Nurse Coach-Led Early Palliative Care for Older Adults With Chronic Obstructive Pulmonary Disease and Their Care Partners: The Project EPIC Pilot Randomized Controlled Trial
Phase: NA
Conditions: COPD
Sponsor: University of Alabama at Birmingham

ii 
PROTOCOL TITLE:  
THE PROJECT EPIC RANDOMIZED 
CONTROLLED TRIAL 
Study Protocol & Statistical Analysis Plan
Date of Last Protocol Approval: July 17, 2024 
NCT05040386 
Principal Investigator: Anand S. Iyer, MD, MSPH 
University of Alabama at Birmingham 
Birmingham, AL, USA 35294 

iii 
THE PROJECT EPIC 
RANDOMIZED CONTROLLED TRIAL 
UAB IRB Protocol Number: IRB-300007901 
Clinical Trials.gov Registration Number:  NCT05040386 
Principal Investigator: Anand S. Iyer, MD, MSPH 
Affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department 
of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA 
Sites: University of Alabama at Birmingham, Cooper Green Mercy Health Services 
Funding Source: National Institute on Aging 
Version Number: July 17, 2024

iv 
Table of Contents 
Section 
Page 
Statement of Compliance 
1 
1. Protocol Summary, Trial Schema, Timeline, Schedules
2 
2. Introduction
7 
3. Aims and Outcomes
11 
4. Study Design
12 
5. Study Population, Eligibility, Flow Diagram
14 
6. Study Intervention, Protocol, Enrollment, Procedures, Fidelity 
19
7. Intervention Discontinuation and Participant     
Discontinuation/Withdrawal
26
8. Study Assessments and Procedures
27 
9. Statistical Considerations
30 
10. Supporting Documentation and Operational Considerations 
33

v 
CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes agreement by the 
recipient that no unpublished information contained herein will be published or disclosed without prior 
approval of the Principal Investigator or other participating study leadership.  

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
1 
STATEMENT OF COMPLIANCE 
 
The trial will be carried out in accordance with International Council on Harmonisation Good Clinical 
Practice (ICH GCP) and the following: United States (US) Code of Federal Regulations (CFR) applicable to 
clinical studies (45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812).  
 
Investigators and clinical trial site staff who are responsible for the conduct, management, or oversight of 
this clinical trial have completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form(s) must 
be obtained before any participant is consented. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the consent form(s) 
will be IRB approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent form. 
 
 
 
 
 

Project EPIC RCT 
v. September 4, 2023
Protocol #: IRB-300007901 
2 
1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS 
Title: 
Project EPIC Randomized Controlled Trial  
Grant Number: 
K76AG064327 (National Institute on Aging) 
Study Description: 
Project EPIC (Empowering People with Independence in COPD) is a 
multiphase study to advance the science of palliative care and geriatrics 
for people living with COPD and their caregivers. Embedded in Project 
EPIC is a multiphase intervention development program to refine and 
pilot test the EPIC early palliative care intervention in older adults with 
COPD and their caregivers informed by the ENABLE (Educate, Nurture, 
Advise Before Life Ends) model for early palliative care. EPIC is a 6-
month early palliative care intervention that uses palliative care-trained 
nurse coach interventionists to deliver the Charting Your Course 
curriculum by phone to patients and their caregivers.  In a formative 
evaluation, the EPIC intervention was refined to meet the needs older 
adults and their caregivers. This study seeks to summatively evaluate 
the refined EPIC intervention for feasibility and acceptability through a 
hybrid type-1, effectiveness-implementation pilot randomized 
controlled trial (RCT) of EPIC + usual COPD care (intervention) versus 
usual COPD care (control).  
Aims: 
Aim 1: Explore feasibility and acceptability of the EPIC intervention. 
Hypothesis 1. Participants can feasibly complete the EPIC intervention 
(>80% of intervention components completed) and will report high 
acceptability (primary outcome). 
Aim 2: Determine the feasibility of a hybrid-type 1 effectiveness-
implementation trial in older adults with COPD and their caregivers.  
Hypothesis 2. It is feasible and not burdensome to recruit, randomize, 
retain, and survey older adults with COPD and their caregivers (primary 
outcome). 
Exploratory Aim: Explore mean and variance estimates on secondary 
outcomes to inform a fully-powered trial (secondary outcome). 
Outcomes: 
Primary outcome: Intervention and trial feasibility and acceptability 
Secondary outcomes: Life-Space mobility, quality of life, emotional 
symptoms, cognitive impairment, functional status, loneliness palliative 
care uptake, and caregiver burden  
 
Study Population: 
30 older adults with COPD and 30 caregivers  
Phase: 
Early Phase I 
Enrollment Sites: 
2 sites: Pulmonary Clinic at The Kirklin Clinic (University of Alabama at 
Birmingham, Birmingham, AL) (primary site) and Cooper Green Mercy 
Health Services-UAB Health Authority (Birmingham, AL) 

Project EPIC RCT 
v. September 4, 2023
Protocol #: IRB-300007901 
3 
Description of Study 
Intervention: 
ENABLE (Educate, Nurture, Advise, Before Life Ends) is a theory-based, 
rigorously tested, and multicomponent early palliative care intervention 
that improved quality of life and emotional symptoms in patients with 
advanced cancer. In Phase 1 of Project EPIC, we conducted a formative 
evaluation from a diverse group of stakeholders to adapt ENABLE for 
adults with COPD and pilot tested the prototype EPIC intervention in 
patients and their caregivers. We then used nominal group technique to 
identify priority care needs of older adults with COPD and used these 
data to further refine the intervention. EPIC includes a series of weekly 
telephone-based, nurse coach-led sessions for patients (six) and their 
caregivers (four) aided by a manualized curriculum and followed by 
monthly check-in calls up to 6 months. Participants also complete 
activities focused on solving problems, improving self-care, eliciting 
values, making difficult decisions, and completing Advance Directives.  
Study Duration: 
6 months 
Participant Duration: 
Enrollment to 6 months 

Project EPIC RCT 
v. September 4, 2023
Protocol #: IRB-300007901 
4 
1.2 
SCHEMA: HYBRID TYPE-1, EFFECTIVENESS-IMPLEMENTATION PILOT RANDOMZIED 
CONTROLLED TRIAL 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
5 
1.3 
STUDY TIMELINE 
 
Key Targets  
Pre-
Award 
Year 1  
Year 2 
Year 3 
Year 4 
Year 5 
-2020 
(Sept 2020 - 
May 2021) 
(June 2021- 
May 2022) 
(June 2022 - 
May 2023) 
(June 2023 - 
May 2024) 
(June 2024 - 
May 2025) 
IRB approval and 
registration 
  
   
  
  
  
  
  
  
  
  
  
Database preparation 
  
   
  
  
  
  
  
  
  
  
  
Focus groups, thematic 
analysis, qualitative 
manuscript (Aim 1), trial 
protocol manuscript  
  
  
  
   
  
  
  
  
  
  
  
Coach training, 
intervention mapping, 
refine EPIC, print 
materials, prepare for 
trial (REDCap, IRB, 
clinical trials.gov, etc) 
   
  
  
  
  
  
  
  
  
  
  
Trial recruitment (2 
dyads/month) 
  
  
  
  
  
  
  
  
  
  
  
R01 development and 
submission 
   
  
  
  
  
 
 
 
 
 
 1st 
Submit 
Feb 
2024 
Data analysis publish 
trial manuscripts 
    
  
  
  
  
  
  
  
  
  
  
Implementation of R01 
   
  
  
  
  
  
  
  
  
  
  
 
 
 
 
 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
6 
1.4 
SCHEDULE OF ACTIVITIES  
 
 
Measures 
Pre-
screening 
(Phone) 
 
Approach, 
screen, & 
consent 
(Phone / In-
person) 
Baseline 
questionnaires; 
Randomization 
(Phone) 
Weeks 
2-24 
(Phone) 
Week 12 
(Phone) 
Week 24 
(Phone) 
EMR Review Eligibility, Screening (PTs) 
X 
 
 
 
 
 
Informed Consent (PTs/CGs) 
 
X 
 
 
 
 
Demographic/Clinical Intake (PTs/CGs) 
 
 
X 
 
 
 
Randomization (after intake) 
 
 
X 
 
 
 
CYC Sessions + follow-up calls (PTs/CGs) 
 
 
 
X 
 
 
Patients (For all measures, see Section 12.1) 
Trial feasibility  
 
 
 
 
 
X 
Intervention feasibility (intervention arm) 
 
 
 
 
 
X 
Acceptability Interview (Qual) 
 
 
 
 
 
X 
Acceptability Survey (Quant) 
 
 
 
 
 
X 
Supportive Care Clinic Visit Survey (Quant) 
 
 
 
 
 
X 
Life-Space Mobility (LSA) 
 
 
X 
 
X 
X 
Quality of Life (CRQ)  
 
 
X 
 
X 
X 
Quality of Life (PROMIS Global Health 10)  
 
 
X 
 
X 
X 
Mood (HADS)  
 
 
X 
 
X 
X 
Cognitive Function (mTICS) 
 
 
X 
 
X 
X 
Loneliness (De Jong Gierveld Loneliness 
Scale) 
 
 
X 
 
X 
X 
Functional Status (Katz Index of ADLs) 
 
 
X 
 
X 
X 
Functional Status (Lawton IADLs) 
 
 
X 
 
X 
X 
Palliative care utilization  
 
 
X 
 
 
X 
Caregivers (For all measures, see Section 12.1) 
Trial feasibility 
 
 
 
 
 
X 
Intervention feasibility (intervention arm) 
 
 
 
 
 
X 
Acceptability Interview (Qual) 
 
 
 
 
 
X 
Acceptability (Quant) 
 
 
 
 
 
X 
Supportive Care Clinic Visit Survey (Quant) 
 
 
 
 
 
X 
Life-Space Mobility (LSA) 
 
 
X 
 
X 
X 
Quality of Life (PROMIS Global Health 10)  
 
 
X 
 
X 
X 
Mood (HADS)  
 
 
X 
 
X 
X 
Loneliness (De Jong Gierveld Loneliness 
Scale) 
 
 
X 
 
X 
X 
Functional Status (Katz Index of ADLs) 
 
 
X 
 
X 
X 
Functional Status (Lawton IADLs) 
 
 
X 
 
X 
X 
Burden (Montgomery-Borgatta)  
 
 
X 
 
X 
X 
Abbreviations:  Patient: PT; Caregiver: CG; LSA: Life Space Assessment; CRQ: Chronic Respiratory Questionnaire; HADS: Hospital Anxiety and 
Depression Scale; ADLs: Activities of Daily Living; IADLs: Instrumental ADLs; TICS:  Telephone Interview for Cognitive Status 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
7 
2 
 
INTRODUCTION 
2.1 
STUDY RATIONALE AND BACKGROUND  
 
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death among older 
Americans and contributes to significant global disability. Lung function declines with age, and over half 
of all COPD patients will be ≥75-years old in the next decade. COPD accelerates loss of quality of life and 
functional independence, and in the last two years of life, nearly all older adults with COPD have 
significant acute care utilization with widely variable hospice use across the country. Our overall 
hypothesis is that older COPD patients and their caregivers could benefit from a proactive geriatrics-
palliative care approach (“GeriPal”) to improve health and well-being before the end of life. 
 
