Living With Colorectal Cancer: Patient and Caregiver Experience
Conditions: Colorectal Cancer
Sponsor: University of Calgary

 
 
 
 
Living with Colorectal Cancer: 
Patient and Caregiver Experience 
 
Principal Investigators 
Lead site 
Calgary, AB 
Aynharan Sinnarajah MD 
Assistant Professor, Division of Palliative Medicine 
Department of Oncology, Cumming School of 
Medicine, University of Calgary 
1331 29th St NW 
Calgary, AB, Canada T2N 4N2 
(403) 944-2304 
Jessica Simon MB ChB, FRCPC 
Division Head and Clinical Assistant Professor 
Division of Palliative Medicine 
University of Calgary 
Room 710 South Tower 
1403 29 St NW 
Calgary, AB, Canada T2N 2T9 
(403) 944-2304 
Principal Investigator 
Participating site 
Edmonton, AB 
Sharon Watanabe, MD, FRCPC 
Professor and Director, Division of Palliative Care Medicine 
Department of Oncology, Faculty of Medicine and Dentistry 
University of Alberta 
Director, Department of Symptom Control and Palliative 
Care 
Cross Cancer Institute 
11560 University Avenue, Room 2001 
Edmonton, AB, Canada T6G 1Z2 (780) 
432-8266 
Co-Investigators 
Patricia Tang 
Marc Kerba 
Peter Faris 
Winson Cheung 
Hubert Marr 
Lyle Galloway 
Yoko Tarumi 
Xiaofu Zhu 
Lisa Shirt 
Safiya Karim 

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GENERAL INFORMATION 
 
Name and addresses of the clinical sites and/or other institutions involved in the study 
1. Cross Cancer Institute 
2001 11560 University Ave 
Edmonton, AB, Canada T6G 1Z2 
2. Tom Baker Cancer Centre 
1331 29 St NW 
Calgary, AB, Canada T2N 4N2 
3. Holy Cross Centre 
2210 2 St SW 
Calgary, AB, Canada T2S 3C3 
 
 
 
Study Summary 
 
Title 
Living with Colorectal Cancer: Patient and Caregiver Experience 
Short title 
Living with Colorectal Cancer 
 
Source of financial 
support 
Canadian Institutes of Health Research (CIHR) Partnerships for Health 
System Improvement for Cancer Control Operating Grant “Palliative 
Care Early and Systematic (PaCES): Impact on Patient and Health 
System Outcomes” 
Protocol Number 
HREBA.CC-17-0429 
Methodology 
Interrupted Time Series (ITS) 
Study Duration 
January 2018 through December 2021 
 
Study Center(s) 
1. Cross Cancer Institute- Edmonton, Alberta, Canada 
2. Tom Baker Cancer Centre- Calgary, Alberta, Canada 
3. Holy Cross Centre- Calgary, Alberta, Canada 
 
 
Objectives 
This observational study will gather outcome and experience data of 
patients living with advanced colorectal cancer and their caregivers. 
The primary objective is to measure how quality of life in this 
population changes over time (before, during, and after a palliative 
pathway becomes the new standard of care in Alberta). 
Number of Subjects 
 
 
 
 
 
Up to 1000 (patients and caregivers combined) 
 
 
 
 
 
 

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Diagnosis and Main 
Inclusion Criteria 
 
>18 years of age with diagnosis of advanced colorectal cancer and one 
or more of the following: 
 
• Failed first line of chemotherapy (disease progression on 
imaging) 
• Unable to receive first line chemotherapy 
• Surprise question: healthcare provider would not be surprised 
if patient died in the next 12 months 
• High symptom need (any score on ESAS-r ≥ 7) 
(Advanced Colorectal Cancer (aCRC) is defined as primary or 
metastatic cancer that is unlikely to be cured, controlled, or put into 
remission with treatment) 
 
Caregivers of patients who meet inclusion criteria/exclusion criteria 
may be invited by the patient to participate 
 
Duration of 
administration 
Recruitment begins January 2018. Enrollment interview to take 
approximately 60 minutes with follow up questionnaire completion 
taking 20 minutes for patient and 45-60 minutes for caregiver 
periodically through December 2020. 

