A Randomized Controlled Trial of Online Cognitive Behavior Therapy for Insomnia (CBT-I) and Perceived Cognitive Impairment (PCI) in Cancer Survivors
Phase: NA
Conditions: Cancer, Insomnia, Cognitive Impairment
Sponsor: Memorial University of Newfoundland

Memorial University of Newfoundland 
 
May 30th, 2023  
 
CLINICAL STUDY PROTOCOL  
VERSION 2.1 (APRIL 2021) 
STUDY SUMMARY 
Full Title: 
A Randomized Controlled Trial of Online Cognitive 
Behavior Therapy for Insomnia (CBT-I) and Perceived 
Cognitive Impairment (PCI) in Cancer Survivors  
 
 
Short Title:                             Online CBT-I for PCI 
Clinical Trials Information 
NCT04026048 
 
Principal Investigator:            Sheila N. Garland, PhD1,2 
 
 
Co-Investigators:                   Joshua Rash, PhD1  
                                              Melanie Seal, MD, FRCP2 
 
Josée Savard, PhD3  
 
Robin Urquhart, PhD4  
 
John Thoms, MD FRCPC2 
 
Kara Laing, MD, FRCP2 
 
 
Patient Co-Investigator: 
Sondria Browne 
 
 
Affiliations:                            
1 Department of Psychology, MUN Faculty of Science 
 
2 Division of Oncology, MUN Faculty of Medicine                         
 
3 Département d'école de psychologie, Université Laval 
 
4 Department of Community Health and Epidemiology, Faculty 
of Medicine, Dalhousie University 
 
 
 
Sponsor:  
Canadian Institutes of Health Research (CIHR) 
 
 
 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
Title 
A Randomized Controlled Trial of Online Cognitive Behaviour Therapy 
for Insomnia (CBT-I) and Perceived Cognitive Impairment (PCI) in 
Cancer Survivors 
Short Title 
Online CBT-I for PCI 
Protocol Number 
HREB Application Ref No: 12843; ClinicalTrials.gov Identifier: 
NCT04026048 
Phase 
Phase IV 
Methodology 
Randomized controlled trial 
Study Duration 
4 year 
Study Center(s) 
Memorial University of Newfoundland (MUN) 
Objectives 
Primary Objective:  
1: To examine whether treating insomnia using online CBT-I improves 
PCI in cancer survivors compared to a waitlist control group. 
Secondary Objectives:  
1: To determine whether treating insomnia using online CBT-I can 
improve objective cognitive function at the end of treatment compared to 
a waitlist control group.  
2: To evaluate whether change in insomnia better accounts for 
improvements in cognition than depression, anxiety, and/or fatigue. 
3: To explore whether treatment of insomnia and PCI reduces work 
presenteeism and absenteeism. 
4: To investigate associations between subjective and objective 
measures of cognitive function and sleep. 
Number of 
Participants 
130 
Diagnosis and 
Main Inclusion 
Criteria 
For individuals with non-hematological malignancies: 
• 
Men and women who are easily able to understand and read 
English 
• 
No current evidence of cancer or clinically stable/inactive 
disease 
• 
Received and completed all adjuvant treatments at least 6 
months prior to study entry to allow for neural stabilization and 
recovery  
• 
Continued maintenance or hormonal therapies are acceptable 
• 
Report PCI as indicated by a score of “quite a lot” or “always” on 
at least one of the two items that assess concentration and 
memory on the EORTC [1] 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
• 
Meet the DSM-5 criteria for insomnia disorder and have a score 
of 8 or greater on the Insomnia Severity Index[2] 
• 
Have an ECOG score of 0-2, indicating that they can care for 
themselves (working, walking), have good daily activity, and 
good physical ability 
• 
Have high-speed internet connection, webcam, and are fluent 
using the internet 
 
For individuals with hematological malignancies: 
• 
Men and women who are easily able to understand and read 
English 
• 
A diagnosis of a hematological malignancy currently in 
remission. 
• 
Completed cancer treatments including transplant, 
chemotherapy and/or immunotherapy at least 6 months prior to 
study entry 
• 
Report PCI as indicated by a score of “quite a lot” or “always” on 
at least one of the two items that assess concentration and 
memory on the EORTC [1] 
• 
Meet the DSM-5 criteria for insomnia disorder and have a score 
of 8 or greater on the Insomnia Severity Index[2] 
• 
Have good performance status as indicated by an ECOG score 
of 0-2 
• 
Have high-speed internet connection, webcam, and are fluent 
using the internet 
Study Product, 
Dose, Route, 
Regimen 
Online delivered CBT-I via video-conferencing 
Duration of 
administration 
Participants will receive seven components of online CBT-I via video-
conferencing over the course of 8 weeks. 
Reference 
therapy 
Waitlist control group 
Statistical 
Methodology 
Primary research question data will be analyzed using mixed-effects 
models. Secondary research questions will be answered using 
mediation/moderation analyses and/or additional mixed effects models.  
 
 
 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
1. ETHICS 
The study will be approved by local research ethics boards, The Health Research Ethics Board 
(HREB) and the Research Proposals Approval Committee (RPAC). 
The study will be conducted in accordance with the Tri-Council Policy Statement on Ethical 
Conduct for Research Involving Humans 2 (TCPS2) http://www.pre.ethics.gc.ca/eng/policy-
politique/initiatives/tcps2-eptc2/Default/ and will adhere to the Memorial University Policy on 
Ethics of Research Involving Human Participants 
http://www.mun.ca/policy/site/policy.php?id=139 .  
2. OBJECTIVES OF THE STUDY 
Primary Objective: To examine whether treating insomnia using online CBT-I improves PCI in 
cancer survivors compared to a waitlist control group. 
Secondary Objectives:  
1: To determine whether treating insomnia using online CBT-I improves objective cognitive 
function compared to a waitlist control group.  
2: To evaluate whether change in insomnia better accounts for improvements in cognition than 
depression, anxiety, and/or fatigue. 
3: To explore whether treatment of insomnia and PCI reduces work presenteeism and 
absenteeism. 
4: To investigate associations between subjective and objective measures of cognitive function 
and sleep.  
3. BACKGROUND, SIGNIFICANCE, AND RATIONALE     
3.1 BACKGROUND: For cancer survivors, one of the biggest barriers to resuming normal 
functioning is perceived cognitive impairment (PCI). Approximately 75% of cancer patients 
report a decline in a variety of cognitive domains during chemotherapy and/or hormonal therapy, 
and up to 35% continue to experience cognitive difficulties for months or years post-treatment.[3] 
While the evidence supports the high prevalence of PCI, the research is inconclusive about how 
to treat these difficulties.[4] Pharmacological interventions have largely been ineffective at 
preventing or treating PCI.[5] The efficacy of cognitive remediation programs is also inconclusive, 
with some, but not all, studies reporting improved cognition.[6] Studies to date have largely 
ignored the possible impact of sleep, which could account for the less than impressive findings. 
Sleep disturbances, primarily in the form of insomnia, are an especially important, but frequently 
overlooked, consequence of cancer and associated treatments.[7, 8] Several large-scale 
epidemiological studies demonstrate that close to 60% of people treated for cancer experience 
insomnia.[9, 10] When patients were asked about the development of their insomnia, most 
reported that it began with, or followed, their cancer diagnosis,[11] and that the effects of poor 
sleep were more overwhelming than the effects of cancer treatment.[12] Unfortunately, once 
chronic, sleep disturbances are unrelenting if not appropriately treated, and can persist for years 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
or even decades.[10] Sleep difficulty is one of the most frequent reasons that cancer survivors 
visit their general practitioners.[13] In Canada, annual indirect costs associated with insomnia-
related absenteeism were estimated at $970.6 million overall, with insomnia-related productivity 
losses estimated at $5.0 billion.[14] The average annual per-person costs (direct and indirect 
combined) were $5,010 for individuals with insomnia compared to $421 for good sleepers.[14]  
Further, 40.6% of Canadians with insomnia reported having experienced reduced productivity 
compared to 12.3% of good sleepers.[15] Sleep disturbance significantly mediates the impact of 
cancer on healthcare expenditures and absenteeism, suggesting that addressing sleep 
disturbance may result in economic benefits in addition to improvements in health and quality of 
life.[16]  
 