Specialist and nurse-led early, palliative care in advanced cancer improve quality of life and reduce 
healthcare utilization by integrating comprehensive supportive care and outlook planning alongside 
standard disease management at the time of diagnosis of a serious illness. The support for early 
palliative care extends to heart failure. GeriPal expands on this approach by delivering comprehensive, 
person-centered care directed at older adults and their families. Compared to cancer and heart failure, 
COPD is an under-recognized epidemic in older Americans.  Unrecognized physical and emotional 
symptoms in COPD can be more severe than those experienced in advanced cancer and yet people with 
COPD rarely receive GeriPal. Research priorities of the National Institute on Aging (NIA) and the 
American Geriatrics Society (AGS) identify a critical need for GeriPal models. However, no GeriPal 
interventions have been systematically developed and tested in community-dwelling older adults with 
COPD. Despite improved access to palliative care across the US, the growing population of older adults 
with COPD will outpace GeriPal workforce trends. There is an especially desperate need for innovative 
GeriPal-COPD models for community-dwelling older adults from rural areas in the southeastern US, 
where COPD is prevalent and only one-third of hospitals report palliative care access.  
 
Project EPIC (Empowering People with Independence in COPD) is a multiphase study to advance the 
science of palliative care and geriatrics for people living with COPD and their caregivers. Embedded in 
Project EPIC is a multiphase intervention development program to refine to refine and pilot test the EPIC 
early palliative care intervention in older adults with COPD and their caregivers, informed by the ENABLE 
(Educate, Nurture, Advise Before Life Ends) model for early palliative care, which improved quality of 
life and mood for patients with advanced cancer. ENABLE has been iteratively refined and tested over 
decades to deliver the essential elements of palliative care.  Mixed methods research evolved the 
original ENABLE intervention from in-person to a telephone-based model to meet the needs of 
underserved rural and older populations, in whom COPD is frequent. ENABLE was the first palliative care 
intervention to successfully apply the Chronic Care Model (CCM) in advanced cancer and now heart 
failure populations to provide specificity and definition to disease-focused self-management. CCM has 
been successfully applied in COPD to improve disease-focused self-management. A systematic review of 
CCM in COPD concluded that patients who received interventions with ³2 CCM components had lower 
healthcare utilization. The CCM also ensures that programs, such as EPIC, activate patients to develop 
effective relationships between the care team, system, and the community to improve COPD outcomes.  
 
Informed by ENABLE, the EPIC intervention utilizes palliative care-trained nurse coaches to deliver the 
manualized “Charting Your Course” curriculum over the phone to patients and their caregivers. The 
curriculum can be completed in 6 weeks for patients and 4 weeks for caregivers. The entire intervention 
including monthly follow up phone calls is completed over 6 months. Sessions 1-3 are founded on 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
8 
MacMillan’s COPE (Creativity, Optimism, Problem-solving, Expert information) model. Sessions 4-6 are 
guided by the OUTLOOK model for life review and leaving a legacy. Palliative nurse coaches begin each 
CYC session with distress screening and identification of potential barriers. Coaches then engage 
participants in learning how to care for themselves and teach family caregivers how to be active 
partners in their loved one’s care. In Phase I of Project EPIC, we formatively evaluated EPIC in a diverse 
and multidisciplinary group of stakeholders and refined the intervention for adults with COPD. In Phase 
II, we pilot tested the potential feasibility of EPIC in patients with COPD and their caregivers. Our 
preliminary work found that the intervention was acceptable and potentially feasible in this population. 
We then used nominal group technique to identify priority care needs of older adults with COPD and 
refined the intervention even further, tailored to needs of older adults. 
 
The theoretical framework guiding our study is Baltes’ Theory of Successful Aging which posits three 
domains of successful aging: 1) selection (S) of relevant goals; 2) optimization (O) of means to achieve 
those goals; and, 3) compensation (C) for losses due to COPD. The SOC framework shifts from coping 
with disability to adapting to disability, addresses barriers to activities of daily living, defines goals in the 
context of aging, and recruits social networks. Interventions that implemented the SOC framework 
resulted in greater self-efficacy, improved mastery and motivation, greater sense of purpose and well-
being, and less restricted Life-Space mobility. However, the SOC framework has not yet been applied to 
COPD. 
 
The current study continues to summatively evaluate EPIC through a hybrid type-1 effectiveness-
implementation pilot randomized controlled trial (RCT) in 30 dyads of community-dwelling older adults 
with moderate to very severe COPD and their caregivers. Consistent with our prior research, we will 
summatively evaluate EPIC using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and 
Maintenance) framework. The primary implementation outcomes are feasibility and acceptability. 
Secondary GeriPal outcomes will be measured at baseline, 12 weeks, and 24 weeks. Data on secondary 
outcomes will inform the R01. Other secondary GeriPal outcomes include: 1) quality of life by the 
Chronic Respiratory Questionnaire and the PROMIS Global Health 10 instruments; 2) emotional 
symptoms by the Hospital Anxiety and Depression Scale; 3) cognitive impairment using the modified 
Telephone Interview for Cognitive Status; 4) Loneliness using the De Jong Gierveld Loneliness Scale; 5) 
functional status (activities of daily living and instrumental activities of daily living), 6) Caregiver burden 
using the Montgomery Borgotta scale; and, 7) palliative care uptake. 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
9 
2.2 
RISK/BENEFIT ASSESSMENT  
2.2.1 KNOWN POTENTIAL RISKS  
 
There is no risk of physical harm in this study; participants will not be ingesting agents or receiving 
medical treatments. There are two general risks associated with study participation. First, participants 
may become distressed after reflecting on their symptoms, mood, and quality of life during survey 
completion and/or during the intervention. In our experience of providing palliative care interventions, 
this risk is quite low. The surveys and intervention also offer the opportunity to reflect upon strengths 
and resilience, and participants often express gratitude for the chance to respond to the surveys and 
share their experiences. See Section 12.2 for our Emotional Distress/Suicide Protocol. The second risk 
concerns a loss of confidentiality regarding the data (i.e., the chance that participant answers to surveys 
will be seen by people not associated with the study). Plans to minimize these risks are described below.  
2.2.2 KNOWN POTENTIAL BENEFITS  
 
There may be no direct benefit to study participants. However, participants may benefit from the skills 
and information in the intervention and may experience better quality of life and less depressive and 
anxiety symptoms. Participants may also benefit from knowing that their participation in the study may 
help other patients with COPD and caregivers caring for persons with COPD by leading to more effective 
geriatrics-palliative care for this population. Participants may benefit from knowing they were able to 
provide feedback into the implementation and dissemination of this novel intervention for COPD.  
2.2.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
The PI will be directly available 24 hours/day and 7 days/week to provide direct oversight and 
supervision of the study. During eligibility screening, we will use the 6-item screener for cognitive 
impairment to identify potentially eligible patients who may have severe cognitive impairment (score 
£3) and are therefore are not eligible.  We are measuring distress symptoms at the beginning of each 
CYC session using the National Comprehensive Cancer Network’s Distress Thermometer. For participants 
with clinically-significant distress at the beginning of the CYC sessions (³4 on the National 
Comprehensive Cancer Network’s Distress Thermometer), the nurse coach will notify the PI and the 
patient’s primary provider. In the event the PI is not available, the participant will be immediately 
referred to Emergency Psychiatric Services Department at UAB which is available 24 hours/day, 7 
days/week. Participants will also have the opportunity to discuss any distress with the nurse coaches 
who have extensive expertise in managing distress as part of their palliative care training. If the nurse 
coach identifies care needs beyond those they feel comfortable with addressing during the telephone 
sessions (eg, increased COPD symptoms of shortness of breath, cough, or wheezing), they will 
encourage the patient to address these issues with his or her primary provider and notify the PI. If needs 
are deemed severe by the nurse coach, such as poor social support, severe physical or emotional 
symptoms, polypharmacy, or difficulty establishing goals of care, the nurse coach will discuss these 
concerns with the PI and engage the clinicians at the Supportive Care clinic at The Kirklin Clinic. If a 
participant has significant cognitive impairment on the screening tool and is not eligible for the study 
(£3 on the Callahan Screen), the study staff will notify the PI, the patient, and their primary clinician for 
further discussion. The PI will host weekly meetings with nurse coaches and will be directly available for 
questions the nurse coach may have and for guidance and will host once weekly team meetings to 
discuss any concerns or questions. The PI will be notified immediately in the event any participant 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
10 
expresses suicidal ideation to the nurse coach or study coordinator. During normal business hours the 
participant will be immediately referred to the PI so that he may perform a risk assessment and develop 
an appropriate management plan with the participant. In the event the PI is not available, the 
participant will be immediately referred to Emergency Psychiatric Services Department which is 
available 24 hours/day, 7 days/week. 
 