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Table of Contents 
STUDY SUMMARY ................................................................................................................................................ 2 
1. BACKGROUND .................................................................................................................................................. 6 
2. STUDY OBJECTIVES .......................................................................................................................................... 6 
3. METHODS ....................................................................................................................................................... 7 
3.1 STUDY DESIGN .............................................................................................................................................................................................. 7 
3.2 SELECTION AND WITHDRAWAL OF SUBJECTS .............................................................................................................................................. 7 
3.2.1 Inclusion/exclusion ...................................................................................................................................... 7 
3.2.2 Subject Withdrawal ..................................................................................................................................... 8 
3.3 PROCEDURES ................................................................................................................................................................................................ 8 
3.3.1. Recruitment and Informed Consent ........................................................................................................... 8 
3.3.2 Study Instruments ..................................................................................................................................... 12 
3.3.3 Baseline/Enrollment .................................................................................................................................. 13 
3.3.4 Enrollment Chart Abstraction .................................................................................................................... 13 
3.3.5 Follow Up .................................................................................................................................................. 14 
3.4 OUTCOME MEASURES ................................................................................................................................................................................ 15 
3.5 DURATION ................................................................................................................................................................................................... 16 
3.6 DATA LINKAGE ............................................................................................................................................................................................ 16 
4. SAMPLE POPULATION FOR ANALYSIS ............................................................................................................ 16 
4.1 SAMPLE SIZE ................................................................................................................................................................................................ 16 
4.2 DATA ANALYSIS .......................................................................................................................................................................................... 16 
5. ETHICAL CONSIDERATIONS ............................................................................................................................ 17 
5.1 RISK/BENEFITS ........................................................................................................................................................................................... 17 
6. DATA HANDLING AND RECORD KEEPING ....................................................................................................... 18 
7. SUPPLEMENTS ............................................................................................................................................... 19 

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List of Abbreviations 
 
aCRC 
Advanced Colorectal Cancer 
ACP 
Advance Care Planning 
AHS 
Alberta Health Services 
CRF 
Case Report Form 
CRC 
Colorectal Cancer 
ESASr 
Edmonton Symptom Assessment System-Revised 
GCD 
Goals of Care Designation 
HREBA-CC 
Health Research Ethics Board of Alberta-Cancer Committee 
ITS 
Interrupted Time Series 
PaCES 
Palliative Care Early and Systematic 
PPF 
Putting Patients First 
PREMs 
Patient Reported Experience Measures 
PROMs 
Patient Reported Outcome Measures 

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1. Background 
 
Patients and families living with advancing cancer experience distress when transitioning from 
active cancer treatment to palliative care.1 Late or no palliative care is associated with lower 
quality of life, higher caregiver distress, and more aggressive and costly end of life care.2,3,4 In 
Calgary, typical of other Canadian centres, 60% of patients with metastatic gastrointestinal 
cancers have a late (< 3 months from end of life) or no palliative care referral (i.e. no contact 
with any palliative care service/provider).5 This lack of timely and early palliative care is 
associated with aggressive cancer care in 50% of patients, as compared to 25% in those who 
received earlier palliative care. 
 
A Knowledge to Action initiative called Palliative Care Early and Systematic (PaCES) has 
identified gaps in providing early and systematic palliative care to advanced colorectal cancer 
(aCRC) patients. To address these gaps, a comprehensive care pathway delivering early, 
systematic palliative care to aCRC patients in Alberta will be developed as a new standard of 
care. The pathway will be implemented first in Calgary, with Edmonton as control site, to allow 
for testing and refinement before dissemination to Edmonton and across Alberta. As a result of 
the development of this new care pathway, over the next 3 years changes are anticipated in the 
delivery of care for aCRC patients. 
 
The purpose of this study is to measure outcomes and experiences of aCRC patients and their 
caregivers during these transformative health system changes. Patient and caregiver data 
collected continuously over this time will monitor how changes in cancer care delivery impact 
patients, and will provide periodic feedback to guide further quality improvement. 
 
