Pragmatic Trial to Enhance Quality Safety, and Patient Experience in COPD
Phase: NA
Conditions: Pulmonary Disease, Chronic Obstructive
Sponsor: Seattle Institute for Biomedical and Clinical Research

EQuiP Protocol v8.5 2026.02.24 
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V1.2 10.07.2024 
 
VA Central IRB Form 100 - Protocol Template  
 
 
 
 
Pragmatic Trial to Enhance Quality, Safety, and Patient experience in COPD 
(EQuiP COPD) 
Funding Agency: Patient-Centered Outcomes Research Institute (PCORI); PCS-2021C2-23668 
Principal Investigator: David Au 
Co-Principal Investigator: Lucas Donovan 
02/24/2026 
Version 8.5 
 
 
VA Central IRB
Effective Date:
March 9, 2026

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V1.2 10.07.2024 
 
VA Central IRB Form 100 - Protocol Template  
 
Revision History 
Revision # 
Version Date 
Summary of Changes 
V8.5 
02/24/2026 
Section 9.5 Study Evaluations 
• 
Addressed typo in Table 2 describing secondary 
outcome of COPD care quality 
• 
For secondary outcome of patient-incurred cost, we 
clarified that we will estimate patient incurred costs for 
COPD services that may be provided as a result of 
the intervention.  
• 
Corrected information in Table 3 to state that data 
informing Veterans drive time will be derived from the 
corporate data warehouse (CDW). 
• 
Updated Table 4 to align with intervention elements 
described in Table 2. 
Section 17 Privacy & Confidentiality 
• 
Addressed two typos in text 
V8.4 
12/15/2025 
Section 1.0 Key Personnel 
• 
Updated VISN 17 Jennifer Gunter qualification 
description to new job position 
Section 9.5: Aims 1 and 2 
• 
Clarified that we will use EHR/administrative data 
from the corporate data warehouse as well as 
chart review to obtain quality of care outcomes 
and clinical outcomes. 
Section 9.5.2 Aim 4 (heterogeneity in treatment effect) 
• 
Added details to heterogeneity of treatment effect 
description re: additional analyses to assess 
associations between patient, provider and health 
system characteristics/processes with care 
delivery and patient outcomes.  
 
V8.3 
09/04/2025 
Section 1.0 Key Study Personnel 
• 
Removing Dr. John T. Huggins from Ralph H. 
Johnson VA Study Personnel 
V8.2 
08/18/2025 
Section 1.0 Key Study Personnel 
• 
Replaced Dr. Givens as site PI at Mann-Grandstaff 
VA with Dr. Lambert 
V8.1 
07/01/2025 
Section 1.0 Key Study Personnel 
• 
Updated Dr. Givens’ credentials and qualifications 
 
V8.0 
5/07/2025 
Updated entire Protocol to current cIRB template 
version 1.2. New sections with content not in 
previous version include: 
• 
2.0 Participating Local Sites 
• 
4.0 Collaborations 
• 
6.0 Risk/Benefit Ratio 
• 
9.7 Data and/or Specimen Use 
• 
15 Sharing of Results 
Changes to Protocol in this submission: 
Section 1.0 Key Study Personnel 
VA Central IRB
Effective Date:
March 9, 2026

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VA Central IRB Form 100 - Protocol Template  
• 
Added biostatistician co-investigator to ECHCS 
• 
Change in co_PI at Mann-Grandstaff VA from Dr. 
Lambert to Dr. Givens 
Section 9.6.2 EHR Abstraction/CDW 
• 
Clarified wording in Description column for some 
of the cost elements 
Section 11.2 Recruitment Methods-Patients 
• 
Updated survey collection methods to be more 
general and include either Qualtrics or REDCap 
Section 17.1 Data Protection 
• 
Updated survey collection methods and storage to 
be more general and include either Qualtrics or 
REDCap 
Section 17.2 Online Surveys 
• 
Changed section header for “Qualtrics” to “Online 
Surveys” to include both Qualtrics and Redcap 
• 
Generalized language to include both Qualtrics 
and Redcap as data capture tools 
      Section 18.2 Data Analysis 
• 
Consistent with best practices in clinical trials 
advocated by FDA, we updated analytic model to 
add stratification variables for randomization as 
covariates (site and clinician type: physician or 
advanced practice practitioner).  
Section 18.4: Sample Size and Power 
• 
In alignment with executive orders, we removed 
the term gender. 
v7.1 
3/10/2025 
Section 5.3.4 Recruitment Methods: Pharmacists and 
Pulmonologists 
• 
Added new information around the recruitment of 
interventionists for qualitative interviews 
Section 5.4.4 Informed Consent Procedures: Pharmacists 
and Pulmonologists 
• 
Added new information around the recruitment of 
interventionists for qualitative interviews 
Section 5.7.3 Qualitative Interviews: 
• 
Added additional interviews of pharmacists and 
pulmonologists as part of Aim 5. 
v7.0 
1/23/2025 
Section 5.1 Study Design 
• 
Updated Figure 3 to reflect the cost outcomes 
added 1/20/2023 
Section 5.7.2 EHR abstraction/CDW: 
• 
Added minor correction to imprecise language 
Section 5.8 Data Analysis 
• 
Revised model back to the originally planned 
general linear mixed model (GLMM).  Through 
ongoing discussions with our biostatisticians, we 
decided to pursue a generalized linear mixed 
model as this approach will average treatment 
effects over the PCP population. Since PCPs 
comprise the unit of randomization, we felt that 
GLMM was the most appropriate approach. 
v6.7 
11/22/2024 
Section 5.1 Study Design 
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VA Central IRB Form 100 - Protocol Template  
• 
Updated Figure 4 to reflect prior change to one 
primary outcome (composite of COPD 
exacerbation, pneumonia, hospitalization, or 
death) 
Section 5.7.2 EHR Abstraction/CDW 
• 
Updated Table 2 to clarify eligible patients for 
each quality-of-care outcome 
Section 5.7.3 Qualitative Interviews 
• 
For PCP and Leadership interviews: Added that 
we may use email or Teams to arrange the 
interview times, and may follow up for minor 
clarifications via encrypted email or Teams 
v6.6 
10/03/2024 
Sections 1.0 Study Personnel 
• 
Removed Dr. George Sayre as Key Personnel 
because he retired from VA 
• 
Revised this section to show only Key Personnel 
Sections 5.8.6 Qualitative Data Analysis 
• 
Replaced Dr. George Sayre with Dr. Lucas Donovan 
who will oversee qualitative data analysis 
v6.5 
8/14/2024 
Section 1.0 Study Personnel  
• 
Added: Kristine Beaver and Jennifer Ives 
• 
Removed: Dyuti Shreya Nandy 
Section 5.2 Inclusion/Exclusion Criteria 
• 
Caregiver qualitative interviews: exclude 
caregiving paid for by the VA or other healthcare 
organization 
Sections 5.4.3 and 5.4.4: Informed Consent 
• 
Corrected typo 
Section 5.7.3 Qualitative Interviews 
• 
Increasing number of caregiver interviews from 10 
to 20 to increase ability to detect themes 
• 
Clarified language to reflect that we may continue 
to interview beyond the target enrollment until 
saturation is reached for all qualitative interview 
participant groups 
v6.4 
05/09/2024 
Throughout:   
• 
Corrected outcomes periods chosen a priori to 
reflect 90 days (previously stated three months) 
for Quality of Care and Quality of life, and 180 
days (previously stated six months) for Clinical 
and Cost outcomes  
Section 6.3 Adverse Event Monitoring 
• 
Clarified ambiguous language defining what 
adverse events are considered expected in the 
EQuiP population of participants who have COPD 
to correspond with DSMB approved Charter v2.1 
v6.3 
04/05/2024 
Section 5.7.3 Qualitative Interviews 
• 
For qualitative interviews, we clarified that we will 
invite providers with a variety of characteristics, 
which may not result in inclusion depending on 
willingness to participate 
Section 5.7.5 Payments 
• 
Adding option of paying participants by gift card 
VA Central IRB
Effective Date:
March 9, 2026

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VA Central IRB Form 100 - Protocol Template  
v6.2 
03/08/2024 
Section 1.0 Study Personnel 
• 
Removed Scott Coggeshall and Kevin Duan as 
key personnel 
Section 6.3 Adverse Event Monitoring 
• 
Our trial defines SAEs as events that result in 
hospitalization or death. The protocol uses 
ambiguous instructions around identifying SAEs, 
causing coordinators to flag emergency room 
visits or outpatient COPD exacerbations as SAEs. 
Emergency room visits and outpatient COPD 
exacerbations are not considered serious unless 
they result in a hospitalization.  We have updated 
the Protocol and DSMB Charter accordingly. 
v6.1 
01/10/2023 
Section 1.0 Study Personnel 
• 
Added Fiona Gillen and Alison McGrath at VA 
Puget Sound 
• 
Removed Anna Pannick, Taran Paul, and Katie 
Tirtanadi at VA Puget Sound 
• 
Removed Erik Sorenson from Mann Grandstaff 
VA 
• 
Added Matthew Griffith and Kevin Josey at 
Eastern Colorado Heath Care System 
• 
Added missing emails 
Section 2.3 Study population and research settings 
• 
Removed specifications for subgroups 
Sections 3.0 Objectives, 5.2 Inclusion/Exclusion criteria, 
5.3 Recruitment Methods, 5.4 Informed Consent 
Procedures, 5.7 Study Evaluations, and 5.8 Data 
Analysis:   
• 
Modified to reflect activities around addition of new 
Patient Cost Aim  
Section 5.7.2 EHR abstraction/CDW 
• 
Updated Table 2: added “continuation” to 
“Escalation of smoking cessation medications”; 
removed “tapering” from “Discontinuation /tapering 
of COPD treatment”; added “COVID vaccination”. 
Section 5.4.3, 5.4.4, and 5.7.3 Qualitative interviews 
• 
Removed outdated text about requesting patient 
consent at a future date 
• 
Added recruitment and consent details for 
Caregivers and VA Leadership 
• 
Added that we will revise interview guides 
iteratively based on data collected and to address 
any participant comprehension or clarity issues 
that arise 
Section 5.7.5 Payments  
• 
Clarified that only patients and patient caregivers 
will receive payment for completing the qualitative 
interviews 
Section 6.3 Adverse Event Monitoring 
• 
We lengthened the SAE reporting period from 90 
days to 180 days to match the primary outcome 
timeframe 
VA Central IRB
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March 9, 2026

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VA Central IRB Form 100 - Protocol Template  
v5.0 
07/18/2023 
Section 1.0 Study Personnel 
• 
Added Howard Li at Ralph H. Johnson VA 
Section 5.3.2. Recruitment Methods: Patients 
• 
Added text messaging to options for sending 
reminders and/or Qualtrics links  
• 
Updated the timeframe to contact non-responders 
to one week to account for faster delivery time for 
those who received an email 
Section 5.4.2 Informed Consent Procedures Patient, 5.7.3 
Qualitative Interviews, and 7.1 Data Protection 
• 
Updated description of qualitative interviews 
including recording and transcription via VA 
Microsoft Teams 
• 
Removed interview guides from appendix  
Section 5.8.1 Data Analysis 
• 
Clarified who are eligible patients and what we 
consider the index date 
v4.1 
06/21/2023 
Cover Sheet: added NCT number 
List of abbreviations: updated 
Section 1.0 Personnel 
• 
Updated staff 
Abstract, Section 3.0 Objectives and 5.8 Data analysis:  
• 
Based on recommendations and feedback from 
the DSMB around multiple comparisons, we 
decided to focus on a single primary outcome. The 
composite outcome of exacerbation, pneumonia, 
hospitalization, or death within 180 days will 
remain as the primary. We reclassified CCQ and 
quality of care received as secondary endpoints 
• 
Revised model from Generalized linear mixed 
model (GLMM) to generalized linear models 
(GLM) to account for correlation of outcomes 
among PCPs. We chose GLM since we do not 
believe that conditioning on PCPs leads to 
substantial precision gains in estimating adverse 
events and since it is robust to model 
misspecification of the within PCP correlation (i.e., 
random effects)  
Section 5.2 Inclusion/Exclusion criteria 
• 
Added diagnosis of COPD to pathway 5 to ensure 
we identify all patients who may benefit from the 
intervention 
Section 5.3.2.2 Qualtrics and 7.2 Qualtrics online surveys:  
• 
Link to Qualtrics will be via generic unencrypted 
email because of new IT limitations on mail 
merging to an encrypted email 
Section 5.6.1 Patient identification: 
• 
Removed list of patient priorities because already 
listed in Section 5.2 
• 
Included EHR notation as a means of notifying 
pharmacists and pulmonologists about patients 
they will review 
Section 6.3 Adverse Event Monitoring: 
VA Central IRB
Effective Date:
March 9, 2026

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VA Central IRB Form 100 - Protocol Template  
• 
Added the following as an expected event: Known 
side effects from recommended pharmacologic 
and non-pharmacologic treatments (e.g., ICS- 
thrush, pneumonia, pulmonary rehabilitation – 
musculoskeletal injuries) 
Appendix 1 and 2: 
• 
Removed from protocol because 
recommendations will occur as part of usual care 
and will vary accordingly 
v3.0 
2/14/2023 
Section 1.0 Personnel 
• 
Added pharmacists and coordinators 
• 
Indicated that LSI staff will not obtain consent 
Section 5.2 Inclusion/Exclusion Criteria and 5.6.1 Patient 
Identification 
• 
Removed Pathway 6 (evidence of COPD); these 
patients are less likely to benefit from the 
intervention than the other five categories which 
identify sufficient numbers of patients 
Section 5.3.1 Recruitment Methods, Providers and 5.4.1 
Informed Consent Procedures, Providers 
• 
Providers who want to opt out will email the study 
team instead of answering a REDCap survey 
question to minimize barriers to opt out 
Section 5.5 Randomization 
• 
Removed median panel size as a stratification for 
randomization (determined no empirical 
justification to include) 
Section 5.6.2 Intervention Delivery 
• 
Clarified text around order entry to recognized 
differences in order entry between sites.  
Section 5.7.3 Qualitative interviews 
• 
Clarified that PCP and leadership interviews are 
under waiver of informed consent; informed 
consent for pt interviews is pending 
Section 6.3 Adverse Event Monitoring 
• 
Updated timing to query the EHR for AEs to 180 
days 
• 
Clarified that we will report unexpected, serious, 
related AEs to the IRB 
Section 8.0 Communication Plan 
• 
Added study-specific SharePoint as a method of 
collaboration 
v2.0 
10/24/2022 
Section 1.0 Study Personnel 
• 
Added staff, updated roles 
Abstract and Section 2.3: Study population and research 
settings 
• 
Changed Massachusetts to South Carolina per 
pervious change in study site not corrected on 
prior protocol version 
Sections 5.1 Study Design, 5.6: Intervention, and 8.0 
Communication Plan 
• 
Modified language to clarify the pragmatic 
approach for recommendation delivery that 
VA Central IRB
Effective Date:
March 9, 2026

