Comparing the Effectiveness of Fatigue Management Programs for People With MS
Phase: NA
Conditions: Multiple Sclerosis
Sponsor: Case Western Reserve University

 
 
Pre-Specified Study Protocol and Statistical Analysis Plan 
 
Original Project Title: Comparing the Effectiveness of Fatigue Management Programs for 
People with MS 
Version date of document: November 01, 2019 
Clinical Trial Registration: clinicaltrials.gov #NCT03550170 
Funding: This work was supported through a Patient-Centered Outcomes Research 
Institute (PCORI) Project Program Award (MS-1610-37015). All statements in this report, 
including its findings and conclusions, are solely those of the authors and do not necessarily 
represent the views of the Patient-Centered Outcomes Research Institute (PCORI), its Board of 
Governors or Methodology Committee. 
 
 
 
 
 
 
 
 
 
 

Method and Analysis 
 
Study Design 
We are conducting a randomized clinical trial to directly compare three delivery formats 
of the Managing Fatigue intervention. We are using a pragmatic design approach in which 582 
participants with MS are being recruited and randomized to teleconference, internet, or in-person 
versions of the intervention led by a licensed OT. All versions contain the same intervention 
content but are presented in ways most appropriate to the delivery format. Our goal is to recruit a 
diverse research sample to examine the effectiveness of each delivery format on different 
subgroups of participants (i.e., disease, demographic, and psychosocial characteristics). 
Outcomes are being measured at baseline, two months, three months, and six months. To help 
facilitate recruitment, the study is being branded as REFRESH (REducing Fatigue and Restoring 
Energy to Support Health).  
 
Sample Size and Inferiority Margin 
A sample size of 582 participants is needed to achieve a power of 0.90 for testing the 
hypothesis and conducting the moderation analyses. Based on previous studies and to err on the 
side of being conservative, we assumed an attrition rate of 35%, a standardized mean difference 
of 0.3, a correlation of 0.45 (rho), and a two-sided alpha level of 0.05.1 An interaction-to-overall 
effects ratio estimated the extra number of participants needed to examine interactions between 
delivery formats and participants’ baseline characteristics.2 The prespecified inferiority margin is 
ten points, which is based on triangulating anchor-based and distribution-based methods to 
calculate the minimally important difference (MID) on the Fatigue Impact Scale (FIS), and is 
consistent with a standardized mean difference of 0.3.3-5 

Recruitment and Eligibility 
The primary recruitment method is community outreach in the Midwestern and 
Northeastern United States, involving four approaches: (1) advertising with non-profit 
organizations (e.g., visiting support groups and going to events), (2) using social media (e.g., 
Facebook), (3) asking neurologists and rehabilitation professionals to provide flyers to their 
patients, and (4) engaging community stakeholders (e.g., snowballing recruitment). Inclusion 
criteria are a self-reported diagnosis of MS, at least 18 years of age, moderate to severe fatigue 
(i.e., Fatigue Severity scale score ≥ 4),6 and ability to speak and read English (i.e., confirmed via 
phone conversation and self-report). Exclusion criteria are the inability to understand the consent 
form (e.g., assessed with five questions about the study) or the inability to participate in the 
intervention (e.g., unwilling or unable to travel outside the home).  
Several steps are being taken to ensure that those who meet the study criteria have the 
opportunity to participate in the intervention: e.g., providing transportation to in-person visits 
and providing participants with a Chromebook to access the internet intervention if needed. 
Universal Design Principles for research are also being implemented.7 For example, recruiting 
participants through various media (i.e., print, audio, and in-person), providing multiple options 
to express interest in the study and complete questionnaires (e.g., paper and pencil, internet, and 
phone), and implementing strategies to include people with low vision (e.g., making reading 
material available in large-print and audio formats and enabling text-to-speech functionality). 
Because of the pragmatic design approach, we are monitoring but not excluding participants for 
receiving other treatments for fatigue or participating in other rehabilitation services before or 
during the study. Participants are permitted to withdraw from the study at any time for any 

reason. Reasons for withdrawal and inability to participate in the intervention are being 
documented and will be examined in sensitivity analyses.  
 