Disrupted sleep has negative consequences for cognition in the general population. Numerous 
experimental studies have demonstrated that both acute total and cumulative partial sleep loss 
lead to deteriorations in a wide range of cognitive functions such as sustained attention, 
executive function, and memory (for a review, see Banks and Dinges [17]). Poor sleep and 
insomnia are significantly associated with subjective and objective cognitive complaints in 
cancer populations as well.[18-20] Recent evidence challenges the conventional idea that the 
cancer treatment itself is 
responsible for the changes 
in cognition and places sleep 
in the spotlight as a potent 
contributor.[21] To guide the 
design, methods, and 
analyses for the proposed 
research, we have built a 
conceptual model (Figure 1) 
that is grounded in the current 
scientific understanding of 
how cancer and its treatment 
and side effects might, 
directly or indirectly, 
contribute to sleep disturbance, which can then, alone or in combination with psychological 
disorders, contribute to PCI.  
 
Cognitive Behaviour Therapy for Insomnia (CBT-I) is specifically designed for insomnia and is 
recommended by the American College of Physicians and the American Academy of Sleep 
Medicine as a first line treatment for chronic insomnia.[22, 23] CBT-I has demonstrated efficacy in 
several randomized controlled trials (RCTs) in the general population.[24-27] CBT-I is also the 
treatment of choice in the context of cancer-related insomnia.[28] Recent evidence also suggests 
that CBT-I has broad effects and offers concomitant improvements in fatigue, anxiety, and 
depression related to cancer treatment,[29] all of which have been associated with PCI. The 
correlation between PCI and insomnia persists more than 18 months post-diagnosis, and there 
is some evidence suggesting that patients with insomnia are more likely to develop PCI.[30] 
Moreover, preliminary evidence from secondary analyses suggests that CBT-I may improve 
PCI[31] but additional research is required to investigate this question a priori with more refined 
subjective and objective measures of cognitive functioning, controlling for other factors that may 
explain this effect.  
 
Figure 1: Conceptual Model 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
Despite the advantages of CBT-I, it is underutilized for a number of reasons such as a limited 
number of trained CBT-I providers, poor geographical distribution of these providers, limited 
insurance reimbursement, and relatively high costs of face-to-face delivered CBT-I.[32, 33]. A 
solution to these issues and an approach to increase access to CBT-I is the online delivery of 
the intervention via video-conferencing platforms. The internet is increasingly being used to 
deliver a wide range of behavioral and mental health programs and has had excellent 
success.[32]  
 
3.2. SIGNIFICANCE: Treatment of PCI in cancer patients is a priority for clinicians, researchers, 
and patients, making the current trial a necessity.[34] Cognitive difficulties have a direct impact on 
work productivity, long-term absence, retirement intentions, and early retirement.[35] The 
proposed study is highly significant in that it is the first RCT specifically designed to examine 
whether PCI in cancer survivors can be improved using the “gold-standard” non-
pharmacological intervention for insomnia.[22] This research will inform our understanding of the 
mechanisms of cognitive impairment associated with cancer and help determine whether CBT-I 
could be used alone or in adjunct to other therapies (e.g., cognitive remediation) to treat PCI. 
 
4. STUDY DESIGN    
4.1. Overall Design: The proposed trial is an RCT of immediate treatment with CBT-I compared 
to a waitlist control for PCI in cancer survivors with insomnia (see Figure 2). Participants will 
receive individual CBT-I delivered by via online video-conferencing over the course of eight 
weeks. Participants in the waitlist control group will be required to monitor their sleep with sleep 
diaries for 8 weeks. They will receive CBT-I delivered by via video-conferencing immediately 
after the waiting period. Both groups will complete follow up assessments three and six months 
after completing treatment. The total study duration for the immediate and delayed treatment 
groups is 8 and 10 months, respectively. We chose a waitlist, or delayed treatment, control 
group because it would be unethical to refuse participants with insomnia the opportunity to 
receive CBT-I. The use of a waitlist control is also more representative of real-world health care 
in Canada, where patients will often have to wait for a certain amount of time before receiving 
treatment and will control for the regression to the mean. 
Figure 2: Trial Design  
 