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VA Central IRB Form 100 - Protocol Template  
includes placing e-consults to pulmonologists and 
pharmacists to conduct standard-of-care review 
• 
Replaced “interventionist” with “specialist” to better 
reflect standard-of-care activities   
v1.2 
9/20/2022 
Section 5.7.3: Qualitative Interviews 
• 
Added information about recording and 
transcribing interviews 
Section 5.7.5: Payments 
• 
Added information about method of payment and 
frequency and SIBCR’s access to identifying 
information 
v1.1 
8/23/2022 
(edits requested by CIRB before review and included in 
v01.2) 
Section 1.0: Study Personnel 
• 
Added Jennifer Gunter for V17 
Section 5.2: Inclusion/Exclusion Criteria 
• 
Clarified inclusion criteria for ICS use is for those 
who do not meet criteria “for ICS use” 
Section 5.3.2, 5.4.2: Recruitment Methods, Patients and 
Section 5.7.3: Study Evaluations, Qualitative Interviews 
• 
Added details around the interview process and 
timing 
• 
Revised consent method for patient interviews 
from Waiver of Documentation of Consent to full 
written consent given that the interview is 
recorded 
• 
Clarified process for sending secure link to 
Qualtrics 
Sections 5.4: Randomization and Section 5.5: Informed 
Consent Procedures  
• 
Sections swapped to reflect flow of the protocol 
Section 5.9: Withdrawal of Subjects 
• 
incorrectly stated that patient activity was 
restricted to the CCQ; corrected to include 
qualitative interview  
Section 6.0: Reporting 
• 
Corrected outlining levels 
v1.0 
8/11/2022 
• 
Major revisions to Procedures, Reporting, Privacy 
and Confidentiality, and Communication plan to 
conduct full trial including recruitment, enrollment, 
and outcome assessment for five VA sites. 
• 
Outline subheadings changed from alphabetical to 
numerical; and some reworded to better reflect 
content 
• 
Minor grammatical/formatting changes throughout 
v00.3 
6/2/2022 
List of Abbreviations:  
• 
Entries added 
Section 5.1: Study Design 
• 
Indicated no participant contact during Phase 1 
Section 5.2: Recruitment Methods 
• 
Clarified EHR information accessed 
Section 7.0: Privacy and Confidentiality 
• 
Specified no data sharing for Phase 1 
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VA Central IRB Form 100 - Protocol Template  
• 
Clarified EHR information accessed 
v00.2 
5/16/2022 
Section 1.0: Study Personnel 
• 
Removed staff no longer with the project 
Section 5.4: Inclusion/Exclusion Criteria 
• 
Clarified criteria involving COPD 
 
Abstract 
Background and Significance: Over 26 million Americans have chronic obstructive pulmonary 
disease (COPD), and for most of these patients, the quality of COPD care is poor. Few patients 
receive evidence-based therapies that are known to improve outcomes, and many patients 
experience avoidable harms after receiving therapies that are known to have safer alternatives. 
Efforts to address poor quality care through education and outreach have been largely 
unsuccessful, primarily due to the competing demands of primary care providers (PCPs) who 
manage COPD for over 90% of patients. To overcome these barriers, our research team 
developed a population management approach where pulmonary specialists provide evidence-
based recommendations as an E-consult with unsigned orders to PCPs. PCPs then review the 
E-consult and sign or discontinue these orders. We found this intervention led to marked 
improvements in the quality-of-care delivered and patients’ COPD-related quality-of-life. While 
promising, this population management approach is limited by a paucity of pulmonary providers 
nationwide. There are regional efforts to involve clinical pharmacists into this type of care as 
pharmacists are 20 times more prevalent as pulmonary specialists. However, the relative 
effectiveness of pharmacist-led management is yet to be established, limiting uptake of 
pharmacist-led population management in usual care.  
Specific Aims: assessing the patient-centered outcomes and health system processes 
impacted by population management:  
• 
Aim 1: Examine whether quality of COPD care is non-inferior among patients with COPD 
who receive proactive population management performed by clinical pharmacists relative to 
pulmonary specialists.     
• 
Aim 2: Examine whether patient-centered outcomes are non-inferior among patients with 
COPD who receive proactive population management performed by clinical pharmacists relative 
to pulmonary specialists.  Patient-centered outcomes will include COPD-related quality of life 
(Aim 2a) and adverse clinical outcomes (Aim 2b).  
• 
Aim 3: Examine whether patient and caregiver cost burdens are non-inferior among 
patients with COPD who receive proactive population management performed by clinical 
pharmacists relative to pulmonary specialists.  
• 
Aim 4. Examine heterogeneity of treatment effect among patients known to be at risk for 
lower quality services.    
• 
Aim 5. Seek patient, caregiver, primary care, and health system leaders’ perspectives on 
acceptability, engagement, satisfaction and/or costs through qualitative interviews.  
Study Description: We propose a cluster randomized clinical trial at 5 medical centers and 
associated clinics within the Department of Veterans Affairs (VA) in the states of Washington, 
Oregon, Minnesota, and South Carolina. We will randomize PCPs to population management 
conducted by either pulmonary specialists or pharmacists. Within PCPs’ panels, we will use the 
electronic medical record to identify patients diagnosed with COPD who have evidence of a 
recent COPD exacerbation or potentially inappropriate treatment.  Pulmonary specialists and 
pharmacists will review patients identified within panels of their assigned PCPs. After review, 
pulmonary specialists and pharmacists will deliver evidence-based recommendations through 
E-consults coupled with unsigned orders for primary care providers to sign, modify or decline.  
VA Central IRB
Effective Date:
March 9, 2026

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VA Central IRB Form 100 - Protocol Template  
 
Outcomes:  
• 
Primary: Incidence of a composite endpoint of COPD exacerbation, pneumonia, 
hospitalization, or death. 
• 
Secondary:  1) the proportion of guideline recommended therapies received by patients, 
2) COPD-related quality-of-life as measured by the Clinical COPD Questionnaire, 3) PCP 
acceptance of recommendations, and 4) incidence of each individual outcome within the 
primary composite endpoint above. 
 
Timeframe: We will follow patients for 180 days after intervention for the primary outcome. 
 
 
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VA Central IRB Form 100 - Protocol Template  
List of Abbreviations 
CBOC: community-based outpatient clinic 
CCQ: Clinical COPD Questionnaire 
CDW: corporate data warehouse 
Co-I: co-investigator 
COPD: chronic obstructive pulmonary disease 
CRADA: Cooperative Research and Development Agreement  
DISCUSS COPD: De-implementing Inhaled Steroids to Improve Care and Safety in COPD 
DUA: Data Use Agreement 
EHR: electronic health record 
EQuiP COPD: Enhance Quality Safety, and Patient experience in COPD 
ER: emergency room 
FTE: full-time equivalent 
GEE: Generalized estimating equation 
GLM: Generalized linear model 
ICC: Intra-cluster correlation 
ICS: inhaled corticosteroid 
InCasE: Integrating Care After Exacerbation of COPD 
ISO: information security officer 
JLV: Joint Legacy Viewer 
MID: minimal important difference 
NCT: National Clinical Trial 
NIH: National Institutes of Health 
OI&T: Office of Information and Technology  
PBM: Pharmacy Benefits Management 
PCORI: Patient-Centered Outcomes Research Institute 
PCP: primary care provider 
PHI: protected health information 
PI: principal investigator 
PO: privacy officer 
PRECIS: Pragmatic Explanatory Continuum Indicator Summaries 
RCI: referral coordination initiative 
RCS: Record control schedule  
REDCap: Research Electronic Data Capture 
SD: standard deviation 
SIBCR: Seattle Institute for Biomedical and Clinical Research 
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VA Central IRB Form 100 - Protocol Template  
VA: Veterans Affairs 
VHA: Veterans Health Administration 
VINCI: VA Informatics and Computing Infrastructure  
VISN: Veterans Integrated Service Network 
VSSC: Veterans Support Service Center 
 
 
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VA Central IRB Form 100 - Protocol Template  
Contents 
1.0 
Key Study Personnel .............................................................................................................................. 15 
2.0 
Participating Local Sites .......................................................................................................................... 17 
3.0 
Coordinating Center ................................................................................................................................ 17 
4.0 
Collaborations ......................................................................................................................................... 17 
5.0 
Background and Rationale ...................................................................................................................... 17 
5.1 
Research Question/Background ..................................................................................................... 17 
5.2 
Preliminary Data ................................................................................................................................ 18 
5.3 
Study population and research setting(s) ...................................................................................... 21 
6.0 
Risk/Benefit Ratio ................................................................................................................................... 21 
7.0 
Objectives ............................................................................................................................................... 22 
7.1 
Specific Aims .................................................................................................................................... 22 
7.2 
Relevance to Veterans and the VA .................................................................................................. 23 
8.0 
Study and Safety Outcomes ................................................................................................................... 23 
9.0 
Research Design and Methods ............................................................................................................... 23 
9.1 
Study Intervention ............................................................................................................................... 23 
9.1.1 
Patient identification: ....................................................................................................................... 24 
9.1.2 
Intervention delivery: ....................................................................................................................... 24 
9.1.3 
Intervention fidelity: ......................................................................................................................... 24 
9.2 
Study Design ....................................................................................................................................... 24 
9.3 
Study Procedures ............................................................................................................................... 26 
9.3.1 
Providers: ........................................................................................................................................ 26 
9.3.2 
Patients: .......................................................................................................................................... 26 
9.3.3 
Caregivers: ...................................................................................................................................... 26 
9.3.4 
VA Leadership, pulmonary and pharmacist interventionists: .......................................................... 26 
9.4 
Randomization .................................................................................................................................. 27 
9.5 
Study Evaluations ............................................................................................................................. 27 
9.6.1 
Self-reported patient questionnaires: .............................................................................................. 27 
9.6.2 
EHR abstraction/CDW: ................................................................................................................... 27 
9.7 
Qualitative interviews (Aim 5: qualitative perspectives): ................................................................. 30 
9.8 
COVID-19 considerations: .............................................................................................................. 31 
9.9 
Payments: ....................................................................................................................................... 31 
9.6 
Study Duration .................................................................................................................................... 31 
9.7 
Data and/or Specimen Use ................................................................................................................. 31 
9.8 
Data and/or Specimen Banking .......................................................................................................... 33 
10.0 
Study Population ..................................................................................................................................... 33 
10.1 
General Characteristics....................................................................................................................... 33 
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10.2 
Inclusion and Exclusion Criteria .......................................................................................................... 33 
10.3 
Populations Requiring Additional Considerations ............................................................................... 34 
11.0 
Recruitment Methods .............................................................................................................................. 34 
11.1 Providers: ............................................................................................................................................ 34 
11.2 
Patients: .......................................................................................................................................... 35 
11.2.4 
Caregivers: .................................................................................................................................. 35 
11.2.5 
VA Leadership including Pharmacists and Pulmonologists: ....................................................... 35 
12 
Enrollment Procedures ........................................................................................................................... 36 
12.2 
Screening ............................................................................................................................................ 36 
12.3 
Informed Consent Process and Documentation ................................................................................. 36 
9.9.1 
Providers: ........................................................................................................................................ 36 
9.9.2 
Patients: .......................................................................................................................................... 36 
9.9.3 
Caregivers: ...................................................................................................................................... 36 
9.9.4 
VA Leadership, pulmonary and pharmacist interventionists: .......................................................... 36 
13 
Participant Payment ................................................................................................................................ 36 
14 
Withdrawal of Participants ...................................................................................................................... 37 
15 
Sharing of Results ................................................................................................................................... 37 
16 
Data Safety, Monitoring and Reporting ................................................................................................... 37 
6.1 
Quality Monitoring ............................................................................................................................ 37 
6.2 
Data Safety and Monitoring Board (DSMB): ................................................................................... 37 
6.3 
Adverse Event Monitoring: .............................................................................................................. 37 
17 
Privacy and Confidentiality ...................................................................................................................... 38 
17.1 
Data protection .................................................................................................................................. 38 
17.2 
Online surveys .................................................................................................................................. 39 
17.3 
Data sharing ...................................................................................................................................... 39 
17.4 
Data destruction ................................................................................................................................ 39 
18 
Data Analysis Plan .................................................................................................................................. 40 
18.1 
Aims 1, 2 & 3: ................................................................................................................................. 40 
18.2 
Aim 4a: ........................................................................................................................................... 40 
18.3 
Aim 4b: ........................................................................................................................................... 41 
18.4 
Sample Size and Power: ................................................................................................................. 41 
18.5 
Alternate approaches, threats to validity, and limitations: ............................................................... 42 
18.6 
Aim 5. qualitative data analysis: ...................................................................................................... 42 
19 
Multi-Site Communication Plan ............................................................................................................... 42 
20 
References .............................................................................................................................................. 43 
 
 
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1.0 
Key Study Personnel  
Role 
Name 
Cred 
Contact Information 
(Email and Phone) 
Affiliation 
Qualifications 
 
Access 
SPI 
VA Puget Sound 
Co-Principal  
Investigator 
 
Lucas M. Donovan 
 
MD, MS Lucas.Donovan@va.gov 
206 – 277 – 6783 
8/8th VA Pulmonary, Critical Care, 
and Sleep physician, Co-
Associate Director of the 
VA HSR&D Denver-
Seattle COIN, Associate 
Professor of Medicine at 
the UW SOM 
Y 
Co-Principal  
Investigator 
    