 
2. Study Objectives 
 
The purpose of this current study is to better understand, guide improvements, and monitor 
outcomes of patients and their caregivers facing aCRC. Input on patient and caregiver reported 
outcome measures (PROMs) and patient and caregiver reported experiences measures (PREMs) 
from aCRC patients and their caregivers will be sought in order to explore how quality of life 
changes before, during, and after a palliative pathway becomes the new standard of care in 
Alberta. 

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3. Methods 
 
3.1 Study Design 
 
An observational cohort study with interrupted time series (ITS) data collection will be used to 
collect PROM and PREM data from aCRC patients and their caregivers over a 36 month period. 
ITS is a powerful method for evaluating change at a population level. The ITS method will allow 
us to assess secular trends, determine if there is evidence of serial dependencies in the monthly 
measures, and to compare measures following system changes in Calgary while observing the 
same measures over the same time periods in Edmonton. 
 
3.2 Selection and Withdrawal of Subjects 
 
3.2.1 Inclusion/exclusion 
 
For three years, all aCRC patients at Cross Cancer Institute (Edmonton), Tom Baker Cancer 
Centre (Calgary) and Holy Cross Centre (Calgary) will be screened and invited by their oncology 
healthcare providers to join the patient outcome and experience data collection. A caregiver, 
identified by each enrolled patient, may be invited to participate. For the purposes of this 
study, caregivers are defined as family or friends who provide unpaid assistance with tasks such 
as transportation and personal care. Advanced Colorectal Cancer (aCRC) is defined as primary 
or metastatic cancer that is unlikely to be cured, controlled, or put into remission with 
treatment. 
 
 
Inclusion criteria: 
 
All aCRC patients > 18 years with one or more of the following: 
1) Failed first-line chemotherapy (disease progression on imaging); 
2) Unable to receive first-line chemotherapy; 
3) High symptom need (any score on the Edmonton Symptom Assessment System 
Revised (ESASr) ≥ 7);6 
4) Surprise question: In the opinion of a healthcare provider, would not be surprised 
if the patient died in the next 12 months. 
 
Caregivers of patients who meet inclusion/exclusion criteria may be invited to participate. 

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Exclusion criteria: 
 
A participant deemed inappropriate by clinic staff to be approached for an outcomes study for 
any reason (for example, in crisis). 
 
3.2.2 Subject Withdrawal 
 
Participation in the study is voluntary. Participants will be advised that they can stop the study 
at any time and will not be required to give a reason for withdrawal. If a participant withdraws 
from the study, he/she will be offered an opportunity to withdraw both him/herself and any 
data gathered this far, or him/herself alone. These options will be made clear to the 
participant. If a participant chooses to withdraw both him/herself AND his/her data, any digital 
or paper files will be deleted/shredded, and excluded from the analysis. Data withdrawal can 
only be done up to the point of analysis. 
 
3.3 Procedures 
 
3.3.1. Recruitment and Informed Consent 
 
Potential participants will be recruited from outpatient clinics at Tom Baker Cancer Centre, Holy 
Cross Centre, and Cross Cancer Institute. A poster/leaflet (Appendix A) will be posted in or near 
the clinics included in the study to advise potential participants about the study and provide 
contact information. Inclusion/exclusion criteria will be provided on a laminated card to the 
clinic staff (Appendix B). Study staff will use the EMR (electronic medical record) to prescreen 
for patients who may be eligible for the study based on the inclusion criteria. Patients 
determined by the clinic staff to meet these criteria will be approached by clinic staff who may 
briefly introduce the study or give them a one-page information poster/leaflet (Appendix A). 
The clinic staff will ask permission for study staff, who will be present in or near the clinic, to 
approach the patient and discuss their possible participation. If patients give permission for 
study staff to speak to them, study staff will introduce the study and give the poster/leaflet 
(Appendix A) to patients who have not received the leaflet from the clinic nurse. 
 
If patients advise clinic staff that they would like to be contacted at a later time, they will be 
asked to complete a consent to provide their contact information to study staff (Appendix C). 
Clinic staff will then provide this information to study staff. Study staff will phone the patient, 
explain the study, give an opportunity to ask questions and then ask if he/she is interested in 
participating in the study. If a participant is interested, arrangements will be made to meet the 
participant at a future clinic appointment. 