5. SUBJECT SELECTION AND WITHDRAWAL 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
5.1. Subject Recruitment: We plan to recruit a sample of 130 cancer survivors from across the 
Atlantic provinces (Newfoundland and Labrador, Prince Edward Island, Nova Scotia, and New 
Brunswick) who completed chemotherapy and/or radiation treatment at least 6 months prior to 
enrollment (for non-hematological malignancies) and completed cancer treatments including 
transplant, chemotherapy and/or immunotherapy at least 6 months prior to study entry (for 
hematological malignancies). We are confident in our ability to recruit the proposed sample. 
Newfoundland and Labrador has the highest age standardized incidence rate for cancer in 
Canada.[36] All of the oncologists providing cancer care at Eastern Health (including Co-Is Drs. 
Thoms and Seal) are highly committed to the successful completion of this study. Because we 
are recruiting cancer survivors at least 6 months after completion of cancer treatment, we will 
have a large pool of participants to draw from. The primary means of recruitment will be self-
referral; however, we will also employ creative strategies that have been successfully used in 
previous studies to recruit local participants including: identification of patients with sleep 
problems through the Personal Well-being Checklist, a distress screening initiative used by the 
Dr. H. Bliss Murphy Cancer Centre; posting announcements and pamphlets available in the 
main areas of cancer centres and other areas where eligible patients may frequent; notification 
of treating physicians across areas (e.g., medical oncology, radiation oncology, hematology 
oncology, general oncology), nurses and allied health professionals; having new patients 
consent to be contacted at a later date; notification of community support groups and posting of 
information on websites frequented by patients; media releases for local newspapers and 
television programs; paid advertising in print media, on the radio, television and/or internet; and 
posting advertisements on Kijiji, Buy and Sell, and Classifieds. A key recruitment method to 
ensure we can make patients across the province and Atlantic Canada aware of the study 
opportunity is to mail study invitation letters to patients through the Newfoundland and Labrador 
provincial cancer registry and the Atlantic Path study. Recruitment via the cancer registry will be 
conducted with the approval and cooperation of the NL Cancer Care Registry (NLCCR). 
Recruitment via the Atlantic Path study will be conducted with the approval and cooperation of 
Atlantic Path. Eligible patients (defined as any individual with no current evidence of cancer or 
clinically stable/inactive disease who completed cancer treatment at least 6 months ago) will be 
identified by registry cancer case and Atlantic Path records and mailed an invitation letter to 
participate in the study. The personal information of the individuals eligible for the invitation 
letter will not be made available to the researchers in this study. Study personnel will provide the 
stuffed envelopes and the registry or Atlantic Path will be responsible for mailing them, to 
ensure protection of privacy. Previous studies conducted by the principal investigator have seen 
successful recruitment through this strategy. 
The mail out will include: 
NLCCR: 
• 
two letters  
o a letter from the NLCCR  
o a letter from the principal investigator 
• 
two brochures 
o 
one about the NLCCR (http://cancercare.easternhealth.ca/wp-
content/uploads/sites/2/2018/02/Cancer-Registry-NLCCR-Brochure_2017-1.pdf) 
o one about our study   
Atlantic Path: 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
• 
a letter from the principle investigator 
• 
a brochure about our study 
Conservative estimates indicate that approximately 15% of patients will be both eligible and 
interested in participating in our research, yielding 525 potential participants per year. We aim to 
recruit 1-3 participants per week or approximately 5 participants per month (30 in Year 1 to 
allow study launch time, 58 in Year 2, and 36 in Year 3). As such, we are more than able to 
recruit 130 participants in the study period. 
Table 1: Study Timeline 
TABLE 1 
YEAR 1 
YEAR 2 
YEAR 3 
YEAR 4 
Hire/Training 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment 
Group (n) 
 
7 
11 
12 
14 
14 
15 
15 
15 
15 
6 
 
 
 
 
 
Waitlist Group 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Follow Up 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data 
Entry/Cleaning 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data Analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Writing/KT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5.2. Inclusion Criteria:  
5.2.1 For individuals with non-hematological malignancies:  
• 
Men and women who are easily able to understand and read English 
• 
No current evidence of cancer or clinically stable/inactive disease 
• 
Received and completed all adjuvant treatments at least 6 months prior to study entry to 
allow for neural stabilization and recovery  
• 
Continued maintenance or hormonal therapies are acceptable 
• 
Report PCI as indicated by a score of “quite a lot” or “always” on at least one of the two 
items that assess concentration and memory on the EORTC [1] 
• 
Meet the DSM-5 criteria for insomnia disorder and have a score of 8 or greater on the 
Insomnia Severity Index[2] 
• 
Have good performance status as indicated by an ECOG score of 0-2. 
• 
Have high-speed internet connection, webcam, and are fluent using the internet 
5.2.2 For individuals with hematological malignancies: 
• 
Men and women who are easily able to understand and read English 
• 
A diagnosis of a hematological malignancy currently in remission. 
• 
Completed cancer treatments including transplant, chemotherapy and/or immunotherapy 
at least 6 months prior to study entry 
• 
Report PCI as indicated by a score of “quite a lot” or “always” on at least one of the two 
items that assess concentration and memory on the EORTC [1] 
• 
Meet the DSM-5 criteria for insomnia disorder and have a score of 8 or greater on the 
Insomnia Severity Index[2] 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
• 
Have good performance status as indicated by an ECOG score of 0-2. 
• 
Have high-speed internet connection, webcam, and are fluent using the internet 
5.3. Exclusion Criteria: 
5.3.1 For individuals with and without hematological malignancies: 
• 
Another sleep disorder, besides insomnia, that is not adequately treated (ie: untreated 
obstructive sleep, sleep apnea) 
• 
The presence of another psychological disorder that is not currently stable and/or would 
impair the ability to participate in the study 
• 
A major sensory deficit (e.g. blindness) 
• 
A neurologic or major medical condition known to affect cognitive function (e.g., 
Parkinson’s) 
• 
A history of cranial radiation 
• 
A history of any other condition that may affect cognitive functioning (e.g., traumatic 
brain injury) 
• 
Previous experience with CBT-I  
 
Participants will not be excluded for using psychotropic medication prior to study entry (e.g. 
antidepressants) provided that the dose was not recently altered (stable over the previous 6 
weeks). Considering the potential for prescription of medications to help with sleep (e.g. 
hypnotics, sedatives, and antidepressants) within the cancer population, medication use 
throughout the study will be tracked and adjusted for in the statistical analysis. 
5.4. Early Withdrawal of Participants: 
Any participant withdrawing their consent to participate in the study or their authorization to use 
their protected health information will be withdrawn from the study. Participants withdrawn may 
be replaced, at the discretion of the principal investigator. 
Reasons why participants are withdrawn will be documented on the Study Termination Form.  
Every effort will be made to continue to collect data on every participant for the entire study 
duration regardless of whether the participant continues to complete assessments, assuming 
the participant has not withdrawn his/her authorization to obtain such information. 
6. STUDY INTERVENTION 
Participants will receive seven individual CBT-I delivered by via video-conferencing over the 
course of eight weeks. Therapists will be doctoral students in clinical psychology supervised by 
Drs. Garland and Rash. CBT-I is a manualized multi-component intervention that includes sleep 
restriction, stimulus control, cognitive restructuring, relaxation training, and sleep hygiene. Sleep 
restriction is designed to restrict time spent in bed to closely match the time actually spent 
sleeping. A sleep efficiency percentage (the amount of time spent sleeping divided by the 
amount of time spent in bed) is calculated, and when the individual is able to achieve 85% sleep 
efficiency, their sleep time is increased. This process continues until the person can achieve a 
restful night’s sleep with few or no disturbances. Stimulus control is based on the theory that the 
body eventually becomes conditioned to associate the sleep time and setting with arousal (e.g. 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
only go to bed when sleepy and refrain from lying awake in bed). This technique is designed to 
break the perpetuating behaviors and re-associate the bed with sleep. Cognitive restructuring 
addresses the dysfunctional thoughts and beliefs that serve to maintain and exacerbate 
insomnia. Individuals are taught to monitor these thoughts and beliefs, challenge their validity, 
and replace them with adaptive cognitions conducive to the sleep process. Relaxation training 
targets the physiological and cognitive arousal that accompanies insomnia, and sleep hygiene 
promotes healthy sleep behaviors and environmental conditions.   
Treatment fidelity (including adherence, competence, etc.) is critical to the successful delivery of 
an intervention in practice.[37] All therapists will receive training in the manualized CBT-I protocol 
and weekly case supervision meetings including video review throughout the duration of the trial 
with Drs. Garland and Rash. A checklist of the main teaching points to be covered in each 
treatment session will be reviewed during supervision and adherence to the CBT-I protocol will 
be examined by calculating a total score on the teaching checklist. Therapists with adherence 
ratings below 90% will be provided with additional supervision. Dr. Rash will rate twenty percent 
of the video recorded sessions selected at random for treatment adherence. These data will be 
used if needed in addition to the Credibility/Expectancy Questionnaire (CEQ)[38] to examine 
possible moderators of treatment effects. 
 
