Home Pulmonary Rehabilitation for COPD
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease (COPD), Emphysema
Sponsor: Mayo Clinic

 
 
Home Pulmonary Rehabilitation for COPD   
 
NCT03480386 
 
August 23, 2021 

Protocol Version 2:  March 1, 2018 
 
 
Page 1 of 17 
 
 
General Study Information 
 
Principal Investigator:  Roberto Benzo       
 
 
 
 
 
 
 
 
Study Title: Home Pulmonary Rehabilitation for COPD   
 
Protocol version number and date:     Protocol Version9, August 23, 2021 
Research Question and Aims 
 
Hypothesis:   
Home-based pulmonary rehabilitation with proper self-management support through health coaching rooted in motivational 
intervention during pulmonary rehabilitation will improve physical wellbeing, quality of life, increase daily physical activity, and 
decrease health care utilization for patients with COPD. 
 
Aims, purpose, or objectives: 
The ideal system for a home PR program requires straightforward, accurate technology to monitor physiological parameters, patient 
engagement, and simple exercises to be performed at home, all ensuring participant safety. Feedback is critical: MI-based health 
coaching, proven effective in COPD,6 can translate to higher self-efficacy, subsequently promoting better SM and improved QOL.15, 16  
The aims of this project: 
• Home-based PR will increase PR uptake and adherence, a significant existing gap in COPD care. 
• The addition of formal SM support through health coaching during PR may promote behavioral change to prolong the effects 
of PR on critical COPD health outcomes.  
• The home-based PR program may meaningfully engage participants in successful SM and translate into sustained improved 
physical wellbeing (QOL), increased daily PA, and decreased health care utilization for patients with COPD.  
• The proposed home-based PR system using “off-the-shelf” hardware and a previously commercialized software (accomplished 
through our Small Business Innovation Research Grant, SBIR 5R44HL114162-03) will have a high likelihood of 
implementation and dissemination once proven effective. 
 
 
Background:  
 
Role of Pulmonary Rehabilitation in Chronic Obstructive Pulmonary Disease care  
International guidelines for managing Chronic Obstructive Pulmonary Disease (COPD), one of the main causes of morbidity and 
mortality worldwide,1 suggest that pulmonary rehabilitation (PR) programs and self-management support (SM) are a critical part of 
treatment. A compelling body of evidence confirms that PR programs deliver improved exercise capacity, reduced breathlessness, and 
improved health-related quality of life (QOL)2 and are associated with fewer acute exacerbations and hospital admissions-the biggest 
costs burden in health care.2, 7 
Adherence to PR is poor 
Despite proven benefits, the proportion of people with COPD who receive PR is very small, with estimates from developed countries 
of <20%.3 The current model of a center-based PR program fails to address the needs of many patients with COPD.5 The most 
common patient barrier to attendance is travel to center-based programs, particularly for frail patients with more severe COPD who 
need transportation assistance.3  
Home-based, unsupervised PR has been proposed as an alternative model4 to hospital-based programs and has been found to be safe 
and effective compared with traditional programs in terms of improvement in exercise tolerance, disease-specific QOL, and degree of 
breathlessness and fatigue.8 However, despite initial results, the implementation and dissemination of home-based PR has been poor 
in the United States due to a lack of simple home-based PR systems that combine proper monitoring and meaningful feedback to the 
patient.8 There is a knowledge and practice gap regarding effective systems that can deliver home PR.2, 5 Further research on feasible 
and effective home-based PR particularly oriented to a sustained behavior change is needed.  
Aiming for home PR programs with lasting results 

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It is well documented that the effects of PR diminish over time, with deterioration in both exercise capacity and health-related QOL 
within six to 12 months of program completion.9 One key reason for this decline is the lack of a behavioral change after completing 
PR (developing new habits). It is now postulated that undertaking PR in the home may promote effective behavior change through 
integration of physical activity (PA) routines into daily life.5 Self-management support (SM), which creates ideal conditions for 
behavior change, is now recommended by guidelines as an essential part of chronic care, particularly in PR programs.2, 10 A recent 
large randomized study of COPD SM11 identified lack of patient engagement as the core problem in adopting new behaviors. In that 
study, significant effects on health-related QOL and health care utilization after the SM intervention occurred only in patients who 
were engaged in their care. Brief advice is not enough to promote behavior change; meaningful engagement is necessary.12 
Health Coaching, promoting a behavior change 
In our previous work, we developed and tested (R01 HL09468), an effective program for SM in COPD through health coaching13 
rooted in motivational interviewing (MI)13, 14 that decreased COPD re-hospitalizations6 and produced a sustained improved QOL at six 
and 12 months.  
Theoretical Framework 
The theoretical framework of the proposed intervention (Fig. 1) is based on two guiding theories: self-efficacy theory15, 17 and MI 
theory.16 In brief, training in MI prepares the health coach to initiate conversations in the spirit of MI (compassion, acceptance, 
evocation of the client’s values, and collaboration) and skills (open questions, a non-coercive approach for change, and making the 
participant the expert and final decision-maker). The latter (spirit and skills) may not only impact social persuasion (part of self-
efficacy theory) but also directly increase self-efficacy (confidence) that leads to higher SM abilities (behavior change). Pulmonary 
rehabilitation directly impacts the foundations of the self-efficacy theory: mastery in PA, by engaging in daily exercises (Aim 3, 
measured by activity monitor), social persuasion (weekly feedback from a trustworthy coach) and emotions and physiology (exercise 
is a known positive factor impacting emotions and COPD physiology). Self-efficacy (Sub aim 2 measured by CRQ Mastery) translates 
into SM or behavior change (Aim 2 measured by SMAS30) which in turn impacts physical QOL (Aim 1). We have recently 
confirmed and published the independent relationship between MI health coaching, SM and quality of life.6, 18, 19 A proposed path 
analysis will confirm the proposed framework. 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Compassion, Acceptance, Evocation, Collaboration; †Open-ended questions, affirmations, reflective listening, and summaries 
Fig. 1. Theoretical framework. 
Motivational 
Interviewing               
(MI) Theory 
 