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A trained member of the study team will complete the consenting process and enrollment 
questionnaires in a quiet place in or near the clinic. Enrollment will take place on the clinic day 
or shortly thereafter at a time convenient for the participant. The study staff will apply the 
remaining inclusion/exclusion criteria (Appendix D). Study staff will review the consent form 
(Appendix E) with all patient participants. If any participant refuses to give consent, he/she will 
not participate in the study. A consented patient participant may also name a caregiver (friend 
or family) to participate in the study. The informed consent form for caregivers will be reviewed 
and signed by the caregiver if interested (Appendix F). Alternatively, the consent form may be 
mailed, and the consenting process take place over the phone. The enrollment interview and 
surveys will be scheduled to take place by phone or in person once the signed consent is 
received. 
 
To accommodate extenuating circumstances due to the COVID-19 pandemic, the consent 
process may take place exclusively over the phone. Patients will be approached by clinic staff 
during their appointment to determine if they are interested in participating in the study. 
Interested patients will complete a consent to contact form or provide verbal consent to allow 
study staff to contact them at a later date. Study staff will contact patients by phone and either 
email or mail the consent form to them. Study staff will then review each section of the consent 
form with the patient over the phone, answering any questions along the way. Study staff will 
make note of telephone consent on the consent form and initial to confirm. The patient will 
sign his/her copy of the consent from and mail or scan and email it back. Participants will 
receive a copy of the completed consent form either by email or mail, whichever they prefer. If 
the patient identifies a caregiver (friend or family) to participate in the study and they are 
interested, telephone consent will be obtained in the same manner mentioned above.  
 
Adult patient participants without capacity will still be considered for the study. The healthcare 
provider screening patients for potential enrollment will indicate whether or not the patient 
has capacity to consent. For individuals lacking capacity, the authorized third party (e.g. 
substitute decision maker named on an enacted personal directive) will be approached. Assent 
will not be sought from the patient; however, expression of dissent will be respected. The 
substitute decision maker may consent to the study on behalf of the patient. See section 3.3.3 
for the information/surveys that will be collected for participants without capacity. If a patient 
regains capacity during the study, the substitute decision maker’s consent will end. The 
substitute decision maker will be asked to agree to contact the study team, or study doctor, if 
the patient regains capacity, at which time the patient will be asked to provide consent on 
his/her own behalf. Caregivers without capacity will not be considered for this study. 
 
 
 

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ActionDignity of Calgary* will provide study material translation to ensure that language is 
not a barrier to inclusion in this study. The forms translated by ActionDignity will include an 
attestation (Appendix Q and R) from a translator certifying that the translated forms 
accurately reflect the approved English forms. The EQ-5D-5L is available in translated versions 
through a licensing agreement with the Alberta PROMs and EQ-5D Research and Support Unit 
(APERSU). If there is a language requested for which there is not a complementary EuroQol-
approved translated version of the EQ-5D-5L, RAs will not administer the EQ to the 
participant. EQ will not be administered in English when all other surveys for the participant 
are administered in their preferred/ non-English language. The ESAS-r is available in 
translated versions through an agreement with Cancer Care Ontario. The EQ-5D-5L and ESAS-
r translated versions will not be accompanied by an attestation. The study consenting process 
will be completed in person with the study participant using the AHS language line and 
translated consent forms. The study team member who is present during the consenting 
conversation will sign as a witness and document the use of the interpreter, including the 
interpreter name, on the consent form. The actual signature of the language line interpreter 
will be waived. Family members or friends will not serve as the primary interpreter. 
Translated consent, recruitment forms, and follow up survey forms in the most commonly 
represented languages are available in the Appendix (Appendices T1-T13). If the recruit 
requests a language that is not currently available, Action Dignity of Calgary will be contacted 
for translation and the newly translated forms will then be submitted as a future ethics 
amendment. Preferred survey follow-up for non-English speaking participants will be via post. 
Online follow up forms will not be available in languages other than English. 
 
If a participant includes comments in the free-text area of the surveys written in another 
language, study staff who are on the ethics application and are fluent in that particular 
language will be contacted to assist with translation. 
 
