content of the course  
3) Participants’ experiences 
4) Use of community 
5) Initial changes to lifestyle 
6) Initial changes to attitudes to MS, health and the future 
 
The 12-month interview will cover the following domains: 

 
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1) Adoption of lifestyle recommendations 
2) Perceived health 
3) Sense of community and support 
4) Attitude to MS, health and the future 
 
Interviews will be digitally recorded and transcribed by voice recognition software. All recordings and 
transcribed files will be securely stored in a re-identifiable format. 
 
STUDY DESIGN 
6.1 
STUDY TYPE & DESIGN & SCHEDULE 
 
1. 
Study Type: Clinical trial 
Randomised controlled trial, involving: 
a. Epidemiological analysis of quantitative data 
b. Qualitative analysis of semi-structured interviews 
 
2. 
Study Design (refer to Table 1) 
 
I. 
This is a single-site study that will be conducted at the Neuroepidemiology Unit in the Centre 
for Epidemiology and Biostatistics, Melbourne School of Population and Global Health at The 
University of Melbourne, involving online recruitment of participants with MS from Australia, 
New Zealand, USA, UK and Canada. The decision was made to make this a single-site study 
to guarantee that all data collected from participants (both personal participant data and 
responses to self-reported questionnaires) will be safely and securely stored in one location 
(on the University of Melbourne server).   
 
II. 
For participant recruitment, details of the RCT will be published on MS society websites and 
social media sites throughout Australia, New Zealand, USA, UK and Canada seeking 
interested people with MS to participate in the MSOC - RCT.  
 
III. 
Interested participants (people with relapsing-remitting MS) will be asked to click on a link on 
the notice advertising the MSOC - RCT which will direct them to 7 eligibility questions related 
to: (1) their age; (2) the type of MS they were diagnosed with; (3) the year they were 
diagnosed with MS (4,5) whether they follow a MS-specific diet and if so, the diet they follow 
(6,7) whether they follow a MS-specific program and if so, the program they follow.  
 

 
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IV. 
Participants with MS over the age of 18 fulfilling inclusion and exclusion criteria from 
Australia, New Zealand, USA, UK, Canada and other countries who read, write and speak 
English will be invited to participate in the study. Note, the recruitment period will be up to 
two months from the date of the first participant recruitment or earlier, if the required number 
of eligible participants have been recruited. 
 
V. 
Interested participants meeting the study eligibility criteria (Refer to Section 6.2 and 6.3 for 
eligibility criteria) after completing the eligibility questions will be emailed a participant 
information form and consent form. Once participants have provided their consent by ticking 
a box online, participants will be emailed a link to the baseline questionnaire to obtain 
demographic data and obtain data on lifestyle and outcome measures (Section 4.3, Table 1). 
Interested participants not meeting the study eligibility criteria will be excluded and notified 
by email that they were not eligible to participate in the study and thanking them for their 
interest.  
 
VI. 
Participants will be randomised to either the MS Online intervention course or the MS Online 
standard-care course at a ratio of 1:1 using simple randomisation. Randomisation will occur 
over a 2-week period after recruitment of eligible participants.  
 
VII. 
Participants will undertake the MS Online course (intervention arm or standard-care arm) 
over a 6-week period. Note, each arm is of comparable length and content-type (video, 
interviews, images, interactivity), to minimise variability in ‘dose’ received between 
intervention and standard-care groups. Both courses will follow a similar structure throughout, 
limiting differences in how the content of the course is presented. 
 
VIII. 
Patient-reported outcomes measures (Section 4.3, Table 1) will be determined after a period 
of 6 months, 12 months and 2.5 years after the completion of the MS Online course. This will 
involve participants from the MS Online intervention arm and the MS Online standard-care 
arm completing validated questionnaires online (following instructions and reminders, if 
necessary, from study team members). These measures will determine participants 
adherence to lifestyle recommendations of the Online intervention and standard course with 
respect to diet, exercise, omega 3 intake, vitamin D intake, meditation and sun exposure 
(Table 1). Health outcomes related to participant’s quality of life, depression, anxiety, fatigue, 
disability and self-efficacy. 
 
IX. 
The primary objective of the study will be assessed at the 12-month and 2.5 year follow-up. 
That is, Health-related quality of life (HRQOL) calculations for Physical Health Composite 

 
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(PHC) and Mental Health Composite (MHC) scores derived from the MSQOL-54 for 
participants in the intervention and standard-care arm will be calculated in the intervention 
and standard-care arms.  
 
We will consider amending the RCT protocol to allow participants in the standard-care arm 
access to the MS Online intervention course before the end of the study (ie before the 2.5-
year follow-up) in the event:  
a) clinically significant increases in either the PHC and MHC scores of MSQOL-54 
(≥5)(Osoba et al., 1998; Taphoorn & Bottomley, 2005) from baseline are found in participants 
in the intervention arm at the 12-month follow-up who are adhering to lifestyle 
recommendations of the Online Lifestyle modifications course, but  
b) clinically significant improvements in either PHC or MHC are not found in participants in 
the standard-care arm at the 12-month follow-up. 
 
If clinically significant improvements in either the PHC and MHC scores of MSQOL-54 are 
not found between baseline and 12 months in participants in the intervention arm adhering 
to lifestyle recommendations of the MS Online intervention course, the RCT will continue to 
as described to the 2.5 year follow-up.  
 
If there are no amendments to the study, all participants will be notified of the study arm they 
were allocated to at the completion of the study. All participants in the standard-care arm will 
be provided with a link to access the MS Online intervention course.  
 
X. 
Qualitative interviewing consisting of semi-structured interviews by trained qualitative 
interviewers will be conducted on a randomly selected subset of participants (approximately 
15 participants from intervention and standard-care arms, respectively) will be performed 
within 1 month of and 12 months after completing the MS Online course. 
 
XI. 
During enrolment in the trial, participants in both arms of the RCT will be advised to continue 
with normal medical treatment with their existing neurologists and healthcare providers and 
to continue with their usual medications, as recommended by their physicians. 
 
Intervention group (MS Online intervention course):  
Structure of delivery  
In a seven-module, seven-session, self-administered program, participants in the intervention arm 
would be presented with an integrated lifestyle modification program including information and 

 
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support regarding each of the key lifestyle modifications. Modules will be released on a timed-
schedule, twice per week, with future modules gated until completion of preceding modules, but 
previous modules available for review throughout the entire intervention period. The total length of 
course is six weeks (7 sessions, 2 sessions per week with 2 weeks added on to the end for catch-
up), specified by participants in the MSOC – feasibility study to be of suitable length. The course 
remains open for a total of six weeks to enable participants to complete the course. 
 
 
 
Mode of delivery  
Delivery of the lifestyle intervention will be via invitation-only, online course. Participants will be 
required to complete each module within specified six weeks of the course. There is no time limit set 
for the completion of each module; however, the next module cannot be accessed until the previous 
module is complete, and all must be completed by the end of the intervention period for participant 
to be considered a ‘completer’. Modules are composed of video content, written content, interactive 
(non-assessed) content, and non-hurdle assessments. Participants are required to self-navigate 
modules with technical support provided only to address functionality issues within the software.  
 
Content 
 
The integrated lifestyle modification program translates the research evidence regarding 
modification of lifestyle related risk factors and health outcomes based on a detailed review of the 
literature around modifiable lifestyle risk factors that may influence MS disease progression, as 
outlined in the book Overcoming Multiple Sclerosis: the 7-step recovery program (Jelinek, 2016).  
The MS Online Course also contains a community forum. Links to articles and other prompts will 
encourage participants to contribute their thoughts. A researcher will be delegated to oversee the 
forum to moderate the forum to facilitate participant engagement and ensure appropriateness of 
content. 
 