 
 
 
 
 
Self-Efficacy Theory 
 
 
 
 
 
 
 
 
 
 
Mastery of PA by 
performing PR (Aim 3) 
Social Persuasion by 
Health Coaching 
Positive Physiological 
and Emotional States 
by doing PR 
Self-
Efficacy 
(Aim 2) 
SM          
(behavior change)    
(Aim 2) 
Increased 
physical QOL: 
dyspnea and 
fatigue (Aim1) 
MI 
Training 
MI 
Skills† 
MI 
Spirit* 

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Innovation 
The project is truly innovative due to the purely home-based nature of the system, the simplicity and accuracy of data collection 
attained with using commercially available monitors, and the addition of health 
coaching to engage and provide weekly feedback to participants. Previous 
studies required participants in home-based training groups to attend SM 
education4, 20 or weekly monitoring in the clinic or hospital.21 These approaches 
fail to overcome the transportation and mobility-related barriers to attendance, 
perpetuating the present lack of adherence. 
The proposed study will be the first of its kind combining monitored home-
based PR with theory-driven health coaching to provide SM support, a novel 
addition to PR which may translate to greater participant engagement, better 
communication, and sustained behavior change.13 Currently, there is no 
research-proven, effective home-based PR system available.  
 
Preliminary Data:  
We present the preliminary data of four projects (tested in previous applications) 
representing critical components that support the proposed home-based PR 
system: 
1. Creating the system using AMs and an Android™ receptor (R44 AG29087-02A1) and pilot of its effect  on disease-specific 
QOL (Aim 1) 
2. Effect of the proposed health coaching on sustainable improvement of QOL (Aim 1). (R01 HL09468) 
3. Pilot testing the integrity of the transmission of physiologic data (R43 HL 114162-01) 
4. Refinement of the system and Pilot testing of the whole proposed intervention (5R44HL114162-03) 
Project 1 – Creating the System. SBIR project NIH (R44 AG29087-02A1 Kramer, PI; 
Benzo, Co I) provides the foundation for the proposed mobile system for home PR in this 
project. In this study, AMs with Bluetooth capabilities were fastened to the ankle and 
connected to an Android™ device (proposed in the present application). The device then 
transferred activity and patient-reported outcomes to a server, which generated a report 
(Fig. 2) for a coach who reviewed the data and provided support to participants. The system 
also included daily participant feedback about their symptoms (Fig. 3), which informed the 
coaching sessions. We tested 50 participants with severe COPD aiming to improve QOL as 
measured by the Chronic Respiratory Questionnaire (CRQ) (as in Aim 1). We found 
improved QOL at eight weeks, (Fig. 4) and this improvement was maintained at six 
months. 
          
Qualitative analysis reported the following participant themes: (1) the system was 
efficacious in motivating increased activity; (2) improved wellbeing; (3) appreciation of the 
coach interaction; and (4) interested in a wrist monitor that enabled them to view activity 
(Garmin monitor with display is proposed in this application; see Fig. 5). Coach interviews 
indicated that coaches found reports useful and actionable. The technology was friendly and 
did not interfere with participant- coach communication. All themes and requests of the 
previous study are now incorporated in this application. 
 
Fig. 2. Project 1 - coach application used.  
Fig. 4. Pilot 1. CRQ scale is 1-7, with 
higher scores indicating better health.*A 
clinically significant difference is ≥0.5 
points. (P<.05)
Fig. 5. Garmin 
Vivofit™. 
Fig. 3. Android™ screen of reported 
t

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Project 2–Effect of the proposed health coaching on 
sustainable improvement of QOL (Aim 1). In a randomized 
study (N=215), 6 we tested the proposed MI-based health 
coaching telephone intervention (NHLBI R01 HL09468 Benzo, 
PI) to decrease  COPD readmission and to improve QOL. We 
discovered significant improvements in Physical QOL (Aim 1) 
and Emotional QOL measured by the CRQ at six months post-
intervention, and also observed that these benefits were 
maintained at 12 months (Fig. 6). Health coaching decreased ER 
visits and hospitalizations (see exploratory aim in this 
proposal).6 The SM worksheet is shown in Appendix 1. 
Qualitative analysis also demonstrated that the SM support 
intervention was acceptable to patients and interventionists, 
increased self-efficacy for dealing with COPD, and promoted an 
effective working alliance with the coach (Fig. 7). Details of the 
intervention are published and publicly available.13  
Project 3–Addition of physiologic monitoring to the system 
in Project 1: Feasibility and Signal Integrity. In R43 HL 
114162-01 (Benzo, Kramer Co I) we tested participants with 
severe COPD, we confirmed the feasibility and integrity of heart 
rate and oxygen saturation transmission during the proposed PR 
exercise routine in a simulated patient’s home, validating 
transmitted data from the monitor with in-site monitors (gold 
standard).  
Project 4–Pilot Study Testing the Proposed System (home-
based 
PR plus coaching). The finalized proposed system, was 
finalized funded by NHLBI (5R44HL114162-03 Home-Based 
Health 
Management of COPD Patients), and was tested in a pilot study 
that 
included health coaching. All participants were able to use the 
technology and were 100% compliant with daily activity 
measures. Participants highly rated the helpfulness of the study 
(8.5, 
scale 0-10) and ease of technology navigation (9.67, scale 0-10). 
A 
preliminary qualitative analysis is shown in Fig. 8. 
 
