The CAPTURE Study: Validating a Unique Chronic Obstructive Pulmonary Disease (COPD) Case Finding Tool in Primary Care
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Sponsor: Weill Medical College of Cornell University

 
 
The CAPTURE Study: Validating a unique COPD case 
finding tool in primary care 
 
Protocol Number: 1R01HL136682 
National Clinical Trial (NCT) Identified Number: 
NCT03581227, NCT03653611, NCT03583099 
Principal Investigators: 
Fernando J. Martinez, M.D., Weill Cornell Medicine 
MeiLan K. Han, M.D., University of Michigan 
Funder: 
National Heart, Lung, and Blood Institute (NHLBI) 
Version Number: v. 8.0 
17 July 2023 

 
Protocol Amendment 8.0 - Summary of Changes 
Location 
Page 
Number 
Type of Change 
Description 
Rationale 
Cover page 
--- 
Administrative 
Update Protocol Version to 8.0 and 
update version date to 17JUL2023 
Amendment version and date 
1.1 Synopsis 
7 
Clarification  
Secondary Endpoints 
• Aim 3 – 
O All of the above endpoints for Aim 3, 
in the population of participants 
defined by each of the following 
instead of CAPTURE+ status: 1) 
clinically significant COPD, 2) 
spirometric COPD, 3) Mild COPD 4) 
preserved ratio, impaired spirometry 
(PRISm), and 5) symptomatic non-
obstructed (SNO)  
Clarification of the secondary 
endpoints and what participants will 
be analyzed.  
1.3 Schedule of 
Assessments 
11,12 
Edit 
Footnote 3: 
3. Recorded for a subset of participants 
who meet any of the following criteria: 
1) CAPTURE+ subjects defined as 
CAPTURE Score > 5 or CAPTURE score 
of 2, 3, or 4 with a low PEF, defined as 
<350 L/min for males and <250 L/min 
for females 2) abnormal spirometry 
defined as post-bronchodilator 
FEV1/FVC < 0.70 or FEV1 < 80% 
predicted at baseline, or pre-
bronchodilator FEV1/FVC < 0.65 or 
FEV1 < 70% predicted for patients who 
do not complete post-bronchodilator 
spirometry; and, 3) a random sample 
of approximately 5% of those who do 
not meet criteria 1 and 2. For 
participants meeting criteria 1 and 2 
who cannot or choose not to complete 
the 12-month assessment, medical 
record review will still be completed. 
For participants meeting criteria 1 and 
2 who change medical practices and 
medical record review cannot be 
completed, patients will be contacted 
for completion of patient reported 
data. For participants meeting criterion 
3 where all of the protocol-specified 
12-month assessments cannot be 
made, another participant will be 
selected at random to replace this 
participant. 
The footnotes were edited to delete 
comment on replacing control 
patients who did not have availability 
of follow up data. 
1.3 Schedule of 
Assessments 
11 
Addition 
CAPTURE questions added to 12-
month evaluations 
CAPTURE item additional 
questionnaire is to be collected at the 
12-Month visit.  