*ActionDignity of Calgary (formerly Ethno-Cultural Council of Calgary) is a community- 
based organization that facilitates the collective voice of Calgary’s ethno-cultural communities 
towards full civic participation and integration through collaborative action. 
 
 
 
 
 
 
 
 
 

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Figure 1 (study flowchart) outlines the screening and enrollment process and participants’ flow 
 
Figure 1. Study flowchart. 
 

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3.3.2 Study Instruments 
 
We have selected patient related outcome measures that are or will be in routine use in cancer 
centers in Alberta. This will be a sustainable source of quality improvement data beyond the 
course of this study. Currently the Advance Care Planning (ACP) Tracking Record is used to 
document conversations about care preferences. Putting Patients First with ESAS-r7 is used 
routinely at every cancer clinic visit across Alberta and will be digitally recorded by the middle 
of 2018. AHS is licensed to implement EQ-5D8,9 across all clinical sites. After the first 3 months 
of data collection, we will evaluate the instrument selection, frequency of data collection, and 
screening methods to determine if changes are required to enhance study feasibility. An ethics 
amendment will be requested for any changes. 
 
Putting Patients First (PPF) with ESAS-r (Appendix G): Includes the Edmonton Symptom 
Assessment System (revised), and the Canadian Problem Checklist and an “at peace” question. 
The PPF was previously known as the “Screening for Distress tool”. 
 
EQ-5D-5L (Appendix H): Descriptive system of health-related quality of life states consisting of 
five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each 
of which can take one of five responses. The responses record five levels of severity (no 
problems/slight problems/moderate problems/severe problems/extreme problems) within a 
particular EQ-5D dimension. 
 
The Preparedness for Caregiving Scale10,11 (Appendix I): A caregiver self-rated instrument that 
consists of eight items that asks caregivers how well-prepared they believe they are for multiple 
domains of caregiving. 
 
My Conversations (Appendix K): A questionnaire exploring an individual’s understanding of and 
satisfaction with discussions about Advance Care Planning and Goals of Care. 
 
Enrollment ECOG-Patient Language Adaption (Appendix L): Scale to measure a patient’s self- 
reported performance status, from which we will calculate the Eastern Cooperative Oncology 
Group score (ECOG) at enrollment. 
 
CaregiverVoice (Appendix S):  Survey exploring care experiences in the last 3 months of life 
administered to enrolled Caregiver of enrolled patient via mail 6-8 weeks after notification of 
death of enrolled patient. 
 
Patient Self-Administered Financial Effects- PSAFE (Appendix U):  Survey exploring patient and 
caregiver costs related to a diagnosis of cancer, administered to enrolled patient periodically.

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3.3.3 Baseline/Enrollment 
 
After consent is obtained, study staff will administer structured questionnaires to participants. 
The enrollment interview will take approximately 60 minutes to complete. Patient 
questionnaires include Patient Enrollment Questionnaire Case Report Form (CRF), Putting 
Patients First/ESAS-r, EQ-5D-5L, My Conversations, Enrollment ECOG, and Participant Contact 
Form. Caregiver questionnaires include Caregiver Enrollment Questionnaire, Preparedness for 
Caregiving Scale, EQ-5D-5L, and Participant Contact Form. 
 
The enrollment questionnaire for patient participants (Appendix M) will include various 
demographic questions such as age, gender, marital status, education, race, religion, language, 
income categories and where the participant is living. The enrollment questionnaire for 
caregivers will include similar information and also their relationship to the patient, and if 
caregiver lives with the patient (Appendix O). 
 
Patients will be given the option of full or partial participation in the study. Full participation 
will include the enrollment questionnaires, disclosure of medical records, and follow up 
questionnaires. Partial participation will include the enrollment questionnaires, disclosure of 
medical records but will not include the follow up questionnaires. A substitute decision maker 
signing on behalf of a patient will complete only the Patient Enrollment Questionnaire on the 
patient’s behalf, and authorize the disclosure of medical records but will not complete the 
additional enrollment or follow-up questionnaires (Appendices G,H,J,K,or L) Caregivers will only 
have the option of full participation. 
 
Participants’ parking costs (if any) for the baseline/enrollment and follow up visits will be 
reimbursed. 
 