7. STUDY PROCEDURES 
7.1. Initial Screening: All potential participants will be identified from across Atlantic Canada.  
Patients will be contacted by the research coordinator and/or primary investigator to explain the 
study procedures in detail. A brief medical, psychological, and sleep disorders screening 
questionnaire will be administered to screen for the presence of other medical and/or 
psychological disorders that may interfere with the participant’s ability to participate in the study. 
This will occur over the telephone. 
7.2 Informed Consent: Informed consent will be obtained in two phases. In phase one, 
participants will be read a simplified consent form over Zoom. In phase two, participants will be 
given a link to the full consent form and participants will be considered consented when they 
check the box on the Qualtrics form. This will occur at the time of their initial screening or will be 
scheduled for a more convenient time prior to the baseline assessment. Once consented, 
participants will be considered enrolled. 
7.3. Assessments: Baseline assessments will be scheduled based on participant availability 
and will last about 60 minutes. All of the assessments will take place over the secure video 
conference sessions that will take place in a secure room in the Sleep, Health, and Wellness 
laboratory. Assessments may also be mailed out to the participants to fill out and return, or 
participants will be sent a link to the assessments on Qualtrics. During the COVID-19 pandemic, 
all assessments will follow the usual protocol to take place over the secure video conference 
platform, however, now this will take place in a secure room in the research coordinator’s home. 
Participants will also be emailed the link to the online component of the assessment which 
occurs on Qualtrics. No mailing of paper copies of the assessments will occur during the 
COVID-19 pandemic.  
At the baseline assessment, we will assess cognitive function and patient reported outcomes of 
sleep, fatigue, anxiety, and depression. During the baseline assessment, a member of the study 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
team will inform the participant if they are randomized to be in the immediate treatment group or 
the delayed treatment group.  
At the mid and post treatment assessments, the participants will also be asked to complete 
questions related to adverse events during the CBT-I treatment. These questions will be added 
to their Qualtrics assessment. The open-ended Qualtrics responses will be thematically 
analyzed to create a record of adverse events experienced by the participants.  
7.3.1. Video-Conference Information 
The CBT-I intervention and the assessments will take place over a video conference platform 
called Zoom (see details about privacy and security below in Section 10). Participants will be 
given a link to the session via email. At the end of the session the link will expire, and each new 
Zoom session will generate a new Zoom ID. Participants will be told to not enter their name but 
to enter their participant number to ensure confidentiality. We previously used telehealth 
systems embedded in the regional health authorities to conduct these assessments, but 
patients reported that this was still a barrier to participation because they had to travel 
(sometimes still quite a distance) to participate in the telehealth meeting. The use of Zoom will 
allow people to participate from the comfort of their own home and ensure privacy and equal 
access to treatment for Atlantic Canadians regardless of geography. Treatment sessions will be 
recorded to assess treatment fidelity and quality assurance.  
7.4. Follow up Assessments: Both groups will complete follow up assessments three and six 
months after completion of treatment to investigate durability of treatment effects.  
7.5. Randomization: Participants will be sequentially randomized to one of the two treatment 
conditions using a 1:1 allocation ratio created by the study biostatistician. The random allocation 
sequence will be prepared in advance and recorded on sequentially numbered, opaque, sealed 
and stapled envelopes to be provided to participants in order of study entrance. During the 
baseline assessment, the research coordinator will inform the participants which group they 
have been assigned to. All research personnel, including the PI, will be blind to the allocation 
sequence. 
7.6. Data Collection Schema 
The data collection schema for both groups are described in Tables 1a and 1b, followed by 
details about the instruments. The average time to complete the patient reported outcomes and 
neuropsychological measures at each assessment time is approximately 45-60 minutes. 
Participants in both the immediate treatment group and the waitlist treatment group will 
complete the sleep diaries. Participants will complete the sleep diary upon waking each morning 
for one week at each assessment period. The time to record the previous night’s sleep is 
approximately 2 minutes. The research team has successfully conducted previous research with 
similar levels of participant burden. During the COVID-19 pandemic, participants will only 
complete the diaries if they are able to do so electronically (print and send back electronically, or 
fill out on their computer and email back). Participants who require a printed copy of the diary to 
be mailed will not complete the sleep diary component during the pandemic.  
Table 1a. Schedule of Assessments and Outcome Collection for Immediate Treatment 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
 
Instrument 
 
T0 
Baseline 
 
T1 
Mid-
Treatment 
 
T2 
Post-
Treatment 
 
T3 
3 Month 
Follow Up 
 
T4 
6 Month 
Follow Up 
CEQ 
X 
 
 
 
 
FACT-COG 
X 
X 
X 
X 
X 
ISI 
X 
X 
X 
X 
X 
MFSI-SF 
X 
X 
X 
X 
X 
HADS 
X 
X 
X 
X 
X 
WPAI 
X 
 
X 
X 
X 
Sleep Diaries* 
X 
X 
X 
X 
X 
HLVT-R 
X 
 
X 
X 
X 
COWAT 
X 
 
X 
X 
X 
Digit Span 
X 
 
X 
X 
X 
BRIEF-A 
X 
 
X 
X 
X 
MMSE 
X 
 
 
 