David H. Au 
 
MD, MS 
david.au@va.gov 
206 – 277 – 6132 
8/8th VA 
Professor of Medicine, 
University of Washington; 
Director, VA Center for 
Care and Payment 
Innovation 
Y 
Co-Investigator  
 
Laura Feemster 
 
MD, MS Laura.Feemster@va.gov 
  206 – 764 – 2504  
8/8th VA Pulmonologist and critical 
care Physician, Co-
Associate Director of the 
Seattle-Denver COIN, 
Associate Professor of 
Medicine at the University 
of Washington School of 
Medicine. 
Y 
Mann-Grandstaff VA 
Co-Investigator 
    
Allison Lambert 
 
MD, 
MHS 
Allison.Lambert3@va.gov 
  509 – 434 – 7264    
8/8th VA Pulmonologist, critical 
care physician, and an 
NIH-funded investigator 
and clinical researcher 
Y 
Portland VA 
Co-Investigator 
 
Christopher 
Slatore 
 
 
MD, MS Christopher.Slatore@va.g
ov 
  503 – 220 – 8262  
8/8th VA 
Professor, Pulmonary & 
Critical Care Medicine; 
VAPORHCS/OHSU 
Y 
Minneapolis VA 
Co-Investigator 
 
Anne Melzer 
 
MD, MS 
Anne.Melzer2@va.gov 
  612 – 725 - 2000 
8/8th VA Associate Professor of 
Medicine at the University 
of Minnesota Medical 
School and a Core 
investigator at the Center 
for Care Delivery and 
Outcomes Research 
(CCDOR) 
Y 
Site Co-
Investigator 
 
Arianne 
Baldomero  
 
MD 
Arianne.Baldomero@va.g
ov 
  612 – 725 - 2000 
8/8th VA Associate Professor of 
Medicine at the University 
of Minnesota Medical 
School and a Core 
investigator at the Center 
for Care Delivery and 
Outcomes Research 
(CCDOR) 
Y 
Ralph H. Johnson VA 
Co-Investigator 
 
Nichole Tanner 
 
MD 
Nichole.Tanner@va.gov 
  843 – 789 – 7341  
8/8th VA Professor of Medicine, 
Director of the Lung 
Precision Oncology 
Program (LPOP).  
Y 
Site Co-
Investigator 
Tatsiana Beiko 
 
MD 
Tatsiana.Beiko@va.gov 
  843 – 577 – 5011  
8/8th VA Associate Professor of 
Medicine, Pulmonologist 
Y 
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specializing in asthma, 
COPD, critical care 
medicine, and pleural 
disease. 
Site Co-
Investigator 
 
William McManigle 
 
MD 
William.McManigle@va.go
v 
  843 – 789 – 7187  
8/8th VA Assistant Professor of 
Medicine 
Division of Pulmonary, 
Critical Care, Allergy & 
Sleep Medicine 
Medical University of 
South Carolina, 
Charleston, SC, 
Staff Pulmonologist 
Pulmonary Section of the 
Medical Service 
Ralph H. Johnson 
Veterans Affairs Medical 
Center, Charleston, SC 
Department of Veterans 
Affairs 
Y 
Site Co-
Investigator 
 
Howard Li 
 
MD 
Howard.Li@va.gov 
843 – 577 - 5011 
8/8th VA Deputy Chief of 
Pulmonary, Ralph H. 
Johnson Veterans Affairs 
Medical Center 
Y 
VISN 17 
Site Co-
Investigator 
 
Jennifer Gunter 
 
 
Jennifer.Gunter@va.gov 
817 – 385 – 5978 
8/8th VA Neurology Clinical 
Pharmacist Practitioner, 
VISN17 Clinical Resource 
Hub 
Y 
Eastern Colorado Health Care System 
Site Co-
Investigator 
 
Matthew Griffith 
 
 
Matthew.Griffith@va.gov 
720 – 723 – 6091 
8/8th VA Staff Pulmonary and 
Critical Care Medicine 
Physician at the Rocky 
Mountain Regional VA 
Medical Center (RMR 
VAMC), Assistant 
Professor in the Division 
of Pulmonary Sciences 
and Critical Care Medicine 
at the University of 
Colorado School of 
Medicine  
Y 
Site Co-
Investigator 
Kevin Josey 
 
Kevin.Josey@va.gov 
303-827-8524 
IPA VA 
Assistant Professor of 
Biostatistics, University of 
Colorado, Denver; 
University of Colorado 
Denver Research affiliate 
 
 
 
 
 
 
 
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2.0 
Participating Local Sites  
 
5 sites 
Site name 
Role in Project 
Seattle, WA - Puget Sound Health 
Care System 
Primary site-recruitment, data 
collection, data storage 
Spokane, WA - Mann-Grandstaff 
VAMC 
Local site for patient care activities 
SC - Ralph H. Johnson VAMC 
Local site for patient care activities 
Portland, OR - Portland VAHCS 
Local site for patient care activities 
Minneapolis, MN - Minneapolis 
VAHCS 
Local site for patient care activities 
Aurora, CO - Eastern Colorado 
VAHCS 
Co-investigator Site 
Temple, TX - Central Texas VAHCS 
Co-investigator Site 
 
3.0 
Coordinating Center  
There is no coordinating center for this project. 
4.0 
Collaborations  
 
 Data Safety and Monitoring Board: 
See more information around DSMB procedures and role in section 16. All information shared with the DSMB 
will be deidentified.  
5.0 
Background and Rationale  
 
5.1 
Research Question/Background 
Chronic obstructive pulmonary disease (COPD) affects up to 26 million Americans and is not only the fourth 
leading cause of disability adjusted life years but also the fourth leading cause of death.1,2 COPD frequently 
causes symptoms of shortness of breath, cough, and wheeze that impair quality of life. These chronic daily 
symptoms escalate quickly during periods of exacerbation, which are life-threatening and can lead to 
permanent reductions in functional capacity.3 Opportunities to improve the well-being of patients exist,4,5 yet 
few patients receive therapies that are known to improve outcomes.6-10 In addition, many patients experience 
avoidable harms6,11 after receiving therapies that are known to have safer alternatives. At a population level, 
the overall quality of care for COPD is poor, and efforts to improve care have been largely unsuccessful. Due 
to this lack of progress, the National Institutes of Health (NIH) set forth the first national COPD action plan in 
2017 that addresses important goals for COPD and emphasizes innovation, quality, and delivery of services to 
improve the well-being of patients with COPD. 12    
Ninety percent of patients receive their COPD care within primary care settings, where providers face 
an increasing number of competing demands. For most Americans, primary care providers (PCPs) serve 
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as the central point of care for health maintenance and the treatment of acute and chronic conditions. Over the 
past several decades, primary care also became the center of care coordination.13 At the same time, medical 
knowledge and innovation for COPD and other conditions expanded at exponential rates, creating greater 
degrees of specialization.14  These forces create tension in healthcare delivery.  Innovation drives potential 
improvements in patient well-being but creates quality gaps when those innovations are adopted 
heterogeneously. For purposes of productivity and revenue generation, PCPs have less time with patients 
while needing to address greater documentation and insurance authorization burdens.15-17  PCPs are also held 
to a growing set of quality measures that are increasingly difficult to achieve.  This accumulation of tasks is 
untenable and forces PCPs to choose among many different priorities.15  As many as 90% of patients with 
COPD have competing conditions that often rise in importance over COPD during PCP visits. These include 
common comorbidities, such as hypertension and diabetes, as well as the need for screening and health 
maintenance.18,19  Though this issue of de-prioritization of COPD has been well established, few innovations 
have sought to address this problem.    
Outdated structures of specialty care involvement further limit the health system’s capacity to promote 
high-quality care in COPD. The traditional approach to receiving specialized care for COPD and other 
conditions relies on referrals.20 Unfortunately, specialty care referrals are dependent on a number of factors 
that drive disparities within and between patients.21,22  Referrals require numerous actions on the part of the 
PCP, including the need to accurately recognize, diagnose, prioritize, and refer20,21 patients. Furthermore, 
patients referred to specialty care are typically more severe than those who are not, and specialists miss the 
opportunity to intervene earlier when COPD is less severe and potentially more amenable to preventive 
care.23,24 Finally, the timing of PCP visits may not align with a patient’s need for specialty services, missing an 
important opportunity to provide “the right care at the right time”.21 Improving equity and quality in referral is 
necessary, but not sufficient to encompass all the limitations of the current approach. For example, specialists 
are typically concentrated at large urban medical centers that are distant from patients and primary care 
settings. This concentration creates specific challenges for patients who live in rural areas or where access to 
public transportation is limited.25,26  Rurality and social determinants of health also affect care delivery and 
coordination between specialty and primary care settings. Moreover, for COPD, the number of available 
patients vastly overwhelms the number of available pulmonary specialists. For instance, in the Department of 
Veterans Affairs (VA) there are 4,000 patients with COPD for every pulmonary specialist.27  How to address 
gaps in care delivery, improve quality of care, and patients’ well-being is at the heart of this application.  
Our research group is uniquely suited to face this challenge. As we describe below, our research team, 
operational leaders, and organization have focused on how to improve delivery of specialty care within existing 
health systems.  We have strong evidence to support a population management approach to COPD care that 
realigns existing care structures and processes around patients’ needs while incorporating modern behavioral 
economics. Our evidence demonstrates improvements in access, care quality and well-being for patients with 
a population management approach.  
While promising, key uncertainties remain including: 1) the type of provider who is capable of delivering 
population management (pulmonary specialist or clinical pharmacist), 2) treatment heterogeneity among those 
at risk for low-quality services, and 3) patient and staff perspectives around acceptability, engagement, and 
satisfaction. 
5.2 Preliminary Data  
The current application arises out of decades of work from our group in identifying gaps in quality of care for 
COPD and uncovering strategies to address them. 
Persistent evidence of poor quality of care for COPD:   Efforts over previous decades have failed to 
improve basic delivery of care for patients with COPD.  The National Lung Health Education Program was 
established in 1997 and sought to increase the use of spirometry to confirm the diagnosis of COPD.28 A 
decade later, National Committee on Quality Assurance implemented quality measures focused on that target. 
Consistent across many healthcare systems, there was little improvement in the use of spirometry (Figure 1). 
We found similar poor-quality care across the NIH funded CONCERT consortium that engaged academic 
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centers, health maintenance organizations, and VA 
Medical Centers.29  Similarly, CMS instituted the 
Hospital Readmission and Reduction Protection in 
2014 that penalized hospitals for excessive COPD 
readmission rates.30 The underlying premise was 
that poor-quality hospital care was leading to 
excessive readmissions. We showed that over time, 
there was little objective evidence of change in 
quality over time with only 18% of patients receiving 
all recommended services.31  In separate analyses, 
we found important deviations from evidence-based 
recommendations known to decrease exacerbation 
risk and, in some cases, mortality. Patients 
frequently did not receive smoking cessation 
counseling and pharmacotherapy, long-acting bronchodilators, or follow-up to correct treatment after 
misdiagnosis.8,32,33 We also found notable gaps around prescribing of inhaled corticosteroids (ICS). ICS 
increase risk of pneumonia and are indicated only for the small subset of patients with frequent or severe 
exacerbations.4,5 Nevertheless, we found that nearly 80% of patients being treated for COPD were exposed to 
unnecessary ICS.  
Limited capacity and priority for COPD management in primary care. To better understand the context for 
our findings, we performed qualitative interviews of VA PCPs to assess perspectives around COPD care. We 
found several themes that helped us understand the findings. For example, PCPs did not prioritize COPD 
among other common conditions such as heart failure, diabetes, or hypertension. PCPs also discounted the 
use and value of spirometry to exclude COPD as a source of symptoms.34 More recently, we asked PCPs 
about overuse of ICS. They reported challenges in keeping up to date on disease specific guidelines and were 
generally unaware of evidence regarding the risk of pneumonia associated with ICS.35 These results 
highlighted the challenges driving change in primary care settings. 
Lack of organizational structures and processes to support COPD care. Given the low priority expressed 
by clinicians,36 we hypothesized that poor quality of COPD care also reflected a low degree of organizational 
engagement with structures and processes to support evidence-based care.  We surveyed all VA medical 
centers about their organizational structures and processes to support COPD relative to chronic heart failure, 
an equally prevalent condition.  Consistent with our hypothesis, we found significant differences in 
organizational structures and processes including fewer COPD clinics (COPD 13 vs. Chronic Heart Failure 
51%), performance indicators (17 vs. 70%), and home monitoring programs (51 vs. 87%).37   
Based on our quantitative and qualitative findings, we inferred that an approach that relied on primary care to 
adapt or change would fail. We determined that it was necessary to utilize and reorganize existing structures 
and develop processes to engage those with expertise to support the delivery of care for COPD in primary care 
settings. We tested and demonstrated that a population approach, using pulmonary specialists with proactive, 
unsolicited virtual electronic consultation was effective at improving quality of life and care for patients with 
COPD. At the same time, VA’s national pharmacy benefits management (PBM) followed an analogous 
approach by developing programs and incorporating clinical pharmacists in the population management of 
patients with COPD.    
Redesigning the specialty care approach: population management to improve quality of care in COPD: 
We have completed two multi-site clinical trials demonstrating the effectiveness of a population-based, 
specialist driven proactive intervention to improve care quality and clinical outcomes among patients with 
COPD. Common elements of the interventions included: 1) Engaging all PCPs at VA medical centers and 
community based outpatient clinics (CBOCs) 2) Interrogation of VA electronic health information system to 
identify patient populations; 3) Pulmonary specialists’ engagement to develop evidence-based COPD care 
recommendations (e.g., diagnostic testing, medications therapies/referrals, and follow-up care); 4) Provision of 
a single proactive E-consult note in the chart summarizing the clinical review and providing recommendations 
Figure 1.  Percent of patients with COPD diagnosis and 
confirmatory spirometry 
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timed to coincide with an upcoming PCP visit; and 5) Facilitating uptake of recommendations by entering 
unsigned orders for PCPs to sign, modify or discontinue. 
▪ 
Integrating Care After Exacerbation of COPD (InCasE) (Principal Investigator (PI):32 We used VA’s 
Electronic Health Record (EHR) to identify recent discharge from hospital after a COPD exacerbation. The 
trial included VA Puget Sound Health Care System, the Boise VAMC and their 10 CBOCs. Using a 
stepped-wedge design we enrolled 98% of the 372 eligible PCPs. Between 5/2015-11/2017, 352 of 
patients were discharged. Of the 161 patients in the intervention arm, we made a total of 892 
recommendations. Of the 519 recommendations entered as unsigned orders, 401 (77.3%) were endorsed 
by PCPs. Recommendations focused on additional therapies (n=281), changes to medications (n=91), and 
additional diagnostic testing (n=147). Patients in the intervention arm experienced better quality of life 
(Clinical COPD Questionnaire (CCQ): adjusted difference -0.47 (95% CI, -0.88 to -0.06) , minimal important 
difference (MID) =0.4), and a non-statistically significant [adjusted OR 0.78 (95% CI, 0.47 to 1.31)] risk of 
readmission. 100% patients in the intervention arm had a pulmonary E-consult with recommendations in 
average 7 days (standard deviation (sd) 4.32) days after discharge. In contrast to less than 50% nationally 
for primary care, let alone pulmonary services (Figure 2).   
 