Randomization and Allocation Concealment 
Each participant will be randomized to receive one of the three interventions. Participants 
are randomized only after availability is confirmed for each delivery format, baseline data 
collection is complete, and there are enough participants within a specific geographic region (18 
to 30 participants) to conduct the group sessions. Permuted block randomization is being 
implemented. A statistician, who is not involved with data collection or participant interactions, 
developed a random number table using a 1:1:1 allocation ratio in blocks of six. The statistician 
directly imported the table into the Research Electronic Data Capture (REDCap)8 system to 
conceal group assignment. REDCap reveals group assignment only after all baseline data are 
collected and verified by the project manager. Participants are permitted to switch group 
assignment only when we are unable to provide services (e.g., an OT becomes sick and is no 
longer able to deliver services or a participant is unable to use a computer). 
 
Masking 
 
As in most behavioral and rehabilitation interventions, direct interaction between participants 
and OTs is required, making complete masking impossible. To mitigate bias, each OT is 
delivering only one intervention format, i.e., teleconference, internet, or one-to-one. Data 
collectors are being masked to group assignment to minimize any biases in baseline or follow-up 
data collection. We are also measuring the expectations of benefits for each delivery format and 
conducting sensitivity analyses on measures of treatment fidelity. The study is being described to 

participants as a comparison of three courses that could all be equally beneficial for reducing the 
impact of fatigue.  
 
Intervention Procedures 
Teleconference, internet, and in-person delivery of the Managing Fatigue intervention 
are being compared because of their contrasting advantages and disadvantages, the useful 
information provided to stakeholders, and prior evidence that this intervention is effective in 
reducing fatigue impact compared to wait-list controls.9-13 The reference group is the one-to-one, 
in-person format because it is consistent with clinical practice and the input we received from 
stakeholders about the need to show remote delivery formats are as effective as in-person 
formats. The comparison groups are the internet and teleconference formats because of the 
potential advantages of delivering the intervention remotely. Regardless of delivery format, the 
following six topics will be covered during the intervention: (1) Importance of Rest and Sleep, 
(2) Communication and Body Mechanics, (3) Activity Stations, (4) Priorities and Standards, (5) 
Balancing Your Schedule, and (6) Course Review and Future Plans. Participants receive 
information on taking rest breaks, re-evaluating priorities, communicating needs, and re-
organizing spaces. Practice activities involve experimenting with strategies for “banking” energy 
and “spending” limited energy to meet personal, meaningful goals. Participants are supported to 
test and tailor fatigue self-management strategies as appropriate to their own situations. 
Strategies to manage sleep difficulties and cognitive fatigue, not included in the original 
intervention, are incorporated into all three delivery formats for this study based on their 
prevalence and severity among people with MS.14 15 

Teleconference. This six-week, group-based intervention involves weekly 80-minute 
teleconference sessions (i.e., phone-only). Group sizes are kept small (five to ten participants) to 
maximize participants’ opportunities for interaction. Participants receive a program manual 
divided into six sections, one for each week, that includes worksheets and practice activities for 
participants to apply what they learn. Participants have the option of receiving the manual via 
email or mail. On the designated date and time, participants and the OT dial a toll-free 
conference call line. If a participant misses a session, research staff will call them to provide an 
abbreviated summary of the session.  
Internet. Similar to the teleconference intervention, the internet intervention lasts for six 
weeks and is group-based; however, unlike the teleconference intervention, participation is 
asynchronous, with participants able to log on whenever convenient for them. As per the 
teleconference program, five to ten participants start the intervention at the same time and 
interact during the intervention, also facilitated by an OT. Participants are given a username and 
a password to view the intervention content via a secure website. Each week, a new session is 
activated. Each session includes content delivered via text and short videos, completion of 
interactive activities and information sharing. OTs facilitate the group discussion boards by 
responding to entries, asking questions and prompting discussion, and providing encouragement. 
Website content can be downloaded by participants who wish to have paper copies. To ensure 
that all participants are able to access and navigate the site, a welcome week session is delivered 
prior to the first session. However, no intervention content is delivered during this session. 
One-to-one, in-person. Unlike the teleconference and internet interventions, the number 
and length of sessions for the one-to-one, in-person intervention vary over the six-week period. 
The OT delivers all six topics, but the pace is tailored to participants’ needs and preferences. 

Thus, although the topics are consistent, OTs can spend more time on those topics that 
participants find most relevant to them. The participants and OT are instructed to meet at least 
three times, with at least seven days between sessions. Similar to the teleconference, participants 
receive a program manual divided into six sections. Sessions are held at a central location or at 
participants’ homes on a day and time convenient for both the OTs and the participants.  
 