 
Adverse 
Events 
Protocol 
 
X 
X 
 
 
Table 1b. Schedule of Assessments and Outcome Collection for Delayed Treatment 
 
Instrument 
 
T0 
Baseline 
 
T1 
Monitoring 
 
T2 
Pre-
Treatment 
 
T3 
Mid-
Treatment 
 
T4 
Post-
Treatment 
 
T5 
3 Month 
Follow Up 
 
T6 
6 Month 
Follow Up 
CEQ 
X 
 
 
 
 
 
 
FACT-COG 
X 
X 
X 
X 
X 
X 
X 
ISI 
X 
X 
X 
X 
X 
X 
X 
MFSI-SF 
X 
X 
X 
X 
X 
X 
X 
HADS 
X 
X 
X 
X 
X 
X 
X 
WPAI 
X 
 
X 
 
X 
X 
X 
Sleep Diaries* 
X 
X 
X 
X 
X 
X 
X 
HLVT-R 
X 
 
X 
 
X 
X 
X 
COWAT 
X 
 
X 
 
X 
X 
X 
Digit Span 
X 
 
X 
 
X 
X 
X 
BRIEF-A 
X 
 
X 
 
X 
X 
X 
MMSE 
X 
 
 
 
 
 
 
Adverse 
Events 
Protocol 
 
 
 
X 
X 
 
 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
 
Medical history and demographics: A medical history and demographics questionnaire will be 
administered at the baseline assessment. This questionnaire will be used to obtain patient 
demographic information (e.g., sex, age, ethnic background, education, marital status, current 
employment status), medical history (e.g., type of cancer, dates of diagnosis and treatment, 
types of treatment received), psychiatric history, and current medication use. The 
Credibility/Expectancy Questionnaire (CEQ)[38] will also be used at baseline to examine possible 
moderators of treatment effects.  
Primary Outcome - The Functional Assessment of Cancer Therapy – Cognitive Function 
(FACT-Cog), version 3: The FACT-Cog will be used as the measure of perceived cognitive 
impairment. It is a 37-item questionnaire with four cognitive subscales: perceived cognitive 
impairments, impact on quality of life, comments from others, and perceived cognitive 
abilities.[20, 39] Responses range from 0, ‘‘never,’’ to 4, ‘‘several times a day,’’ in the previous 7  
days. A change of 10.6-points has been established as clinically meaningful change on the 
FACT-Cog.[39-41]   
 
Secondary Sleep Outcomes: The Insomnia Severity Index (ISI) has 7-items designed to 
specifically assess the severity of insomnia symptoms, the impact on daytime functioning, and 
the amount of associated distress.[2] The ISI has established minimally important change values 
to ensure that the change is not only statistically significant, but also clinically meaningful to 
patients. 
 
The Consensus Sleep Diary (CSD) provides a night-by-night, self-report of sleep duration, 
disruption, and perceived quality and will be used to capture more subtle variations in sleep. 
The sleep diary will be used to calculate sleep efficiency, sleep-onset latency, wake after sleep 
onset, total sleep time, time in bed, number of awakenings, sleep quality, and terminal 
wakefulness. Sleep diaries are considered a reliable and valid patient report of nightly insomnia 
symptoms.[42] Participants will complete the sleep diary for one week at each assessment point. 
However, during the COVID-19 pandemic, participants will only complete the diaries if they are 
able to do so electronically (print and send back electronically, or fill out on their computer and 
email back). Participants who require a printed copy of the diary to be mailed will not complete 
the sleep diary component during the pandemic.  
 
 
Neuropsychological Measures: The use of these measures adheres to the recommendations 
of the International Cognition and Cancer Task Force to improve research design and facilitate 
between-study comparisons and meta-analyses.[43] 
 
The Mini-Mental State Examination (MMSE) is a method used for assessing cognitive metal 
state in clinical practice and in research.[44] A score lower than 24 on the Mini-Mental State 
Examination suggesting the presence of severe cognitive impairments 
 
The Hopkins Verbal Learning Test-Revised (HVLT-R) is a brief assessment of verbal learning 
and memory (immediate recall, delayed recall, delayed recognition).[45] The HVLT-R has six 
alternate forms available.  
 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
The Controlled Oral Word Association Test (COWAT) is a measure of verbal fluency, cognitive 
and motor speed, cognitive flexibility, strategy utilization, suppression of interference, and 
response inhibition.[46] The COWAT has two alternate forms available.  
 
The Digit Span test is a subtest of the Wechsler Adult Intelligence Scale (WAIS) and the 
Wechsler Memory Scale (WMS)[47]. The forward span captures attention efficiency and capacity, 
and the backward span is an executive task dependent on working memory[47]. The digit span is 
not impacted by practice effects making is suitable for repeated testing[48]. 
 
The Behaviour Rating Inventory of Executive Function-Adult (BRIEF-A) is composed of 75 items 
within nine non-overlapping theoretically and empirically derived clinical scales. It has 2 broad 
indexes (Behavioural Regulation and Metacognition), an overall summary score, and three 
validity scales (Negativity, Inconsistency, and Infrequency). The normative sample included 
1,136 adults from a wide range of racial/ethnic backgrounds, educational backgrounds, and 
geographic regions. The BRIEF-A has demonstrated evidence of reliability, validity, and clinical 
utility as an ecologically sensitive measure of executive functioning in individuals with a range of 
conditions across a wide age range. A study that investigated the use of the BRIEF-A in patients 
with primary brain tumors suggests that measuring perceived executive dysfunction with the 
BRIEF-A is feasible.[49]  
 
Work Productivity Loss Measure: The Work Productivity and Activity Impairment (WPAI) 
questionnaire was developed for the purpose of collecting productivity loss data within clinical 
trials and is suitable for direct translation into a monetary figure.[50] 
 
Additional Patient-Reported Outcomes: Fatigue will be measured using the Multidimensional 
Fatigue Symptom Inventory-Short Form (MFSI-SF).[51] Anxiety and Depression will be measured 
using the Hospital Anxiety and Depression Scale (HADS) [52].  
 
8. STATISTICAL PLAN 
 
8.1 Data Management: A data management system will be created by the principal investigator 
permitting tracking of data forms, computer-based editing and error-check, generation of 
periodic reports, and the creation of data sets for statistical analyses. All data will be stored in a 
fashion consistent with patient information privacy guidelines (see below). The data analysis 
sets will be exported to statistical software for analysis.  
 
8.2. Data Analysis Plan 
8.2.1. Analysis Plan: To answer our primary research question, we will use mixed-effects 
models to determine whether treated patients had greater improvements immediately post-
treatment (primary endpoint) compared with patients in the control group after their waiting 
period. Then, data from both groups will be pooled together to assess, with a larger sample 
size, the durability of any effects observed at 6 months (secondary endpoint). This statistical 
procedure considers within-subject correlations from repeated measurements in the same 
subjects and allows estimation of between-group differences without necessitating last 
observation carried forward or exclusion of participants with missing data. Secondary and 
exploratory research questions will be answered using mediation/moderation analyses and/or 
additional mixed effects models.  