It is important to note that the data from this study will not be made available to clinicians to 
guide individual patient care. Participants will be informed in the consent form and with follow 
up contacts that their responses will not be reviewed by individuals not involved in the study 
e.g. their healthcare provider/team. If the participant would like them to know this 
information, they will be advised to additionally bring it to their healthcare provider’s attention. 
 
3.3.4 Enrollment Chart Abstraction 
 
Enrollment Chart Abstraction CRF (Appendix P): Information will be abstracted from the 
patient’s Electronic Medical Record and/or paper chart by the study staff and will be completed 

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on day of enrollment (or as soon as possible thereafter, using information closest to enrollment 
date). Guidance/training for chart abstraction may be provided by study clinicians. 
 
Information abstracted from clinic record at enrollment (Appendix P) will include Goals of Care 
Designation (GCD), ACP Tracking Record completion and diagnosis, metastasis sites, treatments 
and date/method of diagnosis. If a patient is unable to be contacted for a particular month, or if 
study team meets participant at a current clinic appointment, PPF/ESAS-r and EQ-5D-5L (if 
available) may be abstracted from the clinic record by the study team. 
 
3.3.5 Follow Up 
 
Patients will be surveyed by the study staff monthly (+/- 2 weeks, no less than 2 weeks between 
surveys) for 10 months and then every 3 months until death or the end of data collection 
(December 2020). Caregivers will be surveyed at enrollment, 1 month, then every 3 months 
until death of patient or end of data collection (December 2020). Following the notification of 
the death of a patient, the enrolled caregiver will be sent a condolence card. Study staff will 
receive confirmation of patient death from family members, enrolled caregivers or clinic staff. If 
a patient is unreachable after three attempts, study staff will check the patient’s EMR for a 
confirmation of death.  The CaregiverVoice survey (Appendix S) will be administered to the 
enrolled caregiver 6-8 weeks after notification of death of enrolled patient. This survey will be 
administered via post only and will be subsequently entered into the REDCap database by study 
staff. 
 
The patient/caregiver will select their method of follow up as online, by phone, or in person 
during a regularly scheduled clinic visit. The study staff will send an email link to participants 
who choose to complete assessments online via secure Research Electronic Data Capture 
(REDCap) link. If the participant prefers none of these choices, the study team will discuss other 
options (e.g. via post). Follow up questionnaires should take 20 minutes for the patient and 45- 
60 minutes for the caregiver to complete. After 3 attempts to contact a participant via phone, a 
follow up letter will be sent to the unreachable participant asking that they contact the study 
staff. If study staff receives no response to follow up letter the participant will be categorized as 
“lost to follow up”. If the patient is unreachable or declines a monthly follow up contact, the 
study staff will continue to abstract medical record information until the study staff is informed 
of patient withdrawal. 
 
Preferred survey follow-up for non-English speaking participants will be via post. Online follow 
up forms will not be available in languages other than English. 

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3.4 Outcome measures 
 
Objective 
Measurement construct 
Instrument 
PRIMARY 
Changes in EQ-5D-5L over time for 
patients and caregivers 
Patient: EQ-5D-5L (Appendix H) 
monthly for 10 months then 
every 3 months until death or 
end of data collection. 
Caregiver: EQ-5D-5L at 
enrollment, 1 month and every 
3 months until death of patient 
or end of data collection. 
SECONDARY 
Patterns of ESAS-r distress score 
observed over time 
Patient: Putting Patients First 
(PPF) ESAS-r (Appendix G) 
monthly for 10 months then 
every 3 months until death or 
end of data collection. 
Caregiver readiness for caregiving role 
Caregiver: 
Preparedness 
for 
Caregiving Scale (Appendix I) at 
enrollment, 1 month and every 
3 months until death of patient 
or end of data collection. 
Patients knowledge of their own GCD 
Designation 
Patient: “My Conversations” 
(Appendix K) at enrollment, 
then every month for 10 
months, then annually until 
death or end of data collection. 
Patient’s perceived engagement and 
satisfaction with ACP conversations 
Patient: “My Conversations” 
(Appendix K) at enrollment, 
then every month for 10 
months, then annually until 
death or end of data collection. 
# of patients with ACP Tracking Record 
discussions documented at enrollment 
Patient: Enrollment Chart 
Abstraction CRF (Appendix P) 
at enrollment 
 
Measurement of care experiences 
across multiple settings in the last 3 
months of life. 
Caregiver: CaregiverVoice 
(Appendix S) Administered to 
enrolled caregiver no sooner 
than 8 weeks after notification of 
death of enrolled patient. 