 
 
Session 1:  Introduction to the Program and participants 
Welcome to the course and overview of MS (medical definition). How to study the course; 
introduction to the web-based intervention: how to proceed, how to navigate, what to expect and to 
outline the endpoints for participants. Validating Overcoming MS program à providing previous 
research/evidence on efficacy.  
 
Session 2: Diet  

 
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Evidence behind a dietary influence on MS disease activity and QOL: evidence on saturated fat, and 
evidence regarding diet and its relationships with MS onset and progression. Introduction to dietary 
plan and benefits of different food groups.  
 
Session 3:  Sunlight and vitamin D 
Detailed background information about how vitamin D is made from the action of sunlight is 
presented, along with evidence supporting a role of vitamin D in MS disease activity. 
Recommendations for optimal levels of supplementation and blood levels are presented.  
 
Session 4: Physical activity/Exercise 
The benefits of exercise are explained for people with MS (neurological, cognitive, physical), how 
and why. In addition, evidence regarding the benefits of exercise will be presented. How to 
implement an exercise plan with video examples provided. 
 
Session 5: Stress and stress reduction 
Introduction to mental health and relevance in MS. Participants are introduced to the science behind 
stress and its link to inflammation/MS. Mind-body connection, meditation and other stress reduction 
techniques to supplement the practical sessions on meditation they receive throughout the program. 
How to develop a mental health and wellbeing improvement strategy.  
 
Session 6: Family primary prevention 
Participants are introduced to the issue of primary prevention of MS in close family members who 
are at increased risk of developing the disease, and strategies for reducing this risk. This session 
will cover risks associated with smoking and excessive alcohol intake and MS progression. 
 
Session 7: Review and consolidation 
Program overview and recap, and an outline of next steps to take. Advise on follow-up 
questionnaires for longitudinal follow-up, and link to forums for further engagement (aimed at 
enhancing retention).  
 
 
Standard-Care Group (MS Online standard-care course): 
 
Structure and mode of delivery: 
The standard-care course will be structured and delivered in the same way as the intervention 
course. That is, the total length of course is six weeks (7 sessions, 2 sessions per week with 2 weeks 
of catch-up). 

 
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Content: 
The content of the standard-care course will be delivered in the same seven modules as the 
intervention course (as above). The standard-care course will be populated with information 
collected from a multitude of MS society websites from around the world, such as MS Australia, MS 
Research Australia and The National MS Society (United States); text, video and image/animation 
content has been compiled into modules to mirror the intervention course’s modules. The standard-
care course aims to reproduce the advice that people with MS typically receive during medical 
consultations and online advice from MS Societies.   
 
A separate community forum is available as part of the standard-care course specifically for 
standard-care participants. 
 
MS Online Intervention course group and MS Online Standard-care course group: 
Data collection, management and analysis: 
 
Quantitative data 
Quantitative data will be collected via validated self-reported questionnaires completed by 
participants at specified time points (Table 1). 
 
Para data (administrative data such as number of participant logins, etc) will be collected via Google 
Analytics and functionality integrated into the WordPress platform. Google Analytics provides data 
tracking on how participants interact with the online course, such as average time per page, what 
interactive elements participants are engaging with, what pages people commonly exit the course 
on, and many others. The analytics integrated into the platform itself will allow us to analyse the 
number of participants that drop-out over the length of the course, and when they do so. 
 
Data will be stored in a re-identifiable format as described in Section 10. 
 
 
Quantitative data collection feasibility 
As assessed by the qualitative component of the MSOC – Feasibility study, participants indicated 
that the MS Online course over six weeks with two sessions every week was feasible to complete. 
Importantly, participants have the option to complete the MS Online course at a time and location 
that is convenient to them. 
 

 
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The complete patient-reported questionnaire with approximately 150 questions has been found to 
take approximately 60 minutes to complete. Participants will be able to login and complete this 
questionnaire over time. The participants will be requested to complete this questionnaire on four 
separate occasions (baseline, 6 months, 12 months and 2.5 years) and due to previous studies that 
we have performed within the Neuroepidemiology Unit utilising questionnaires of a similar length 
over 7.5 years ((Marck et al., 2018; Weiland et al., 2018), we do not believe the questionnaire will 
create an unacceptable burden on participants. 
 
Quantitative data analysis: 
We will measure adherence to lifestyle modification recommendations in people with MS enrolled in 
the MS Online intervention and the MS Online standard-care arm (control) using validated patient-
reported questionnaires. 
 
We will examine and compare clinical and health outcomes of depression, anxiety, fatigue, disability, 
self-efficacy and quality of life in people with MS in the short-term (6 months and 12 months) and 
medium-term (2.5 years) in people enrolled in the MS Online Intervention course arm and people 
enrolled in the MS Online standard-care course arm.  
 
Statistical analyses will enable us to examine whether a causal relationship exists between lifestyle 
factors and clinical and health outcomes in people with MS. These analyses are anticipated to be 
completed within 6-12 months of collecting data for short-term and long-term analyses, respectively. 
 
Qualitative data: 
Qualitative data will comprise edited transcripts of recordings from semi-structured interviews from 
15 randomly selected participants from the intervention arm and the standard-care arm carried out 
within one month of completing the MS Online course and 12 months after completing the MS Online 
course (the same people will be interviewed at both time points).  
Interviews will be digitally recorded and transcribed by voice recognition software. Data will be stored 
in a re-identifiable format and encrypted files will be securely stored as described in Section 10. 
 
Qualitative data collection feasibility: 
The qualitative component of the MSOC – RCT is similar to the qualitative component of the MSOC 
– Feasibility study we performed. This interviewing technique was found to be both effective and 
participants reported positive feedback following interviews.  
 
Qualitative data analysis: 

 
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Data interpretations from interviews one month after completing the MS Online course and 12 
months after completing the MS Online course will be performed individually at each time-point. 
Comparisons between data interpretations at the different time intervals will also be performed. 
 
Student participation: 
This protocol may be used towards a student PhD project in the future but at present, no student 
has been assigned to work on this research project. 

 
 
Table 1: Summary of RCT time frame  
 
  
 
Timeframe 
Assessment/Measure 
No.  
Questions 
 
 
Screening 
Baseline 
Complete 
Online 
course 
One month 
after Online 
course 
6 months after 
Online course 
12 months after 
Online course 
2.5 years after 
Online course 
Informed consent 
1 
 
X 
  
  
  
  
  
Age 
1 
X 
X 
 
 
 
 
 
MS type diagnosed 
2 
X 
X 
  
  
X 
X 
X 
MS duration 
2 
X 
X 
  
  
X 
X 
X 
Do you follow a MS-specific lifestyle 
program? 
2 
X 
X 
  
  
X 
X 
X 
Do you follow a MS-specific diet 
2 
X 
X 
 
 
X 
X 
X 
Sex and gender 
2 
 
X 
 
 
 
 
 
Residential address and country 
1 
 
X 
 
 
 
 
X 
Country of birth 
1 
 
X 
 
 
 
 
 
Height/weight 
2 
 
X 
  
  
X 
X 
X 
Comorbidities 
2 
 
X 
 
 
X 
X 
X 
Marital status 
1 
 
X 
  
  
X 
X 
X 
Education 
1 
 
X 
  
  
 
 
 
Employment status 
1 
 
X 
  
  
X 
X 
X 
Alcohol and smoking 
4 
 
X 
  
  
X 
X 
X 
Medications 
4 
 
X 
  
  
X 
X 
X 
Perceived Social Support 
12 
 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Lifestyle factors 
  
 
  
  
  
  
  