 
 
 
 
 
 
 
 
 
Study Design and Methods 
 
Methods:  Describe, in detail, the research activities that will be conducted under this protocol:   
 
Pilot Study:  When the technology is ready, we will conduct a pilot study enrolling fifteen or fewer participants.  The 
participants in the pilot study will not be randomized and will receive the Intervention.  The purpose of the pilot study is to 
observe how the technology works in real life and to refine the intervention if needed.  The participants in the pilot study will 
complete all measures and activities of the randomized control trial, minus the randomization.   
 
Fig. 6. Quality of life outcomes from health coaching 
Fig. 7. Qualitative feedback of health coaching 
Fig. 8. Qualitative pilot feedback of the home pulmonary rehabilitation program. 

Protocol Version 2:  March 1, 2018 
 
 
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Randomized Study:  
Participants will be randomly assigned in equal proportion to one of two treatments: home PR with health coaching or the attention 
waitlist control (Fig. 9). Participants randomly assigned to the intervention will receive three months of home PR followed by six 
months of usual care.  
Participants randomly assigned to the active control group will receive three months of usual care plus educational materials and non-
coaching calls (matching the number of contacts in the intervention group), followed by three months of home PR plus health 
coaching and three months of usual care.  
Phase 2:  Participants randomized to intervention will not change; three months of home PR followed by six months of usual care.  
Participants enrolled in the active control group will follow the scheme listed above; 3 months of usual care followed by three months 
of home PR and three months of usual care.  During the control wait period they will receive a pamphlet of 12 Healthy Habits during 
the enrollment period as well as two letters during the control period.  The letters will remind them to review the 12 Healthy Habits 
and will remind them that the exercise portion of the study will start soon.    
 
Phase 3:   Forty Mayo participants who have competed the intervention (the 12 weeks of home-based pulmonary rehab with health 
coaching) will be randomly selected to complete a qualitative interview to explore areas related to the intervention, quality of life and 
symptom severity.    The purpose of the qualitative interview is to take an in-depth look at the appropriateness of the intervention as a 
potential method of treatment as well as examining the impact on the participant as a whole.  Mayo Clinic participants who have 
completed the intervention portion of the study will be contacted via the telephone to inquire about their interest in participating in the 
interview.   If interested, oral consent will be conducted.  A mutually agreed upon time and date for the interview will be confirmed.   
(A phone script will be used.)  The participants will receive $40 for consideration of their time.   
The interviews will be recorded for subsequent transcription of the interactions.  The transcribed interviews will be examined for 
common themes.    Each interview will vary between 20 and 30 minutes and will be performed by a member of the Mindful Breathing 
Laboratory who is trained in Motivational Interviewing and Qualitative Interviewing.   Additional members from the Lab will assist in 
the transcription of the interviews as well as theme identification. Data collection and analysis will be overseen by Dr. Benzo. (A 
guided interview script will be used.)   
 
In addition, the five Mayo Clinic staff who served as health coaches on the study will also be offered the opportunity to be interviewed 
to learn their experiences in the program.  The interviews will be conducted by Qualitative Expert, Dr. Jennifer Ridgeway, either in a 
private space or by phone call.  The interview will be recorded so that it can later be transcribed and analyzed.   An email inviting the 
health coach to participate will be sent to the health coach.  The health coach will be orally consented and will have the option to opt 
out.  
 
 
 
 

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Questionnaires:  
Physical QOL will be assessed by the CRQ (Aim 1), SM abilities, self-efficacy (Aim 2), and daily PA and self-efficacy for exercise 
(Aim 3). These QOL components will be measured at baseline, three, six, and nine months after randomization in both groups. 
Qualitative analysis (Aim 4) will occur after the intervention in order to further understand the intervention’s acceptability and to help 
interpret the comparative effectiveness findings from Aims 1-3.  
Additional QOL questionnaires will include the Interpersonal Support Evaluation List (ISEL-12), the Meaning of Life Questionnaire 
(MLQ6), and the Longitudinal Analogue Self-Assessment (LASA6).    Recent research has indicated that social support and sense of 
meaning of life are important indicators in the perception of quality of life.  The added questionnaires will better measure these 
important factors. 
 
Study Sites: 
The clinical study sites include (1) Mayo Clinic—Rochester, Rochester, MN, (2) Mayo Clinic-Jacksonville, Jacksonville, FL, and (3) 
HealthPartners® Specialty Center-Regions Hospital, St. Paul, MN. The engineer site is Minnesota HealthSolutions, Maple Grove, MN. 
These study partners have collaborated for the past five years. 
 
Recruitment  
The study coordinator will utilize ACE to generate a list of eligible participants with research authorization (avoiding any HIPAA 
noncompliance) and send invitation letters. In addition, patients presenting to the clinic with COPD may be referred to the study by 
Month 3 
Measures, AM, 
HCU 
Final 
Analysis 
Arm 1: Intervention 
(n=100) 
COPD patients 
eligible for PR 
are invited 
through letters 
and clinic 
Screening Call  
-Able to walk 
-Not in PR in past 3 
months 
-Not in exacerbation 
-Past or current smoker
Arm 2: Attention 
waitlist control 
(n=100) 
12 Weekly HC Calls 
HCU: Health care  utilization  
AM: Activity monitor 
HC: Health coaching 
 
6 Educational Guides & 6 
Calls = 12 contacts 
Clinic Visit 
-Baseline Measures 
-Taught technology 
-Sent home with AM (1 week) 
 
12 Weekly HC Calls 
Measures 
-CRQ                -mMRC 
-SMAS-30       -PAM 
-WAI (after intervention)
Month 6 
Measures, AM, 
HCU 
Month 9 
Measures, AM, 
HCU 
Randomization          
(after AM received) 
Fig. 9. Randomized study design. 