Regarding risks related to loss of confidentiality, all participants’ contact information will be stored in 
the password protected REDCap database that exists within the firewalled network of the School of 
Medicine and School of Nursing. Each participant will be assigned an identification number so that 
survey data will not be labeled with the participant’s name. All paper data will be stored in locked 
cabinets and password protected computers within the offices and laboratories at the School of Nursing. 
Only study personnel will be allowed to access the data. Transcripts from interviews will be reviewed by 
the PI and identifiable information such as names and places will be removed from the transcript. Post-
intervention interviews of participants who completed the intervention arm will be conducted by the PI 
or trained study coordinator in their private offices to minimize any risk of overheard conversations. The 
study coordinator will ask participants if this is a good time to talk and will remind the participant that 
the interviews are audio recorded and transcribed. The study coordinator will allow the participant to 
skip any questions if needed. The electronic audio file will be stored on a password-protected computer 
by the study coordinator and uploaded to the secure website of Landmark Associates for verbatim 
transcription. 
 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
11 
3 
AIMS AND OUTCOMES  
TRIAL OUTCOMES - SUMMATIVE EVALUATION 
RE-AIM Implementation Framework (Aims 1 & 2) 
Reach 
  Trial feasibility 
Rates of screening, enrollment, retention, reasons for exclusion and refusals, randomization, and attrition.  
Adoption 
  Intervention feasibility  
Mean rates of completion of core EPIC components out of possible 10 for patients and 8 for caregivers. 
Feasibility:  Overall average completion of ≥8 sessions for patients ≥6 sessions for caregivers.  
  Acceptability 
Quantitative (Patients/Caregivers): Post-intervention survey on intervention acceptability. Acceptability: 
Overall average score ≥8 of 10. 
Qualitative (Patients/Caregivers): Post-intervention semi-structured, in-depth interviews by telephone to 
explore acceptability, barriers, facilitators, and survey burden.  
Implementation 
  Intervention fidelity 
A random sample of 50% of palliative nurse coach sessions will be reviewed monthly using a rigorous 
fidelity checklist. Palliative nurse coaches who exhibit a pattern of non-adherence on three consecutive 
ratings will receive additional supervision and training. 
  Survey completion 
Quantitative: Survey completion rates. Feasibility: ≥80% of participants complete all surveys 
  Define usual care arm 
Review electronic medical record to capture elements of “usual COPD care”. 
Maintenance  
Nurse coaches check in monthly to reinforce EPIC. Interviews explore barriers to maintenance.  
“Effectiveness” (Exploratory Aim; Secondary Outcomes at Baseline, 12 weeks, and 24 weeks, where indicated) 
Life-Space Mobility 
(Target Secondary 
Outcome; R01 outcome)  
UAB Life Space Assessment (LSA) (Patients/Caregivers): 15-item measure of community mobility; 
frequency, distance, and independence of movement in the 4 weeks prior to administration; LSA<60 
(restricted Life-Space mobility) Lower scores à more restricted; MCID=5 points (a=0.80).  
Quality of Life 
Chronic Respiratory Questionnaire (Patients): 20-item measure of quality of life in COPD; domains of 
dyspnea, fatigue, emotional function, and mastery. Higher scores à better. MCID=0.5 (α=0.70) 
PROMIS Global Health 10 (Patients/Caregivers): 10-item measure; physical and mental health domains; 9 
questions rated on a 5-point Likert-scale, and 10th question rates pain on a scale of 0 to 10. Raw scores 
converted to standardized t-scores ranging from 0 to 100, with lower scores à worse QOL.  
Caregiver Burden 
Montgomery Borgatta Caregiver Burden (Caregivers): 14-item measure of caregiver burden along domains 
of objective burden (a=0.87-0.90), subjective demand burden (a=0.68-0.82), and subjective stress burden 
(a=0.81-0.88); higher scores à greater burden 
Emotional Symptoms 
Hospital Anxiety and Depression Scale (HADS) (Patients/Caregivers): 14-item measure of emotional 
symptoms has a 7-item anxiety and 7-item depression subscale with 4-point Likert scale per item; validated 
in COPD. Higher scores à more severe symptoms; MCID 1.5 points on subscale (a=0.82-0.83) 
Cognitive Impairment 
Modified Telephone Interview for Cognitive Status (mTICS) (Patients/Caregivers): 11-item measure, which 
has been validated in COPD. Higher scores associated with more cognitive impairment and validated over 
telephone (alpha=0.80). 
Loneliness 
De Jong Gierveld Loneliness Scale (Patients/Caregivers):  6-item scale, 3 statements about ‘emotional 
loneliness’ and 3 about ‘social loneliness’ (alpha=0.88). 
Functional Status 
Katz Index of Activities of Daily Living (Patients/Caregivers): 6-item measure of independence in activities. 
Range 0-6. Higher scores à more independence (MCID=0.47) 
Lawton Instrumental Activities of Daily Living (Patients/Caregivers): 8-item measure of functioning in 
independent living. MCID=0.47; Higher scores à higher functioning (a=0.85).  
Palliative Care Uptake  
Patients only (across study period): Advance Directive completion, code status, identified surrogate 
decision maker, goals of care documentation 
Intake Survey (Baseline 
only; Demographic, 
clinical characteristics) 
 
Patients/Caregivers: Age, race/ethnicity, gender, living situation, marital status, income, education, 
employment, smoking/alcohol history; spiritual history (religion, attendance at religious services, pray for 
one’s health, pray for others’ health), health literacy  
 
Patients only: Charlson Comorbidity Index, number of medications, spirometry data, oxygen use, non-
invasive ventilation, cardiopulmonary rehabilitation, home health, vaccinations; history of, falls, weight 
loss, dizziness, vision impairment, hearing impairment, vision/hearing/mobility aids, incontinence 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
12 
4 
STUDY DESIGN 
4.1 
OVERALL DESIGN 
This hybrid type-1 effectiveness-implementation pilot RCT is designed to answer the question “Is EPIC 
feasible and acceptable in older adults with COPD and their caregivers?”. The primary aims are to assess 
implementation feasibility and acceptability (intervention and trial) over 24 weeks (Aims 1 and 2). We 
will also explore means and variance estimates of the secondary GeriPal outcomes to guide future R01 
development (Exploratory Aim). We will recruit 30 dyads of older adults with moderate to very severe 
COPD (FEV1 <80%) from pulmonary clinic and their caregivers. Half of the dyads will be randomized to 
EPIC + usual care (n=30 patients and n=30 caregivers). To reflect current clinical realities and uphold the 
pragmatic design, the other half of dyads (n=30 patients and n=30 caregivers) will be assigned to usual 
care alone (see Section 1.2 for Design Schema). Participants will complete assessments at enrollment 
(T1), week 12 (T2), and week 24 (T3). The T2 assessment captures the short-term outcomes of the most 
intensive part of the intervention. The T3 assessment will capture the long-term outcomes of the 
intervention. Assessments will be administered by phone and entered into the REDCap database system 
by a data collector blinded to study arm. For non-responders after 2 weeks, assessments will be 
additionally attempted by the data collector.  
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
 
Guided by the NIH Stage Model for the Behavioral Health Interventions, this study implements a hybrid 
type-1 effectiveness-implementation pilot RCT trial in NIH Stage 1 of intervention generation and 
refinement. We determined that a usual care condition was the optimal comparator to best serve the 
aims of this pragmatic trial. We considered an alternative control condition with equal attention by 
telephone (i.e. attention control); however, this could threaten the pragmatic trial design that is meant 
to reflect clinical realities for older COPD patients. Part of the design consideration of Aim 2 is also to 
better define “usual care”. Usual COPD care at UAB consists of pulmonary clinic visits, illness education, 
medications (inhalers, nebulizers), vaccinations, advanced COPD therapies, imaging, treatment of COPD 
exacerbations, cardiopulmonary rehabilitation, and specialist referral. All of this is predominantly 
focused on the patient; no specific direct caregiver services exist to support their needs. To further 
examine and describe usual care, we collect information from participants in both conditions on 
accessed services. The information collected on secondary GeriPal outcomes will guide future R01 study 
and trial design.  
4.3 
JUSTIFICATION FOR INTERVENTION 
 
COPD is an under-recognized epidemic in older Americans. Research priorities of NIA and AGS identify a 
critical need for GeriPal models. However, GeriPal integration is rare in COPD, and no GeriPal 
interventions have been systematically developed and tested in community-dwelling older adults with 
COPD. This study is innovative in the following ways: First, the ENABLE model for early, concurrent 
palliative care in oncology is successful in patients with advanced cancer to improved quality of life and 
survival. Second: EPIC’s palliative nurse coaches guide both patients and their caregivers, and its 
telephone delivery model is primed to reach isolated older adults from rural settings. Third, eligibility 
will not be limited to end-stage COPD as in other studies; instead, we will include participants with less 
severe COPD who also have significant COPD symptoms such as breathlessness, use oxygen, or have 
been hospitalized in the prior year, which are associated with high emotional burden and reduced and 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
13 
quality of life in adults with COPD. Fourth, our multiphase study is the first to use Baltes’ Theory of 
Successful Aging to refine the geriatrics content of ENABLE to meet specific care needs of the old-old. 
Fifth, we will measure critical data on feasibility, acceptability, and GeriPal secondary outcomes to 
inform the R01. 
 
4.4 
END-OF-STUDY DEFINITION 
 
Participants are considered to have completed the study if they have completed week 24 
questionnaires.  
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
14 
5 
STUDY POPULATION 
5.1 
INCLUSION CRITERIA 
 
In order to be eligible to participate in this study, potential participants must meet all of the following 
criteria: 
 
Patient Participant Inclusion Criteria (must meet all of the following): 
1. ≥60 years; 
2. COPD on routinely collected spirometry (FEV1/FVC <0.70 + FEV1<80%); 
3. Able to speak English; 
4. At least one of the following:  
o 4a) Severe breathlessness as defined by a documented modified Medical Research 
Council (mMRC) Dyspnea Scale Score >2 in the medical record or any of the following 
levels of severe breathlessness by medical review: breathless after walking about 100 
yards, breathless after a walking few minutes on level ground, or too breathless to leave 
the house or when dressing); OR,  
o 4b) ≥1 hospitalization in the year prior but >30 days from enrollment; OR,  
o 4c) On supplemental oxygen (exertional or continuous). 
 