Memorial University of Newfoundland 
 
May 30th, 2023  
 
The primary analyses will occur after the treatment completion (primary endpoint) and durability 
analyses will occur after the 6-month follow-up (secondary endpoint). 
Subsidiary analyses will be conducted to examine the role of sex, gender, and sexual 
orientation in participant recruitment and retention, pre-treatment symptom severity, as well as 
the overall efficacy of online CBT-I, and results will be reported separately. 
8.2.2. Missing Data: A drawback of any study is the risk of missing data and attrition bias. Our 
first line of defense will be to minimize the occurrence of missing observations, using a well-
constructed study design, well-trained research staff, and acceptable subject burden.[53] We will 
decrease barriers to recruitment/retention by scheduling study visits at a convenient time. For 
those who voluntarily withdraw from the study, we will record their reasons for withdrawing and 
use this information in a sensitivity analysis. To minimize missing data, all surveys will be 
checked right after completion. If needed, calls will be made to participants to complete missing 
data over the phone. For individuals who miss a study visit, RAs will call at least three times 
(morning/afternoon/evening) over the next week to try rescheduling the assessment. 
 
Our second line of defense is to apply data analysis strategies that are as robust as possible to 
data losses.[54] Seeing that no universally accepted method exists for handling missing data, we 
will initially perform intent-to-treat analyses. We then will perform sensitivity analyses to evaluate 
the robustness of our results, including compete-case analysis, single imputation methods, such  
as last-observation and baseline carry forward analyses, and multiple imputation analyses. To 
avoid reporting bias, we will register our trial with ClinicalTrials.gov and follow the CONSORT 
recommendations for reporting randomized trials of nonpharmacological interventions.[55]  
 
8.2.3 Sample Size Considerations: Our sample size is based on our primary outcome of PCI 
using the FACT-Cog immediately post-treatment. Since the primary outcome is continuous, we 
powered our trial using a t-test to detect the difference between two independent means for 
score at post-treatment. This is a conservative way to estimate sample size since the 
longitudinal analysis using the mixed-effects model specified in the analysis plan will provide 
greater power than a t-test. With power of 0.8 and two-sided alpha of 0.05, we will need at least 
62 participants per treatment group and 124 in total to detect an effect size of 0.5.  
 
9. RISKS, BENEFITS, RISK/BENEFIT RATIO 
9.1. Potential Risks and Protection against Risks: Although the risks associated with 
participation in the proposed study are minimal, all potential risks that might occur as a result 
of participation will be detailed in an informed consent form and will also be fully discussed 
with each subject prior to enrollment.  
Confidentiality Risks: Information about study participants will be kept confidential and 
managed according to the requirements of HREB and RPAC. The use of Zoom and Qualtrics 
adhere to confidentiality standards that protect participant anonymity.  
Risk of psychological discomfort: It is possible that participants may be upset by some of the 
questions or by their performance on the neurocognitive testing. If the participant 
demonstrates clinically significant distress, he or she will be referred for psychosocial 
counseling. Dr. Garland, the PI, is a registered clinical psychologist and has extensive clinical 
experience in treating physical and psychological distress related to cancer or cancer 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
therapy. During the study period, if the research staff identifies any patients who are 
psychologically distressed they will notify Dr. Garland immediately to facilitate appropriate 
evaluation and treatment. 
9.2. Potential Benefits: 
Participants may experience an improvement in their insomnia and/or other cancer-related 
co-morbidities (e.g. cognition, fatigue, mood disturbance). Improving insomnia and other 
problematic symptoms often leads to an improvement in overall physical and emotional well-
being.  
10. DATA HANDLING AND RECORD KEEPING 
10.1. Confidentiality 
Information about study participants will be kept confidential and managed according to the 
requirements of the Tri-Council Policy Statement on Ethical Conduct for Research Involving 
Humans 2 (TCPS2) and will adhere to the Memorial University Policy on Ethics of Research 
Involving Human Participants.  
Data from the online assessments will be downloaded from Qualtrics and stored on a secure 
and locked drive. Information collected from the video-conference assessments will be stored 
in a locked office in the Department of Psychology at Memorial University of Newfoundland. 
Dr. Sheila Garland is the person responsible for keeping it secure. Information collected 
during the COVID-19 pandemic will be stored in a sealed envelope in a secure room in the 
research coordinator’s home. Only the research coordinator will have access to this. Upon 
returning to the lab, these documents will be transferred to the secure locked office in the 
Department of Psychology at Memorial University of Newfoundland.  
Use of Zoom Video-Conferencing: Communication (CBT-I intervention, assessments) via 
Zoom will be kept confidential as Zoom is a secure and confidential video platform. Zoom 
offers end-to-end encryption which is an added layer of application security that prevents 
third-parties from accessing data while it's transferred from one end system or device to 
another. Zoom can encrypt all presentation content at the application layer using TLS 1.2 
with Advanced Encryption Standard (AES) 256-bit algorithm. Zoom sessions will be recorded 
for quality assurance and treatment fidelity and deleted immediately after review.                                                 
Use of Qualtrics Online Survey Tool: Assessments from Qualtrics will be kept confidential as 
Qualtrics is ISO 27001 certified with industry standard encryption. They have been approved 
by security compliance and health information protection such as FedRAMP and HIPAA. 
Qualtrics’ servers are protected by high-end firewall systems, and scans are performed 
regularly to ensure that any vulnerabilities are quickly found and patched. All data collected 
from this study will be stored in Canada in Qualtrics’ Toronto data centre. 
In the event that a subject revokes authorization to collect or use personal health information, 
the investigator, by regulation, retains the ability to use all information collected prior to the 
revocation of subject authorization.  