▪ 
De-implementing Inhaled Steroids to Improve Care and Safety in COPD (DISCUSS COPD) (PIs: 
Au/Helfrich, Co-Investigators (Co-I): Feemster, Sayre, Wiener-NCT 02896257): We identified 550 patients 
with COPD prescribed an ICS without an identifiable indication using EHR data.  Patients were seen at the 
VA Puget Sound Health Care System, Bedford VA Medical Center, and their 11 CBOCs. We randomized 
181 PCPs to either the intervention (academic detailing to promote unlearning combined with proactive E-
consult) or control groups (academic detailing alone). Of the 269 patients in the intervention arm, we made 
recommendations to discontinue ICS in 180 (67%) of patients. 171 had accompanying unsigned orders, of 
which 161 (94%) were accepted by PCPs. At six months, patients cared for by intervention providers were 
more than 3 times less likely to be on an ICS [adjusted OR 3.66 (95%CI, 2.50 to 5.38)].  We found no 
increased risk of exacerbation [adjusted OR 0.80 (95% CI, 0.44 to 1.47)] and a non-significant reduction in 
pneumonia [adjusted OR 0.63 (95% CI, 0.20 to 1.96)– not designed to detect effect].   
 
 
Collectively, these interventions demonstrate the potential of proactive specialty care consultation.  The 
intervention systematically overcame geospatial, referral and other access barriers while utilizing existing 
clinical and data infrastructure to improve care delivery and outcomes. We improved specialty care with 
minimal burden to PCPs, patients, or the health system (no new clinic structures or visits required). 
While effective, pulmonary specialists remain a scarce resource nationwide, which has spurred interest in other 
staff capable of engaging in population management. Pharmacists are one such option, given their skillset in 
pharmacotherapy and their prevalence. There are over 20 pharmacists for each pulmonary specialist 
nationwide.38,39 
In the past several years, the VA PBM has engaged 
pharmacists to improve management of numerous chronic 
conditions including COPD.40 PBM created a national 
tracking dashboard to monitor progress and identify 
patients who may benefit from intervention, either directly 
with primary care based clinical pharmacy specialists or 
academic detailing pharmacists. Their dashboard 
highlights that among the 7,723 patients with COPD 
hospitalized each year, 60% do not have follow-up within 
14 days of discharge. Among the 203,964 patients with 
COPD who are prescribed an ICS, 75% do not have an 
indication for ICS in the EHR. Finally, among the 266,319 
patients nationwide with COPD and evidence of tobacco 
use, 70% do not receive pharmacotherapy for smoking 
cessation (Figure 2). 
Figure 2. Widespread gaps in care delivery. 
 
0%
10%
20%
30%
40%
50%
60%
70%
80%
Lack of
Follow Up
After
Exacerbation
Rx for ICS
without
LAMA/LABA
Rx for ICS
despite no
exacerbation
>2 years
Ongoing
tobacco use
and no Rx for
cessation aid
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Pharmacist-led population management of COPD is feasible and extends evidence-based practices. 
Modeled on the population health approach for pulmonary specialists, Jennifer Gunter, PharmD led a similar 
approach to COPD in seven medical VA centers in Texas (Veterans Integrated Service Network (VISN)-17). 
Starting in February 2021, academic detailing pharmacists have conducted proactive patient reviews and 
made recommendations on more than 120 patients. These recommendations included comprehensive 
guideline-based recommendations around ICS discontinuation (88%), inhaler education (15%), spirometry 
(46%), tobacco cessation (28%), and vaccination (56%). Dr. Gunter’s local activities mirror those of the 
national pharmacist-led COPD Care initiative. This initiative is active in 17 facilities nationwide and engages in 
the transition period after discharge from hospital after COPD exacerbations.  
Although pharmacist-led management of COPD is promising, current deployment of these services is on a 
small scale relative to the magnitude of the problem. As confirmed by VA policy leaders, the main barrier to 
wider adoption is a lack of evidence around the effectiveness of pharmacist-led care relative to the default 
specialist physician-led option. The EQuiP trial directly addresses this question. Our non-inferiority design 
mirrors the approach taken previously in assessing the role of pharmacists in other conditions (e.g., 
antimicrobial stewardship) where pharmacist-led care is now widespread.41  
Experience translating programs of non-physician led specialty care services to widespread national 
roll-out:  Decision-making in specialty care has traditionally been restricted to physicians and advanced 
practice providers.42 Such gatekeeping is intended to promote quality, but can limit capacity.42,43 To challenge 
the specialist-only approach, we tested a system known as the referral coordination initiative (RCI) to include 
registered nurses in the decision-making for new specialty care referrals. Nurses and specialists collaboratively 
developed protocols for nurses to make initial management decisions among patients referred to sleep 
medicine. We found nurses in our program were able to make guideline-based decisions in a manner that 
exceeded that of board-certified specialists (Risks of guideline-discordant care 0.5, 95%CI 0.3-0.9).44 
Expanding the pool of decisionmakers led to marked improvement in specialists’ capacity (800 additional 
patient visits/1000 referrals sent to RCI nurses) and timely access to care42. On the basis of our robust 
quantitative and qualitative evaluation, policy leaders in the Office to Veterans Access to Care have supported 
nationwide expansion. Currently, RCI is utilized at over 80% of VA facilities nationwide across multiple 
specialties.  
 
5.3 Study population and research setting(s) 
The VA healthcare system is the largest integrated healthcare system in the country.  VA serves as an 
important safety net system caring for more than nine million Veterans per year. VA includes over 170 
VA Medical Centers and their associated CBOCs nationwide.45 Nearly 1.3 million Veterans have 
COPD, and COPD is the second leading cause of medical hospitalization within VA nationwide.27,46 Our 
trial will recruit all non-trainee PCPs practicing at five VA Medical Centers and their 38 associated 
outpatient clinics in Washington, Oregon, Minnesota, and South Carolina. These academic and non-
academic centers are geographically and clinically diverse with full and part time PCPs (294 full-time 
equivalent (FTE) across 495 individual providers) who together care for nearly 30,000 Veterans 
diagnosed with COPD. Within each PCPs’ panel, we will identify patients with COPD using previously 
validated algorithms.47 We propose to enroll and intervene on at least 200 PCPs and make 
recommendations on approximately 4,000 patients (100 PCPs, and 2,000 patients per arm). We will 
include specific subgroups that have been previously shown to receive lower quality services, including 
patients receiving care at rural facilities. 
6.0 
Risk/Benefit Ratio 
 
This is a minimal risk project, which tests two ways of promoting existing evidence-based and guideline 
concordant usual care. The probabilities and magnitude of harm or discomfort anticipated in the 
research are not greater in and of themselves than those ordinarily encountered in daily life or during 
the performance of routine physical or psychological examinations or tests.   
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Anticipated risks to participants include potential invasion of privacy and/or confidentiality.  To minimize 
this risk, we will remove identifying information from data and store data using a coded number.   
Participants do not receive any direct medical benefit from their participation, as stated in our 
Information Statements.  Potential benefits to science and society include the potential to provide a 
model for integrating pharmacists into population-based COPD care that, if adopted, may improve 
access, care quality, and well-being for Veterans living with COPD. 
7.0 
Objectives 
 
7.1 
Specific Aims  
We are conducting a large pragmatic clustered randomized trial to Enhance Quality Safety, and Patient 
experience in COPD (EQuiP). Directed at PCPs (minimum n=200), we will assess if proactive, population 
management recommendations by clinical pharmacists and pulmonary specialists lead to non-inferior 
outcomes for patients with COPD. 
• 
Aim 1: Examine whether quality of COPD care is non-inferior among patients with COPD who receive 
proactive population management performed by clinical pharmacists relative to pulmonary specialists.   
o Hypothesis 1a: Patients whose PCP was randomized to clinical pharmacist will have non-
inferior quality of care when compared to pulmonary specialists. 
o Hypothesis 1b: PCPs will accept a non-inferior proportion of recommendations from clinical 
pharmacists compared to pulmonary specialists.  
• 
Aim 2: Examine whether patient-centered outcomes are non-inferior among patients with COPD who 
receive proactive population management performed by clinical pharmacists relative to pulmonary 
specialists.  
o Aim 2a: Assess whether COPD-related quality of life is non-inferior among patients with COPD 
who receive proactive population management performed by clinical pharmacists relative to 
pulmonary specialists 
▪ 
Hypothesis 2a: Patients whose PCP was randomized to a clinical pharmacist will have 
non-inferior COPD-related quality of life compared to pulmonary specialists 
o Aim 2b: Assess whether clinical outcomes are non-inferior among patients with COPD who 
receive proactive population management performed by clinical pharmacists relative to 
pulmonary specialists  
▪ 
Hypothesis 2b (PRIMARY HYPOTHESIS FOR TRIAL): Patients whose PCP was 
randomized to a clinical pharmacist will have non-inferior clinical outcomes compared to 
pulmonary specialists. 
• 
Aim 3: Examine whether patient and caregiver cost burdens are non-inferior among patients with 
COPD who receive proactive population management performed by clinical pharmacists relative to 
pulmonary specialists.  
o Hypothesis 3: Patients and caregivers with population health management conducted by 
pharmacists will incur non-inferior personal costs of care when compared to those with care 
conducted by pulmonary specialists. 
• 
Aim 4. Examine heterogeneity of treatment effect among patients known to be at risk for lower quality 
services.   
o Aim 4a: Examine heterogeneity for the primary and secondary outcomes described in aims 1 
and 2.  
▪ 
Hypothesis 4a: The intervention will have non-inferior effects for patients with higher 
degrees of complex multimorbidity, those living in rural areas, and those of different race 
and sex. 
o Aim 4b: Across both arms, assess heterogeneity in patient and caregiver incurred costs among 
groups known to be at high risk for access barriers and lower quality care.  
▪ 
Hypothesis 4b: Patient/caregiver-incurred costs will be higher for patients with greater 
degrees of complex multimorbidity, those living in rural areas, underrepresented minority 
groups, and women 
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• 
Aim 5. Assess qualitative perspectives across a range of stakeholders.  
o Aim 5a: Elicit patient, primary care, and health system leaders’ perspectives on acceptability, 
engagement, and satisfaction through qualitative interviews.  
o Aim 5b: Assess patient and caregiver perspectives about their costs of care incurred through 
qualitative interviews.  
 
7.2 
Relevance to Veterans and the VA 
The intervention is currently standard practice at sites in VISN 12 and 17. Our successful intervention will 
provide a model for integrating pharmacists into population-based COPD care nationwide that, if adopted, may 
improve access, care quality, and well-being for Veterans living with COPD. 
8.0 
Study and Safety Outcomes 
 
We carefully chose outcomes based on importance to patients, caregivers, and key stakeholders. Table 1 
shows a summary of measures, power, and non-inferiority thresholds. More detail is included in section 9. 
 
 
9.0 
Research Design and Methods 
 
9.1 
Study Intervention 
 
Theoretical basis of the intervention: The goal of our intervention is to improve quality of care in a way 
that overcomes barriers arising from clinician biases (i.e., beliefs about COPD) and clinical inertia 
(prioritization). The basis of the intervention is grounded on Nobel Prize winning behavioral economic 
principles referred to as “nudging”.57 Nudges seek to improve the quality of decision-making by changing the 
way that choices are presented. Nudges do not limit choices, reduce agency, or change economic 
incentives.57,58 Instead, nudges use our knowledge of human decision making to make selecting the 
recommended choice easy. In our trial, we will alert pulmonary specialists and pharmacists to create nudges 
for PCPs in the form of recommendations with evidence-based explanations of next steps coupled with 
Table 1. Primary and Secondary Outcomes 
 
 
Aim 
Name of 
outcome 
Specific measure to be used 
Source 
Timing 
(days) 
Power 
Non-Inf  
Thresh 
Aim 1a 
(Secondary) 
Quality of COPD 
care 
Proportion of evidence-based 
practices received (Table 2) 
EHR/CDW  
90 
>0.95 
5%  
Aim 1b 
(Secondary) 
Acceptance of 
Recommendations  
Proportion of recommendations that 
are accepted by PCPs 
EHR/CDW 
90  
 
 
Aim 2a 
(Secondary) 
COPD-related 
quality- of-life 
Clinical COPD Questionnaire 
(CCQ) 
Self-report 
90  
>0.95 
0.25 pts 
Aim 2b 
(Primary trial 
outcome) 
Clinical Outcomes 
(composite 
outcome) 
Proportion of COPD exacerbation, 
pneumonia, hospitalization, or 
Death  
EHR/CDW 
180  
0.90 
6% 
Aim 2b 
(Secondary) 
Clinical Outcomes 
(individual 
outcomes) 
Individual outcomes COPD 
exacerbation, pneumonia, 
hospitalization, and death. 
EHR/CDW 
180  
 
 
Aim 3 
(Secondary) 
Patient costs 
Patient-perspective cost burdens 
EHR/CDW 
180 
NA 
NA 
Aim 4 
(Secondary) 
Heterogeneity of 
treatment effect 
Compare heterogeneity for primary 
and secondary outcomes 
EHR/CDW 
180 
NA 
NA 
Aim 5 
(Secondary) 
Qualitative 
perspective 
Acceptability, engagement, 
satisfaction, and experience: 
patient, caregivers, primary care, 
and health system leaders  
Interview 
90 
NA 
NA 
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unsigned orders that providers can quickly review and sign. This approach aligns with usual care processes 
and permits autonomy by allowing PCPs the ability to decline any recommendations they do not believe are 
appropriate.  
 