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Fig. 10. 
ActiGraph™ 
wGT3X-BT. 
their provider.  The coordinator will approach potential participants through a screening call (review inclusion and exclusion criteria) 
and will schedule an enrollment visit and to demonstrate the Home Rehab and to obtain consent.   
 
Subject Information 
 
Target accrual:  
400 total participants.  Mayo Clinic Rochester has a target enrollment of 150 participants, Mayo Clinic Florida and Health Partners 
have a target enrollment of 70 participants each.  Up to fifteen total participants will be enrolled in a Pilot Study. 
 
Inclusion Criteria: 
• 
Clinical diagnosis of COPD, confirmed by spirometry 
• 
Age ≥40 years (to avoid recruiting participants with asthma rather than COPD) 
• 
Current or previous smoker (≥10 packs per year)  
• 
Confidence in using the proposed PR system  
• 
English language fluency  
Exclusion Criteria: 
• 
Study candidate experiencing an acute COPD exacerbation (can  be included after the acute event) 
• 
Inability to walk (orthopedic-neurologic problems or confined to a bed) 
• 
Currently in PR or finished PR in the last three months (unlikely to improve)  
• 
Pregnant women 
• 
Live in an area where cell phones do not work/ 
 
Research Activity 
 
Randomization 
Eligible participants (after the screening call) will visit the site for the consenting process. In the clinic visit, all consented participants 
will receive baseline questionnaires, and information about the system. They will complete the questionnaires during the visit, and 
take home the ActiGraph™ AM (Fig. 10), to wear for one week. On return of the AM, the study coordinator will randomly assign the 
participant to intervention or attention waitlist control through a centralized program, Research Electronic Data Capture (REDCap). 
Randomization will be stratified by whether the participant has poor lung function (forced expiratory volume [FEV1] <50% predicted) 
and whether the participant has severe dyspnea (recorded modified Medical Research Council Dyspnea Scale [mMRC] score, 3-4; 
scale, 0-4); critical factors that can make the study arms unbalanced regarding risk factors. The study coordinator will call the 
participant and inform him or her of the results of randomization. Intervention participants will be mailed the home-based PR system 
(pulse oximeter, tablet and Garmin Vivofit™). While blinding participants will not be possible, as most behavioral interventions, the 
arms will be blinded to the research team in charge of the data entry and statistical analysis and revealed only at study conclusion. 
 
Clinic Visit: Face-to-Face Encounter 
The participant will practice the use of the proposed system and the PR routine in the PR lab to ensure understanding and safety; 
therefore, no home visits are planned. The clinic visit is the best opportunity to evaluate the confidence of the individual in using the 
system. The study team will provide step-by-step instructions on how to perform the daily home-based PR routine (Fig. 11) and 
discuss the home environment where PR will take place to define the optimal conditions, particularly safety, for exercise. The 
participant will be asked to rate their confidence to use the technology presented and their confidence (self-efficacy) to perform the 
home rehabilitation routine on a scale from 0 (no confidence) to 10 (great confidence). A rating of six or greater will be deemed an 
acceptable confidence level to participate in the study. 

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Each participant will be asked to define a 
particular place and time they can perform the 
home-based PR. The physical and mental 
environment is critical for the successful 
adoption of new behavior (PR). Each 
participant will learn about the weekly calls 
with the coach to discuss their rehabilitation 
and monitored measures (steps, level of 
shortness of breath, wellbeing and fatigue). 
They will then go over the daily answers to 
wellbeing questions (mood, energy, and 
breathlessness as tested in the pilot study) (Fig. 
3). After performing the PR routine (to ensure 
safety and understanding) and reviewing use of 
the monitors, a plan for the following week 
will be discussed. The coach will also confer 
with the participant and caregiver to identify 
possible exercise-related fall hazards in the 
home environment (see Human Protections 
section).  
Strategies for promoting recruitment and 
retention 
A thorough explanation of the technology and 
measures required will contribute to a better 
understanding of the study and decrease the 
risk of dropout. In the screening visit, the study 
coordinator will clearly and carefully explain 
the benefits of enrolling and the duties in this 
study from the perspective of potential 
participants. These benefits include access to 
home-based PR and a coach, who is describe 
safety and benefits of the proposed exercise in 
the home, the weekly call with a coach, the steps, oxygen and heart rate monitoring, and SM 
support. All tasks related to study participation (e.g., questionnaires and utilization of AMs) will 
be carefully explained.  We believe that the proposed study design will be attractive to both 
intervention and control participants.  
Intervention Group  
Participants are to engage in the home PR at least six days a week. The Garmin Vívofit™ AM 
(Fig. 5) is to be worn at all times (battery lasts one year) to capture daily steps and metabolic 
equivalent of task (METs) per day. The PR routine begins with a slow breathing awareness 
exercise, “pursed lips breathing,” followed by upper-extremity exercises (Fig. 12) and a 6-minute walk (in the home or outside) 
finishing with another slow breathing-awareness exercise.  
Participants will complete two 6-minute walks, either right after or at another time of day. The exercise protocol lasts about 24 
minutes, which is the amount of dedicated exercise time associated with a risk reduction in hospitalization and improved QOL23, 24 and 
is recommended by current PR guidelines.2 The proposed protocol is currently being used by the PI of this proposal in a prospective 
COPD trial (NIH NCI R01CA163293-03). The PR coach will contact the primary care or referring provider before PR to introduce the 
provider to the study as well as coordinate and develop a strategy in case of a COPD exacerbation (a common cause of PR 
abandonment).  
The proposed home-based PR system (Fig. 11) consists of three commercial devices and two software application. The devices are a 
Garmin Vívofit™ AM,  a Nonin 3150 WristOx2® Pulse Oximeter (PO), and a 7” Android™ tablet with 3G/4G cellular service. The 
AM and PO wirelessly communicate with the tablet via Bluetooth. During the upper extremity exercise routine (Fig. 12) and 6-minute 
walks, the PO measures the participants’ heart rate (HR) and oxygen saturation (SpO2). Near the end of the day, the tablets 
 
Fig. 12. Depiction of 
exercises. 
Fig.11. Proposed home pulmonary rehabilitation system with self-management 
support. 