Ensuring the Fidelity of the Interventions 
Bellg et al.’s16 recommendation to monitor all aspects of treatment fidelity are being 
followed. Our goal is to strike a balance between delivering each format consistently, 
capitalizing on the unique features of each delivery format, and providing OTs with flexibility to 
deliver the intervention in a way that meets the participants’ needs. This balance is needed to 
maintain internal validity while helping ensure the generalizability of the intervention when 
implemented under usual circumstances.  
 
Theory fidelity: The Managing Fatigue intervention is congruent with Social Cognitive 
Theory17 and supports increasing self-efficacy to promote engagement in fatigue self-
management behaviors. Self-efficacy18 and fatigue self-management behaviors19 are being 
measured and will be tested for mediation. All three interventions are expected to increase self-
efficacy and encourage engagement in self-management behaviors. Each delivery format 
includes strategies to address emotional states, promote social persuasion, practice and master 
skills, and provide opportunities for peer modeling. However, each delivery format implements 
these strategies in a different way. For example, each format uses a different approach for 
eliciting social persuasion and peer modeling: the internet format uses discussion boards and 
written testimonials from people with MS; the one-to-one format involves in-person interactions 

with a clinician and the review of written testimonials from people with MS; and the 
teleconference format involves group interactions among peers and clinicians. It is unknown 
whether these different ways of eliciting social persuasion and peer modeling influences changes 
in self-efficacy and behavior. Thus, the proposed mediation analysis might have broader 
implications for understanding the “active ingredients” of interventions and whether their 
delivery format influences self-efficacy, behavioral change, and the impact of fatigue.   
Training of OTs: Multiple OTs in each state are being hired to deliver the intervention over 
the duration of the study. Consistent with a pragmatic research design, licensed OTs, regardless 
of experience level, are being hired. However, all OTs receive training to deliver the intervention 
consistently and as intended. Training is composed of four online sessions about 1) study 
procedures (part one), 2) MS and fatigue, 3) study procedures (part two), 3) theoretical 
underpinnings of Managing Fatigue, and 4) the specific format assigned to deliver. Proficiency 
is documented using quizzes. OTs also receive ongoing training during the study for the specific 
format they are delivering. Digital recordings of teleconference and in-person sessions and data 
on therapist internet activity, along with a review of notes (see below), are used to provide the 
OTs with continuous training and specific feedback.  
Implementation fidelity: In addition to the training, each OT is provided with an intervention 
manual (or internet site) to facilitate the consistent delivery of the intervention as intended. OTs 
are asked to use checklists during the sessions (teleconferences and one-to-ones) and to write 
notes (i.e., clinical impressions) each week. The notes are standardized using a Subjective, 
Objective, Assessment, and Plan (S.O.A.P.) format and include instructions to document the 
amount of time spent on each topic, a summary of the interactions, and participants’ questions 
and concerns. Digital recordings of teleconferences and in-person sessions and data on OTs’ 

internet activity are being used to examine whether the course is being delivered consistently and 
as intended. 
Receipt and enactment fidelity: The extent to which participants participate in the 
interventions and the extent to which participants enact recommendations are being documented. 
This includes documenting attendance, participants’ level of involvement using the S.O.A.P. 
format, and the number of internet log-ins and webpages visited. Enactment is being examined 
with a validated questionnaire on fatigue self-management behaviors.19 Quizzes adapted from a 
previous study are being used to measure understanding and retention of intervention material at 
two months.10  
 
Outcome Measures 
Primary and secondary outcomes are being collected using the survey function in 
REDCap. Participants can request a phone interview from research staff masked to intervention 
assignment and/or a paper and pencil version mailed to their homes if they are unable to 
complete the surveys in REDCap. The primary outcome is the FIS20; the secondary outcome is 
the Multiple Sclerosis Impact Scale;21 and the tertiary outcome is the Community Participation 
Indicators.22 These questionnaires are valid and reliable for people with MS.20-23 The primary 
outcome has been shown to be responsive in previous comparable trials of the Managing Fatigue 
intervention.9-13 24 Primary and secondary questionnaires account for a wide range of daily 
activities and social situations impacted by fatigue and results from anchored- and distribution-
based analyses can be used to establish meaningful changes.20-22 25-27 Potential mediators, 
moderators, and other covariates and possible confounders, as well as time points of 
administration, are listed in Table1. Plans to reduce missing outcome data and avoid attrition 