9.1.1 Patient identification:  
Weekly, we will run previously validated algorithms to query the CDW to identify patients with COPD 
within the panels of randomized providers at each site. We will prioritize patients who may benefit most 
from intervention as described in Section 10.2. We will identify qualifying patients each week within each 
arm and disseminate, via secure network folder or EHR notation, to pulmonologists and pharmacists at 
the participating sites.  
 
9.1.2 Intervention delivery:  
The core population health management approach will be the same between trial arms. The only 
difference will be whether patients are forwarded to pulmonary or pharmacy staff at each center for 
usual care review. Proactive recommendations around COPD quality from pulmonologists or 
pharmacists are part of usual care in VA (e.g., COPD cares program, DISCUSS program). As part of 
this process, pulmonologists and pharmacists review Veterans’ relevant history and generate an E-
consult detailing their rationale and recommendations. Pulmonologists and pharmacists also create 
orders as needed in the electronic medical record for PCPs to either endorse (sign), modify, or delete. 
As part of the trial, we will distribute draft guides to pulmonologists and pharmacists at each institution 
outlining guideline-recommended best practices, which the pulmonologists can use if they wish. All final 
decisions regarding care will be made by the PCP and their patients as part of usual care.  We will 
monitor orders placed by the pharmacists and pulmonologists and follow-up with them for greater 
education around order placement as appropriate.  
 
9.1.3 Intervention fidelity:  
Fidelity refers to the degree to which an intervention is delivered as intended. Consistent with Thorpe’s 
recommendations for maximizing external validity of pragmatic trials,59 we will monitor fidelity but will 
not artificially control it. We will use a fidelity rubric based on intervention templates and procedures 
finalized during the kickoff meetings, with revisions as necessary based on regular meetings as 
described above. Every six months, study staff will review at least 5% of intervention E-consults in each 
arm and compare documented care against the fidelity rubric.  
 
9.2 
Study Design  
 
Our goal is to test the non-inferiority of pharmacist-led relative to pulmonary specialist-led population 
management to improve meaningful and patient-centered outcomes in COPD. We will conduct a two-
arm clustered randomized trial with PCPs being the unit of randomization and patients clustered within 
providers.  We chose cluster randomization as the intervention is focused on providers. We considered 
individual-level randomization, but we chose against this approach out of concerns for contamination.48 
We will use the VA EHR to systematically identify patients who may benefit from the intervention. The 
trial will alert pharmacists or pulmonary specialists to provide usual care clinical reviews and any 
resulting recommendations to PCPs through E-consult. Consistent with usual care, they will facilitate 
adoption by preparing unsigned orders for PCPs, in consultation with their patients, to accept, modify, 
or discontinue as appropriate.  Figure 3 shows the trial flow. 
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Rationale for proposed 
design and methods: To 
align with the major 
knowledge gaps around 
population health 
management in COPD, we 
will compare pulmonary and 
pharmacist-led management 
in real-world settings. We 
designed this trial to align 
with principles of pragmatic 
trials, applying the Pragmatic 
Explanatory Continuum 
Indicator Summaries 
(PRECIS-2) Wheel to assess 
its pragmatic nature.49 While 
emphasizing data quality, 
EQuiP scores 43 out of 45, 
indicating a highly pragmatic 
trial (Figure 4). Research 
addresses major public 
health issue of clinical 
importance: Over 1.3 million 
Veterans have COPD.27 While evidence-based practices exist for COPD that can substantially improve 
patient-centered outcomes, Veterans frequently receive care that is not evidence-based.6-10,27,50-54 
Design should be scientifically rigorous and practically feasible: EQuiP preserves internal validity 
through PCP randomization and maximizes external validity by testing an intervention capable of 
dissemination in a remote and asynchronous manner. Participants are representative of everyday 
patients: Broad eligibility criteria with minimum exclusions will facilitate inclusion of representative 
PCPs and patients. Intervention should be suitable for real-world implementation: The population 
health interventions tested in this trial leverage clinical information systems and trained personnel (e.g., 
pulmonary specialists and clinical pharmacists) who are available across the VA. Similar systems led 
by pulmonologists and clinical pharmacists are already ongoing in facilities across the enterprise. 
Results from this trial will inform choices around wider expansion. Outcomes should be clinically 
meaningful: Our outcomes are highly relevant to patients (CCQ, clinical outcomes, quality of care) and 
payor/health system (clinical outcomes, quality of care, health system efficiency and value).  
 
Figure 3. Overview of the EQuiP Trial 
Identify PCPs 
&
 randomize to  
pulmonologist 
or pharmacist
Pulmonologist: 
• Clinical review
• Recommendations to PCP
     - E-consult
     - Complete unsigned 
        orders for PCP
Intervention
Outcomes
Clinical Outcomes
180 days
COPD Care Quality
90 days
COPD-Related Quality of Life
90 days
Cost Burdens
180 days
Qualitative Perspectives
Pharmacist: 
• Clinical review
• Recommendations to PCP
     - E-consult
     - Complete unsigned 
        orders for PCP
Identify PCP s
 patients with 
COPD
COPD patients 
of PCPs 
randomized to 
pulmonologist
COPD patients 
of PCPs 
randomized to 
pharmacist
Cohort and Randomization
 
Figure 4. Pragmatic nature of the EQuiP trial.  
 
Recruitment
All patients included if 
PCP does not opt out
Setting
Intervention and all 
study activities occur in 
regular clinical care, 
asynchronous/remote 
e-consults
Organization
Care relies on existing 
structures. Pharmacists 
supported with study funds, 
similar to existing VA 
processes for implementing 
new practices
Flexibility (Delivery)
Remote and asynchronous 
intervention, no restrictions 
on co-interventions
Flexibility (Adherence)
PCPs have high degree of 
flexibility including opting out 
of interventions, opting out of 
intervention recommendations 
Follow Up
EMR, mail, and 
phone-based
Primary Outcome
Composite of COPD 
exacerbation, pneumonia, 
hospitalization or death
Primary Analysis
Intention to treat with 
all available data 
Eligibility
Broad inclusion, 
minimal exclusions. 
Veterans with COPD 
within a PCP’s panel
0
1
2
3
4
5
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Conceptual framework: Broadly, we 
conceptualized a Donabedian framework 
when considering how to have patients 
experience high quality outcomes36 (Figure 5). 
Structure refers to the physical facilities, 
human resources, and organization of a 
healthcare system and its personnel. Our 
interventions are structural in nature, as they 
adapt the roles and activities of 
pulmonologists and pharmacists. Importantly 
for adoption, we are reorganizing existing, 
rather than creating new data infrastructure 
and staff. Process refers to the care delivered 
by a healthcare system. We have changed the 
processes of care using a population-based 
model along with proactive e-consults and 
facilitation/nudging to promote adoption.  We 
will track the delivery of evidence-based care 
for COPD, and the avoidance of care that is 
not evidence based. Outcomes refer to quality 
of care and patient-centered outcomes (e.g., 
symptoms, quality of life, mortality) achieved 
as a result of care delivery.   
 
 
9.3 
Study Procedures  
9.3.1 Providers:  
As described in Section 11.1, we will consider a provider consented after one week from 
sending the invitation if they have not opted out. For providers who opt-out, we will not make 
further contact.  
 
9.3.2 Patients:   
Surveys: As described in Section 11.2.1, we will consider patients consented if they 
choose to complete the outcome and demographic survey (section 9.5.1). 
Qualitative Interviews: Patients who complete the surveys and indicate on the interview opt 
in/opt out sheet that they are interested in participating in the interview are considered 
consented for interviews.  
 
9.3.3 Caregivers:   
Qualitative Interviews: We will interview Caregivers who agree to participate under a Waiver of 
Documentation of Informed Consent.  We consider Caregiver consented upon agreeing to 
participate in the interview. 
 
9.3.4 VA Leadership, pulmonary and pharmacist interventionists:   
Qualitative Interviews: We will interview VA leaders as well as pulmonologists and pharmacists 
who provided treatment recommendations to PCPs at study sites. These interviewees will agree 
to participate under a Waiver of Documentation of Informed Consent. We consider these 
leaders consented upon agreeing to participate in the interview. 
 
 
 
 
 
Figure 5. Donabedian model of quality (SCI-2, 
SCI-5) 
Patients
Process
-Identify patients in EHR
-Apply quality checklists
-Recommendations to PCP
       - E-consult
       - Unsigned Orders
Structure
-Electronic health record    
 (EHR CDW/CDW3)
-Staff to perform COPD
  population  management  
    Arm 1: Pulmonologists 
    Arm 2: Pharmacists
Outcome
Aim 1:   Quality of COPD  
      Care delivered
Aim 2a: COPD-Related  
      Quality of Life
Aim 2b: Clinical  
  
      Outcomes
 
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9.4 
Randomization 
Among PCPs who do not opt out, we will randomize them 1:1 to pulmonologist-led or pharmacist-led 
population health management within strata using block sizes of 4. We will stratify randomization by site and 
clinician type (physician or APP) for 4 total strata. Stratification is intended to avoid potential maldistribution 
of confounding factors potentially associated with readiness to accept intervention recommendations and 
quality of care56 (e.g., severity of patient illness).  
 
Given the nature of primary care staffing, we expect there to be turnover in PCPs. We will repeat 
recruitment and randomization efforts every month at each site among new providers. 
 
Patient participants are not randomized; their PCPs are the unit of randomization. 
 
9.5 
Study Evaluation 
 
We carefully chose outcomes based on importance to patients, caregivers, and key stakeholders. Table 1 in 
Section 8 shows a summary of measures, power, and non-inferiority thresholds.    
 
We will collect study outcomes as follows: 
 
9.5.1 Self-reported patient questionnaires:  
CCQ: We will measure patient symptoms using the well-validated CCQ. The CCQ assesses symptoms, 
functional status, and COPD control and has been used widely in the setting of clinical trials to 
discriminate across a range of COPD severity. The CCQ possesses strong internal consistency 
(Cronbach’s alpha 0.91), stability (test-retest, r = 0.94), convergent and divergent validity.60-62 The CCQ 
also is highly responsive to change, with improvements detected in healthy smokers just two months 
after smoking cessation.62 The CCQ includes 10 items encompassing three domains (symptoms, 
functional state, and mental state). Response options range from “never” to “almost all the time” and 
are scored from 0-to-6. The total score is calculated by the addition of each item divided by the total 
number of items, producing a range of scores between 0-6 with a minimally important difference (MID) 
of 0.39 and a standard error of 0.21. The instrument has been administered by telephone in previous 
studies.63 We estimate the time to complete will be approximately 5 minutes. We will ask patients to 
complete the survey by the methods described in Section 9.3.2.   
 
Costs: We will measure caregiver involvement using a locally developed survey.  
    
9.5.2 EHR abstraction/CDW: 
Aim 1 (quality of COPD care; proportion of evidence-based practices): 
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Study staff will abstract 
pertinent information from the 
EHR using an appropriate 
application such as Joint 
Legacy Viewer (JLV). We will 
integrate data queried from the 
CDW with this abstracted data. 
We will measure quality of 
COPD care based on the 
presence or absence of key 
evidence-based practices listed 
in Table 2.4,5,64,65 These 
evidence-based practices are 
supported by current 
guidelines,4,5,64-66 and we will 
adapt this list as guidelines are 
updated. For each patient, we 
will calculate the proportion of 
evidence-based practices that 
are performed. The 
denominator will be the number 
of evidence-based practices 
that apply to a particular 
patient. The numerator will be 
the number of those practices 
received. We will also assess 
the proportion of 
recommendations made by 
pulmonary specialists and 
pharmacists that are signed by 
primary care. As additional 
secondary outcomes, we will 
assess the proportion of 
evidence-based practices delivered that are general vs. COPD-specific and pharmacologic vs. non-
pharmacologic in nature. 
 
Aim 2b (composite endpoint of COPD exacerbation, hospitalization, pneumonia, or death): We will 
manually abstract from the electronic health record and query the CDW using validated algorithms to 
identify these outcomes in the 180 days following intervention consultation.33,67  These clinical 
outcomes are important because high quality care has been demonstrated to modify these events.4,5,64-
66 While each component outcome is important on its own, we will use a composite outcome to address 
issues of competing risks and minimize misclassification.68 For instance, pneumonia and COPD 
exacerbation are often clinically difficult to distinguish and may lead to misclassification.  
 