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periodically sound a musical alarm and display a short health status  questionnaire (as demonstrated in the pilot study, Fig. 3)25 asking 
participants to rate their wellbeing,25 ease of breathing, and energy level. At night, the tablets securely transmit the device data and 
wellbeing questionnaire answers to a remote Web server, which securely stores the data and generates reports. Health coaches call the 
participants weekly to discuss their progress in PR and SM (see below). 
Participant software application: When the participant turns on the Android™ tablet, the application logs in, and the participant 
accesses two main screens (see appendix for all graphics). First Screen: 
 
1) The top left corner of the screen displays the participant’s step count, step goal, and remaining number of steps. The top 
center of the screen shows a motivational message (based on the participant’s progress). The top right corner displays the 
weather, an important factor for the PR coach to consider when interpreting a participant’s PA. The remainder of the screen 
displays the daily PR activities.  
 
2) To initiate one of these activities, the user selects the corresponding activity from the “To-Do” column. Selecting 
“Exercise” from the “To-Do” column initiates a video guiding the user through the PR exercises. Similarly, selecting “Walk” 
from the “To-Do” column starts a 6-minute countdown once the application detects that the participant has initiated walking. 
Before displaying the exercise and walking videos (asked to be followed), the application verifies that the participant is 
wearing the AM and PO to assure measure and compliance (during exercise an increase in heart rate is expected). When the 
participant finishes the selected activity, it appears in the “Done” column. The application provides instructions before and 
between each activity.  
The second screen plots historical data, allowing the participant to see trends as in the pilot study. From this screen, the user 
is able to view daily steps, average heart rate, SpO2, and questionnaire answers. The user also is able to select the historical 
window (e.g., last week, last month, last quarter).  
Coaching Calls (weeks 1-12) content for PR feedback plus SM: After the in-person visit, coaching calls will occur weekly for 12 
weeks following the published protocol:13  
1) Set the call agenda. Listen for the participant’s exercise description, ask which exercises were successful, and affirm. 2) 
Provide feedback of monitored sessions and generate dialog by listening for “change talk” (participant’s comments on 
anticipated activities he or she wants to do). 3) If problems arise, resist the urge to attempt to solve the participant’s 
problems and barriers. 4) Listen carefully and kindly (ambivalence from the participant in changing their behavior). 5) 
Discuss how behaviors connect to the participant’s values and strengths. 6) Collaborate in setting goal(s) for the 
following week. 7) Discuss the process of action planning: elicit the participant’s preferences/desires for behavior 
change. 8) Elicit the participant’s choice; do not assign goals, and use the participant’s language to describe the goal. 9) 
Assess confidence for goal completion, reaffirm commitment to the action plan, and express optimism. 10) Thank the 
participant and plan the next call.  
All calls will be recorded to ensure compliance with the protocol and MI principles (10% of all calls will be reviewed).    
Recorded files are saved on the restricted research drive, accessible only to study staff.  The recorded files are to be 
deleted off the drive after analysis of the intervention is completed and study is finished.  Only ten percent of the calls 
are reviewed, and that is to feedback and training to the health coach. 
 
Coach Training 
Details of the health coach training have been published and publicly available.13 In brief, the health coach intervention is purposefully 
designed to be delivered by PR professionals, respiratory therapists, or nurses, the most common providers of care in PR, as opposed 
to psychologists.  Training includes: 1) face-to-face education on theory and strategies associated with SM education and MI in 
general (six hours); 2) reading materials detailing skills and strategies associated with SM education and MI; 3) role play-based 
experiential learning of intervention strategies with participant vignettes (five hours); and 4) recorded and reviewed intervention 
sessions in which interventionists provide tailored training to discuss strengths, missed opportunities for use of intervention strategies, 
and any deviations from the intervention protocol (10 hours over six months). The rationale for the latter is that training sessions that 
incorporate feedback from coded sessions increase skill retention. All training sessions will be audio or video recorded for future 
review to minimize drift from intervention protocol.  
Health Coach Software Application: (see Appendix 1 for full size graphics and reports). 
The health coach software application provides three types of reports. The overview report (Fig. 13) allows health coaches to 
succinctly ascertain the status of their participants and flag anyone who may be experiencing problems. The health coach may select a 