Caregiver Participant Inclusion criteria: 
1. ≥18 years; 
2. Self-reporting as "an unpaid spouse or caregiver, relative, or friend who knows [the patient] well 
and is involved in their medical care"; 
3. Able to speak English. 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
15 
5.2 
EXCLUSION CRITERIA 
 
An individual who meets any of one of the following criteria will be excluded from participation in this 
study: 
 
Patient Participant Exclusion Criteria (can be excluded for ANY of the following):  
1. No access to a dedicated telephone service; 
2. Recent hospitalization for any reason or exacerbation of COPD in the past 30 days or ongoing 
exacerbation symptoms requiring treatment with antibiotics and steroids; 
3. Treated within the past 60 days for an advanced cancer defined as metastatic and/or 
recurrent/progressive stage III/IV cancer, including brain, lung, breast, gynecologic, head and 
neck, gastrointestinal, genitourinary cancer, and hematologic malignancies by self report or chart 
review; 
4. Active schizophrenia, major depressive disorder, bipolar disorder, suicidal ideations, or substance 
abuse by self-report or chart review (Active means currently being treated for schizophrenia, 
bipolar disorder, or suicidal ideations or having active and untreated major depressive disorder, 
i.e. not under the care of a clinician or not on medications such as antidepressants or mood 
stabilizers, or having active and untreated substance abuse, i.e. not on medication or enrolled in 
a substance abuse program) 
5. Non-correctable hearing impairment (i.e. hearing impairment despite hearing aids); 
6. Severe cognitive impairment (score ≤3 points on 6-item Callahan Screener): a) Correctly identify 
current year (1 point); b) Correctly identify current month (1 point); c) Correctly identify current 
day (1 point); d) Correctly recall "apple" after 5 minutes (1 point); e) Correctly recall "table" after 
5 minutes (1 point); f) Correctly recall "penny" after 5 minutes (1 point) 
 
 
Caregiver Exclusion Criteria:  
1. No access to a dedicated telephone service;  
2. Active schizophrenia, major depressive disorder, bipolar disorder, suicidal ideation, or substance 
abuse by self-report (Active schizophrenia, major depressive disorder, bipolar disorder, suicidal 
ideation, or substance abuse by self-report or chart review (Active means currently being treated 
for schizophrenia, bipolar disorder, or suicidal ideations or having active and untreated major 
depressive disorder, i.e. not under the care of a clinician or not on medications such as 
antidepressants or mood stabilizers, or having active and untreated substance abuse, i.e. not on 
medication or enrolled in a substance abuse program) 
3. Non-correctable hearing impairment (i.e. hearing impairment despite hearing aids); 
4.   Severe cognitive impairment (score ≤3 points on a 6-item Callahan screener): a) Correctly identify 
current year (1 point); b) Correctly identify current month (1 point); c) Correctly identify current 
day (1 point); d) Correctly recall "apple" after 5 minutes (1 point); e) Correctly recall "table" after 
5 minutes (1 point); f) Correctly recall "penny" after 5 minutes (1 point) 
 
 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
16 
5.3 
LIFESTYLE CONSIDERATIONS 
 
N/A 
5.4 
SCREEN FAILURES 
 
Screen failures are defined as participants who consent to participate in this study but are not 
subsequently randomized. Reasons for screen failure include:  
1) Failure of the patient and/or the caregiver to complete baseline measures within 14 days of signing 
informed consent.  
2) Death of the patient and/or caregiver prior to completing baseline measures.   
 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
Duration of Humans Subjects Involvement: Participant enrollment will begin in study year 2 (Tentatively: 
June 2022) and last until the study year 4 (Tentatively: June 2024). Some participant activity may extend 
into study year 5 depending on recruitment.  
 
Length of Active Enrollment: We will recruit 2 dyads per month during study years 2 through 4 (2022-
2024), to reach our target sample size of 30 dyads by study year 4.  
 
Loss to Follow-Up: We are considering an estimated 20% attrition rate based on the nature of serious 
illness and have accounted for this loss to follow up by inflating the sample size from 24 to 30 patient 
participants. 
 
Referral Sources and Estimated Enrollment Rate. The study population will be recruited from the 
pulmonary clinics at The Kirklin Clinic (UAB). Depending on recruitment goals, we may also include 
recruitment from Cooper Green Mercy Health Services (UAB Health Authority). We aim to recruit 30 
dyads over 3 years. The UAB Pulmonary program saw nearly 800 older adults with COPD in 2018. Our 
benchmark is 2 dyads per month  
Recruitment and Enrollment Procedures. Study staff identify potential patients and their caregivers with 
a COPD diagnosis in the electronic medical record (UAB IMPACT system; after gaining HIPAA waiver) who 
have a planned office visit at study recruitment sites in the next 1-2 weeks. After gaining opt out 
permission from the patient’s attending pulmonologist, the study coordinator calls the patient at home. 
The coordinator informs the patient about the study, answers any questions, invites those interested and 
eligible to participate, and asks permission from the patient to present the study to the caregiver. Patients 
and their caregivers (with permission) are screened at this time for eligibility, and agreeable and eligible 
patients and caregivers complete consent.  
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
17 
Figure. Flow diagram of study procedures.  
 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
18 
Procedures to Monitor Enrollment and Track and Retain Participants. The study coordinator who is 
based at UAB, will prepare weekly enrollment reports that are reviewed at weekly team meetings. The 
reports will summarize the number of patients and caregivers identified, screened, and enrolled.  
Strategies to Promote Retention. Numerous retention strategies are being used to maximize participant 
intervention and questionnaire completion rates, consistent with best practices:  
• 
Participants will each receive remuneration for each survey assessment completed: $40 for baseline, 
$50 for 12 weeks, $60 for 24 weeks. Participants will also receive $50 for completing a post-trial 
feedback session and $25 for completing a post-supportive care clinic visit feedback survey for those 
who complete that visit.  
• 
Use of a trained, experienced study coordinator at UAB who has familiarity with the university, a PI 
with established relationships with the pulmonologists and their staff, a study team with training in 
cultural sensitivity and who follow study-team developed recruitment scripts, and who have prior 
experience recruiting from the cancer population.   
• 
Telephone-based intervention delivery, allowing for flexible scheduling with participants at a day 
and time that maximizes convenience.  
• 
Participants will be mailed a welcome letter with information about UAB and resources.  
• 
Because lag time between study activities can result in participants not remembering what they 
have been asked to do for the study, protocol windows consistent with our prior studies will be 
instituted to ensure timely contact between steps in the procedures.    
 
Contingency Plans. Our pulmonary clinics at UAB see on average 800 adults who are 60 years or older 
with COPD each year and could potentially meet eligibility criteria. This is sufficiently large enough to 
target our goal recruitment. If enrollment falls significantly below the accrual benchmarks, defined as less 
than 2 participants per month, we will consult with the Recruitment and Retention Shared Facility of the 
UAB Division of Preventive Medicine to identify alternative strategies. These may include face-to-face 
recruitment by the study coordinator or expansion to include primary care clinics at UAB and Cooper 
Green Mercy Health Services (UAB Health Authority). 
 
Potential Study-Related Barriers. We have identified that attendance at a separate palliative care clinic 
visit may be burdensome for some older adults with COPD due to transportation needs, mobility issues, 
supplemental oxygen, and severe dyspnea. We also identified that some electronic We will continue to 
explore this barrier in the current study and consider switch to telehealth visits. Our qualitative data reveal 
that the telephone delivery model of the EPIC intervention resonates with older adults from rural and 
underserved areas where COPD is prevalent, that the weekly phone calls are not burdensome, and that 
completion of all patient and caregiver telephone sessions is feasible. 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
19 
6 
STUDY INTERVENTION 
6.1 
STUDY INTERVENTION 
6.1.1 STUDY INTERVENTION  
 
The basic delivery elements of the EPIC intervention are as follows:  
 
• Initiation across COPD severity stages: The intervention is administered to patients across COPD 
severity stages (moderate to very-severe COPD)    
• Nurse coach-led: The intervention is led by trained nurse coaches with weekly and as needed 
supervision by the PI and specialist palliative care clinicians.  
• Charting Your Course (CYC) Curriculum: An Intervention for Patients with COPD and their Caregivers: 
The CYC curriculum is a reproducible and scalable telephone-based coaching curriculum informed by 
prior ENABLE trials with telephone scripts and patient and caregiver guidebooks.  
o Patients complete six sessions, and caregivers complete four weekly sessions, followed by 
monthly check-in calls and homework assignments.  
o Sessions 1-3 are founded on MacMillan’s COPE (Creativity, Optimism, Problem-solving, 
Expert information) model. Sessions 4-6 are guided by the OUTLOOK model for life review 
and leaving a legacy.  
o Palliative nurse coaches begin each CYC session with distress screening and barrier 
identification.  
• 
Telephone coaching sessions: These sessions cover specific topics every 1 to 2 weeks. Each last 20 
minutes/session [or up to 1 hour if needed] and are followed by monthly telephone follow-up. 
Coaches engage participants in learning how to care for themselves and teach caregivers how to be 
active partners in their loved one’s care. 
• 
Distress screening and individualized problem solving support: Each encounter begins with distress 
screening (based on the NCCN distress thermometer) to identify potential problems that may need 
assistance with and to help customize core sessions.  
• 
EPIC Toolkit: Participants receive an EPIC toolkit (hereafter “Toolkit”), a packet that contains 
educational information pertaining to the coaching sessions. The Toolkit also serves as a tool to 
organize intervention materials and as a resource guide for the participant. The Toolkit is hand 
delivered at the first session or mailed prior to initiation of core sessions. 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
20 
6.1.2 SUMMARY OF PROTOCOL 
Training of Study Team Members  
The intervention requires two nurse coaches who are hired and trained by the PI and co-investigator, 
Dr. Wells. Advanced training specific to EPIC consists of independent readings, review of all 
intervention materials and the protocol, in-depth discussions on COPD and its management, and 
thorough review of the protocol. The PI will chair weekly nurse coach meetings to review progress and 
intervention receipt.  
 
Enrollment Procedures. 
All agreeable and eligible patient participants who consent to participate in the study complete an 
intake form that includes demographic data (all participants), clinical data (patients only), and 
symptom surveys (patients and caregivers). We are measuring Life-Space mobility, quality of life, 
caregiver burden, functional status, mood symptoms, loneliness, and cognitive impairment. If time 
allows for participants, baseline surveys will be completed immediately after consent. If time does not 
permit in the patient’s schedule, the intake surveys will be completed by telephone at a mutually-
agreed upon time. Agreeable and eligible caregivers who consent to participate in the study will also 
be provided a short intake form of their demographic and background information as well as intake 
symptom surveys. If the time does not permit in the caregiver’s schedule, the intake surveys will be 
completed by telephone at a mutually agreed upon time.  
 