  
Physical activity: IPAQ-SF 
7 
 
X 
  
  
X 
X 
X 
Meditation: MAQ 
3 
 
X 
  
  
X 
X 
X 
Sun exposure 
4 
 
X 
  
  
X 
X 
X 
Diet quality: DHQ 
21 
 
X 
  
  
X 
X 
X 
Omega-3 intake: dose, frequency 
3 
 
X 
  
  
X 
X 
X 

 
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Vitamin D intake: dose, frequency 
3 
 
X 
  
  
X 
X 
X 
 
 
 
 
 
 
 
 
 
Health outcomes 
  
 
  
  
  
  
  
  
HRQOL: MSQOL-54 
54 
 
X 
  
  
X 
X 
X 
Disability: PDDS 
1 
 
X 
  
  
X 
X 
X 
Anxiety and depression: HADS 
14 
 
X 
  
  
X 
X 
X 
Fatigue: FSS 
9 
 
X 
  
  
X 
X 
X 
Self-efficacy: UWSE-6  
6 
 
X 
  
  
X 
X 
X 
Qualitative interviewing 
(7) 
 
 
 
X 
 
X 
  
 
 
 
 
 
 
 
 
 
 
If clinically significant improvement 
in HRQOL subset scores in 
Intervention group from baseline, 
we will consider an amendment to 
the RCT to provide participants in 
the standard-care access to the 
intervention course 
 
 
 
 
 
 
 
X 
 
 
 
 
If no clinically significant 
improvement in HRQOL subset 
scores in Intervention group from 
baseline, the RCT will not be 
amended 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
  
Total no. quantitative data questions  
 
      5 
         166 
  
  
          159 
             166 
160 
(not including qualitative) 
  
 
  
  
  
  
  
  

 
 
6.2 
STANDARD CARE AND ADDITIONAL TO STANDARD CARE PROCEDURES  
 
Not applicable. 
  
6.3 
RANDOMISATION 
 
Allocation  
Sequence Generation  
Participants will be randomly assigned to either control or intervention group with a 1:1 allocation as 
per a computer-generated simple randomisation program such as https://www.randomizer.org/.  
Implementation 
All patients who: 1. fulfil the study inclusion and exclusion criteria 2. give consent for participation in 
the study, and 3. complete the baseline assessment questionnaire will be randomised to either the 
intervention or standard-care arm of the study before being provided with a link to access to the MS 
Online course. 
An assigned study investigator will be responsible for allocating participants to either the intervention 
or standard-care arm.  
Participants will be blinded to the nature of the other study arm. That is, there will be no identifying 
information in the MS Online course and participants will be notified that they are enrolled in a “MS 
Online Education Course”. Participants will be allocated to the intervention or standard-care arm at 
a 1:1 ratio using simple randomization.  
Research staff (including those researchers performing statistical analyses) will be blinded to the 
group allocation. Only the researcher responsible for allocating participants to either the intervention 
or standard-care arm and the data manager will have access to participant allocation information. 
The same researcher will be responsible for inviting participants to be involved in the qualitative 
study. In the event this researcher leaves the study, an external researcher will take over this 
position.  
Group allocation information will be concealed from study participants.  
 
6.4 
STUDY METHODOLOGY  
 
No clinical or laboratory assessment/s will be carried out as part of this study.  
 
STUDY POPULATION 
7.1 
RECRUITMENT PROCEDURE 
 

 
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Our study group comprises people over the age of 18 years with a neurologist-confirmed diagnosis 
of relapsing remitting MS. 
Details of the RCT will be published on MS society websites, Facebook and Instagram sites 
throughout Australia, New Zealand, USA, UK, Canada, providing information about the MSOC - RCT 
and asking them to contact members of the study group by email if they are interested in 
participating. These sites include: 
UK MS Register website 
Multiple Sclerosis Research Australia (MSRA) website 
Multiple Sclerosis Association of America (MSAA) website 
Multiple Sclerosis Society of New Zealand website 
MS Society of Canada website 
Multiple Sclerosis Trust (UK-based)  
National Multiple Sclerosis Society  
 
The same information will also be posted on related Facebook sites including: 
National Multiple Sclerosis Society 
Multiple Sclerosis Australia 
Multiple Sclerosis Foundation 
Multiple Sclerosis Society of Canada 
Multiple Sclerosis Trust (UK-based) https://www.facebook.com/groups/multiplesclerosistrust/ 
https://www.facebook.com/groups/multiplesclerosiswarriors/ 
https://www.facebook.com/groups/LDNRT/ 
https://www.facebook.com/groups/32407464137/ 
https://www.facebook.com/groups/48020086285/ 
https://www.facebook.com/groups/49480728240/ 
https://www.facebook.com/groups/msclerosis/ 
https://www.facebook.com/groups/MSnDIET/ 
https://www.facebook.com/groups/msfriends/ 
https://www.facebook.com/groups/149551588442843/ 
https://www.facebook.com/groups/tifms/ 
https://www.facebook.com/groups/multiplesclerosisawareness/ 
https://www.facebook.com/groups/raiseawareness/ 
https://www.facebook.com/groups/mshopeandhealing/ 
https://www.facebook.com/groups/340467112677741/ 
https://www.facebook.com/groups/1000713966608065/ 
https://www.facebook.com/groups/1718909785011262/ 
 
The information about the study will be posted on a Facebook webpage and Instagram that will be 
available to individuals with MS and MS social groups worldwide. 
Interested participants (people with relapsing-remitting MS) will be asked to click on a link on the 
notice advertising the MSOC - RCT which will direct them to seven eligibility questions related to: (1) 
their age; (2) the type of MS they were diagnosed with; (3) the year they were diagnosed with MS 
(4,5) whether they follow a MS-specific diet and if so, the diet they follow (6,7) whether they follow a 

 
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MS-specific program and if so, the program they follow. Eligibility will be assessed by the research 
team and those participants fulfilling study eligibility will be will invited to participate in the study and 
will be a sent a Participant Information Sheet and Consent Form to confirm their consent to 
participate in the study. Once consent has been confirmed, participants will be sent a link to complete 
the baseline questionnaire online. Following the collection of baseline data from all recruited 
participants, randomisation of participants to their respective study arm will be performed. Each 
participant will then be emailed a link to the MS Online course they have been allocated to (either 
the MS Online intervention or the MS Online standard-care course) along with general information 
about the respective MS Online course.  
Interested participants assessed as being ineligible for the study will receive an email thanking them 
for their interest and notifying them of their study ineligibility and explaining why they were ineligible 
for the study. 
 
Strategies for retention 
Retaining participants in the study will maximise the study sample number, the power of statistical 
analyses, and the likelihood of representativeness. We will undertake multiple strategies to 
encourage participants to retain in all aspects of the study through consistent follow-up 
correspondence and social media engagement. All participants will be annually thanked for 
participating in the RCT. 
 
7.2 
 INCLUSION CRITERIA  
 
Eligible participants must: 
1. Be able to read, write, and speak English; 
2. Be 18 years old or over; 
3. Have a confirmed diagnosis of relapsing-remitting MS (by a neurologist); 
4. Be able to access the internet and be able to view sessions. 
 
7.3 
EXCLUSION CRITERIA  
 
Exclusion criteria of participants include: 
1. Experiencing any serious co-morbid chronic illness or neurological illness/injury other than 
MS that would threaten regular participation or significantly affect the outcome measures in 

 
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its own right, such as motor neurone disease or stroke, as determined by the study 
investigators;  
2. Currently participating in another study or self-management program involving modification 
of lifestyle. 
 
7.4 
CONSENT  
 
Potential participants will be informed of the requirements of participating in the study, which will 
include:  
• 
Willingness to participate in an MS Online course related to lifestyle modification over a six-
week study period; 
• 
Follow-up protocol at baseline, 6 months, 12 months and 2.5 years; 
• 
Potential invitation to be involved in a voluntary qualitative study  
• 
Ability to opt-out at any time.  
 