Memorial University of Newfoundland 
 
May 30th, 2023  
 
There are not currently plans to destroy the data. The data will be kept in a password protected 
and encrypted file and all identifiers will be stripped after completion of the trial. 
11. TRIAL STEERING COMMITTEE:  
 
We will convene a Trial Steering Committee (TSC) that consists of an independent chair and at 
least two other independent members, the nominated principal applicant, and the patient 
collaborator in the project. The TSC will meet quarterly throughout the study period to review: 1) 
the study protocol and any amendments and deviations: 2) rates of recruitment and retention; 3) 
any adverse events; 4) completeness of data collected; and 5) any other organizational 
problems or trial issues. The TSC will meet on an as needed basis to discuss adverse events, 
serving as the data safety monitoring board (DSMB). We deemed the TSC an appropriate 
DSMB given that adverse events associated with CBT-I are rare. 
12. STUDY FINANCES 
12.1. Funding Source 
This study is supported by a grant from Canadian Institutes of Health Research (CIHR). 
12.2. Conflict of Interest 
None of the study investigators have any conflicts of interest to disclose.  
12.3 Subject Stipends or Payments 
To encourage retention and adherence to the study procedures, each participant will be paid 
$100 in total if in the immediate treatment group or $140 in total if in the delayed treatment 
group ($20 per assessment). The participants will be given a choice to receive one of the four 
following e-gift-cards: Amazon, Tim Hortons, Home Hardware, or Esso. Each gift-card is 
available online and will be delivered to the participants through e-mail. A number of participants 
have peers who may be eligible for the study and we will compensate participants for their 
referrals. To compensate participants for their time and effort, they will receive an additional $10 
to their gift cards for each eligible person they refer to the study and can receive a maximum of 
$20 (2 referrals).  
13. PUBLICATION PLAN 
The Principal Investigator will be responsible for publishing the primary results of this study. All 
subsequent publications will be at the discretion of the Principal Investigator. 
14. AMENDMENTS 
May 2023 – Increased sample size to 130 participants; added recruitment of qualitative exit 
interviews after trial completion.  
May 2021 – Added study invitation mailout letters to patients from Atlantic Path study. 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
October 2020 – Eligibility criteria adjusted to allow individuals who have finished their cancer 
treatments 6 months prior to participate; added adverse event questionnaire at mid- and post-
treatment.  
September 2020 - Removal of participants wearing actigraphy watches (due to COVID-19).  
June 2020 – Increased referrals from all Atlantic provinces instead of only Newfoundland and 
Labrador.  
December 2019 – Added new recruitment strategy (local media and newspaper); added 
treatment fidelity (adherence, competence, etc.) as a component of the trial.  
October 2019 – Added eligibility criteria for participants with hematological malignancies. 
 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
15. REFERENCES 
1. 
Aaronson, N.K., et al., The European Organization for Research and Treatment of 
Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in 
oncology. Journal of the National Cancer Institute, 1993. 85(5): p. 365-376. 
2. 
Savard, M.H., et al., Empirical validation of the Insomnia Severity Index in cancer 
patients. Psychooncology, 2005. 14(6): p. 429-41. 
3. 
Janelsins, M.C., et al., Prevalence, mechanisms, and management of cancer-related 
cognitive impairment. International Review of Psychiatry, 2014. 26(1): p. 102-113. 
4. 
Joly, F., et al., Impact of Cancer and Its Treatments on Cognitive Function: Advances in 
Research From the Paris International Cognition and Cancer Task Force Symposium 
and Update Since 2012. J Pain Symptom Manage, 2015. 50(6): p. 830-41. 
5. 
Argyriou, A.A., et al., Either called "chemobrain" or "chemofog," the long-term 
chemotherapy-induced cognitive decline in cancer survivors is real. J Pain Symptom 
Manage, 2011. 41(1): p. 126-39. 
6. 
Argyriou, A.A., et al., Destructive cervical spine osteoblastoma at C5 in a young patient 
initially presenting with quadriparesis: case report and review of the literature. J Emerg 
Med, 2013. 44(1): p. e1-4. 
7. 
Savard, J. and M.H. Savard, Insomnia and cancer: Prevalence, nature, and non-
pharmacological treatment strategies. Sleep medicine clinics, 2013. 8: p. 373-387. 
8. 
Palesh, O., et al., Sleep disruption in breast cancer patients and survivors. Journal of the 
National Comprehensive Cancer Network, 2013. 11(12): p. 1523-1530. 
9. 
Palesh, O.G., et al., Prevalence, demographics, and psychological associations of sleep 
disruption in patients with cancer: University of Rochester Cancer Center-Community 
Clinical Oncology Program. J Clin Oncol, 2010. 28(2): p. 292-8. 
10. 
Savard, J., et al., Natural course of insomnia comorbid with cancer: an 18-month 
longitudinal study. J Clin Oncol, 2011. 29(26): p. 3580-6. 
11. 
Garland, S.N., et al., A qualitative examination of the factors related to the development 
and maintenance of insomnia in cancer survivors. Palliat Support Care, 2018: p. 1-6. 
12. 
Fleming, L., S. Gillespie, and C.A. Espie, The development and impact of insomnia on 
cancer survivors: a qualitative analysis. Psychooncology, 2010. 19(9): p. 991-6. 
13. 
Heins, M.J., et al., For which health problems do cancer survivors visit their General 
Practitioner? European Journal of Cancer, 2013. 49(1): p. 211-218. 
14. 
Daley, M., et al., The economic burden of insomnia: direct and indirect costs for 
individuals with insomnia syndrome, insomnia symptoms, and good sleepers. Sleep, 
2009. 32(1): p. 55-64. 
15. 
Daley, M., et al., Insomnia and its relationship to health-care utilization, work 
absenteeism, productivity and accidents. Sleep Med, 2009. 10(4): p. 427-38. 
16. 
Gonzalez, B.D., et al., Cancer survivors in the workplace: sleep disturbance mediates 
the impact of cancer on healthcare expenditures and work absenteeism. Support Care 
Cancer, 2018. 
17. 
Banks, S. and D.F. Dinges, Behavioral and physiological consequences of sleep 
restriction. J Clin Sleep Med, 2007. 3(5): p. 519-28. 
18. 
Hartman, S.J., et al., Lifestyle factors associated with cognitive functioning in breast 
cancer survivors. Psychooncology, 2015. 24(6): p. 669-75. 
19. 
Caplette-Gingras, A., et al., Is insomnia associated with cognitive impairments in breast 
cancer patients? Behav Sleep Med, 2013. 11(4): p. 239-57. 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
20. 
Von Ah, D. and E.F. Tallman, Perceived cognitive function in breast cancer survivors: 
evaluating relationships with objective cognitive performance and other symptoms using 
the functional assessment of cancer therapy-cognitive function instrument. J Pain 
Symptom Manage, 2015. 49(4): p. 697-706. 
21. 
Xu, S., et al., Cognition, quality-of-life, and symptom clusters in breast cancer: Using 
Bayesian networks to elucidate complex relationships. Psychooncology, 2018. 27(3): p. 
802-809. 
22. 
Morgenthaler, T., et al., Practice parameters for the psychological and behavioral 
treatment of insomnia: an update. An american academy of sleep medicine report. 
Sleep, 2006. 29(11): p. 1415-9. 
23. 
Qaseem, A., et al., Management of Chronic Insomnia Disorder in Adults: A Clinical 
Practice Guideline From the American College of Physicians. Ann Intern Med, 2016. 
165(2): p. 125-33. 
24. 
Edinger, J.D., et al., Cognitive behavioral therapy for treatment of chronic primary 
insomnia: a randomized controlled trial. JAMA, 2001. 285(14): p. 1856-1864. 
25. 
Edinger, J.D., et al., Cognitive behavioral therapy for patients with primary insomnia or 
insomnia associated predominantly with mixed psychiatric disorders: a randomized 
clinical trial. Sleep, 2009. 32(4): p. 499-510. 
26. 
Morin, C.M., et al., Behavioral and pharmacological therapies for late-life insomnia: a 
randomized controlled trial. JAMA, 1999. 281(11): p. 991-999. 
27. 
Morin, C.M., et al., Cognitive behavioral therapy, singly and combined with medication, 
for persistent insomnia: a randomized controlled trial. JAMA, 2009. 301(19): p. 2005-15. 
28. 
Johnson, J.A., et al., A systematic review and meta-analysis of randomized controlled 
trials of cognitive behavior therapy for insomnia (CBT-I) in cancer survivors. Sleep Med 
Rev, 2016. 27: p. 20-8. 
29. 
Fleming, L., et al., Does cognitive behaviour therapy for insomnia reduce clinical levels 
of fatigue, anxiety and depression in cancer patients? Psychooncology, 2014. 23(6): p. 
679-684. 
30. 
Savard, J. and I. Ivers, Insomnia and subjective cognitive impairments in cancer 
patients: A prospective analysis., in International Cognition and Cancer Taskforce 
Conference. 2014: Seattle, WA. 
31. 
Quesnel, C., et al., Efficacy of cognitive-behavioral therapy for insomnia in women 
treated for nonmetastatic breast cancer. J Consult Clin Psychol, 2003. 71(1): p. 189-200. 
32. 
Ritterband, L.M., et al., Initial evaluation of an Internet intervention to improve the sleep 
of cancer survivors with insomnia. Psychooncology, 2012. 21(7): p. 695-705. 
33. 
Zachariae, R., et al., Internet-Delivered Cognitive-Behavioral Therapy for Insomnia in 
Breast Cancer Survivors: A Randomized Controlled Trial. J Natl Cancer Inst, 2018. 
110(8): p. 880-887. 
34. 
Vardy, J., et al., Cancer and cancer-therapy related cognitive dysfunction: an 
international perspective from the Venice cognitive workshop. Annals of Oncology, 2008. 
19(4): p. 623-629. 
35. 
Mols, F., et al., Long-term cancer survivors experience work changes after diagnosis: 
results of a population-based study. Psychooncology, 2009. 18(12): p. 1252-1260. 
36. 
Canadian Cancer Society’s Advisory Committee on Cancer Statistics, Canadian Cancer 
Statistics 2015. 2015: Toronto, ON. 
37. 
Carroll, C., et al., A conceptual framework for implementation fidelity. Implementation 
Science, 2007. 2(1): p. 40. 