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participant from the overview to display the trend report (Fig. 14). The trend report allows the health coach to review the participant’s 
progress between weekly health coaching sessions. Finally, the health coach may select a day from the trend report to display a 
detailed report (Fig. 15). These three reports are updated after the results of the pilot studies (preliminary data projects 1 and 3) are 
generated. 
While participant monitoring does not occur in real time, any 
significant physiologic abnormality measured during 
rehabilitation and transmitted to the server (O2 saturation less than 
80% or heart rate >140 or <40 beats per minute) prompts a 
message to the coach to call the participant to investigate the 
event. The PI also is alerted within 24 hours by text message if a 
physiologic abnormality is measured to ensure the appropriate 
response. In 5R44HL114162-03 Home-Based Health 
Management of COPD Patients, the remote rehabilitation and 
health coaching systems have been pilot tested together and found 
feasible, accurate, and acceptable to participants.  
Attention Waitlist Control Group Procedure  
Our experience with behavioral studies has shown that retention 
in a pure control arm is very poor 
when the active intervention 
seems intuitively very useful to 
participants.  A waitlist 
randomized attention control 
design not only permits each 
participant to receive an active 
intervention if assigned to control 
initially but also maximizes 
retention and helps fulfill 
immediate expectations.  
During the control group period, 
participants receive a educational 
materials on healthy habits for 
physical activity based on the 12 
Habits of Highly Healthy People 
featured by Mayo Clinic.  The 
control group will also receive 
two letters aimed at 
acknowledging the materials.  National Institute of We plan to control for a likely 
Hawthorne effect that can be observed in the control group as participants may 
receive more attention than normal. Hence, the difference observed in the control group over time will be deducted from the effects 
observed in the intervention group when interpreting the results of the study as part of our analysis. The control group then receives 
the active intervention at month four after being randomized and upon completion of the active control period and the three month 
measures. 
 
Questionnaires 
Questionnaires pertaining to quality of life are administered in the project.   The questionnaires are reviewed and entered into REDCap 
in a timely basis.  If a participant indicates a score of 3 or higher on the PHQ 9, the PI will be notified.  
 
Review of medical records, images, specimens – Category 5 
 
The target population consists of patients who have COPD receiving outpatient care at Mayo Clinic (Rochester).  We plan to enroll 
200 patients in the study through referral from the Mayo Clinic Pulmonary Division ACE Database. Once enrolled, study staff will 
review the medical records and will document the most recent Pulmonary Function Test data and demographics. 
Fig. 13. Overview report. 
Fig. 14. Weekly individual report. 
Fig. 15. Detailed report. 

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HIPAA Identifiers and Protected Health Information (PHI) 
 
 
Check all that apply: 
INTERNAL 
EXTERNAL 
Name 
X 
 
Mayo Clinic medical record or patient registration number, lab accession, specimen or 
radiologic image number  
X 
 
Subject ID, subject code or any other person-specific unique identifying number, 
characteristic or code that can link the subject to their medical data   
X 
 
Dates: All elements of dates [month, day, and year] directly related to an individual, their 
birth date, date of death, date of diagnosis, etc.   
Note: Recording a year only is not a unique identifier.  
X 
 
Social Security number 
 
 
Medical device identifiers and serial numbers 
 
 
Biometric identifiers, including finger and voice prints, full face photographic images and any 
comparable images 
X 
 
Web Universal Resource Locators (URLs), Internet Protocol (IP) address numbers, email 
address 
 
 
Street address, city, county, precinct, zip code, and their equivalent geocodes 
X 
 
Phone or fax numbers 
X 
 
Account, member, certificate or professional license numbers, health beneficiary numbers 
 
 
Vehicle identifiers and serial numbers, including license plate numbers 
 
 
Check ‘None’ when none of the identifiers listed above will be recorded, maintained, or 
shared during the conduct of this study.  (exempt category 4) 
 None 
 None 
 
 
Data will be stored in Mayo Clinic’s REDCap database.  Mayo Clinic Florida and Health Partners will only be able to see data from 
their site.  Mayo Clinic Rochester will have access to data entered into REDCap as they are the coordinating site for this trial.  
REDCap (Research Electronic Data Capture) is a secure, web-based application designed to support data capture for research studies, 
providing:1) an intuitive interface for validated data entry; 2) audit trails for tracking data manipulation and export procedures; 3) 
automated export procedures for seamless data downloads to common statistical packages; and 4) procedures for importing data from 
external sources. 
 
Health Coaches located at Mayo Clinic Rochester may fill in as Health Coaches at other sites to cover vacations, absences and 
employment gaps in health coaches.  Mayo Clinic Rochester Health Coaches only have access to data in REDCap (demographics and 
health coach notes) and not the medical record.   
 
 
 
 
Data Analysis and Data Safety Monitoring 
 
DSMB 
See Data Safety Monitoring Charter. 
 
 
 