Summary of Randomization Procedures. 
Randomization will take place after the informed consent and intake are obtained from both the 
patient and the caregiver. We will randomize 30 patient-caregiver dyads in a 1:1 fashion to the study 
arms: 1) EPIC + usual care (n=15 dyads); and 2) usual care alone (n=15 dyads). A randomization table 
will be generated to allocate all 30 dyads to the study arms. Randomization procedures will be 
supervised by the biostatistician, Dr. Kim (Co-I and trial statistician) at UAB. The randomization scheme 
will be executed using an Excel randomization table and recorded in REDCap. The study coordinator 
complete the randomization procedure and record study group in REDCap. The study coordinator will 
inform the usual group participants of their group assignment and will also alert the interventionists to 
initiate intervention activities with the intervention group participants. 
 
 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
21 
6.1.3 SUMMARY OF TRIAL PROCEDURES 
Control Arm  
The control arm of the study will be usual care for COPD in pulmonary clinic (Table 1) which includes 
symptom management, inhalers, advanced COPD therapies as needed, illness education, informal 
tobacco cessation counseling, supplemental oxygen testing, and referral to cardiopulmonary 
rehabilitation and other services as appropriate per the clinician.  
Table 1. Control Arm Procedures and Timeline (Usual Care)  
Study 
Week 
Type of 
Session 
Investigator 
Participant 
Estimated 
Participant 
Time 
(minutes) 
Description 
1 
In-
person/ 
Phone 
Coordinator 
Patient + 
Caregiver 
60 
Study introduction, informed consent, 
intake surveys 
2-24 
N/a 
N/a 
Patient + 
Caregiver 
N/a 
Usual COPD care 
12 
Phone 
Data 
Collector 
Patient + 
Caregiver 
60 
Midpoint surveys 
24 
Phone 
Data 
Collector 
Patient + 
Caregiver 
60 
Exit surveys 
24 
Phone 
Coordinator 
Patient + 
Caregiver 
30 
Post-intervention acceptability survey 
Post-intervention feedback interview 
Intervention Arm 
Dyads randomized to the intervention arm will receive EPIC along with usual care (Table 2). EPIC 
includes weekly, telephone-based palliative care nurse coaching aided by the manualized curriculum, 
“Charting Your Course (CYC): An Intervention for Patients with COPD and their Caregivers”. This is 
followed by brief telephone follow-up calls monthly until study completion. Patient participants are 
also scheduled for a visit with the Supportive Care Clinic at The Kirklin Clinic, where trained clinicians 
complete a comprehensive palliative care assessment, virtually if preferred. Current intervention 
materials for EPIC and nurse coach CYC phone scripts are being edited and refined. Final copies of all 
intervention materials and phone scripts will be submitted as an amendment at a later date.  
Table 2. Intervention Arm Procedures and Timeline  (EPIC + Usual Care) 
Study 
Week 
Type of 
Session 
Investigator 
Participant 
Estimated 
Participant 
Time 
(minutes) 
Description 
1 
In-
person/ 
Phone 
Coordinator 
Patient + 
Caregiver 
60 
Study introduction; consent; intake 
surveys 
2-12 
In-person/ 
Virtual 
N/A 
Patient + 
Caregiver 
60 
Supportive Care Clinic visit; 
comprehensive palliative care assessment 
3 
Phone 
Nurse coach 
Patient + 
Caregiver 
45 
CYC Session 1: Problem solving 
4 
Phone 
Nurse coach 
Patient + 
45 
CYC Session 2: Self-care management 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
22 
Caregiver 
5 
Phone 
Nurse coach 
Patient + 
Caregiver 
45 
CYC Session 3: Assessing, prioritizing, and 
managing symptoms 
6 
Phone 
Nurse coach 
Patient + 
Caregiver 
45  
CYC Session 4: Communication skills, 
decision-making, and advance care 
planning.  
7 
Phone 
Nurse coach 
Patient only 
30 
CYC Session 5: Life review, supportive 
counseling 
8 
Phone 
Nurse coach 
Patient only 
30 
CYC Session 6: Leaving a legacy 
12 
In-person 
or Phone 
Data 
Collector 
Patient + 
Caregiver 
60 
Midpoint surveys 
12-24 
Phone 
Nurse coach 
Patient + 
Caregiver 
20 
Monthly telephone check-in call  
24 
In-person 
or Phone 
Data 
Collector 
Patient + 
Caregiver 
60 
Exit surveys 
24 
Phone 
Coordinator 
Patient + 
Caregiver 
30 
Post-intervention acceptability survey + 
phone feedback interview 
24 
Phone 
Coordinator 
Patient + 
Caregiver 
30 
Post-supportive care clinic visit survey 
CYC sessions refer to the chapters in the patient and caregiver guidebooks. The coordinator and nurse coaches 
record completion of the sessions in REDCap.  Patient participants complete CYC Sessions 1-6, while caregiver 
participants complete CYC Sessions 1-4.  
Materials  
Participants randomized to the intervention arm will be mailed a study packet consisting of the 
following: 1) EPIC introductory materials including an introduction of the study team; and 2) EPIC 
toolkit for patients and caregivers consisting of CYC materials, blank activities sheets, resources, and a 
blank Advance Directive.  
 
Charting Your Course Curriculum 
The project coordinator will notify the nurse coaches of participant enrollment and randomization to 
the intervention arm to schedule the CYC sessions at home by telephone. Patients randomized to the 
intervention arm will receive telephone calls by a trained nurse coach guided by telephone scripts. 
Caregivers will receive separate telephone calls by a different nurse coach following the same 
procedures.  In the first telephone call, the nurse coach will introduce themselves and will describe the 
overall EPIC intervention. Patient participants will then begin 6 weekly intervention telephone sessions 
with the nurse coach. The nurse coach will call the patient at home for each session at a time that is 
convenient for the patient. The sessions cover the materials found in the CYC guidebook and follow 
telephone scripts. All CYC sessions will be audio-recorded as conducted in previous trials for fidelity 
monitoring. The PI will conduct fidelity monitoring on at least 50% of all audio-recordings as described 
below.  
 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
23 
Each telephone session with the nurse coach begins by asking if the time is convenient for the 
participant, a reminder that the calls are audio-recorded for fidelity monitoring and quality assurance, 
and an assessment of the patient participant’s level of distress using the National Comprehensive 
Cancer Network’s Distress Thermometer included in the guidebooks. The nurse coach uses the 
telephone script to guide conversation with the participant. The nurse coach will call back monthly 
after completing the last CYC session to review any needs of the patient participant per the nurse 
coach telephone script and to assess maintenance of practices. Caregiver participants will separately 
complete 4 intervention telephone sessions using their own guidebook. Phone calls will be scheduled 
at a day and time that is convenient for the caregiver participant, and the nurse coach.  
 
Post-intervention Interviews 
Post-intervention interviews of participants will be conducted by the trained project coordinator using 
an interview guide to seek participant feedback and experiences of the intervention for those 
randomized to intervention and the overall project for all participants. The study coordinator will 
conduct the interviews by telephone. He or she will ask participants if this is a good time to talk and 
will remind the participant that the interviews are audio recorded and transcribed. The study 
coordinator will allow the participant to skip any questions if needed. The electronic audio file will be 
stored on a password-protected computer by the study coordinator and uploaded to the secure 
website of Landmark Associates for verbatim transcription. The PI will review every 5 transcripts for 
fidelity monitoring and to refine the interview. The transcription text will be coded with the 
participant's study identification number and reviewed by the PI to remove any protected health 
information from the text, including names, places, and affiliations. The digital file of the audio 
recording will be deleted after review of the transcript. 
 
 
Figure. EPIC CYC Sessions for Patients and Caregivers 
Sessions 
1 
2 
3 
4 
5 
6 
Follow-Up 
Patient 
COPE, 
Problem 
Solving 
Self-
care 
Symptom 
Management 
Communication, 
Support, Decision-
Making 
Life Review, 
Accomplishments 
Forgiveness, 
Regrets,  
Creating a 
Legacy 
Monthly 
Follow-Up 
(Telephone) 
Caregiver 
COPE, 
Problem 
Solving, 
Role 
Self-
care 
Being a 
Partner in 
Symptom 
Management 
Communication, 
Support, Decision-
Making 
Monthly Follow-Up 
(Telephone) 
Activities 
Medications and Symptom List, Activity Log, Communicating with Providers Checklist, Ottawa Personal Decision Guide, 
and Advance Directive  

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
24 
6.2 
FIDELITY MONITORING 
6.2.1 INTERVENTIONIST TRAINING AND TRACKING 
 
Training. We have a structured orientation checklist and treatment manual that will be used to train 
interventionists. Drs. Iyer (PI) and Wells (Co-I) will train two nurse coaches (one for each participant 
type) to deliver the intervention. Nurses are well suited to learn EPIC as it builds upon their expertise in 
therapeutic relationship building, distress screening, and resource referral. The training program is 
approximately 70 hours in length and is modeled on procedures developed by our study team over the 
course of several clinical trials of behavioral interventions and our current pilot trial. The training 
consists of independent readings, interactive online modules, videos including demonstration of 
coaching techniques (e.g., active listening, single and double-sided reflections), review of all study 
protocols and procedures, provision of the treatment manual, and role play of six training cases.  
 
Supervision. Throughout the study, interventionists will have weekly supervisory meetings with Drs. Iyer 
and Wells to review calls and sessions with all active intervention-group participants. In addition, nurse 
coaches will have 24-7 access to Drs. Iyer and Wells for any participant issues that arise. 
 