include providing monetary incentives ($20 for completion of questionnaires at each time point), 
using multiple methods to engage participants (e.g., newsletters, email, text messages, and phone 
calls), and addressing questions and concerns promptly. 
<<<Insert Table 1 >>> 
Data Management and Analysis 
Participants expressing interest in the study will first be screened over the phone by 
research staff using a script in REDCap. Participants meeting study criteria will then be 
scheduled for an in-person baseline visit. Participants have the option of undergoing the 
informed consent over the phone or during the in-person baseline visit. At the baseline visit, 
trained research staff who are masked to group assignment will administer the MS Functional 
Composite. Baseline visits are typically held in private conference rooms in hotels or libraries in 
the communities where participants live. Once enough participants in a specific geographic 
region complete the baseline visit and indicate their availability, they are asked to complete 
baseline questionnaires via REDCap, phone, or mail. Research staff masked to group assignment 
are available to address questions and enter in data received by phone or mail. Once the 
questionnaires are completed, participants are then randomized by the project manager.  
REDCap8 is being used to organize research operations, conceal randomization, track 
data generation, securely collect data, help ensure consistent research procedures, and score 
questionnaires in real time. At each time point, questionnaires on anxiety, depression, 
exacerbations, falls, and injuries are being used to monitor for adverse events. REDCap 
automatically notifies research staff when a possible adverse event has occurred based on 
participants’ responses to questionnaires (e.g., increases in symptoms of depression or anxiety or 
worsen of symptoms indicative of an exacerbation). OTs are also provided with instructions to 

notify the research office immediately if they suspect an adverse event. The participant’s 
physician is informed when additional services are needed for the treatment of an adverse event. 
Because it is unlikely that these adverse events will be related to the study protocol, an 
independent Data and Safety Monitoring Board is not being utilized. If a serious adverse event is 
related to the protocol, the Institutional Review Board and study sponsor will be notified 
immediately. Quality control checks (e.g., data generation and attrition rate) will occur 
throughout the study (i.e., every few months) by the statistician not involved in data collection or 
delivery of the intervention. Concerns about adverse events or quality control checks will be 
discussed in the monthly team meetings and conveyed to other stakeholder groups convened 
during the study, including people with MS. 
 Data will be downloaded from REDCap into a statistical software program. Linear 
mixed effects model will serve as the primary analysis tool for examining the differential effects 
of the intervention delivery format on outcomes. The models will include the group assignment 
variable, time, and interaction of time and group, as well as the subject-specific random intercept 
and slope for accounting for individual heterogeneity. Using the fitted model, the trajectory of 
outcomes will be plotted over the study period. Direct estimates of the treatment effect at specific 
times will be derived by specifying the least squares means for the Treatment × Time interaction. 
Noninferiority will be established with a 95% confidence interval (CI) using the prespecified 
margin of inferiority at each time point, which is set at ten points on the total composite score of 
the FIS. The prespecified inferiority margin for the Multiple Sclerosis Impact Scale is set at eight 
points for the physical function subscale and six points for the psychological function subscale. 
These margins are based on anchored-based methods calculated from previous studies.25 26  

The purpose of the moderator analysis will be to examine the consistency of the 
intervention’s effect across the following subgroups: (1) disability status (i.e., people with 
moderate to severe disabilities vs. people with mild impairments, (2) race (i.e., Hispanic and 
non-whites vs. non-Hispanic whites, (3) environment (i.e., people living in rural areas vs. urban 
areas), and (4) psychosocial characteristics (i.e., people experiencing societal barriers, 
depression, low health literacy, low social support, and/or low patient activation vs. people 
without these characteristics). This analysis will involve adding an additional interaction term of 
group × time × characteristic and the two-way interaction term of time × characteristic and group 
× characteristic using the mixed effects model that will be used to detect the main treatment 
effects on fatigue impact.  
 
The purpose of the mediator analysis will be to examine whether changes in self-efficacy 
and fatigue self-management behaviors influence the relationship between the interventions and 
outcomes. Significant changes across time in self-efficacy and fatigue self-management 
behaviors will be evaluated using the proposed mixed effects analysis. Following Hayes et al.,28 
the mediation analysis will involve a series of regression analyses to quantify mediation effects 
using bias-corrected bootstrapped 95% CI. 
We will conduct analyses using both intention-to-treat and per-protocol principles. When 
using intention-to-treat principles, the treatment of missing values will depend on the type of 
missingness. In the case of missing at random, the proposed mixed effects models should be 
sufficient. In the case of missing not at random or non-ignorable, a Bayesian method to jointly 
model response data and missing data will be applied. When using per-protocol principles, 
participants who provide complete data and attend four or more intervention sessions will be 
included in the analysis.   