Consent forms will be provided for review by the Human Research Ethics Committee at the 
University of Melbourne. 
 
 
PARTICIPANT SAFETY AND WITHDRAWAL  
8.1 
RISK MANAGEMENT AND SAFETY 
 
There will be no physical distress to participants in the proposed study as the study involves watching 
an educational course and completing questionnaires online. The exercise component of the MS 
Online Course in both arms of the study recommends a gentle exercise regimen, if participants 
decide to implement recommendations, that would not be expected to cause harm.  
The research team in conjunction with participants involved in the qualitative interviewing component 
of the MSOC – Feasibility study found that the MS Online course, questionnaires and qualitative 
interviewing posed very low psychological distress to participants.  
While we do not anticipate potential psychological distress, the following continency plans will be 
implemented to address any psychological distress that may arise: 
 
Quantitative research risk management 
To address any psychological distress associated with completing online questionnaires at baseline 
and after 6 and 12 months and 2.5 years after completing the MS Online Course, links will be 

 
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provided at the end of questionnaires to country-specific help resources that the participant could 
access in the event that completing the questionnaires has raised issues for the participant. 
Participants will also be provided with the contact details of study team members and reminded that 
they can make contact with a team member if completing the questionnaires has raised any issues 
for them.  
 
With regards to the HADS survey, while it is a validated tool for assessment of depression, it is not 
a diagnostic tool. However, we will also provide relevant country-specific resources and/or provide 
information/links to country-specific help/information at the end of the HADS. Notably, the HADS is 
the final questionnaire in the survey so this information will be provided directly after answering 
questions with the greatest potential to cause distress.  
 
 
Qualitative research risk management 
Dr Sandra Neate is a specialist emergency physician with 30 years’ experience dealing with critically 
ill and distressed patients. She has skills in managing people in crisis. She has extensive experience 
dealing with acute and chronic mental health conditions. She is also a member of the Victorian 
Mental Health Tribunal where she speaks directly with patients with acute mental health disturbance 
including depression and those at risk of suicide. Although Dr Neate will not provide formal 
counselling to any participants she has skills to manage difficult emotions and advise appropriate 
follow up.  
 
Dr Pia Jelinek is a general practitioner with 5 years of clinical experience. She deals with patients 
experiencing emotional distress and providing counselling on a daily basis. Although Dr Jelinek does 
not intend to provide formal counselling to any participants she has skills to manage difficult emotions 
and advise appropriate follow up. 
 
Dr Reece conducted qualitative interviews in the MSOC feasibility study but has no formal training 
in managing people with emotional distress.  
 
At the completion of all qualitative interviews, interviewers will ask participants if the questions or 
discussions during the interview have raised any distress or psychological difficulties to the 
participant. In the event any issues have been raised, the interviewer will refer the participant to the 
relevant 
country-specific 
resources 
and/or 
provide 
information/links 
to 
country-specific 
help/information. The interviewer will also notify the participant that they are free to contact them at 
any later stage if they experience distress after the interview and the same country-specific 
resources will be supplied to the participant. 

 
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Withdrawing participants: 
Withdrawing participants will be contacted and provided links to help resources. 
 
8.2 
HANDLING OF WITHDRAWALS  
 
Participants will be notified that they can withdraw from the study at any time for any reason. If a 
participant wishes to withdraw from the study, we would advise them to contact us so as to avoid 
receiving unwanted study emails and phone calls related to follow-up in the future. 
We do not anticipate any adverse events for the participant if they wish to withdraw from the study, 
however, we will provide withdrawing participants links to help resources. The participant will also 
be notified that all of their data we be retained and stored in a confidential and secure manner 
(Section 10).  
 
8.3 
REPLACEMENTS 
 
Participants that withdraw from the study will not be replaced. (That is, participants that do not 
complete the MS Online course and all related follow-up in the form of completing MS Online 
questionnaires). The calculation of the sample size (Section 8.1) allows for a proportion of 
participants not complete to all components of the MS – RCT study (42% loss to follow-up) and still 
retain sufficient statistical power.  
 
STATISTICAL METHODS 
9.1 
SAMPLE SIZE ESTIMATION & JUSTIFICATION   
 
The two primary outcome measures for this study are changes in Physical Health Composite (PHC) 
and Mental Health Composite (MHC) derived from the MSQOL-54. PHC and MCH are derived by 
combining scores of relevant subscales (Vickrey et al., 1995). For the proposed MSOC – RCT, 
sample sizes were calculated in order to detect a 5-point difference in the PHC and MHC scores (a 
minimum clinically meaningful change in these HRQOL measures, between the intervention and 
standard-care arms). 
 
To further account for loss-to-follow-up from the study period, based upon MSOC - Feasibility results, 
we anticipated a 42% loss-to-follow-up between randomisation and follow-up at 12 months. It is likely 

 
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this level of loss-to-follow-up is an overestimate of what will be observed in the proposed MSOC – 
RCT due to redevelopment of the intervention based upon feasibility data, but this overestimate will 
account for participants in the standard-care course that request access to the MS Online 
Intervention course after unblinding at 12 months after participants undertake the MS Online 
Standard-care course.  
Taking these factors into account, we estimate 1054 participants, 527 in each arm (1:1 allocation) 
with data at baseline and follow-up would give 80% power to detect a 5-point change in HRQOL 
across both PHC and MHC outcomes. This estimation of power is based on the mean PHC and 
MHC scores and their SD, which is the SD between groups at baseline. 
 
9.2 
POWER CALCULATIONS  
 
Power calculations were estimated using the Bonferroni correction. The Bonferroni correction 
adjusts probability (p) values because of the increased risk of a type I error when making multiple 
statistical tests (in this instance, the increased risk of type I error for the multiple outcomes of PHC 
and MHC scores of HRQOL, as assess by the MSQOL-54 questionnaire) (Osoba et al., 1998; 
Taphoorn, et al., 2005). 
 
9.3 
STATISTICAL METHODS TO BE UNDERTAKEN 
 
Quantitative data analysis: 
Clinically significant fatigue will be defined as a mean FSS>5 (Krupp et al., 1989). Anxiety and 
depression will be defined as  higher HADS (Zigmond & Snaith, 1983). The UWSE will be assessed 
as a continuous term and dichotomised at the median as there is no established cut off point 
indicating sufficient self-efficacy.  
 
Characteristics of quality of life (QoL) will be measured by the MSQOL-54, including physical and 
mental health composite scores and multiple subdomains. Linear regression will be used to 
determine cross-sectional and prospective relationships with QoL.Characteristics of disability will be 
assessed using linear regression. Characteristics of dichotomous clinically significant fatigue, 
depression and anxiety will be assessed by log-binomial regression. Characteristics of Self-efficacy 
composite scores will be assessed by linear and log-binomial regression for continuous and 
dichotomised self-efficacy, respectively. Characteristics of perceived social support scores will be 

 
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assessed by linear regression. All models will be assessed for potential confounders and appropriate 
adjustments will be made in analyses.  
 
Qualitative data analysis: 
Audio recordings will be transcribed for analysis and stored within Nvivo Software 
(www.qsrinternational.com) to enable data management. Data analysis will be conducted within a 
qualitative paradigm using reflexive thematic analysis (Braun 2014).  Reflexive thematic analysis is 
considered the most appropriate analytic process due its lack of grounding in a particular philosophy 
(Braun 2006), and as a method suitable to exploring people’s experiences, views and perceptions 
(Braun 2014) and its allowing expression of results in a way accessible to those in the wider 
community. Reflexive thematic analysis also emphasises the importance of the researcher being 
deeply involved in the research. Data will be analysed by the process of data familiarisation, coding, 
and theme development and refining. Data extracts (quotes) will illustrate themes. 
 STORAGE OF BLOOD AND TISSUE SAMPLES 
10.1 DETAILS OF WHERE SAMPLES WILL BE STORED, AND THE TYPE OF CONSENT FOR 
FUTURE USE OF SAMPLES 
 
Not applicable. No blood or tissue samples will be taken from participants. 
 