 
Analysis Plan 

Protocol Version 2:  March 1, 2018 
 
 
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There are three distinct quantitative study hypotheses (inform different aspects of the process). Hypothesis 1 (Aim 1) states that 
participants on home-based PR will have higher physical (dyspnea fatigue) QOL at month three than participants in the waitlist 
control group as measured by the CRQ physical summary score. Hypothesis 2 (Aim 2) is that participants on home-based PR will 
have better SM abilities at month three than participants in the waitlist control group. The SMAS-30 will be used to test this 
hypothesis. Hypothesis 3 (Aim 3) is that participants on home-based PR will have more daily PA than participants in the control group 
at month three. This will be measured by steps and minutes spent in sedentary, light, and moderate activity measured by the 
ActiGraph34, 35 and greater self-efficacy for exercise. This study has two activity monitors, the ActiGraph, a gold standard activity 
monitor used for outcome measures (7-day wearing) at baseline, 3, 6 and 9 months. The Garmin Vivofit PR activity monitor used 
daily during PR period will NOT be used as an outcome measure, just for health coaching and participant awareness of physical 
activity (participant will keep this activity monitor after PR).  
For the continuous study outcomes, changes from baseline to three months will be compared between the study arms using two-
sample, two-sided t-tests with 5% type I error rates. Changes in QOL and number of steps will be compared between the two 
treatment sequences using two-sample two-sided t-tests. No adjustments will be made for multiple testing. Means, SDs, medians, 
ranges, and frequency distributions will be reported and plotted over time by study arm. Additional analyses will compare changes 
from baseline to three months. Linear models will be used to assess the impact of treatment arm on three month outcomes after 
adjusting for the corresponding baseline measure and other variables related to the outcome (age, degree of breathlessness at baseline 
using the mMRC, and FEV1. Repeated measures mixed models will be used to estimate the intervention effect over the three months 
of the comparison study. Although there is a crossover element to the study design, crossover analyses will not be used due to the 
anticipated carryover effect in the intervention arm. Intent-to-treat analyses will also be performed to determine the sensitivity of the 
results to dropouts and missing values. In the intent-to-treat analyses, if a month three measure is missing for any reason, it will be 
described as not changing from baseline. Health care utilization (number of ED visits, hospitalizations, and length of stay) between 
baseline and three months will be treated (analyzed) as both binary (for incidence rates) and continuous (for the number of events). 
The binary endpoints will all be compared between groups using Fisher’s exact test. Logistic regression models will also be fit to look 
for differences in these outcomes by arm after adjusting for age, mMRC, FEV1, baseline levels of anxiety, depression, and fear, and 
baseline health care utilization (before starting the study). While significant missing-ness (>5%) in the Aim 1 outcome is not expected, 
imputation is planned in case it is.  
Descriptive summaries of the changes between baseline, three, six, and nine months will be used to assess the effect of the delayed 
intervention on the control arm and the residual beneficial effect on the intervention arm. These results will be only descriptive and 
exploratory. No formal hypothesis testing will be done. All data will be stored in REDCap and analyzed using SAS (Cary, NC). 
Missing Values treatment: Initially, Little’s test for missing completely at random (MCAR)36 will be used along with Potthoff and 
colleagues assessment of missing at random (MAR+).37 Contingent on either MCAR or MAR data, imputation will be considered in 
order to respond to the level of missing-ness and to be able to use the optimal amount of information in our model. In case of 
participant withdrawal, all available data will be used. 
Path analysis: The hypothesized framework will be tested using structural equation modeling (SEM), which allows us to examine 
multiple dependent variables in one model and concurrently describe multiple paths of direct and indirect effects among the theoretical 
constructs. We will use two steps in SEM analyses. First, the validity of the measures will be assessed by fitting a measurement model 
and investigating whether the items are strong indicators of the latent constructs (e.g., self-efficacy and quality of life). The second 
step involves testing the effect of the predictor variables (e.g., MI training, mastery in PA, social persuasion, physiological and 
emotional states) on the outcome variables (e.g., self-efficacy, self-management, and physical QOL) with a particular interest in the 
role self-efficacy has in increasing self-management and physical QOL. In addition to the direct effects of MI training on self-efficacy, 
self-efficacy on self-management, self-management on physical QOL, mediating effects can be tested, such as the effects of MI 
training on self-management and physical QOL, or effects of self-efficacy on physical QOL by estimating their indirect effects. The 
model will be tested using lavaan, the R software package for SEM.38 The model fit will be examined by its model χ2, goodness-of-fit 
index (GFI), and root mean square error of approximation (RMSEA). 
Qualitative Analysis (Aim 4): Perceptions of the participants and the interventionist will be captured using qualitative methods. 
Qualitative inquiry in randomized controlled trials help interpret results and variation in results.39 It can also help ensure that 
interventions meet stakeholder needs and therefore aid in future transferability of interventions like the proposed system. This is 
increasingly important as trials move out of controlled settings and into the social context of natural settings,40 including participant 
homes. 
This qualitative approach is part of an embedded mixed-methods design, a design commonly used when individuals’ perspectives 
inform experimental results.(33)  This aim also helps us better understand the contextual factors related to implementation. As such, it 