A series of sensitivity analyses are planned to explore how various assumptions and 
potential confounders might influence the results. Four pre-specified sensitivity analyses are 
planned: (1) significant differences in time-varying factors between groups after randomization 
(e.g., exacerbations, changes in medications, or changes in health and wellness services), (2) 
assumptions of missing data, (3) differences in prespecified margins, and (4) treatment fidelity 
measures (e.g., attendance, quizzes, and experience of OT). We plan to examine these factors by 
comparing adjusted to non-adjusted models. Significant differences in time-varying factors 
between groups after randomization will be entered into the model as covariates during 
hypothesis testing. We will examine whether any differences exist in results based on how 
missing data are treated (e.g., missing at random versus missing not at random). We will also use 
prespecified margins of 4.8 (i.e., standard error of measurement), 15.5 (the mean of 12 anchored-
based MIDs), and 20 (upper limit of the triangulated anchored and distribution-based MIDs). 
Last, we will assess whether measures of treatment fidelity, such as OT experience and 
participants’ understanding of material, influence outcomes as well as whether differences exist 
in the per-protocol analysis when participants who provide complete data and attend all six 
intervention sessions (compared to four and five of the six sessions) are only included in the 
analysis. 
 
Public and Patient Involvement 
Stakeholder groups comprising individuals with MS, policy advocates, insurance 
representatives, clinicians, and researchers on the project are informing all aspects of the study. 
This includes drafting and reviewing recruitment and intervention material, branding of the 
study, selecting which delivery formats to examine, assessing and finding both the ease and 

length of completing the online questionnaires as acceptable, examining policies and procedure 
for participant interactions, reviewing the informed consent process, and providing firsthand 
testimonies about the impact of fatigue and ways to reduce it. Eliciting opinions from 
stakeholders and encouraging their engagement is being accomplished via multiple approaches, 
including in-person focus groups, emails, online surveys, teleconference calls, and one-to-one, 
in-person meetings. Multiple approaches are also being used to accommodate various work 
schedules and obtain diverse stakeholder input (e.g., diversity in race/ethnicity, functional status, 
and constituents represented). Stakeholder groups will continue to meet at least once a month 
throughout the study to guide the recruitment of a diverse sample, present and disseminate 
results, and create an infrastructure to support the delivery of the Managing Fatigue intervention 
after the study’s completion. The stakeholder groups are chaired by the first author and all major 
decisions are voted upon (e.g., selection of interventions and outcomes).   
 
Ethics and Dissemination 
The protocol is approved by the Institutional Review Board (IRB, STUDY20180027) at 
Case Western Reserve University, University of Minnesota, University of Illinois at Chicago, 
Queen’s University, and Dalhousie University. The study is being carried out according to the 
principles in the Declaration of Helsinki.29 Eligible participants are being enrolled and 
randomized into the study only after giving consent to participate. Protocol modifications will be 
submitted to IRB before being implemented. Research staff will undergo extensive training to 
properly obtain informed consent. REDCap will be used to securely store data and maintain 
confidentiality. Study results will be published in peer-reviewed academic journals and presented 
at local, national, and international scientific conferences as possible. We will follow guidelines 

from the International Committee of Medical Journal Editors to determine authorship.30 De-
identified datasets and statistical code generated during the study will be made publicly 
available. We have formed collaborations with several stakeholder organizations that will be 
involved in the dissemination of the study results. For example, we will conduct clinical in-
services, write lay articles to post on social media and publish in magazines with a relevant 
readership, and meet with advocacy groups, like the National Multiple Sclerosis Society. 
Participants will also receive a newsletter at the end of the study to inform them about the study 
results.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Trial status 
Protocol V3.04 (09/20/2019):  This RCT was first registered online at ClinicalTrials.GOV in 
June, 2018. The first participant was recruited and randomized in March, 2019. Recruitment is 
expected to continue until March, 2021 with 6-month follow-up to be completed in October, 
2021. Data analysis is expected to be completed in December, 2021.  
 
Contributors  
MAP, TP, KP, VM, SG, FB, and MF designed the study and helped draft the original grant 
proposal. MAP and TP provided trial leadership. MAP, TP, VM, SG, MF and SA provided 
methodological expertise. SA also provided statistical and data management expertise. TP, KP, 
VM, SG, MF, and FB provided clinical expertise. MAP, KP, and VM provided training and 
supervision to the OTs. VM oversaw delivery of 1-to-1, in-person intervention format. TP and 
SG oversaw delivery of internet intervention format. KP and MF oversaw delivery of 
teleconference intervention format. All authors reviewed and approved the final version of this 
manuscript. 
 