 DATA SECURITY & HANDLING 
11.1 DETAILS OF WHERE RECORDS WILL BE KEPT & HOW LONG WILL THEY BE STORED 
 
Data storage: 
All data from baseline and follow-up surveys will be entered by the participant themselves and 
stored electronically. This data will be managed and stored in accordance with the Information 
Privacy Principles of the Privacy Act,1988 (Cth) (see Appendix 2), the Standards Australia 
Personal Privacy Protection in Health Care Information Systems (AS4400-1995) and the National 
Statement 3.1.45 and 3.1.56.  
 
All computer files will be password protected and participant data will be coded to a re-identifiable 
format. 
 

 
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11.2 CONFIDENTIALITY AND SECURITY  
 
The data will be stored on the University of Melbourne's secure server. The server room at the 
University of Melbourne is a locked room with limited access and has uninterruptible power 
supply.  Access to server room is permitted to authorised University of Melbourne IT staff. Data 
backup and restoration checks are routinely undertaken in accordance with documented 
procedures. Manual and automated log files document the status of each backup.  The outcome of 
each backup process is checked daily. Backup media is securely stored off-site at an organisation 
that specialises in the storage of such equipment. The backup site is monitored by closed circuit 
television with keypad entry to all entrances. McAfee Active Defense is employed to protect 
servers and desktops from the threat of viruses. Virus definition files are automatically and 
routinely updated to ensure that The University of Melbourne systems are protected from the 
constant threat that new viruses present. 
  
Only the five principal investigators from the Centre of Epidemiology and Biostatistics at The 
University of Melbourne will be have access to the secure drive where the data will be stored 
(Sandra Neate, Will Bevens, Jeanette Reece, Maggie Yu, Steve Simpson-Yap).  All access to data 
files will be available by password and only the five PIs listed will have permission to access this 
data. Access by the five PIs will be exclusively to check the data and perform statistical analyses 
relevant to the proposed study and the data will not be used for any other purpose. 
  
In the event that any principal investigator ceases to be engaged in the project, the four other 
investigators will still have access. New staff members, as necessary, may be given access to the 
data in the event two or more of the main investigators are no longer involved in the study at the 
discretion of Dr Sandra Neate or the highest senior researcher involved in the project in the event 
that Dr Neate is no longer working in the NEU. In the event that all of the original researchers are 
no longer involved in the study, the ethics application will be updated with new researcher details. 
 
 
Results of research will be published in a form that does not permit the identification of individual 
participants and in a form which gives due regard to cultural or other sensitivities. 
All participant data will be stored indefinitely following completion of the study. 
 
 
11.3 ANCILLARY DATA 
 
Data will be stored indefinitely on a secure server indefinitely at the Centre for Epidemiology and 
Biostatistics at the University of Melbourne and will not be disposed of. 4 principle investigators will 

 
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have access to the drive where the data will be stored (Sandra Neate, Will Bevans, Jeanette 
Reece, Steve Simpson-Yap) at the Centre for Epidemiology and Biostatistics, The University of 
Melbourne. In the event that the principle investigator (Sandra Neate) ceases to be engaged in the 
project, the 3 other investigators will still have access and an additional person (Head of the 
Informatics at the Centre for Epidemiology and Biostatistics, The University of Melbourne, currently 
Dr. Adrian Bickerstaffe, or his equivalent at the time if he is no longer employed at the Centre for 
Epidemiology and Biostatistics, The University of Melbourne) will be given access to this drive. 
 
Explain how confidentiality of participants and their data will be protected in the dissemination of 
research results: 
The confidentiality of participants and their data will be protected by researchers applying new 
codes to participants at the Centre for Epidemiology and Biostatistics, The University of Melbourne 
in peer reviewed publications, presentations at international and international conferences and 
progress reports disseminating research findings. Additionally, no specific details to enable 
participants to be identified will be reported eg. specific dates of birth, death, clinical and 
demographic information will not be reported. 
 
 CONSUMER INVOLVEMENT 
 
Consumers have been extensively consulted on developing the MS Online Course (both the 
delivery and the content). 
Prior to commencing the feasibility study (MSOC - Feasibility) assessing the delivery of the 
intervention and standard-care course conducted between April and June 2021, a focus consumer 
advisory group comprising up to 6 people with MS was established. Regular meetings were 
conducted for participants to provide input towards the structure and content of the Online course. 
Questions asked of the consumer advisory group included: 
- 
How can web-based technology improve the management of MS? 
- 
What online resources do you currently use or are you aware of to manage MS? 
- 
How could a web-based technology improve your self-management of MS? 
- 
How could a web-based technology improve the delivery of the OMS program? 
- 
What are your experiences with online communities? For MS? How do they compare for 
you to face-to-face communities? 
 
The consumer advisory group were asked to provide feedback towards the MS Online course prior 
to the MSOC – Feasibility study. Questions asked of these groups included: 
- 
How accessible is the format/layout to you? What are your thoughts on accessibility? 

 
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- 
What things about the format / layout do you find most / least appealing / inviting / engaging, 
and why? 
- 
Are the technologies presented in the plan helpful or a hindrance? Will you use them? Do 
they hinder the learning? 
- 
What are some ways the layout could be improved? Any technologies you would like to see 
included? 
 
The consumer advisory group were then asked to review the MS Online course prior to 
implementation in a program participant questionnaire to assess: 
 
1. Accessibility: 
a. What features make this course most accessible to you, considering your needs?  
b. What aspects are difficult for you, in terms of accessibility?  
c. Which of the accessibility features detract from the overall course? 
d. How can any of these accessibility features be improved? 
2. Learnability: 
a. In what ways did you find the course easy or hard to navigate? 
b. What elements of the course (non-content) were difficult to grasp? 
c. How well or how poorly did this course and its elements work, compared to other 
websites with which you are familiar with? 
3. Desirability: 
a. On a scale of 1 (not at all) to 10 (very much), how satisfying was your experience of 
doing this course? Please explain the rating you give 
b. What would you say about this course to other people with MS who might be 
considering it? 
c. What made this different from any other alternative learning program you have 
encountered?  
d. What changes would you prioritise for the developers of the course to improve it? 
4. Are there any other comments you’d like to make about the design of this course? 
 
As part of the MSOC - Feasibility, qualitative interviewing of 14 participants who undertook the 
course (8 intervention and 6 standard-care) was undertaken. These interviews assessed the 
experiences and perceptions of the course. In particular, participants were asked open-ended 
questions as to how the MS Online course could be improved for future people with MS 
undertaking the course. Some of the questions asked included:  
- 
What parts of the course worked well for you? 
- 
Were there any parts of the course that didn’t work well for you? 

 
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- 
What areas or subject matter did you want more information on or hadn’t been covered in 
the course? 
- 
Were there any areas in the course that needed improving? 
- 
Was there an adequate mix of presentations, videos and reading? 
- 
Was there anything that you wanted less of 
- 
Did the technical aspects of the course work well? 
 
Participants of the MSOC - Feasibility study were also asked to provide any other information they 
considered relevant for improving the course. 
 
An additional focus group was also organised with 5 people that participated in the MSOC – 
feasibility study aimed to specifically determine what type of research people with MS considered 
was important and whether or not they thought answering questions related to their lifestyle and 
health outcomes was important or burdensome to them.  
 