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3.5 Duration 
 
January 2018 through December 2021 
 
 
3.6 Data Linkage 
 
Concurrent with the Living with Colorectal Cancer outcomes study, the PaCES project will be 
collecting data on healthcare resource use by all aCRC patients (from diagnosis) using 
administrative databases from July 2011 until study end/death (separate study with separate 
ethics submission to be submitted). That data collection will begin at July 2011 for 
administrative data, January 2018 for clinical data and continue through December 2021. We 
are seeking consent from patients to pair their PROMS and PREMS data with that health 
resource utilization data. 
 
Study staff will also check the EMR (electronic medical record) periodically, to obtain the 
date of death, if applicable, for all enrolled patients. In addition to this, the study team will 
request death date data for all enrolled patients from CMORE, every 3 months in order to 
obtain information that is not available in the EMR. 
 
4. Sample population for analysis 
 
In each centre, approximately 120 patients per year are diagnosed and die with metastatic CRC. 
For the primary outcome, we will have 12 months of observation measures prior to system 
changes in Calgary (while observing the same measures over the same time periods in 
Edmonton) and an additional 24 months following the system change. We anticipate a total 
sample size of 840 (420 in each centre). We estimate that 60% of patients will consent to 
participate in data collection. We will have 84% power to detect a 20% improvement in our 
primary outcome using logistic regression, and 77% power to detect this improvement using ITS 
analysis. For secondary outcomes (e.g. symptom burden), we have similar power to detect 
clinically meaningful changes. 
 
4.1 Sample size 
 
Up to 1000 (patients and caregivers combined). 
 
 
 
 

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4.2 Data Analysis 
 
Descriptive statistics will be used to present the study variables. We will use means and 
standard deviations to summarize continuous measures that are approximately normal, and 
otherwise we will use medians and inter-quartile range. We will summarize binary and 
categorical variables as frequencies and proportions within a given period of time. Events that 
can occur more than once in a time period will be expressed as rates. ITS will be used to 
evaluate changes in service delivery that occur during the study timeframe. SAS (SAS Institute 
Inc., Cary, NC) version 9.3 will be used for all statistical analysis. 
 
5. Ethical Considerations 
 
This study will be conducted in compliance with the protocol approved by the Health Research 
Ethics Board of Alberta-Cancer Committee (HREBA-CC) and according to Good Clinical Practice 
standards. No deviation from the protocol will be implemented without the prior review and 
approval of the HREBA-CC except where it may be necessary to eliminate an immediate hazard 
to a research subject. In such case, the deviation will be reported to the HREBA-CC as soon as 
possible. 
 
All subjects with capacity will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in  
this study. Consent forms will be submitted with the protocol for review and approval by 
HREBA-CC (Appendices E and F). The formal consent of a subject, using the HREBA-CC approved 
consent form, will be obtained before that subject is submitted to any study procedure. This 
consent form will be signed by the subject and the investigator-designated research 
professional obtaining the consent. An authorized third party (e.g. substitute decision maker on 
an enacted personal directive) may consent to the study and sign the consent form on behalf of 
a patient without capacity. If the patient regains capacity during the study, the authorized third 
party‘s consent will end. The authorized third party will be asked to contact the study team, or 
study doctor, if the patient regains capacity, at which time the patient will be asked to provide 
consent on his/her own behalf. 
 
Patients and caregivers will be notified that their respective data will be linked to each other. 
 
5.1 Risk/Benefits 
 
Risks. There are no physical risks to study participants. The risk of emotional discomfort is 
minimal. Due to the nature of considering end-of-life care, the study may cause mild emotional 
distress in some participants. However, it is anticipated that patients who are uncomfortable 

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with the topic will not agree to participate to begin with. 
 