Memorial University of Newfoundland 
 
May 30th, 2023  
 
38. 
Devilly, G.J. and T.D. Borkovec, Psychometric properties of the credibility/expectancy 
questionnaire. Journal of Behavior Therapy and Experimental Psychiatry, 2000. 31(2): p. 
73-86. 
39. 
Jacobs, S.R., et al., Evaluation of the functional assessment of cancer therapy cognitive 
scale with hematopoietic stem cell transplant patients. Journal of Pain and Symptom 
Management, 2007. 33(1): p. 13-23. 
40. 
Wagner, L.I., et al., Measuring Patient Self-Reported Cognitive Function: Development 
of the Functional Assessment of Cancer Therapy - Cognitive Function Instrument. The 
Journal of Supportive Oncology, 2009. 7: p. W32-W39. 
41. 
Cheung, Y.T., et al., Minimal clinically important difference (MCID) for the functional 
assessment of cancer therapy: cognitive function (FACT-Cog) in breast cancer patients. 
Journal of Clinical Epidemiology, 2014. 67(7): p. 811-820. 
42. 
Carney, C.E., et al., The consensus sleep diary: standardizing prospective sleep self-
monitoring. Sleep, 2012. 35(2): p. 287-302. 
43. 
Wefel, J.S., et al., International Cognition and Cancer Task Force recommendations to 
harmonise studies of cognitive function in patients with cancer. The Lancet Oncology, 
2011. 12(7): p. 703-708. 
44. 
Crum, R.M., et al., Population-based norms for the Mini-Mental State Examination by 
age and educational level. Jama, 1993. 269(18): p. 2386-91. 
45. 
Brandt, J. and R. Benedict, Hopkins Verbal Learning Test-Revised: Professional Manual. 
2001, Florida: PAR. 
46. 
Lezak, M.D., D.B. Howieson, and D.W. Loring, eds. Neuropsychological Assessment. 
4th ed. ed. 2004, Oxford University Press: New York, NY. 
47. 
Fink, H.A., et al., AHRQ Technology Assessments, in Cognitive Outcomes After 
Cardiovascular Procedures in Older Adults: A Systematic Review. 2014, Agency for 
Healthcare Research and Quality (US): Rockville (MD). 
48. 
Bartels, C., et al., Practice effects in healthy adults: a longitudinal study on frequent 
repetitive cognitive testing. BMC Neuroscience, 2010. 11(1): p. 118. 
49. 
Loughan, A.R., S.E. Braun, and A. Lanoye, Executive dysfunction in neuro-oncology: 
Behavior Rating Inventory of Executive Function in adult primary brain tumor patients. 
Appl Neuropsychol Adult, 2019: p. 1-10. 
50. 
Reilly, M.C., A.S. Zbrozek, and E.M. Dukes, The validity and reproducibility of a work 
productivity and activity impairment instrument. PharmacoEconomics, 1993. 4(5): p. 
353-365. 
51. 
Stein, K.D., et al., Further validation of the multidimensional fatigue symptom inventory-
short form. J Pain Symptom Manage, 2004. 27(1): p. 14-23. 
52. 
Bjelland, I., et al., The validity of the Hospital Anxiety and Depression Scale. An updated 
literature review. Journal of psychosomatic research, 2002. 52(2): p. 69-77. 
53. 
Little, R.J., et al., The design and conduct of clinical trials to limit missing data. Statistics 
in Medicine, 2012. 31(28): p. 3433-3443. 
54. 
Little, R.J., et al., The prevention and treatment of missing data in clinical trials. The New 
England Journal of Medicine, 2012. 367(14): p. 1355-1360. 
55. 
Boutron, I., et al., Extending the CONSORT statement to randomized trials of 
nonpharmacologic treatment: explanation and elaboration. Ann Intern Med, 2008. 
148(4): p. 295-309.