Fidelity. Consistent with our prior trial procedures, all palliative care coach phone sessions will be audio 
recorded, and a random sample of at least 50% of these audio recordings will be scored quarterly using 
a checklist to ensure that treatment is being administered reliably over time and across palliative care 
coach. For each scored session, feedback will be reviewed with the palliative care coach in order to 
maximize performance and expertise. A palliative care coach who exhibits a pattern of non-adherence 
on three consecutive ratings will be required to receive additional training and supervision. The PI and 
study coordinator will also randomly sample 50% of the geriatric-palliative care assessments from the 
supportive care clinic visits at least quarterly to ensure the elements of the assessment were completed. 
 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
The randomization scheme will be executed via REDCap, a clinical trials management software program 
used for randomization and data tracking. Participants will be randomly assigned to group in a 1:1 
fashion using a computer-generated program overseen by Dr. Kim (Co-I and trial statistician) at UAB. The 
study coordinator will be alerted to the assignment in REDCap. The study coordinator will inform the 
usual group participants of their group assignment and will also alert the interventionist to initiate 
intervention activities with the intervention group participants. Data collectors will remain blind to 
group assignment, and participants will be instructed not to discuss their assignment with the UAB data 
collector facilitating questionnaire completion over the telephone.   
6.4 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION ADHERENCE 
 
Four strategies (consistent with NIH and TIDieR guidelines) will ensure intervention fidelity: 1) 
Interventionist training will be standardized and overseen by Drs. Iyer and Wells; 2) Nurse coaches will 
follow study-team developed intervention scripts for each of the core sessions and monthly follow-up; 
3) For each intervention contact, charting templates will be used by interventionists to further ensure 
that essential topics are addressed; and, 4) During the study, 50% of nurse coach sessions will be 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
25 
randomly selected for treatment fidelity monitoring by Dr. Iyer using a fidelity checklist developed in our 
pilot trial. Of the sessions chosen for fidelity checks, audio-recorded sessions of the CYC sessions will be 
randomly selected for ratings. If ratings are below 80% adherence, supervision will focus on necessary 
techniques to improve the score. 
6.5 
CONCOMITANT THERAPY 
6.5.1 RESCUE THERAPY 
N/A 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
26 
7 
INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
 
Participants may withdraw or voluntarily stop their intervention sessions at any time. The reason(s) for 
discontinuing the intervention will be documented (e.g., intervention too burdensome, repeated missed 
intervention sessions, too busy, patient too ill, etc.), and the participant will be invited to continue with 
data collection at 12 and 24 weeks and beyond.   
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
 
Participants are free to withdraw from participation in the study at any time upon request. Reasons for 
participant discontinuation or withdrawal from the study will be recorded. The PI may discontinue a 
participant from the study for the following reasons: 
 
• 
Significant study intervention non-adherence  
• 
Lost-to-follow up; unable to contact participant (see Section 7.3, Lost to Follow-Up) 
• 
Any event or medical condition or situation occurs such that continued collection of follow-up 
data would not be in the best interest of the participant 
7.3 
LOST TO FOLLOW-UP 
 
A participant will be considered lost to follow-up if he or she fails to show up for 3 scheduled 
appointments with the nurse coach, and study staff are unable to contact the participant after at least 3 
attempts. All lost-to-follow up decisions will be made by the PI as special circumstances may warrant 
additional study contact attempts.  The following actions are taken if a participant fails to complete 
intervention sessions or data collection time points: 
• 
Research staff will attempt to contact the participant, reschedule the missed component (eg. CYC 
session), counsel the participant on the importance of adhering to the assigned schedule and 
ascertain if the participant wishes to and/or should continue in the study 
• 
Before a participant is deemed lost to follow-up, the research team will make every effort to regain 
contact with the participant. Contact attempts will be documented in the study’s tracking system.  
• 
Should the participant continue to be unreachable, he or she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up. Withdrawal letters are found in the 
Appendices section. 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
27 
8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
 
Patient and caregiver participants are asked to complete baseline surveys and follow-up questionnaires 
at 12 and 24 weeks by phone. Baseline surveys are collected by the trained study coordinator after 
consent and prior to randomization. For the baseline, 12-week, and 24-week surveys, a blinded data 
collector will call the participant at home to complete.  
 
• 
There is a 14-business day window on either side of the due date for participants to complete their 
follow-up questionnaires. Participants can complete study questionnaires within a 28-business day 
timeframe from 14 days before the time point to 14 days after.  
• 
Participants have 30 business days to complete baseline questionnaires after completing informed 
consent. Caregivers will complete follow-up questionnaires as per the timeline (i.e., even if the 
patient baseline is completed three weeks after the caregiver baseline, both parties will complete 
the first follow-up questionnaire 12 weeks after the patient baseline questionnaire completion 
date).  
• 
Data collected outside of these time points will not be evaluable.  
• 
To minimize missing data, a postcard reminder of an upcoming questionnaire window will be sent 1-
2 weeks prior to opening of the data collection window (Survey Reminder Postcard: Section 12.4.9). 
Data collectors will also begin calling participants within 14 days of the study window to ascertain if 
they would like to complete questionnaires by phone or web. 
 
A screening and tracking log will be used to track whose follow-up questionnaires are due, and when the 
windows open and close.  
 
If a participant refuses to complete a questionnaire or says it is too much, attempts will be made to try to 
have them at least complete the mood and quality of life measures (patient and caregiver).  
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
28 
8.2 
SAFETY ASSESSMENTS 
 
N/A 
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.3.1 DEFINITION OF ADVERSE EVENTS 
 
Very broadly, an adverse event is any untoward event occurring to a participant while enrolled on a clinical 
trial, which may or may not be related to the intervention and/or study procedures.   
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
 
Broadly, an adverse event is any untoward event occurring to a participant while enrolled in a clinical trial, 
which may or may not be related to the intervention and/or study procedures. In our experience of 
providing palliative care interventions using highly experienced palliative care nurse coaches, the risk of 
emotional distress is quite low. Furthermore, the intervention offers participants the opportunity to 
reflect upon strengths and resilience, and participants often express gratitude for the chance to share 
their experiences. This trial is considered minimal risk as there are not expected to be any serious adverse 
events related to the study intervention or procedures, and we are not collecting blood samples or 
prescribing new medications in this study. While death and hospitalization are anticipated of patient 
participants, these are is due to medical illness rather than the study intervention.  
 
8.4 
UNANTICIPATED PROBLEMS 
 
This protocol uses the definition of Unanticipated Problems as defined by the Office for Human Research 
Protections (OHRP).  OHRP considers unanticipated problems involving risks to participants or others to 
include, in general, any incident, experience, or outcome that meets all of the following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-approved 
research protocol and informed consent document; and (b) the characteristics of the participant 
population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 
8.5 
REPORTING OF ADVERSE EVENT AND UNANTICIPATED PROBLEMS  
 
A summary of anticipated serious adverse events (i.e. death and hospitalizations) will be reported to the 
Safety Officer and NIA PO quarterly. The PI will report unanticipated problems to the reviewing IRB, SO 
and the NIA PO within 48 hours. The report will include the following information: 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
29 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project number 
• 
A detailed description of the event, incident, experience, or outcome  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP 
• 
A description of any changes to the protocol or other corrective actions that have been taken or are 
proposed in response to the UP 
8.5.1 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
 
N/A 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
30 
9 
STATISTICAL CONSIDERATIONS  
9.1 
HYPOTHESES 
 
Aim 1: Explore feasibility and acceptability of the EPIC intervention. 
Hypothesis 1. Participants can feasibly complete the EPIC intervention (>80% of intervention 
components completed) and report high acceptability (primary outcome). 
 
Aim 2: Determine the feasibility of a hybrid-type 1 effectiveness-implementation trial in older adults 
with COPD and their caregivers.  
Hypothesis 2. It is feasible and not burdensome to recruit, randomize, retain, and survey older 
adults with COPD and their caregivers (primary outcome). 
 
Exploratory Aim: Explore mean and variance estimates on Life-Space mobility by the UAB Life Space 
Assessment and other GeriPal outcomes to inform a fully-powered trial (secondary outcome). 
 
9.2 
SAMPLE SIZE DETERMINATION 
 
As this is a feasibility study, sample size is justified based on the measurement precision of LSA 
parameters for a larger study. Using a sample size of 24 patients (48 participants including patients and 
caregivers) and 12 patients per study arms, we can estimate the 95% confidence interval of mean LSA 
with a margin of error of 14.3. This margin of error is equal to 0.567 standard deviation when we 
observe a reference standard deviation for the LSA of 25.2 from a general population of older adults. 
This sample size also includes an estimated 20% attrition rate from a sample of 30 dyads (or 60 patient 
and caregiver participants), which is consistent with palliative care trials. 
9.3 
POPULATIONS FOR ANALYSES 
 
Led by the study statistician and PI, an intent-to-treat main analysis will use all available data from baseline 
onwards for patient and caregivers to examine effectiveness.  
9.4 
STATISTICAL ANALYSES 
9.4.1 GENERAL APPROACH 
 
Overall considerations. We will use an intention to treat approach for all analyses. That is, all 
participants will be included in their respective assigned conditions, regardless of their degree of 
participation in the study. Dr. Kim (Co-I; Statistician) and the data analyst will lead and conduct the 
analysis. The data analyst and project staff will perform data cleaning and validation throughout the 
study. Primary data analysis will begin with descriptive statistics for baseline characteristics and 
outcomes. We will examine balance between study groups with respect to baseline characteristics using 
effect sizes such as the standardized mean difference for numerical variables and Cramer's V for 
categorical variables. Conceptually relevant baseline factors showing non-trivial imbalances between 
groups will be then used as adjusting covariates in the longitudinal group comparisons. Distributional 
assumptions will be examined and, when appropriate, we will employ inferential and modeling 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
31 
procedures robust to distributional assumptions such as normality. We will calculate and present means, 
variances, and ranges of the LSA and other secondary outcomes at baseline, 12 weeks, and 24 weeks. 
We will use the latest versions of SAS and R for all analyses and reports. 
 
Handling of missing data. We will examine patterns of missing data, and whether baseline 
characteristics are associated with dropout. Conceptually relevant baseline factors predictive of dropout 
will then be used as adjusting covariates in the longitudinal group comparisons. Mixed-effect modeling 
techniques and covariate adjustment will reduce the impact of missing data, as the missingness is not 
assumed completely at random (MCAR) but conditionally (on the covariates) at random (i.e., MAR, a 
milder assumption).  
 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
 
We will summatively evaluate EPIC using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, 
and Maintenance) evaluation framework.  
 
Reach: We will use REDCap to track rates of screening, eligibility, enrollment, reasons for non-consent of 
eligible participants, and drop out.  
 