All participants in this forum expressed that their primary motivation to participate in research 
studies was to improve their own health and to help others with MS by contributing to research into 
MS. They wanted to be part of a “new era” of MS management that focused on the positive 
aspects of what people with MS could do to help themselves and to continue to live full and active 
lives. 
 
All participants provided very positive feedback that evidence-based research to examine whether 
changes in lifestyle behaviour led to improved mental and physical health was extremely important 
to them and potentially others with MS, especially as disease-modifying therapy was costly and 
had adverse side effects.  Participants emphasised that they didn’t want to have to rely on 
medications to achieve better health and quality of life and if they could make changes to their 
lifestyle that would benefit them then this was the research that they wanted to see conducted in 
the future. They also mentioned that the results of evidence-based research, if positive 
associations were found, would be most beneficial as it would help validate their own lifestyle 
choices and would provide the inspiration for other people with MS to also adopt potentially 
beneficial lifestyle changes. 
 
We also asked people in this group if they would consider it a burden to be asked to answer 
questions online that would take around 1 hour. They were specifically asked to consider whether 
the proposed questions were interesting and relevant and whether they felt the questions would 
cause them distress. Importantly, all participants expressed that the length of the questionnaire did 
not influence whether or not they would enroll and participate in the proposed study. That is, 

 
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participants did not consider completing questions that would take around 1 hour to complete 
would be onerous and did not consider it would be a barrier for other people with MS participating 
in the study, provided it could be done over time (as is the case with our online questionnaires). 
Many said they would complete hundreds of questions if it could help other people with MS. In fact, 
all participants were commited to do what they could to help people with MS. 
 
We asked whether they thought completing these questionnaires would pose any psychological 
distress to themselves or other people with MS. None of the participants experienced any 
psychological distress from either set of questionnaires and also thought other people with MS 
would also consider that the questionnaires would pose low psychological distress. 
 
Following this consultative process, analysis of the qualitative interviews and focus group 
discussions, the MS Online course and validated participant questionnaires were modified to 
address the needs and research priorities of people with MS.  
 
Additionally, study participants will be emailed with a plain language summary of results at the end 
of the study period. Additionally, as all publications will be open-access, participants and the 
general public will have access to them.  
 
 
DATA ANALYSIS 
 
This will be led by Dr Steve Simpson-Yap. Oversight will be provided by other study investigators.  
 
Responsibilities of the data management team will include: development of a statistical analysis 
plan, participant tracking, data cleaning, and data analysis at the conclusion of the trial. 
Researchers responsible for data cleaning and validation throughout the study will be blinded to 
allocation. 
 
 
 
 
 
 
 
 
 

 
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Appendix 
 
List of Attachments included: 
Document Name 
Version 
Number 
Date  
(eg. 18 January 2012) 
DHQ.pdf 
(Dietary Habits Questionnaire) 
1 
30 August 2021 
HADS.pdf 
(Hospital Anxiety and Depression) 
1 
13 December 2021 
Self-efficacy: UWSE-6  
1 
13 December 2021 
Perceived social support: MSPSS 
1 
13 December 2021 
MSQOL54.pdf 
1 
30 August 2021 
FSS.pdf 
(fatigue severity score questionnaire) 
1 
30 August 2021 
MSOC Qualitative interviews.docx 
(telephone/internet script) 
1 
30 August 2021 
Participant Information form.docx  
(includes consent form) 
3 
13 December 2021 
Withdrawal form – MSOC – RCT.docx 
1 
30 August 2021 
Effectiveness survey.pdf 
3 
13 December 2021 
MSOC protocol.pdf 
3 
13 December 2021 
 