Acknowledgements  
The authors would like to thank the participants for their time. We also would like to thank Clara 
Adegbite, Nataliya Bukhanova, Julie Hewitt, Kaitlin Sibbald, Toni Van Denend, and Yue Wu for 
assistance with intervention refinement and/or development as well as ongoing recruitment, 
enrollment, data collection, and/or intervention delivery. 
 
 

Conflict of Interest 
Dr. Bethoux has financial relationships with pharmaceutical and devices companies outside the 
submitted work. The other authors declare that they have no potential or actual conflict of 
interest pertaining to this research study. 
 
 
Funding 
This work was supported through a Patient-Centered Outcomes Research Institute (PCORI) 
Project Program Award (MS-1610-37015). All statements in this report, including its findings 
and conclusions, are solely those of the authors and do not necessarily represent the views of the 
Patient-Centered Outcomes Research Institute (PCORI), its Board of Governors or Methodology 
Committee. 
 
 
 
 
 
 
 
 
 
 
 

Key: t1 = 2 months; t2 = 3 months; t3 = 6 months 
Table 1. Schedule of enrolment, interventions, and assessments 
 
STUDY PERIOD 
 Enrolment 
Allocation 
Interventions 
Post-allocation 
TIMEPOINT** 
-t1 
0 
 
t1 
t2 
t3 
ENROLMENT: 
 
Eligibility screen 
X 
 
 
 
 
 
Informed consent  
X 
 
 
 
 
 
In-person assessment 
X 
 
 
 
 
 
Return baseline questionnaire packet 
X 
 
 
 
 
 
Allocation 
 
X 
 
 
 
 
MANAGING FATIGUE INTERVENTION: 
 
One-to-one, in-person 
 
 
 
 
 
 
Internet 
 
 
 
 
 
 
Teleconference 
 
 
 
 
 
 
PRIMARY OUTCOME: 
 
Fatigue Impact Scale20 
X 
 
 
X 
X 
X 
SECONDARY OUTCOMES: 
 
Multiple Sclerosis Impact Scale21 
X 
 
 
X 
X 
X 
Community Participation Indicators22 27 
X 
 
 
X 
X 
X 
MODERATORS 
 
 
 
 
 
 
Multiple Sclerosis Functional Composite31 
X 
 
 
 
 
 
Medical Term Recognition Test32  
X 
 
 
 
 
 
Neuro QOL – Anxiety33  
X 
 
 
X 
X 
X 
Neuro QOL – Sleep33 
X 
 
 
X 
X 
X 
Patient Health Questionnaire–834  
X 
 
 
X 
X 
X 
Patient Activation Measure35 
X 
 
 
 
 
X 
Craig Hospital Inventory of Environmental Factors36 
X 
 
 
 
 
 
Demographics (i.e., urban/rural and race)   
X 
 
 
 
 
 
Self-report Comorbidity Questionnaire37 
X 
 
 
 
 
 
Modified Social Support Survey38 
X 
 
 
 
 
X 
MEDIATORS 
 
Energy Conservation Strategies Survey19 
X 
 
 
X 
X 
X 
Self-Efficacy for Performing Energy Conservation 
Strategies Assessment18 
X 
 
 
X 
X 
X 
Chronic Disease Self-management Scale39 
X 
 
 
X 
X 
X 
COVARIATES & POSSIBLE CONFOUNDERS  
 
 
 
 
 
 
Sociodemographic (e.g., age, gender, income, 
education, living arrangements, and employment) 
X 
 
 
 
 
 
Godin Leisure-Time Exercise Questionnaire40 
X 
 
 
X 
X 
X 
Adverse events (e.g., exacerbations41 and injuries)  
X 
 
 
X 
X 
X 
Health and wellness services42 (e.g., occupational 
therapy, counseling, and prescribed medications)  
X 
 
 
 
 
X 
Expectation of benefits/Past Experience/Quizzes 
X 
 
 
X 
 
 
Satisfaction survey (open- and close-ended questions) 
 
 
 
X 
 
 
Symptoms of MS Scale43 
X 
 
 
X 
X 
X 
Neuropsychological Screening Questionnaire44 
X