Aim 3 (patient costs) 
We will capture patient-perspective cost burdens for care that may be provided as a result of the 
intervention (Table 2). We will prioritize EHR data where possible to maximize generalizability in this 
pragmatic trial. Given the role of the intervention in preventing downstream events of hospitalizations, 
COPD exacerbations, and pneumonia, we also will capture costs related to those events (Table 3,4). 
Cost-related burdens of care include transportation (e.g., gas/vehicle depreciation), copays for visits 
and medications, and opportunity costs for time spent on care.69-71 We will inform these cost estimates 
by integrating data from chart reviews, and electronic medical record data from VA’s corporate data 
warehouse (CDW, Table 3). 
Table 2: Key evidence-based practices used to define quality of COPD care 
Evidence-based practice 
Eligible COPD patients 
1. Completion of spirometry-C,NP 
All 
2. Assessment of smoking status-G , NP 
All 
3. Influenza vaccination during appropriate season-G, P 
All 
4. Pneumococcal vaccination-G, P (PSV23, PCV-13) 
All 
5. COVID-19 vaccination – G, P 
All 
6. Assessment of resting O2 saturation or PaO2, C,NP 
All 
7. Assessment of respiratory symptoms burden-C, NP 
All 
8. At least one long-acting bronchodilator (LABA, 
LAMA) as first-line therapy- C, P 
Symptomatic 
9. Referral/counseling for smoking cessation G,NP 
Active smoker at index 
10. Prescription of smoking cessation aide –G, P 
Active smoker at index 
11. Continuation or escalation of smoking cessation 
medications- G, P 
Active smoker at index – 
received cessation 
medication in past 12 
months 
12.Addition of at least one controller agent (e.g., ICS ) 
to first-line therapy –C, P 
Prior severe or frequent 
exacerbations in past 12 
months 
13. Discontinuation of ICS-C, P 
No frequent or severe 
exacerbations past 12 
months and no asthma 
diagnosis 
14. Discontinuation/tapering of COPD treatment –C, P 
Patients without 
evidence of COPD 
15. Provision of O2 for long-term continuous therapy-C, 
NP 
Resting SpO2≤88% or 
PaO2≤55mhg 
16. Offer/referral to pulmonary rehabilitation program-C, 
NP 
Dyspnea or severe 
exacerbation in past 12 
months 
Legend: C-Metric applies to COPD-specific care quality. G-Metric of General Care 
Quality; P-Pharmacologic Management; NP-Non-Pharmacologic Management 
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Table 3. Components of Patient-incurred Cost Calculation 
Cost Element 
Source 
Description 
Transportation 
costs 
CDW 
• Drive distance derived from Veterans’ home 
address and site of care for in-person encounters 
multiplied by standard mileage rates.72 
Co-pays  
CDW 
• Veteran’s assigned co-payment tier multiplied by 
number of visits and prescriptions73 
Opportunity Costs 
 
 
1) Drive time 
CDW 
• Drive time for patients’ travel to each in-person 
encounter.   
2) Outpatient visit 
time (virtual or in-
person) 
CDW/ 
NAMCS
/ATUS 
• Encounter Duration: Average NAMCS/NHAMCS 
visit duration for billing code, location (primary 
care vs. ER)74 
• Waiting room: (In-person only) using ATUS 
estimates75 
3) Hospitalizations 
CDW 
• Total duration based on admit and discharge time 
4) Caregiver 
involvement 
Survey 
• Patient-reported caregiver presence for: in-person 
encounters, virtual encounter, hospitalizations 
Opportunity Costs 
All 
• Cumulative patient/caregiver time multiplied by 
average hourly wage for age/sex69,71 
CDW-Corporate Data Warehouse; NAMCS-National Ambulatory Medical Care Survey; 
NHAMCS- National Hospital Ambulatory Medical Care Survey; ATUS-American Time 
Use Survey; ER-Emergency room 
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Aim 4 (heterogeneity in treatment effect): we will compare heterogeneity in treatment effect for the 
primary and secondary outcomes. We will assess effect modification between treatment arm and 
patient characteristics thought to potentially impair access to treatment and delivery of high-quality 
care. Specifically, we will assess effect modification with 1) complex multimorbidity, 2) those living in 
urban and rural areas, and those of different 3) race and 4) sex.33,76,77 We will conduct additional 
analyses to assess associations between patient, provider, and health system characteristics and 
processes with care delivery and patient outcomes. For patient-incurred costs, we will pool data from 
both arms and assess differences in costs according to these four characteristics of interest.  
 
9.5.3 Qualitative interviews (Aim 5: qualitative perspectives):  
We will assess experiences with the intervention among patients, PCPs, and health system leaders, 
and perspectives on acceptability, engagement, and satisfaction. Consistent with a Donabedian model 
of quality36, our interviews will also address perspectives related to structures, processes, and 
outcomes of care. We will assess perspectives around incurred costs among patients and their 
caregivers.  We will audio record and transcribe the interviews using VA Microsoft teams under a 
waiver of documentation of informed consent. Study staff will verify the transcriptions. Interviews will 
focus on interviewee’s perceptions of COPD population management in the EQuiP trial. We will 
specifically address the intervention’s perceived acceptability, feasibility, and sustainability, as well as 
perceptions around engagement and communication with the program (e.g., PCPs engagement with 
pulmonary specialists /pharmacists, patients’ engagement with PCPs). Consistent with the Donabedian 
model of quality,36 we will address perceived positive and negative impacts on care 
processes/workflows and patient outcomes.  We will revise interview guides iteratively based on data 
collected and to address any participant comprehension or clarity issues that arise. 
Veteran Patients: We will conduct an interview for a subset of patients soon after they complete the 
CCQ.  We will invite patients with diverse demographic and regional characteristics, and baseline levels 
of quality of care. The interview may be about their experiences with the EQuiP intervention or about 
their incurred costs. For the former, we will interview about 40 participants (aiming for 20 in each arm), 
or until saturation is reached. For the cost perspective, we will interview about 30 patients (15 in each 
arm), or until saturation is reached.  
Caregivers: Among patients who participate in an interview and indicate they received support from a 
family member, friend, or other caregiver for their COPD care, we will invite the caregiver to participate 
in an interview.  The interview will help evaluate costs of COPD care at the VA and how those costs 
may shape care decisions.  We will interview about 20 caregivers, or until saturation is reached. 
PCPs: We will invite about 40 PCPs (aiming for 20 in each arm), or until saturation is reached, to 
participate in interviews. We will invite providers from urban and rural facilities, physicians and APPs, 
and those practicing in CBOCs as well as medical centers. We may use email or Teams to arrange the 
Table 4. Evidence Based Practice for review 
Anticipated direct patient costs 
1. Confirmation of COPD by spirometry 
Time, transportation costs, co-pay 
2. Influenza vaccination during appropriate season 
Time, transportation costs, 
3. Pneumococcal and COVID-19 vaccination  
Time, transportation costs, 
4. Assessment of resting oxygen saturation  
Time, transportation costs, co-pay 
5. Assessment of smoking status and respiratory symptom burden 
Time, transportation costs, co-pay 
6. Use of at least one long-acting bronchodilator as first-line therapy 
if symptomatic 
Medication co-pay 
7. Appropriate smoking cessation therapy 
Medication co-pay 
8. Appropriate prescribing of medications to prevent exacerbations 
Medication co-pay 
9. Discontinuation of inhaled corticosteroid when not appropriate 
Absence of co-pay 
10. Appropriate supplemental oxygen prescribing 
Time, transportation costs, co-pay 
11. Appropriate pulmonary rehabilitation referrals 
Time, transportation costs, co-pay 
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interview time. After the interview, we may follow up for minor clarifications via encrypted email or 
Teams. 
Local Leadership, Pulmonologists, and Pharmacists: We will aim to interview about 10-15 site leaders, 
or until saturation is reached, in the fields of primary care, pharmacy, and pulmonary medicine. We will 
also include additional pharmacists and pulmonologists (n=5-15) who also deliver intervention 
recommendations to PCPs. We may use email or Teams to arrange the interview time. After the 
interview, we may follow up for minor clarifications via encrypted email or Teams. 
9.5.4 COVID-19 considerations:  
Given the remote nature of the intervention and outcome collection, we do not anticipate difficulty in 
conducting our trial despite evolving health system responses to the COVID-19 pandemic.  
 
9.5.5 Payments:  
The Seattle Institute for Biomedical and Clinical Research (SIBCR) will compensate patient 
participants $25 after completing the one-time survey, and another $25 to patients and patient 
caregivers who participate in the one-time qualitative interview.  SIBCR will have access to 
participant names and addresses for the purpose of mailing payment in the form of a check or 
gift card.  Envelopes containing payment will not have study identifiers on the exterior.  We will 
not compensate providers or healthcare leadership for their participation. 
 
9.6 
Study Duration  
 
 
9.7 
Data and/or Specimen Use 
 
As outlined in section 8.0, data is collected from EHR/CDW, self-report, chart abstraction 
and interview. 
Data sources:  
• 
VA Internal Data (eg. CAPRI, CDW, VINCI, JLV, MVP, CPRS, etc...)  
• 
Research Subject (Questionnaires, Surveys, Interview, Audio/Recordings, Wearable 
Technologies, Biospecimens, Radiological Imaging, etc...)  
• 
VHA Support Services Center (VSSC) 
Identify/ 
randomize 
PCPs:  
pulmonologist 
or pharmacist
Pulmonologist: 
• Clinical review
• Recommendations to PCP
• E-consult
• Complete unsigned 
orders for PCP
Intervention
Outcomes
Patient reported:
3 mos
Health system: 
3 mos
Health & Safety 
outcomes:
6 mos
Pharmacist: 
• Clinical review
• Recommendations to PCP
• E-consult
• Complete unsigned 
orders for PCP
Identify PCP s
 patients with 
COPD
(refreshed 
monthly)
COPD patients 
of PCPs 
randomized to 
pulmonologist
COPD patients 
of PCPs 
randomized to 
pharmacist
Cohort and Randomization
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Data collection methods are listed below. See section 9.5 for specific procedures used to 
collect data. 
Data collection methods: 
• 
Audio recordings 
• 
Chart Reviews 
• 
Interviews 
• 
Questionnaires (paper/electronic) 
• 
MS Teams 
• 
Download data from CDW and VSSC 
Information sharing: 
IRB approved staff at participating VA sites will have access to study data as needed to 
complete study.  IRB approved staff at each participating VA sites (VA Puget Sound HCS; 
Mann-Grandstaff VAMC; Ralph H. Johnson HCS; Portland HCS; Minneapolis HCS; Central 
Texas VHCS, Eastern Colorado VHCS) will be able to access data stored on VA Puget Sound 
servers (described previously); data will stay on VA Puget Sound servers, and not moved to the 
other VA sites. 
 
Storage: 
Facility Name: Seattle, WA - Puget Sound Health Care System 
Building: Seattle VAMC, 
Building 101, 4th floor 
Room Number: locked file room 4W75 
Secured Information: 
4th floor is a locked floor accessible to authorized personnel via PIV, fileroom 4W75 is a locked 
fileroom accessible by authorized personnel only and within the fileroom, hard copies are stored 
in a locked file cabinet. 
Electronic VA File Location(s): 
VA Network  
VA REDCap  
HSR&D SQL server OITPUGSQLRES019.va.gov\HSRDSQLSERVER;  
VINCI servers: vhacdwrb02.vha.med.va.gov; local study drive 
\r01pughsm03.r01.med.va.gov\research\Projects\Donovan_EQuiP_IRBN1682961 
Electronic File Storage Details: 
Electronic questionnaire responses will be stored initially on TLS 1.1, TLS 1.3 encrypted 
Qualtrics servers: https://vhaordfedramp.gov1.qualtrics.com or VAREDCap server (https:// 
varedcap.rcp.vaec.va.gov/redcap/); data is then ingested and stored on HSR&D SQLserver 
OITPUGSQLRES019.va.gov\HSRDSQLSERVER; VINCI servers 
vhacdwrb02.vha.med.va.gov; local study drive \r01pughsm03.r01.med.va.gov\research\Projects 
\Donovan_EQuiP_IRBN1682961 
 
Website/Cloud-Based Software: 
Name: VA REDCap URL: https://varedcap.rcp.vaec.va.gov/ 
redcap/index.php 
Website Owner Type: VA Non-VA 
Purpose: 
Provider recruitment: We will attempt to invite all eligible providers via email. Under a Waiver 
of Documentation of Informed Consent, we will use REDCap or Qualtrics to send an 
introductory email including a study description, Information Statement, study contact 
information for those who have questions, instructions on how to opt out, and a survey with 
demographics questions. 
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Patient recruitment: For patients that have an email address in CDW, we will send an email 
with link to a secure online platform (ie Qualtrics or REDcap). The link will show a study 
flyer, invitation letter, Information Statement, and surveys. 
Name: VA Qualtrics URL: https:// 
vhaordfedramp.gov1.qualtrics.com/ 
Website Owner Type: VA Non-VA 
Purpose: 
Provider recruitment: We will attempt to invite all eligible providers via email. Under a Waiver 
of Documentation of Informed Consent, we will use REDCap or Qualtrics to send an 
introductory email including a study description, Information Statement, study contact 
information for those who have questions, instructions on how to opt out, and a survey with 
demographics questions. 
Patient recruitment: For patients that have an email address in CDW, we will send an email 
with link to a secure online platform (ie Qualtrics or REDcap). The link will show a study 
flyer, invitation letter, Information Statement, and surveys. 
Name: VINCI URL: https://sps.vinci.med.va.gov:28001/ 
projects/CorrespondenceSite/ 
- 4 - Generated on IRBNet 
Donovan_202207055D/SitePages/ 
Home.aspx 
Website Owner Type: VA Non-VA 
Purpose: 
VINCI services: Communicate with the VINCI team to coordinate data pulls to the study VINCI 
database. 
 
Study data will be coded with a unique study ID. See section 17.1. 
9.8 
Data and/or Specimen Banking  
 
Not applicable. 
10.0 Study Population  
 
10.1 General Characteristics  
 
As described in section 5.3, our trial will recruit all non-trainee PCPs practicing at five VA 
Medical Centers and their 38 associated outpatient clinics in Washington, Oregon, 
Minnesota, and South Carolina. These academic and non-academic centers are 
geographically and clinically diverse with full and part time PCPs (294 full-time 
equivalent (FTE) across 495 individual providers) who together care for nearly 30,000 
Veterans diagnosed with COPD. Within each PCPs’ panel, we will identify patients with 
COPD using previously validated algorithms.47 We propose to enroll and intervene on at 
least 200 PCPs and make recommendations on approximately 4,000 patients (100 
PCPs and 2,000 patients per arm). We will include specific subgroups that have been 
previously shown to receive lower quality services, including patients receiving care at 
rural facilities. 
 
10.2 Inclusion and Exclusion Criteria 
 
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Participants may be PCP physicians and advance practice providers (APP) practicing at 
participating sites, and their patients who are diagnosed with or treated for COPD based 
on the following criteria: 
 
1) 
Recent discharge from hospital for COPD exacerbation  
2) 
Recent outpatient exacerbation (emergency room (ER), primary care) 
3) 
Received prescription for an ICS but does not meet criteria for ICS use 
4) 
Diagnosis of COPD and/or treatment and active smoker not receiving smoking 
cessation aide 
5) 
Treatment for or diagnosis of COPD without evidence of spirometry within 10 
years, or no airflow obstruction on existing spirometry 
 
We may identify up to 2500 PCPs to approach for enrollment.  For patients, we will 
access up to 450,000 patient records and enroll up to 25,000 individuals. 
For patients who indicate they receive support for their COPD care by a family member, 
friend, or other caregiver, we may invite their support person to participate in an 
interview. We are examining personal costs of care; therefore, will exclude caregiving 
paid for by the VA or other healthcare organization. 
 