 
REFERENCES 
 
Agland, S., Lydon, A., Shaw, S., Lea, R., Mortimer-Jones, S., 
& Lechner-Scott, J. (2018). Can a stress management 
programme reduce stress and improve quality of life in 
people diagnosed with multiple sclerosis? Mult Scler J 
Exp Transl Clin, 4(4), 2055217318813179. 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
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Page 43 of 51 
Amato, M. P., Ponziani, G., Rossi, F., Liedl, C. L., Stefanile, 
C., & Rossi, L. (2001). Quality of life in multiple sclerosis: 
the impact of depression, fatigue and disability. Mult 
Scler, 7(5), 340-344. 
Amtmann, D., Bamer, A. M., Cook, K. F., Askew, R. L., 
Noonan, V. K., & Brockway, J. A. (2012). University of 
Washington self-efficacy scale: A new self-efficacy scale 
for people with disabilities. Archives of physical medicine 
and rehabilitation, 93(10), 1757-1765. 
Bardus, M., Smith, J. R., Samaha, L., & Abraham, C. (2016). 
Mobile 
and 
Web 
2.0 
interventions 
for 
weight 
management: an overview of review evidence and its 
methodological quality. European Journal of Public 
Health, 26(4), 602-610. 
Bossen, D., Veenhof, C., Dekker, J., & de Bakker, D. (2014). 
The Effectiveness of Self-Guided Web-Based Physical 
Activity Interventions Among Patients With a Chronic 
Disease: A Systematic Review. Journal of Physical 
Activity and Health, 11(3), 665-677. 
Coe, S., Tektonidis, T. G., Coverdale, C., Penny, S., Collett, 
J., Chu, B. T. Y., et al. (2021). A cross sectional 
assessment of nutrient intake and the association of the 
inflammatory properties of nutrients and foods with 
symptom severity in a large cohort from the UK Multiple 
Sclerosis Registry. Nutr Res, 85, 31-39. 
Craig, C. L., Marshall, A. L., Sjostrom, M., Bauman, A. E., 
Booth, M. L., Ainsworth, B. E., et al. (2003). International 
physical activity questionnaire: 12-country reliability and 
validity. Med Sci Sports Exerc, 35(8), 1381-1395. 
D'Hooghe M, B., Nagels, G., Bissay, V., & De Keyser, J. 
(2010). Modifiable factors influencing relapses and 
disability in multiple sclerosis. Mult Scler, 16(7), 773-785. 
Duan, S., Lv, Z., Fan, X., Wang, L., Han, F., Wang, H., et al. 
(2014). Vitamin D status and the risk of multiple 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
Protocol Number: 1 
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Page 44 of 51 
sclerosis: a systematic review and meta-analysis. 
Neurosci Lett, 570, 108-113. 
Evers, I., Heerings, M., de Roos, N. M., Jongen, P. J., & 
Visser, L. H. (2021). Adherence to dietary guidelines is 
associated with better physical and mental quality of life: 
results from a cross-sectional survey among 728 Dutch 
MS patients. Nutr Neurosci, 1-8. 
Fischer, A., Schröder, J., Vettorazzi, E., Wolf, O. T., Pöttgen, 
J., Lau, S., et al. (2015). An online programme to reduce 
depression in patients with multiple sclerosis: a 
randomised controlled trial. The Lancet Psychiatry, 2(3), 
217-223. 
Fitzgerald, K. C., Tyry, T., Salter, A., Cofield, S. S., Cutter, G., 
Fox, R., et al. (2018). Diet quality is associated with 
disability and symptom severity in multiple sclerosis. 
Neurology, 90(1), e1-e11. 
Fragoso, Y. D. (2014). Modifiable environmental factors in 
multiple sclerosis. Arq Neuropsiquiatr, 72(11), 889-894. 
Giovannetti, A. M., Schiavolin, S., Raggi, A., Quintas, R., 
Cerniauskaite, M., Confalonieri, P., et al. (2016). 
Psychosocial difficulties of individuals with multiple 
sclerosis: the PARADISE-24 questionnaire. Int J Rehabil 
Res, 39(4), 339-345. 
Hadgkiss, E. J., Jelinek, G. A., Taylor, K. L., Marck, C. H., van 
der Meer, D. M., Pereira, N. G., et al. (2015). 
Engagement 
in 
a 
program 
promoting 
lifestyle 
modification is associated with better patient-reported 
outcomes for people with MS. Neurol Sci, 36(6), 845-
852. 
Hadgkiss, E. J., Jelinek, G. A., Weiland, T. J., Pereira, N. G., 
Marck, C. H., & van der Meer, D. M. (2015). The 
association of diet with quality of life, disability, and 
relapse rate in an international sample of people with 
multiple sclerosis. Nutr Neurosci, 18(3), 125-136. 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
Protocol Number: 1 
Version & date: Version 3, dated 13 December 2021 
Page 45 of 51 
Hadgkiss, E. J., Jelinek, G. A., Weiland, T. J., Rumbold, G., 
Mackinlay, C. A., Gutbrod, S., et al. (2013). Health-
related quality of life outcomes at 1 and 5 years after a 
residential retreat promoting lifestyle modification for 
people with multiple sclerosis. Neurol Sci, 34(2), 187-
195. 
Hassed, C., Flighty, A., Chambers, R., Hosemans, D., Bailey, 
N., Connaughton, S., et al. (2021). Advancing the 
Assessment of Mindfulness-Based Meditation Practice: 
Psychometric Evaluation of the Mindfulness Adherence 
Questionnaire. Cognitive Therapy and Research, 45, 
190-204. 
Hind, D., Cotter, J., Thake, A., Bradburn, M., Cooper, C., 
Isaac, C., et al. (2014). Cognitive behavioural therapy for 
the treatment of depression in people with multiple 
sclerosis: a systematic review and meta-analysis. BMC 
Psychiatry, 14, 5-5. 
Hohol, M. J., Orav, E. J., & Weiner, H. L. (1999). Disease 
steps in multiple sclerosis: a longitudinal study 
comparing disease steps and EDSS to evaluate disease 
progression. Mult Scler, 5(5), 349-354. 
Holper, L., Coenen, M., Weise, A., Stucki, G., Cieza, A., & 
Kesselring, J. (2010). Characterization of functioning in 
multiple sclerosis using the ICF. J Neurol, 257(1), 103-
113. 
Jelinek, G. A. (2016). Overcoming multiple sclerosis: the 
evidence-based 7 step recovery program (2nd ed.). 
Crows Nest: Allen & Unwin. 
Jelinek, G. A., De Livera, A. M., Marck, C. H., Brown, C. R., 
Neate, S. L., Taylor, K. L., et al. (2016). Associations of 
Lifestyle, Medication, and Socio-Demographic Factors 
with Disability in People with Multiple Sclerosis: An 
International Cross-Sectional Study. PLoS One, 11(8), 
e0161701. 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
Protocol Number: 1 
Version & date: Version 3, dated 13 December 2021 
Page 46 of 51 
Jelinek, G. A., Hadgkiss, E. J., Weiland, T. J., Pereira, N. G., 
Marck, C. H., & van der Meer, D. M. (2013). Association 
of fish consumption and Omega 3 supplementation with 
quality of life, disability and disease activity in an 
international cohort of people with multiple sclerosis. Int 
J Neurosci, 123(11), 792-800. 
Jelinek, G. A., Marck, C. H., Weiland, T. J., Pereira, N., van 
der Meer, D. M., & Hadgkiss, E. J. (2015). Latitude, sun 
exposure and vitamin D supplementation: associations 
with quality of life and disease outcomes in a large 
international cohort of people with multiple sclerosis. 
BMC Neurol, 15, 132. 
Jongen, P. J., Kremer, I. E. H., Hristodorova, E., Evers, S. M. 
A. A., Kool, A., van Noort, E. M., et al. (2017). Adherence 
to Web-Based Self-Assessments in Long-Term Direct-
to-Patient Research: Two-Year Study of Multiple 
Sclerosis Patients. Journal of Medical Internet Research, 
19(7), e249. 
Kirsten van, K., Trecia, W., & Rona, M.-M. (2015). A New 
Zealand pilot randomized controlled trial of a web-based 
interactive self-management programme (MSInvigor8) 
with and without email support for the treatment of 
multiple sclerosis fatigue. Clinical Rehabilitation, 30(5), 
454-462. 
Knittle, K., Nurmi, J., Crutzen, R., Hankonen, N., Beattie, M., 
& Dombrowski, S. U. (2018). How can interventions 
increase motivation for physical activity? A systematic 
review and meta-analysis. Health Psychology Review, 1-
48. 
Kohl, L. F. M., Crutzen, R., & de Vries, N. K. (2013). Online 
Prevention Aimed at Lifestyle Behaviors: A Systematic 
Review of Reviews. Journal of Medical Internet 
Research, 15(7), e146. 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
Protocol Number: 1 
Version & date: Version 3, dated 13 December 2021 
Page 47 of 51 
Krupp, L. B., LaRocca, N. G., Muir-Nash, J., & Steinberg, A. 
D. (1989). The fatigue severity scale. Application to 
patients with multiple sclerosis and systemic lupus 
erythematosus. Arch Neurol, 46(10), 1121-1123. 
Learmonth, Y., Dlugonski, D., Pilutti, L. A., Sandroff, B. M., 
Moti, R. W., & Klaren, R. E. (2013). Reliability, Precision 
and Clinically Meaningful Change Of Fatigue Outcomes 
In MS. Paper presented at the ACTRIMS. Retrieved from 
https://cmsc.confex.com/cmsc/2013/webprogram/Paper
1612.html 
Lerdal, A., Celius, E. G., & Moum, T. (2003). Fatigue and its 
association with sociodemographic variables among 
multiple sclerosis patients. Mult Scler, 9(5), 509-514. 
Marck, C. H., De Livera, A. M., Brown, C. R., Neate, S. L., 
Taylor, K. L., Weiland, T. J., et al. (2018). Health 
outcomes and adherence to a healthy lifestyle after a 
multimodal intervention in people with multiple sclerosis: 
Three year follow-up. PLoS One, 13(5), e0197759. 
Marck, C. H., Hadgkiss, E. J., Weiland, T. J., van der Meer, 
D. M., Pereira, N. G., & Jelinek, G. A. (2014). Physical 
activity and associated levels of disability and quality of 
life in people with multiple sclerosis: a large international 
survey. BMC Neurol, 14, 143. 
Marck, C. H., Learmonth, Y. C., Chen, J., & van der Mei, I. 
(2020). Physical activity, sitting time and exercise types, 
and associations with symptoms in Australian people 
with multiple sclerosis. Disabil Rehabil, 1-9. 
Marck, C. H., Probst, Y., Chen, J., Taylor, B., & van der Mei, 
I. (2021). Dietary patterns and associations with health 
outcomes in Australian people with multiple sclerosis. 
Eur J Clin Nutr. 
Marrie, R. A., Cutter, G., Tyry, T., Hadjimichael, O., 
Campagnolo, D., & Vollmer, T. (2005). Validation of the 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
Protocol Number: 1 
Version & date: Version 3, dated 13 December 2021 
Page 48 of 51 
NARCOMS registry: fatigue assessment. Mult Scler, 
11(5), 583-584. 
Martinez-Lapiscina, E. H., Mahatanan, R., Lee, C. H., 
Charoenpong, P., & Hong, J. P. (2020). Associations of 
serum 25(OH) vitamin D levels with clinical and 
radiological outcomes in multiple sclerosis, a systematic 
review and meta-analysis. J Neurol Sci, 411, 116668. 
McKellar, S., Horsley, P., Chambers, R., Bauer, J. D., 
Vendersee, P., Clarke, C., et al. (2008). Development of 
the diet habits questionnaire for use in cardiac 
rehabilitation. Australian Journal of Primary Health, 
14(3), 43-47. 
Mohr, D. C., Lovera, J., Brown, T., Cohen, B., Neylan, T., 
Henry, R., et al. (2012). A randomized trial of stress 
management for the prevention of new brain lesions in 
MS. Neurology, 79(5), 412-419. 
Moss-Morris, R., McCrone, P., Yardley, L., van Kessel, K., 
Wills, G., & Dennison, L. (2012). A pilot randomised 
controlled trial of an Internet-based cognitive behavioural 
therapy self-management programme (MS Invigor8) for 
multiple sclerosis fatigue. Behaviour Research and 
Therapy, 50(6), 415-421. 
Motl, R. W., & Gosney, J. L. (2008). Effect of exercise training 
on quality of life in multiple sclerosis: a meta-analysis. 
Mult Scler, 14(1), 129-135. 
Neve, M., Morgan, P. J., Jones, P. R., & Collins, C. E. (2010). 
Effectiveness of web-based interventions in achieving 
weight loss and weight loss maintenance in overweight 
and obese adults: a systematic review with meta-
analysis. Obes Rev, 11(4), 306-321. 
Norman, G. R., Sloan, J. A., & Wyrwich, K. W. (2003). 
Interpretation of changes in health-related quality of life: 
the remarkable universality of half a standard deviation. 
Med Care, 41(5), 582-592. 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
Protocol Number: 1 
Version & date: Version 3, dated 13 December 2021 
Page 49 of 51 
Olson, C. M. (2016). Behavioral Nutrition Interventions Using 
e- and m-Health Communication Technologies: A 
Narrative Review. Annual Review of Nutrition, 36(1), 
647-664. 
Organization, W. H. (2017). Body Mass Index.   Retrieved 
19/4/17, 2017, from http://www.euro.who.int/en/health-
topics/disease-prevention/nutrition/a-healthy-
lifestyle/body-mass-index-bmi 
Osoba, D., Rodrigues, G., Myles, J., Zee, B., & Pater, J. 
(1998). Interpreting the significance of changes in health-
related quality-of-life scores. J Clin Oncol, 16(1), 139-
144. 
Sangha, O., Stucki, G., Liang, M. H., Fossel, A. H., & Katz, J. 
N. 
(2003). 
The 
Self-Administered 
Comorbidity 
Questionnaire: a new method to assess comorbidity for 
clinical and health services research. Arthritis Rheum, 
49(2), 156-163. 
Senders, A., Hanes, D., Bourdette, D., Carson, K., Marshall, 
L. M., & Shinto, L. (2019). Impact of mindfulness-based 
stress reduction for people with multiple sclerosis at 8 
weeks and 12 months: A randomized clinical trial. Mult 
Scler, 25(8), 1178-1188. 
Simpson-Yap, S., Jelinek, P., Weiland, T., Nag, N., Neate, S., 
& Jelinek, G. (2021). Self-reported use of vitamin D 
supplements is associated with higher physical quality of 
life scores in multiple sclerosis. Mult Scler Relat Disord, 
49, 102760. 
Simpson-Yap, S., Nag, N., Probst, Y., Jelinek, G., & Neate, 
S. (2021). Higher quality diet and non-consumption of 
meat are associated with less self-determined disability 
progression in people with multiple sclerosis: a 
longitudinal cohort study. Eur J Neurol. 
Simpson-Yap, S., Oddy, W. H., Taylor, B., Lucas, R. M., 
Black, L. J., Ponsonby, A. L., et al. (2020). High Prudent 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
Protocol Number: 1 
Version & date: Version 3, dated 13 December 2021 
Page 50 of 51 
diet factor score predicts lower relapse hazard in early 
multiple sclerosis. Mult Scler, 1352458520943087. 
Smedal, T., Beiske, A. G., Glad, S. B., Myhr, K. M., Aarseth, 
J. H., Svensson, E., et al. (2011). Fatigue in multiple 
sclerosis: associations with health-related quality of life 
and physical performance. Eur J Neurol, 18(1), 114-120. 
Statistics, A. B. o. (2012). Australian standard classification 
of cultural and ethnic groups.   Retrieved 12/4/17, 2017, 
from 
http://www.abs.gov.au/AUSSTATS/abs@.nsf/allprimary
mainfeatures/388FA150E28D57E2CA257FF1001E65F
6?opendocument 
Stolwijk, C., van Tubergen, A., Ramiro, S., Essers, I., Blaauw, 
M., van der Heijde, D., et al. (2014). Aspects of validity 
of the self-administered comorbidity questionnaire in 
patients with ankylosing spondylitis. Rheumatology 
(Oxford), 53(6), 1054-1064. 
Stroud, N., Minahan, C., & Sabapathy, S. (2009). The 
perceived benefits and barriers to exercise participation 
in persons with multiple sclerosis. Disabil Rehabil, 
31(26), 2216-2222. 
Taphoorn, M. J., & Bottomley, A. (2005). Health-related 
quality of life and symptom research in glioblastoma 
multiforme 
patients. 
Expert 
Rev 
Pharmacoecon 
Outcomes Res, 5(6), 763-774. 
Taylor, K. L., Hadgkiss, E. J., Jelinek, G. A., Weiland, T. J., 
Pereira, N. G., Marck, C. H., et al. (2014). Lifestyle 
factors, demographics and medications associated with 
depression risk in an international sample of people with 
multiple sclerosis. BMC Psychiatry, 14, 327. 
Taylor, P., Dorstyn, D. S., & Prior, E. (2020). Stress 
management interventions for multiple sclerosis: A meta-
analysis of randomized controlled trials. J Health 
Psychol, 25(2), 266-279. 