This potential risk is mitigated by two features of the study design. First, participants will be 
told that they may end their study participation at any time. They will also be told that they do 
not have to answer any questions that they do not feel comfortable with. Secondly, 
enrollment and administration of questionnaires will be structured; the study staff will follow 
a script with interview questions. The study staff will receive training about ethical conduct of 
studies involving human subjects, and be oriented to symptoms, treatment and potential 
issues in the relevant settings. Participants will be reminded that if they have concerns or are 
distressed to contact their health care provider. 
 
Benefits. Potential benefits to study participants include encouragement to talk about their 
health care experiences and concerns. The results of the study may help improve quality of care 
patients receive in the future. 
 
6. Data Handling and Record Keeping 
 
Participants will be assigned a unique study number as a subject in this study. Only this number 
will be used on any research-related information, including medical records, personal data, and 
research data collected during the course of this study, so that the participant’s identity will be 
kept confidential. Information that directly discloses a participant’s identity will remain only 
with the Principal Investigator and/or designate. Participants will not be identified by name in 
any reports of the completed study. 
 
A master subject identification list will be created to link study participant information with 
assigned study identification number. The list that matches names to the unique identifier that 
is used on research-related information will not be removed or released without consent unless 
required by law. Access to this master list will be approved only for researchers involved in the 
study. The master subject identification list and consent forms will be kept separate from the 
study data and will be kept in a locked cabinet in a locked office at the University of Calgary/ 
University of Alberta. Additionally, we will have a password protected electronic file of the 
master identification log housed in the University of Calgary’s Cumming School of Medicine 
Information Technologies Secure Computing Data Storage service, as well as firewalled AHS 
servers of the Principal Investigators. 
 
Answers for assessments will be entered into REDCap using University of Calgary/University of 
Alberta owned laptops. REDCap is a secure, web-based application locally hosted by the 
University of Calgary’s Clinical Research Unit. 
 

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All electronic data (e.g. digital files) will be uploaded and stored within a secure drive on a 
University of Calgary/University of Alberta encrypted and password protected computer (e.g. 
within the University of Calgary Cumming School of Medicine’s Information Technologies 
Secure Computing Data Storage Service), as well as firewalled AHS servers of the Principal 
Investigators. 
 
Access to study data will be restricted only to study personnel, and to authorized 
representatives from the University of Calgary, University of Alberta, and the HREBA-CC, who 
may review identifiable medical/clinical study records for quality assurance purposes. 
 
De-identified data will be shared with Canadian Partnership Against Cancer (CPAC) for the 
purposes of conducting the economic analysis (including analysis of PSAFE data). 
 
Retention. Participant consent forms, case report forms, interview notes, and the master 
subject identification list will be kept for 5 years from the end of the project to comply with 
federal regulations and to accommodate data validation queries. Study data may be 
transported and retained for long-term storage at a secure data repository owned by the 
University of Calgary called the High Density Library, located at the Spy Hill Campus, for the 
length of time specified by the ethics board before destruction. All files will be deleted using 
document shredding and deletion of any electronic files from the secure drives. 
 
Data collected from or about participants who pass away during the study will be used. 
 
 

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7. Supplements 
 
Appendix 
Title 
A 
Study Information poster-leaflet 
B 
Clinician’s inclusion/exclusion criteria checklist card and script 
C 
Consent-to-contact form 
D 
Inclusion/Exclusion Criteria Case Report Form 
E 
Informed Consent Form-Patient 
F 
Informed Consent Form-Caregiver 
G 
Putting Patients First (PPF) with ESAS-r and Canadian Problem Checklist 
H 
EQ-5D-5L Questionnaire 
I 
The Preparedness for Caregiving Scale 
K 
My Conversations Questionnaire 
L 
Enrollment ECOG-Patient Language Adaption 
M 
Patient Enrollment Questionnaire 
N 
Participant Contact Form 
O 
Caregiver Enrollment Questionnaire 
P 
Enrollment Chart Abstraction Case Report Form 
Q 
Translation Attestation form 
R 
Translation Attestation signature form 
S 
Caregiver Voice 
T  
Language Translations of Appendices applicable to participants (T1- T13) 
U 
Patient Self-Administered Financial Effects (PSAFE) 

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