“Effectiveness”: We will measure several secondary GeriPal outcomes and will explore participant 
perspectives on the acceptability and impact of EPIC as well as barriers and facilitators to implementation. 
The PI will train the project coordinator to conduct post-intervention semi-structured in-depth interviews 
of patients and their caregivers by telephone using an interview protocol developed during our pilot trial. 
The separate patient and caregiver interviews will be audio-recorded and transcribed using Landmark 
Associates. The PI will review every five transcripts for quality assurance to review with the coordinator 
and for ongoing interview guide refinement. We will conduct a thematic analysis of transcripts using NVivo 
Software (Version 12, QSR International). Informed by a within- and across- case comparison approach, 
we will code the data using concepts introduced by participants. Emerging codes across cases will be 
operationally defined and entered into a formal codebook. Member checking will be ongoing as previous 
participant insights will be asked of future participants (e.g. “A number of participants have said X. What 
is your perspective on this issue?”). To corroborate findings and establish trustworthiness, the PI and co-
investigators will examine the data collection and analysis monthly and provide critical feedback on the 
emerging codes. We will explore within and across coded texts to extract converging themes and reach 
consensus on themes.  
 
Adoption: We will record completion of intervention components (CYC sessions, follow up call, advance 
directive, activities) in REDCap and tabulate intervention completion rates (# participants completing 
component). Consistent with our prior intervention development studies, ≥80% completion rates for 
intervention sessions will be considered as evidence of feasibility.  
 
Implementation: Informed by our prior fidelity monitoring procedures, we will audio record all palliative 
care coach intervention sessions for fidelity monitoring and will quarterly review at least 50% of the 
recordings to ensure standardized intervention delivery and further training.  
 
Maintenance: The thematic analysis will explore barriers to maintenance, and nurse coaches assess 
maintenance of practices at the follow-up calls.  

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
32 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
 
The statistician and the data analyst will lead and conduct the analysis, and the data analyst will perform 
data cleaning and validation throughout the study. Descriptive statistics for baseline characteristics will 
be presented and compared between study arms using t-test and chi-square as appropriate. The 
secondary geriatrics-palliative care outcome measures will be summarized by tabulating and plotting 
descriptive statistics (means, ranges, and variances) at baseline and at six months. All analyses will be 
performed by using SAS 9.4, and statistical significance will be defined at α<0.05. 
 
9.4.4 SAFETY ANALYSES 
 
N/A 
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
 
Intervention groups will be compared on baseline characteristics (e.g., demographics, baseline 
questionnaire values) using descriptive statistics.  
 
9.4.6 PLANNED INTERIM ANALYSES  
 
N/A 
9.4.7 SUB-GROUP ANALYSES 
 
N/A 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
Individual participant data will not be listed by measure and time point. 
9.4.9 EXPLORATORY ANALYSES 
 
N/A 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
33 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 SCREENING AND RECRUITMENT  
Given ongoing constraints of the COVID-19 pandemic, all attempts will be made to recruit and consent 
participants virtually to maintain patient and study staff safety. We have submitted a HIPAA waiver to 
screen the electronic medical record to identify potentially eligible patient participants. The PI, study 
coordinator, and study staff will daily screen potentially eligible patient participants from the list of 
patients who have a planned visit in pulmonary clinics in the next 1-2 weeks. These procedures have 
been used successfully in recruiting patients with COPD in prior UAB studies.  
Prior to recruitment, the PI will reach out to individual UAB pulmonologists by email to describe the 
study, to discuss recruitment of their patients, and to allow them to opt-out of recruitment. The PI has 
ready access to the clinic lists of all patients seen in both pulmonary clinics as part of routine clinical 
care.  
After gaining permission from the patient’s attending pulmonologists via the above opt out email, the 
PI, study coordinator, and study staff will screen electronic medical records in the UAB IMPACT system 
to identify potential participants from their list of patients who meet the inclusion criteria and have a 
planned office visit at the pulmonary clinic in the next 1-2 weeks.  The PI or study coordinator will send 
potentially eligible patient participants a study information and opt-out letter by mail (included in the 
appendix) with details about the study and consent forms to introduce the study and let them know that 
a member of the study team will be contacting them by phone to talk to them about the study. 
Individuals will be given a number to call if they do not wish to be contacted further for the study. The PI 
or study staff will call patients 5 business days after the opt out letter is sent to introduce, enroll, and 
consent them to the study.  
At the time of the recruitment phone call, the PI or study coordinator will inform the patient about the 
study, answer any questions, and invite those interested and eligible to participate. Patient participants 
will be screened at this time for eligibility, and agreeable and eligible patient participants will complete 
consent. The study coordinator will confirm with the patient that they have a caregiver defined as, “a 
person who knows you [the patient] well and is involved in your medical care”. The study coordinator 
will then ask permission from the patient to inform the caregiver about the study, and if agreeable, will 
screen the caregiver for eligibility criteria and perform consent in a similar fashion. 
 
 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
34 
10.1.2 INFORMED CONSENT PROCESS 
10.1.2.1 CONSENT PROCEDURES AND DOCUMENTATION 
Given ongoing constraints of the COVID-19 pandemic, all attempts will be made to recruit and consent 
participant virtually over REDCap whenever possible to maintain patient and study staff safety. For 
patients and caregivers who are agreeable and meet eligibility criteria, the study coordinator will review 
the informed consent over the phone and explain all elements of the study, including: a statement that 
the study involves research; the research purpose; the expected duration of participant’s participation; a 
description of the procedures; foreseeable risks and discomforts; description of benefits expected; efforts 
to maintain confidentiality; the PI’s and UAB IRB’s contact information; and a statement that participation 
is voluntary and that there is no penalty for non-participation. The informed consent will be electronically 
signed and dated by the participant and the project coordinator. A copy will be sent electronically to the 
participant to keep for his or her records.  
 
The study coordinator who performs the consent discussion for this study will have appropriate 
education, expertise, and background to understand and relay the concepts in the study and answer 
questions. They will have documented protocol-specific training so they are familiar with the research 
project. Electronic consent will be obtained after the protocol has been fully explained and all questions 
have been answered. They will use the teach-back method of evaluating comprehension. Participants are 
asked to describe in their own words the key aspects of study participation.  
 
10.1.3 STUDY DISCONTINUATION AND CLOSURE 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be provided 
by the suspending or terminating party to study participants, investigator, funding agency, and regulatory 
authorities. If the study is prematurely terminated or suspended, the PI will promptly inform study 
participants, the Institutional Review Board (IRB), and sponsor/funding agency and will provide the 
reason(s) for the termination or suspension. Study participants will be contacted, as applicable, and be 
informed of changes to study procedures. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
 
The study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the funding agency, sponsor, IRB, or other relevant regulatory or oversight bodies. 
 
 
10.1.4 CONFIDENTIALITY AND PRIVACY  
 
Participant confidentiality and privacy is strictly held in trust by the PI and study team. This confidentiality 
is extended to the data being collected as part of this study. Data that could be used to identify a specific 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
35 
study participant will be held in strict confidence within the research team. No personally-identifiable 
information from the study will be released to any unauthorized third party without prior written approval 
of the sponsor/funding agency.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study participant’s contact information will be securely stored with the firewalled, password-
protected firewall of UAB for internal use during the study. At the end of the study, all records will 
continue to be kept in a secure location for as long a period as dictated by the reviewing IRB, 
Institutional policies, or sponsor/funding agency requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be stored at the UAB School of Nursing. This will not include the participant’s contact or identifying 
information. Rather, individual participants and their research data will be identified by a unique study 
identification number. The study data entry and study management systems used research staff will be 
secured and password protected. At the end of the study, all study databases will be de-identified and 
archived at the UAB School of Nursing. 
10.1.5 FUTURE USE OF STORED SPECIMENS AND DATA  
 
Data collected for this study will be analyzed and stored at the UAB School of Nursing. We are not 
collecting any specimens in this study.  
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
36 
10.1.6 KEY ROLES AND STUDY GOVERNANCE 
 
The organizational structure summarized below is appropriate for early start-up and implementation 
phase of the trial and may change over time. The primary decision-making body is the Oversight 
Committee, chaired by the PI and comprised by the co-investigative team, lead statistician, and study 
coordinator. The oversight committee will convene biannually to review progress on all study processes, 
timeline, and milestones and high level scientific and administrative issues. This committee will also 
oversee publications.  
 
A Project Management Subcommittee, comprised of the PI, project manager, recruitment and data 
collection staff, and other study staff will meet weekly to address day-to-day operational issues and to 
set short term priorities.  
 
A Nurse Coach Subcommittee comprised of the PI, nurse coaches, and other clinical co-investigators will 
meet weekly to debrief on intervention sessions. 
 
As PI, Dr. Iyer is responsible for all aspects of study execution. Dr. Wells, assisted by Dr. Iyer, will train 
and monitor the nurse coaches’ fidelity to the intervention treatment protocol. Dr. Kim will oversee 
design and implementation of the REDCap data collection procedures and analysis. Dr. Bakitas and Dr. 
Dionne-Odom will provide regular advisory consultation to the PI on all palliative care clinical trial study 
procedures. Dr. Dransfield and Dr. Brown will oversee clinical trial implementation and help to resolve 
barriers.  
 
Once caregivers and patients are consented, the study coordinator (Ms. Coffee-Dunning) will use 
the REDCap computer generated randomization schema to randomize to the intervention and usual 
care conditions. Ms. Coffee-Dunning will notify the data collector who is blinded to group to collect 
data as needed. Ms. Coffee-Dunning will also notify the nurse coaches who will contact participants 
by phone and follow up with a letter describing the study activities for their assigned condition.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
37 
10.1.7 SAFETY OVERSIGHT 
 
This project will involve enrolling 30 older adults with COPD and 30 caregivers into a pilot randomized 
controlled trial. After signing consent, participants will complete a baseline surveys. Dyads randomized 
to the intervention arm will engage in the EPIC intervention delivered over telephone by trained 
palliative care nurse coaches. The interventions and assessments are not invasive and do not involve 
pharmacological agents. The informed consent process, the recruitment process, and the timeliness and 
quality of the data will be monitored by the principal investigator, the Institutional Review Board, and a 
Safety Officer (SO).  
 
The SO will provide safety oversight and be composed of individuals with the appropriate expertise, 
including oncology, medicine, nursing, and clinical trials. The SO will be independent from the study 
conduct and free of conflict of interest. The SO will review quarterly safety reports from the PI to assess 
safety. The SO will provide its input to the IRB.  
 
The SO has an established procedure of operation and guidelines for determining the methods and 
frequency for study review. Below is the table that guides the risk assessment for this study. Based on 
our SO established guidelines, the proposed study’s score of five on the 10-point scoring system 
indicates that the principal monitor for the study will be the PI (Dr. Iyer), and he will present the SO 
with a summary of the accumulated data and safety information during an annual review for each 
year of the study. 
  