10.3 Populations Requiring Additional Considerations 
 
Not applicable. 
 
11.0 Recruitment Methods 
 
Before we begin recruitment, we will refine the algorithms that we will apply to the Corporate Data 
Warehouse (CDW)/ Veterans Support Service Center (VSSC) data to identify potentially eligible 
participants and verify with chart review using approved platforms such as Joint Legacy Viewer. 
 
11.1 Providers:  
Information Sharing Before the Intervention: A few months prior to trial launch, we will work with primary 
care leadership to provide information to PCPs at each site. We will hold tele/videoconference-based 
information sessions with the opportunity for question and answer for PCPs at each site. We will 
provide a brief overview of the study’s rationale, previous trials, and overall approach. We will review 
the overall COPD quality of care and how the trial is intended to improve and measure changes in our 
outcomes.   
 
Approaching providers: Using validated algorithms, we will obtain names and contact information for 
PCP physicians and APPs at participating sites via the CDW/ VSSC 55. We will not approach trainee 
providers (e.g., residents) given frequent turnover. Using VA Research Electronic Data Capture 
(REDCap) or Qualtrics, we will attempt to invite all eligible providers via email.  Under a Waiver of 
Documentation of Informed Consent, we will use REDCap or Qualtrics to send an introductory email 
including a study description, Information Statement, study contact information for those who have 
questions, instructions on how to opt out, and a survey with demographics questions.  We will consider 
them enrolled in the study if they do not respond within one week (default opt-in), and that they may 
withdraw at any time without penalty.  
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Providers hired after trial launch:  Every month, we will identify any new PCPs operating at any of the 
study sites. Similar to our initial recruitment strategy, we will use REDCap to email these new PCPs an 
information sheet and provide them with instructions about how to opt out if desired.  
 
11.2 
Patients:   
11.2.1 
Surveys: Providers are the target of the intervention. We will engage patients only at the 
time of CCQ administration, described in section 9.5.1. Potential patient participants are Veterans 
diagnosed with or treated for COPD whose PCP is a randomized provider in this trial.  Using a 
Waiver of Documentation of Informed Consent, we will approach patients for survey completion as 
follows:  
11.2.2 
Mail:  Around 90 days after the intervention, we will mail the CCQ, a brief patient cost 
survey, a brief sociodemographic survey, and an interview opt in/out sheet.  The mailing will include 
a flyer, letter informing them that their provider is taking part in the study, and an Information 
Statement providing more detail. The letter will invite them to indicate interest by completing one of 
the following: 
• 
return a postcard requesting to receive a telephone call with a research coordinator to learn 
more about the study 
• 
return an opt-out card to avoid further contact 
• 
participate (i.e., consent) by completing and returning the outcomes and sociodemographic 
surveys using a self-addressed stamped envelope.  
 
11.2.3 
Electronic/Online (see Section 17.2):  For patients that have an email address in CDW, 
we will send an email with link to a secure online platform (ie Qualtrics or REDcap). The link will 
show a study flyer, invitation letter, Information Statement, and surveys. To emulate paper surveys, 
the online version will prompt participates to respond to questions if they accidently left them blank 
and will direct participants to the next action. Other slight modifications (e.g., bolded fonts, transition 
pages, and sub-headers) will facilitate the online interface. The electronic survey link can be re-sent 
via email or text at the request of the participant. 
 
11.2.4 
Telephone:  For those who do not respond to the above or indicate that they want to 
speak with study staff, we will administer the surveys over the telephone if the participant prefers.  
We also will ask if we may contact them soon about participating in a telephone interview to learn 
their opinions about the study. 
 
For those who do not respond after one week, we will follow up by mail, email, text, and/or telephone 
call.     
 
11.3 
Caregivers:   
For patients who participate in an interview (see section 9.5.3) and indicate a family member, friend, or 
other caregiver provides support for their COPD care, we will ask the patient at the conclusion of the 
interview if their caregiver might be interested in participating in a similar interview.  If yes, we will ask 
for the caregiver’s contact information so that we may mail an invitation containing a letter informing 
them that the patient is taking part in the study, an Information Statement providing more detail, and an 
opt-in/out card. The letter will invite them to indicate interest by completing one of the following: 
• 
return the postcard requesting to receive a telephone call with research staff to learn more 
about the interview 
• 
return an opt-out card to avoid further contact. 
 
For those who do not respond after one week, we may follow up by mail and/or telephone call to review 
the Information Statement and assess interest. 
 
11.4 
VA Leadership including Pharmacists and Pulmonologists:  
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We will identify local leaders including service line leaders, clinic leaders, and section chiefs for primary 
care, pharmacy, and pulmonary medicine at EQuiP sites as well as interventionists-pulmonologists and 
pharmacists who provided treatment recommendations to PCPs at EQuiP sites.  We will send an email 
asking them to share their perspective on the EQuiP intervention. The email will include a study 
description, Information Statement, study contact information for those who have questions, and 
instructions on how to opt out.  
 
For those who do not respond after a few days, we may follow up by email, Teams and/or telephone 
call to review the Information Statement and assess interest. 
12 Enrollment Procedures  
 
Enrollment for all participants will be done through the Seattle VA site. 
 
12.2 
Screening  
 
Not applicable. 
 
12.3 
Informed Consent Process and Documentation  
 
12.3.1 Providers:  
As described in Section 11.1, we will consider a provider consented after one week from sending the 
invitation if they have not opted out. For providers who opt-out, we will not make further contact.  
 
12.3.2 Patients:   
Surveys: As described in Section 11.2.1, we will consider patients consented if they choose to 
complete the outcome and demographic survey (section 9.5.1). 
Qualitative Interviews: Patients who complete the surveys and indicate on the interview opt in/opt out 
sheet that they are interested in participating in the interview are considered consented for interviews.  
 
12.3.3 Caregivers:   
Qualitative Interviews: We will interview Caregivers who agree to participate under a Waiver of 
Documentation of Informed Consent.  We consider Caregiver consented upon agreeing to participate in 
the interview. 
 
12.3.4 VA Leadership, pulmonary and pharmacist interventionists:   
Qualitative Interviews: We will interview VA leaders as well as pulmonologists and pharmacists who 
provided treatment recommendations to PCPs at study sites. These interviewees will agree to 
participate under a Waiver of Documentation of Informed Consent. We consider these leaders 
consented upon agreeing to participate in the interview. 
 
13 Participant Payment 
 
The Seattle Institute for Biomedical and Clinical Research (SIBCR) will compensate patient 
participants $25 after completing the one-time survey, and another $25 to patients and patient 
caregivers who participate in the one-time qualitative interview.  SIBCR will have access to 
participant names and addresses for the purpose of mailing payment in the form of a check or gift 
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card.  Envelopes containing payment will not have study identifiers on the exterior.  We will not 
compensate providers or healthcare leadership for their participation. 
14 Withdrawal of Participants 
 
We do not anticipate a need to withdraw providers from the research.  For most patients, participation is a 
one-time event based on their completion of the CCQ. We will invite a small subset of patient participants 
who complete the survey to take part in a qualitative interview, which they may refuse. If an enrolled 
provider informs the research team they no longer wish to participate, we will not include them in future 
intervention activities, nor invite them to participate in a qualitative interview. 
 
15 Sharing of Results 
 
At the end of the project after analysis is complete, we may send a summary of results to 
participants via email or mail. 
16 Data Safety, Monitoring and Reporting 
 
16.1 Quality Monitoring 
The PIs will be primarily responsible for data safety and monitoring and will work closely with the project 
manager to audit data collection for completeness and accuracy.   
 
16.2 
Data Safety and Monitoring Board (DSMB):  
We will assemble an external DSMB consisting of a Chair, Executive Secretary, and a member with 
expertise in biostatistics, epidemiology, and clinical trials. DSMB will meet every six months or as 
needed. At the first meeting the DSMB will approve the charter and research protocol. At subsequent 
meetings the DSMB will review adverse event data, other safety data, quality and completeness of 
study data, and enrollment data to ensure proper trial conduct.   
 
The DSMB will provide objective recommendations, as appropriate, with respect to: 
• 
Determination of any actions to be taken in response to adverse events 
• 
Reports related to study operations and the quality of the data 
• 
Consideration of early termination of the study because of treatment safety concerns or 
inadequate performance 
• 
Modifications in the study protocol concerning recruitment, participant retention, data quality, 
outcome assessment, statistical analysis, or general trial operations 
 
16.3 
Adverse Event Monitoring:  
To ensure unbiased determination across treatment arms, VA Puget Sound staff will query the EHR at 
least 180 days after treatment recommendations were provided to systematically identify SAEs and 
UPs that occurred within 180 days as part of a hospitalization. Designated study investigators will 
review potential AEs for expectedness, seriousness, and relatedness. We will report events to the IRB 
and DSMB as required by IRB/DSMB policy.  
 
The following are expected adverse events in the EQuiP population of participants who have COPD: 
• 
COPD exacerbation lower respiratory event  
• 
Worsening of COPD (worsening of lung function, development of severe resting hypoxemia, 
death from COPD) 
• 
Side effects of spirometry/albuterol: Fainting, dizziness; throat irritation, palpitations, 
nervousness, shakiness, stomach upset, headache, dizziness, weakness, sweating, chest pain 
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• 
Development of other conditions associated with unhealthy health behaviors, such as from 
tobacco and alcohol disorders, (e.g., cancer, CVD); Cancers related to smoking or alcohol are 
expected, e.g.  lung, oral pharyngeal, breast, colon 
• 
Age related illnesses, such as pneumonia, urinary tract, and skin infections 
• 
Known side effects from recommended pharmacologic and non-pharmacologic treatments (e.g. 
ICS- thrush, pneumonia, pulmonary rehabilitation – musculoskeletal injuries) 
• 
Death from any of the expected causes listed above 
• 
Exacerbation of any pre-existing condition 
 
Upon discovering an unexpected, serious, and possibly related SAE, we will provide the IRB and 
DSMB a report describing the duration (start and stop dates and times), severity, outcome, treatment, 
and relation to study activity, according to the required timelines. The DSMB may request additional 
information if it deems additional deliberation is warranted.  
 
For all other events, staff will summarize and report to the DSMB on a semi-annual basis the numbers 
and types of all AEs by unidentified treatment arms. At their discretion, the DSMB may request 
unblinded results to determine the nature and extent of effect of the intervention.  Should the DSMB 
make this request, we will maintain blinding of the investigators and the staff involved in follow-up data 
collection and analysis.  If, at any time, the investigators believe they are seeing an unexpected 
increase in SAEs that is a cause of concern, they will bring this to the attention of the DSMB. This 
systematic, non-biased monitoring process will ensure that any group disparities will be effectively 
addressed. 
 
We will provide DSMB report to the IRB at annual review. 
 
17 Privacy and Confidentiality 
We will collect the following protected health information (PHI) from patient participants: name; dates of 
birth, death, and health care utilization; social security number; street address, and medical record 
number.  We will collect providers names, email addresses, dates of VA employments, and provider 
class. 
 
17.1 Data protection 
We will employ the following procedure to ensure privacy, confidentiality, and data protection: 
• Obtain identifiable information only as approved by the IRB 
• Process and store data only in the designated VA Informatics and Computing Infrastructure (VINCI) 
workspace, and on secure password protected and permission-specific VA network server(s) located 
at the VA Puget Sound Health Care System - Seattle VAMC. Using this network, we will employ the 
following:  
o Data entry systems will employ automatic, real-time range, logic, and missing value checks 
o Employ double data entry and logic controls to minimize data entry error  
o Maintain one official copy of all the study data and a master data dictionary 
• For online surveys, 
o Initial electronic questionnaire responses will be stored on TLS 1.1, TLS 1.3 encrypted Qualtrics 
servers: https://vhaordfedramp.gov1.qualtrics.com or on the VA REDCap server 
(https://varedcap.rcp.vaec.va.gov/), hosted on the VA Enterprise Cloud (VAEC) 
o Response data will be downloaded from online servers and stored on 
\r01pughsm03.r01.med.va.gov\Research\Projects\   
o Response data is then ingested and stored on HSR&D SQL server: 
OITPUGSQLRES019.va.gov\HSRDSQLSERVER   
• For qualitative interviews: 
o Record via VA Microsoft Teams 
o Transcribe recording via VA Microsoft Teams and verify/update manually 
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o Save recordings and transcriptions only on HSR&D secure servers 
• Identify participants and obtain data for research purposes only 
• Use a unique study ID for study data 
• Store the file linking the study ID and participant identifiers separately from the study data 
• Restrict access to IRB approved staff on a need-to-know basis. 
• Store paper copies in a secure office suite in locked files accessible by approved study staff only, or 
archived and retrievable through R&D service at the National Archives 
• Ensure all staff receive and remain current on the following training: Human Subjects and Good 
Clinical practice; Privacy and HIPAA; VA Privacy, Information Security, and Rule of Behavior 
• Notify the Information Security Officer (ISO) and Privacy Officer (PO) about improper use within 
required timeline 
• Follow all local and national VA data security policies 
 
17.2 Online surveys 
We will recruit patients and offer the option of responding to questionnaires online via a web-based survey 
platform licensed by VHA ORD (such as REDCap). The loss of privacy with online surveys is no greater than 
the risk of responding to questionnaires on paper and by mail. As part of the informed consent decision-making 
process, we will describe the process of responding to online questionnaires. A limited amount of contact 
information is stored on the Qualtrics or REDCap platform to allow distribution of unique anonymized survey 
links. Information is transmitted to Qualtrics or REDCap via secure, encrypted, web-based portal.  
 