 
Study Name: An Online Educational Course for People with MS: A randomised controlled trial of course effectiveness 
Protocol Number: 1 
Version & date: Version 3, dated 13 December 2021 
Page 51 of 51 
Vickrey, B. G., Hays, R. D., Harooni, R., Myers, L. W., & 
Ellison, G. W. (1995). A health-related quality of life 
measure for multiple sclerosis. Qual Life Res, 4(3), 187-
206. 
Weikert, M., Suh, Y., Lane, A., Sandroff, B., Dlugonski, D., 
Fernhall, B., et al. (2012). Accelerometry is associated 
with walking mobility, not physical activity, in persons 
with multiple sclerosis. Med Eng Phys, 34(5), 590-597. 
Weiland, T. J., De Livera, A. M., Brown, C. R., Jelinek, G. A., 
Aitken, Z., Simpson, S. L., Jr., et al. (2018). Health 
Outcomes and Lifestyle in a Sample of People With 
Multiple 
Sclerosis 
(HOLISM): 
Longitudinal 
and 
Validation Cohorts. Front Neurol, 9, 1074. 
Weiland, T. J., Jelinek, G. A., Hadgkiss, E. J., Marck, C. H., 
Pereira, N. G., Taylor, K. T., et al. (2015). Clinically 
significant fatigue: Prevalence and associated factors in 
an international sample of adults with multiple sclerosis. 
PLOS One, 10(2), e0115541. 
Weiland, T. J., Jelinek, G. A., Marck, C. H., Hadgkiss, E. J., 
van der Meer, D. M., Pereira, N. G., et al. (2015). 
Clinically significant fatigue: prevalence and associated 
factors in an international sample of adults with multiple 
sclerosis recruited via the internet. PLoS One, 10(2), 
e0115541. 
Zigmond, A. S., & Snaith, R. P. (1983). The hospital anxiety 
and depression scale. Acta psychiatrica scandinavica, 
67(6), 361-370. 
Zimet, G. D., Dahlem, N. W., Zimet, S. G., & Farley, G. K. 
(1988). The multidimensional scale of perceived social 
support. Journal of personality assessment, 52(1), 30-
41.