Tasks related to patient safety will include Dr. Iyer’s assessment of potential risks associated with study 
recruitment and participation, as well as the design and implementation of procedures to minimize 
these risks should they arise. Additionally, Dr. Iyer and the Co-Investigators will implement a system to 
document adverse events should they occur. The IRB Institutional Review Board currently has 
procedures in place for reporting adverse events and those protocols will be followed for the current 
study. This risk monitoring will be reviewed on a regular basis and will be modified as needed.  
 
The primary risks of study participation are a loss of confidentiality and the discomfort associated 
with discussing aspects of one’s experience coping with advanced cancer. To address these 
concerns, Dr. Iyer will train all project staff to recognize signs of distress and to be supportive 
and/or make alternative plans for completing study-related tasks at a later date, if necessary. If a 
participant exhibits suicidal ideation at any point, Dr. Iyer and other key clinical members of the 
study team will be contacted immediately to implement a crisis intervention plan (see Section 12.2 
for Emotional Distress/Suicide Protocol). 
 
Plans to Monitor Trial Performance (e.g., assure fidelity to protocol and integrity of data) 
Dr. Iyer and Dr. Wells have developed and utilized structured processes for ensuring fidelity in study 
protocols including: 1) core training and study-specific refresher course in standardized interviewing 
that includes role-playing and supervision; 2) weekly team meetings to troubleshoot recruitment and 
data collection issues; and, 3) use of data entry software that provides entry validation range tests 
and is designed to minimize missing data by flagging missed items before surveys are submitted. 
 
A data analyst study team member will manually extract data from the medical record regarding 
patient participants’ clinical characteristics of stage, treatment, and co-morbidities. To ensure accuracy, 
the analyst will audit a random 10% of the medical records to verify the accuracy of the abstracted 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
38 
information. The study coordinator will maintain and monitor the database regularly throughout the 
study. The database is password-protected and sits behind the firewall of UAB. 
 
Interim Analyses and Stopping Rules 
Early Termination for Significant Risk or Injury. - This is unlikely due to the supportive, non-invasive 
nature of the intervention. However, we will summarize adverse event data annually to the SO for 
consideration of study continuation. The study design does not include planned interim analyses to 
identify the need to stop early due to significant benefit, i.e., inferential analyses will be conducted 
when data collection has been completed. However, primary outcome data will be summarized 
quarterly and presented to the SO to decide if an interim inferential analysis is warranted to determine 
whether the study should be terminated early due to relevant benefit.  
 
Table 1. Study Risk Assessment * 
SCORE 
I. Experimental Treatment 
Low Risk 
No experimental treatment in the study 
1 point 
 
 
Moderate Risk 
Treatment effects documented from studies with 
similar and/or different populations and/or settings. 
No serious adverse events expected. Specific plans to 
monitor AE’s detailed in DSM plan. 
2 points  
2 
High Risk 
The experimental treatment is being regulated by the 
FDA (e.g., an investigational drug, device, or biologic) 
 4 points  
 
II. Procedures, Measurement, and Data Collection Methods 
Low Risk 
Minimally invasive with a low degree of emotional 
and/or physical discomfort. The probability of 
adverse events is low. 
Severity (magnitude) of adverse events is low. 
(Procedure may be rated as low if the probability of 
AE is moderate to high as long as the severity is low, 
as in the case of a bruise from phlebotomy.) 
Procedures that meet IRB criteria for expedited 
review are commonly rated as low. 
 1 point 
 
 
Moderate Risk 
A moderate degree of emotional and/or physical 
discomfort. The probability of adverse events is 
low. The severity of adverse events is moderate to 
high (e.g., PET scan, lumbar puncture, arterial line 
insertion).  
2 points  
2 
III. Decision-Making Capability 
Non-vulnerable 
Adult who (1) demonstrates decision-making capacity 
and (2) demonstrates no perception of undue influence 
or coercion.  
1 point 
Non-
vulnerable 
population 
1 
Vulnerable 
Any minor. Adult who (1) demonstrates limitations in 
decision-making capacity and/or (2) is prone to the 
perception of undue influence or coercion to participate 
2 points  
 
Total 
5 
 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
39 
10.1.8 CLINICAL MONITORING 
 
Clinical monitoring will be conducted to ensure that the rights and well-being of trial participants are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of 
the trial is in compliance with the currently approved protocol/amendment(s), with International 
Council on Harmonisation Good Clinical Practice (ICH GCP), and with applicable regulatory 
requirement(s).  
 
10.1.9 QUALITY ASSURANCE AND QUALITY CONTROL 
 
Overseen by the PI, study staff will perform internal quality management of study conduct, data collection, 
documentation and completion on at least a quarterly basis.  
 
Quality control (QC) procedures will be implemented as follows: 
 
Informed consent --- Study staff will review both the documentation of the consenting process as well as 
a percentage of the completed consent documents.  This review will evaluate compliance with GCP, 
accuracy, and completeness.  Feedback will be provided to the study team to ensure proper consenting 
procedures are followed.  
 
Source documents and the electronic data --- All data will be entered into the REDCap study database.  
To ensure accuracy, staff will review data entered into the database for completeness. 
 
Intervention Fidelity — Consistent delivery of the study interventions will be monitored throughout the 
intervention phase of the study. Procedures for ensuring fidelity of intervention delivery are described in 
Section 6.2.1, Interventionist Training and Tracking.  
 
Protocol Deviations – The study team will review protocol deviations on an ongoing basis and will 
implement corrective actions when the quantity or nature of deviations are deemed to be at a level of 
concern. 
 
Should independent monitoring become necessary, the PI will provide direct access to all trial related 
sites, source data/documents, and reports for the purpose of monitoring and auditing by the 
sponsor/funding agency, and inspection by local and regulatory authorities. 
 
 

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
40 
10.1.10 
DATA HANDLING AND RECORD KEEPING  
10.1.10.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Data collection will be the responsibility of the study staff under the supervision of the PI. The PI will be 
ultimately responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data 
reported. Sources of materials to be collected include all measures listed in 1.4 Schedule of Activities. 
Study materials will also include digital recordings of the intervention sessions (for fidelity monitoring) 
and post-intervention feedback interviews with transcripts. All materials will be used specifically for the 
purposes outlined in this proposal and not for any other purpose.  
 
All data collected during the study will be de-identified. Participants will be informed that all responses 
will be kept confidential. Data will be linked to participants’ names only by means of an assigned study 
identification number. Authorized study staff are the only individuals who will have access to 
participants' identification numbers and personal information. This information will be stored in a 
password protected database on the secure UAB School of Nursing server as well as in hard copy format 
in a locked file cabinet in a locked office that is only accessible to the study PI and relevant study staff. 
All necessary precautions will be taken to ensure that there is no breach of confidentiality.  
 
Participants’ completed self-report measures will be saved in a password protected file (electronic 
format) or stored in a locked file cabinet in a locked office (hard copy format) accessible only to the PI 
and relevant study staff. Study staff will double-key enter de-identified questionnaire responses into the 
encrypted, password protected (front and back end) REDCap electronic database (Research Electronic 
Data CAPture). REDCap is software for building and managing questionnaires and facilitating electronic 
data collection and storage. It supports a HIPAA best practice, secure web-based application. Hard stops 
prevent missing data due to inadvertent skipping of items. This database will be accessed on a secure 
network server that is password protected. Descriptive statistics will be used to conduct quality control 
on the preliminary datasets and identify missing/extreme data values. Study staff who have received 
intensive training (typically 10 hours including role play and inter-rater reliability checks) will assure high 
quality data collection from participants. The PI will follow-up and resolve any data queries resulting 
from the quality control process. Care will be taken to ensure that the collected data are as complete as 
possible, and patterns and impact of missing data will be examined. If appropriate, statistical techniques 
to handle missing data such as multiple imputations will be employed.   
 
Digital recordings of sessions will be labeled with participants’ study identification number and stored in 
a locked file cabinet in a locked office accessible only to the PI and relevant study staff.  
 
All personnel involved in the proposed protocol will be CITI certified, educated regarding HIPAA 
regulations, and will fully understand their responsibility to safeguard the personal health information of 
every participant involved in the research. 
10.1.10.2 
STUDY RECORDS RETENTION  
 
Study documents will be retained for a minimum of 3 years after the completion of the data analysis 
period. These documents may be retained for a longer period, however, if required by IRB or other UAB 
regulatory authorities (e.g., UAB Comprehensive Cancer Center).  

Project EPIC RCT 
 
v. September 4, 2023 
Protocol #: IRB-300007901 
 
 
 
 
41 
10.1.11 
PROTOCOL DEVIATIONS   
 
This protocol defines a protocol deviation as any noncompliance with the clinical trial protocol, 
International Council on Harmonisation Good Clinical Practice (ICH GCP), or Manual of Procedures (MOP) 
requirements. The noncompliance may be either on the part of the participant, the investigator, or the 
study site staff. As a result of deviations, corrective actions will be developed by the PI and study team 
and implemented promptly.  
10.1.12 
PUBLICATION AND DATA SHARING POLICY  
 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As 
such, this trial is registered at ClinicalTrials.gov (NCT05040386), and results information from this trial 
will be submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-
reviewed journals.   
10.1.13 
CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence is critical. Therefore, any actual 
conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect 
of this trial will be disclosed and managed. Furthermore, persons who have a perceived conflict of 
interest will be required to have such conflicts managed in a way that is appropriate to their 
participation in the design and conduct of this trial.  
10.2 ADDITIONAL CONSIDERATIONS 
 
N/A 
10.3 ABBREVIATIONS AND SPECIAL TERMS 
 
COPD = chronic obstructive pulmonary disease 
GeriPal = geriatrics-palliative care 
FEV1 = forced expiratory volume in 1 second 
RCT = randomized controlled trial 
ENABLE = Educate Nurture Advise Before Life Ends 
EPIC = Empowering Independence with COPD 
LSA = UAB Life Space Assessment 
CRQ = Chronic Respiratory Questionnaire 
HADS = Hospital Anxiety and Depression Scale 
mTICS = Modified Telephone Interview for Cognitive Status 
ADL = activities of daily living 
IADL = instrumental activities of daily living 
CCM = chronic care model 
SOC = selection-optimization-compensation 
RE-AIM = Reach, Effectiveness, Adoption, Implementation, and Maintenance 
CYC = Charting Your Course