We will send survey links to participants via unencrypted email or text message.  The message will not 
specifically mention the EQuiP study or contain PHI. Incoming emails or text messages may either be bounced 
back to the sender as nondelivered, or an automatic response may contain an out-of-office and unmonitored 
message. We will confirm telephone number and supported carriers (e.g., T-Mobile, Verizon, AT&T, etc.)  prior 
to delivering text messages. Responses stored on the online servers will be associated with a unique study 
code, password protected, and encrypted. We will store online questionnaire responses collected through the 
online platforms on password protected and encrypted servers. We will use online platforms such as REDCap 
that are is FedRamp authorized, and all data will remain property of ORD. 
 
17.3 Data sharing 
We will share limited analytic datasets between authorized study personnel via secure transmission 
and/or via a secure virtual private network employing industry-standard password protection and data 
encryption. 
 
The funding entity, PCORI, in their Policy for Data Management and Data Sharing, requires that we 
share a de-identified data set (in accordance with the HIPAA Privacy Rule) to the  PCORI-designated 
repository: University of Michigan’s Inter-University Consortium for Political and Social Research 
(ICPSR).   We will seek appropriate approvals (IRB/DUA CRADA, etc.) for data sharing once data 
collection is complete.  
 
17.4 Data destruction 
After the study is completed, the data will be destroyed in accordance with all VA and VHA records 
disposition requirements. The data will be retained for the minimum period required for records 
retention in accordance with the National Archives and Records Administration (NARA) VHA Record 
Control Schedule (RCS). The VA Puget Sound Health Care System Research and Development Office 
will be responsible for overseeing the storage of the data during the RCS required records retention 
period and for the eventual destruction of the data as authorized by the RCS. When the minimum data 
retention period has ended, all data records in the possession of VA Puget Sound will be destroyed. At 
this same time, VINCI staff will be responsible for destroying project records from any applicable VINCI 
server(s). For electronic data, the Office of Information and Technology (OI&T) is responsible for 
maintaining the security of the electronic records during the records retention period. The data will be 
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destroyed in a manner that is compliant with VA Handbook 6500 and National Institute of Standards 
and Technology NIST SP 800-88. 
 
18 Data Analysis Plan 
 
18.1 Aims 1, 2 & 3:  
We designed this cluster randomized trial to assess the non-inferiority of pharmacist-led versus pulmonary 
specialist-led population health management among patients with COPD. To do so, we will use generalized 
linear mixed models (GLMM) to estimate the effect of provider randomization on primary and secondary patient 
outcomes. Of relevance to our current trial, GLMMs can accommodate continuous outcomes (Hypothesis 1, 
Hypothesis 2a, Hypothesis 3) and binary outcomes (Hypothesis 2b).78  
For each analysis we will use the following GLMM model: 
𝐸(𝑌𝑖𝑗∣𝑋𝑖, 𝑺, 𝑄𝑖, 𝑫𝑖𝑗) = 𝑔−1(𝛾𝑖+ 𝛽0 + 𝛽1𝑋𝑖+ 𝜷2
𝑇𝑺𝑖+ 𝛽3𝑄𝑖+ 𝜷4
𝑇𝑫𝑖𝑗) 
 
Where 𝑌𝑖𝑗 refers to the aim-specific outcome for patient 𝑗= 1,2, … , 𝑚𝑖 within primary care provider 𝑖=
1,2, … 𝑛,  𝑋𝑖 is an indicator variable for randomization assignment (1=clinical pharmacist, 0=pulmonary 
specialist), and 𝛾𝑖 is a random intercept with expectation zero included to account for clustering between 
patients seeing the same provider. Consistent with guidance around analytic model design for randomized 
trials,49 we include 𝑺𝑖 and 𝑄𝑖, which refer to the stratification variables for provider randomization site ( 𝑺𝑖) and 
provider type (𝑄𝑖, physician or advanced practice practitioner). We also adjust the means by 𝑫𝑖𝑗, which is a 
vector indicating the qualifying priority group for patient inclusion. 𝐸(𝑌𝑖𝑗|𝑋𝑖, 𝑺𝑖, 𝑄𝑖, 𝑫𝑖𝑗) refers to the expectation 
of the outcome given provider randomization, randomization strata, and patient pathway. The function 𝑔(⋅) 
refers to the link function. For continuous outcomes, we will use the identity link function assuming 𝑌𝑖𝑗∼
𝑁[𝐸(𝑌𝑖𝑗|𝑋𝑖, 𝑺𝑖, 𝑄𝑖, 𝑫𝑖𝑗), 𝜎2], whereas for binary outcomes we will set the link function to be the logistic 
cumulative density function and assume 𝑌𝑖𝑗∼𝐵𝑒𝑟𝑛𝑜𝑢𝑙𝑙𝑖[𝐸(𝑌𝑖𝑗|𝑋𝑖, 𝑺𝑖, 𝑄𝑖, 𝑫𝑖𝑗)].  We will perform an “intention-to-
treat” analysis, including all eligible patients of participating primary care providers regardless of 
patients’ or providers’ adherence to treatment or intervention recommendations. Standard errors and 
confidence intervals of the intervention effect will be estimated using a nonparametric cluster bootstrap, which 
involves iteratively resampling primary care providers, including all of their patients,  with replacement to 
generate an empirical distribution of estimator of interest. 
Missing Data: Our pragmatic trial prioritizes outcome collection from the EHR to reduce participant 
burden and enhance generalizability. While necessary for our approach, we will likely encounter 
missing and misclassified data, which we anticipate will be non-differential across arms. We will use 
established methods to minimize measurement error around COPD and COPD-related events within 
administrative data.47 For data entered by study staff, we will employ automatic logic and missing value 
checks to ensure accuracy. We will document the extent, pattern, and reasons for missing data. Our 
primary analysis will proceed using multiple imputation using chained equations to impute missing data 
points and we will conduct sensitivity analyses using a complete case analysis to explore the impact of 
missing data on the stability of our results.  
18.2 
Aim 4a:  
In addition to the main effects for primary and secondary outcomes described above, we will evaluate 
for effect modification to assess treatment heterogeneity. For each outcome, we will specify a 
regression equation that evaluates for interaction between treatment arm and potential modifiers of 
interest identified from VA Administrative Data including complex multimorbidity (Charlson 
comorbidities), rural residence, self-described racial group, and sex. We will also assess interaction 
based on each of the priority classes for intervention (e.g., recent hospitalization, recent exacerbation). 
We will display subgroup specific treatment effects to characterize the degree of heterogeneity.  
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18.3 Aim 4b:  
To assess heterogeneity of patient and caregiver costs, we will pool data from both arms. We will 
assess whether three important social determinants of health (rurality, underrepresented minority 
group, women) and multi- morbidity (quartile of Charlson Comorbidity index) are associated with patient 
costs. We will use the same analytical model described above to test the effect of each characteristic 
on patient/caregiver incurred costs.79 In the event of one arm having higher costs, we will also account 
for treatment effect by stratification and entering an interaction to the model.  In this model, we will 
specify a regression equation that evaluates for interaction between randomization arm and each 
characteristic. We will also assess interaction based on each of the priority classes for intervention 
(e.g., recent hospitalization, recent exacerbation), and we will display subgroup-specific pooled 
analyses and treatment effects to characterize the degree of heterogeneity.  
18.4 
Sample Size and Power:  
We designed this trial to have 90% power to detect non-inferiority of pharmacist-led population 
management for our primary outcome, which is the presence of COPD exacerbation, hospitalization, 
pneumonia, or death within 180 days. We assume a one-sided type I alpha of 0.05. Based on VA 
administrative data, there are over 500 PCPs with patients who qualify for our trial across the five study 
sites.  We anticipate enrolling at least 200 PCPs with an average of 20 patients each for whom they 
receive an e-consult. Based on administrative data at our centers, approximately 25% of patients with 
COPD will experience our primary outcome.  With 200 clusters, assuming an intra-cluster correlation 
(ICC) of 0.06 and cluster size of 20 patients, we will have 90% power to reject a non-inferiority margin 
of 6% between groups.  
We also explored power for the important secondary outcomes of CCQ and quality measures. For 
CCQ, we designed our analyses to have greater than 95% power to detect a non-inferiority threshold of 
0.25 points for this secondary outcome. The most conservative estimates of minimum important 
difference for the CCQ is 0.3 points,80 although most range between 0.4 to 0.5.81 Based on prior work, 
we expect patients’ responses to CCQ surveys across our population to be ~40% (8 patients per 
cluster). We will also account for clustering by provider, and in prior trials we found patient-reported 
outcomes to have an intra-cluster correlation of 0.10. For perspective, our prior trials demonstrate that 
pulmonary specialist led population health management improved CCQ by 0.5 points. Using these 
same assumptions, we will also have at least 95% power to rule out non-inferiority margins 
of 5% for the secondary outcome of proportion of quality-of-care items received (Table 2).  
Based on the average cluster size of 20, we will include at least 2,000 Veterans per arm across the 
course of the trial. Each week, each arm will need to intervene on at least ~13 patients (2-3 on average 
per site) for us to achieve adequate power. The conservative nature of our intervention will also allow 
us to maintain adequate power should there be unexpected declines in patients per cluster or greater 
difficulty than expected in recruiting and retaining PCPs.  
Power/Sample Size for Patient/caregiver incurred costs (Aim 3, 4b): The sample size for our trial is 
fixed based on the overall scope and design of the EQuiP-COPD trial.  EQuiP plans for 200 clusters 
(100/arm) with average cluster size of 20. This leads to 4,000 patients with population health 
management overall (N=2,000/arm). Our preliminary estimates suggest that Veteran patients enrolled 
in VA primary care and their caregivers incur $205 (SD $363) in the 180 days following PCP visits, with 
intracluster correlation by PCP of 0.04. Based on these estimates, we project 85% power to detect a 
non-inferiority margin of 15% ($31) and 97% power to detect a non-inferiority margin of 20% ($41). With 
regard to heterogeneity of treatment effect for our four subgroups, the expected minimum detectable 
differences in incurred costs ranges from $34-$97. The estimates are summarized in Table 7 below.  
 
 
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Table 7. Minimum detectable differences in incurred costs 
Patient Subgroup 
Expected Prevalence 
(number of patients, % 
of total) 
Alpha Power 
Cost Difference we expect to detect 
between each subgroup over follow-up 
period (total cost difference by group) 
Living in rural areas 
1,800 (45.0%) 
0.05 
0.85 
$34 
Multimorbidity 
(Charlson Score >1) 
2,700 (67.5%) 
0.05 
0.85 
$36 
Female  
131 (3.3%) 
0.05 
0.85 
$97 
Underrepresented 
minority  
579 (14.5%) 
0.05 
0.85 
$49 
 
18.5 
Alternate approaches, threats to validity, and limitations:  
The primary threat to most trials is failure to recruit.  We have more than double the providers needed 
at our 5 medical centers and associated CBOC’s.  We have strong relationships with each of the site 
PI’s. If performance issues arise, we may recruit/replace sites from within numerous other VA sites with 
whom we have worked. Threats to validity: We discussed the need to blind. Knowing whether 
pharmacy and pulmonary recommendations led to similar care quality is a high priority of this study. We 
therefore could not blind providers to treatment assignment.  Practically, we also cannot blind providers 
as clinicians are required to sign their E-consults. We also considered blinding on outcome 
assessment. Data collected from patients and the CDW are not subject to bias. Research staff will 
collect outcome data on quality at 90 days after intervention. Like providers, we will not be able to 
practically blind staff. We believe that the overall threat to bias is also low in that we have ongoing 
training and data quality checks. In addition, research staff would have to differentially abstract data 
based on being a pulmonologist or pharmacist, which we believe is unlikely. If data is not available to 
us in Cerner, we will manually abstract event data using the joint legacy viewer (JLV). This system is 
used to syndicate health information between VA EHR and Cerner. A potential limitation is that despite 
targeting the overall population, women are less represented among veteran populations. Female 
veterans are also typically younger decreasing their prevalence of COPD overall.  
18.6 
Aim 5. qualitative data analysis:  
Aim 5a, Analysis (General Intervention Experience): We will analyze transcripts using simultaneous 
inductive and deductive content analysis.82 Inductive content analysis consists of open (unstructured) 
coding, allowing for the emergence of previously unidentified themes. In contrast, deductive content 
analysis is structured and consists of identifying themes that fit within a priori categories. A priori 
categories will be based on domains within the Donabedian model of quality, and we will use quotes 
that do not accurately fit within existing a priori codes to iteratively develop novel codes.36  
18.7 
Aim 5b, Analysis (Patient/Caregiver Incurred Costs): We will analyze interviews around patient 
and caregiver incurred costs using simultaneous inductive and deductive content analysis.82 Deductive 
content will rely on themes and corresponding codes identified a priori based on costs/burdens for 
caregivers centered around the five domains of access outlined in the Fortney model.83 
We will use ATLAS.ti analysis software for recording and managing codes. The project team will review 
the results of the analytic process to assess completeness. Dr. Lucas Donovan will oversee qualitative 
data collection and analysis.  
19 Multi-Site Communication Plan 
 
The staff at VA Puget Sound will manage the Equip trial and conduct data collection and 
analysis.  Pulmonary specialists are located at each of the five sites.  Pharmacy specialists for 
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Puget Sound and Portland are hired through the Puget Sound Research and Development. All 
other pharmacy specialists will be employed at the remaining three sites. Each local site will hire 
a part-time coordinator to facilitate administrative/regulatory tasks at their site.  
 
To ensure all sites: 
• 
are IRB approved in a timely manner; 
• 
are informed of changes to the protocol and informed consent; 
• 
are informed of SAEs or UPs that may impact the conduct of the study; 
• 
conduct the study according to the IRB-approved protocol; 
• 
are notified when the trial reaches the point that it no longer requires engagement of the 
local facility; 
We will: 
• 
conduct regular meetings led by the co-PIs and/or project manager with project staff to 
review study procedures, site status, barriers encountered, and develop remedies to any 
identified issues 
• 
post templates, working drafts, and approved study documents in a shared network 
folder accessible by approved study staff 
• 
communicate pertinent ad hoc and/or urgent information to sites via email, study-specific 
Sharepoint, and/or VA Microsoft Teams  
20 References  
 
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1806-6 
 
 
 
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