Protocol Version 2:  March 1, 2018 
 
 
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reflects the principles of a type 1 hybrid effectiveness-implementation design, the rationale for which is to study barriers and 
facilitators to widespread implementation alongside the intervention’s effectiveness, speeding future translation into practice.41 
The interview instruments will be informed by the quantitative study aims, and quantitative results will guide the qualitative sampling 
plan. Specifically, the purposive sampling for interviews and in order to increase the breath of representativeness of the interviewees , 
we will use baseline scores on the Patient Activation Measure to stratify the population available for interview recruitment, and we 
will aim to interview 10 patients with lower levels of activation at baseline (Stages 1 and 2 indicating lower participant engagement) 
and 10 patients with higher levels (stages 3 and 4 indicating higher engagement) AND patients with high severity defined by a MRC 
dyspnea score 3-4 (10 participants) vs. low severity -score 0-2-(10 participants). This variation in the sample will better ensure a range 
of experiences in the data and allow understanding of different opinions and outcomes. Patient activation in particular has been shown 
to impact adherence to self-care regimens, including home monitoring. 
Data Collection 
The primary method of qualitative data collection will be individual semi-structured interviews with a sample of participants in the 
intervention arm (n=40) and study interventionists (n=4). Interviews will be conducted at approximately week 12 (around the time of 
the last interventionist call). We will use an interview guide—reviewed by experts (patients and clinicians)—to ask a combination of 
broad, open-ended questions and focused questions eliciting information about: 1) the participant’s impressions of the program; 2) 
impressions of program effectiveness or perceived benefits; and 3) participant’s prior experience with coaching. The interview guide 
will be informed by program theory, (i.e., self-efficacy theory and MI)15, 16 and the underlying constructs of measures from Aims 1-3.  
To understand the feasibility and acceptability of the program, participants will be asked if they would recommend the program to 
another patient with COPD and what, if anything, they would change. Questions will also elicit feedback on the use of technology and 
barriers and facilitators to long-term adoption. We will ask interventionists to assess perceptions of how well the program fits within 
the current clinical services delivery system and which methods should be modified to enhance feasibility, acceptability, and 
durability of the intervention. Interventionists will be interviewed twice during the study in order to assess program delivery, including 
whether the intervention is being delivered as expected, at different points in the study implementation.  Interviews will be conducted 
by a qualitative research analyst not involved in the intervention. They will take place by phone and be audio recorded and transcribed 
verbatim. After each interview, the interviewer will take detailed notes that describe the context of the interview, emerging themes or 
issues that arose in the interview, areas for clarification, and other comments. These notes and transcripts will be used in analysis. Per 
the reviewers’ suggestions, we purposefully included a qualitative expert, Jennifer Ridgeway, to conduct this analysis and work 
collaboratively with Dr. Matthew Clark, as they have previously reported  qualitative analysis  together.42 
Qualitative Analysis Plan 
Qualitative methods will use directed content analysis. This approach is useful when existing theory informs research questions, and 
researchers are interested in extending the theory or using it to make predictions or look for relationships among variables.43 At least 
two investigators will review the data and use an iterative process to develop labels or codes and then higher-order categories that 
represent key themes related to the study aims. These will be informed by the theoretical assumptions in Aims 1-3. A coding 
framework will be independently applied to transcripts before the investigators discuss and agree on coding. Data will be entered into 
NVivo software (NVivo 10.1, QSR International Pty. Ltd.) or another system for text data management to facilitate queries.  
Integration with Aims 1-3: The function of the mixed-methods design is elaboration of the quantitative data on effectiveness with the 
qualitative findings. After initial quantitative and qualitative analyses are complete, the investigators will place findings side-by-side 
to explore connections as well as divergent findings that need further exploration. This includes within- and between-case analysis to 
understand the perspectives of participants who differed on comparative effectiveness outcomes (Aim 1-3) as well as those who 
differed in important baseline characteristics such as participant activation.  
Sample Size:  We will enroll at total of 200 participants, with 100 in each arm. Sample size calculations are based on two-sample, 
two-sized t-tests comparing the two groups at 3 months. Aim 1: We calculated the sample size based on estimates from our previously 
published data6. From this research, the CRQ has a SD of about 1.13. A total sample of 189 participants (94 or 95 per group) is needed 
to detect a difference of 0.5 (the minimal clinically important difference) in the CRQ with 80% power. Based on our previous health 
coaching application (R01HL09468 Benzo, PI),6 we expect 5% attrition.  We will therefore enroll 200 participants, 100 in each arm.  
Aim 2: A sample size of 128 is needed to detect a half SD change in SMAS-30 based on COPD studies using this measure. Aim 3: 
The number of steps recorded by the AM is considered a valid measure of PA in patients with COPD and the elderly. The clinically 
meaningful difference in steps is estimated at 1100. Therefore, a sample size of 170 participants (85 per group) is needed considering 
a SD of 2500 steps from our previous study.6 Aim 4: The sample size of 40 completed participant interviews is within standards for 
qualitative research, but interviewing and analysis will take place concurrently and iteratively to inform the sampling plan. We will 
continue interviewing until saturation (the point at which interviews are not yielding much new information) is reached; the sample 

Protocol Version 2:  March 1, 2018 
 
 
Page 14 of 17 
 
will be increased as needed to more fully understand variation in the data,44 especially between those who have low (versus high) 
levels of initial participant activation or those who differ in comparative-effectiveness outcomes. We will ensure ample participants to 
represent a range of opinions and investigate variation, rather than statistical testing. In regard to interventionist data collection, we 
will invite all interventionists (n=4) in the study to complete an interview; based on our pilot data, we expect high participation.   
Limitations: While comparing the proposed intervention to center-based PR would be the  ideal study , it would not be feasible 
because most participants cannot attend PR weekly (about 70%)3 and the study would be unlikely to accrue sufficiently. This study is 
geared to capture the population willing to do home PR, and individuals who are confident using technology:  results may not be 
generalizable to all individuals with COPD. We realize that some participants randomly assigned to the control group will receive 
center-based PR, and we plan to document and adjust our model analyses accordingly (intention-to-treat analysis) despite this 
limitations, the study will address a critical need in COPD care: bringing PR to all individuals with COPD. 
Conclusions 
The proposed study will be the first of its kind combining monitored home-based PM with theory-driven SM support 
through health coaching. Since there is no system available for home-based PR delivery the results of this application are 
critically needed in the field of COPD. We envision that the proposed intervention is feasible (already tested) and using 
commercially available software and hardware will be ready to be disseminated if effective.  Health Coaching will bring higher 
participant engagement, better participant provider communication, and possibly improved outcomes. Inclusion of qualitative 
inquiry will strengthen our understanding of our results and provide further information for implementation/ dissemination  
Timeline: This project will take five years to complete. The first year will be spent on institutional approvals (two months); 
development of materials (four months); training of health coaches on site; database creation; and the start of the clinical trial. Years 
2-4 will involve the accrual of all subjects and the completion of the clinical trial. A Method Paper will be produced and published in 
Year 2. The final year will involve the end of the clinical trial (first quarter) data analysis, triangulation of the quantitative with the 
qualitative analysis manuscript publication, and preparations for grant renewal. 
 
YEAR 1 
YEAR 2 
YEAR 3 
YEAR 4 
YEAR 5 
Task  
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Database 
Development  
  
  
  
  
  
  
  
  
  
  
  
  
HC Training 
  
  
  
  
  
  
  
  
  
  
  
  
Recruitment  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Clinical Trial 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Monthly 
Team 
Meetings 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Qualitative 
Interviews 
  
  
  
  
  
  
  
  
  
  
  
  
Data Analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Publication 
  
  
  
  
  
  
  
  
  
  
  
  
Renewal 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
 
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