3.0 Objectives and 
Endpoints 
21 
Clarification  
Aim 3 Endpoints:  
All of the above endpoints for Aim 3, in 
the population of participants defined 
by each of the following instead of 
CAPTURE+ status: 1) clinically 
significant COPD, 2) spirometric COPD, 
3) Mild COPD, 4) preserved ratio, 
impaired spirometry (PRISm), and 5 4) 
symptomatic non-obstructed (SNO). 
Clarification of the secondary 
endpoints and what participants will 
be analyzed. 
5.1 Inclusion 
Criteria 
27 
Addition 
4. Able to read and speak English or 
Spanish. 
Study participants could complete 
the baseline visit and any required 
follow up in English or Spanish 
8.2 Longitudinal 
Follow-Up 
Assessments and 
Data Collection 
34 
Deletion 
Data collected from medical record: 
Deleted “oral anti-inflammatory” 
medications 
Deleted * and footnote for * 
This edit confirms that oral anti-
inflammatory medications will not be 
collected during the 12-month chart 
review.  
8.2 Longitudinal 
Follow-Up 
Assessments and 
Data Collection 
35 
Edit 
Data Collection by the COPD 
Foundation 
Deleted “oral anti-inflammatory” 
medications 
Added- CAPTURE questions 
Added- CAPTURE Additional Items 
Questionnaire 
Deleted * and footnote for * 
Data collected by the COPD 
Foundation will now include 
CAPTURE Questions and CAPTURE 
Additional Item Questionnaire.  
9.3.2 Practice 
Behavior (Aim 3) 
47 
Addition 
All additional secondary analyses will 
also be applied to patients with 
clinically significant and spirometrically 
defined COPD, Mild COPD, PRISm, and 
symptomatic non-obstruction. 
Secondary analyses include Mild 
COPD as reflected throughout the 
protocol.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
STATEMENT OF COMPLIANCE .................................................................................................................. 1 
Abbreviations ............................................................................................................................................. 1 
1 
PROTOCOL SUMMARY .................................................................................................................... 3 
1.1 
Synopsis ................................................................................................................................... 3 
1.2 
Schema .................................................................................................................................... 7 
Figure 1. Overall structure of aims ................................................................................................................ 7 
Figure 2. structure of aim 2 ............................................................................................................................ 7 
1.3 
Schedule of Activities (SoA) ..................................................................................................... 9 
2 
INTRODUCTION .............................................................................................................................. 10 
2.1 
Study Rationale ...................................................................................................................... 10 
2.2 
Background ............................................................................................................................ 12 
Aims 1 and 3. ............................................................................................................................................. 12 
2.3 
Risk/Benefit Assessment ........................................................................................................ 14 
2.3.1 
Known Potential Risks .......................................................................................... 14 
2.3.2 
Known Potential Benefits ...................................................................................... 15 
2.3.3 
Assessment of Potential Risks and Benefits ........................................................ 15 
3 
OBJECTIVES AND ENDPOINTS .................................................................................................... 15 
4 
STUDY DESIGN .............................................................................................................................. 19 
4.1 
Overall Design ........................................................................................................................ 19 
4.2 
Scientific Rationale for Study Design ..................................................................................... 21 
4.3 
End of Study Definition ........................................................................................................... 23 
5 
STUDY POPULATION ..................................................................................................................... 23 
5.1 
Inclusion Criteria ..................................................................................................................... 23 
5.2 
Exclusion Criteria .................................................................................................................... 24 
5.3 
Screen Failures ...................................................................................................................... 24 
5.4 
Strategies for Recruitment and Retention .............................................................................. 25 
6 
STUDY INTERVENTION ................................................................................................................. 25 
6.1 
Study Intervention(s) Administration ....................................................................................... 25 
6.1.1 
Study Intervention Description .............................................................................. 26 
6.2 
Measures to Minimize Bias: Randomization and Blinding ...................................................... 27 
6.3 
Study Intervention Compliance .............................................................................................. 27 
6.4 
Concomitant Therapy ............................................................................................................. 28 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL .......................................................................................................... 28 
7.1 
Discontinuation of Study Intervention ..................................................................................... 28 
7.2 
Participant Discontinuation/Withdrawal from the Study .......................................................... 28 
7.3 
Lost to Follow-Up ................................................................................................................... 28 
8 
STUDY ASSESSMENTS AND PROCEDURES .............................................................................. 29 
8.1 
Baseline assessments and data collection ............................................................................. 29 
8.2 
Longitudinal follow-up assessments and data collection ........................................................ 31 
8.3 
aim 2 assessments and data collection .................................................................................. 32 
8.4 
Adverse Events and Serious Adverse Events ........................................................................ 35 
8.4.1 
DEFINITION OF ADVERSE EVENTS (AE) ................................................. 35 
8.4.2 
DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) ........................... 35 
1 
TABLE OF CONTENTS 

8.4.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND 
FOLLOW-UP 
37 
8.4.4 
Adverse Event Reporting...................................................................................... 37 
8.4.5 
Serious Adverse Event Reporting ........................................................................ 37 
8.5 
Unanticipated Problems ......................................................................................................... 37 
8.5.1 
Definition of Unanticipated Problems (UP) ........................................................... 37 
8.5.2 
Unanticipated Problem Reporting......................................................................... 38 
8.6 
Safety Oversight ..................................................................................................................... 38 
9 
STATISTICAL And analytical plans ................................................................................................. 38 
9.1 
Sample size and POWER ...................................................................................................... 38 
9.2 
Populations for Analyses ........................................................................................................ 42 
9.3 
Statistical Analyses ................................................................................................................ 42 
9.3.1 
SENSITIVITY AND SPECIFICITY (Aim 1) ........................................................... 42 
9.3.2 
PRACTICE BEHAVIOR (Aim 3) ........................................................................... 43 
9.3.3 
CAPTURE IMPLEMENTATION RECOMMENDATIONS (Aim 2) ........................ 44 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 45 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ...................................................... 45 
10.1.1 
Informed Consent Process ................................................................................... 45 
10.1.2 
Study Discontinuation and Closure ...................................................................... 46 
10.1.3 
Confidentiality and Privacy ................................................................................... 46 
11 
STUDY ADMINISTRATION AND OVERSIGHT .............................................................................. 47 
11.1 
Study Leadership ................................................................................................................... 47 
11.1.1 
Principal Investigators .......................................................................................... 47 
11.1.2 
practice based research networks (pbrn) ............................................................. 47 
11.1.3 
Spirometry Core ................................................................................................... 48 
11.1.4 
Implementation core ............................................................................................. 49 
11.1.5 
Data coordinating center (DCC) ........................................................................... 49 
11.1.6 
Clinical Coordinating Center ................................................................................. 49 
11.1.7 
12 month survey Coordinating Center .................................................................. 51 
11.2 
Organizational Structure ......................................................................................................... 51 
12 
Quality Assurance and Quality Control ............................................................................................ 52 
13 
Data Handling and Record Keeping................................................................................................. 52 
13.1 
Data Collection and Management Responsibilities ................................................................ 53 
13.2 
Study Records Retention ....................................................................................................... 53 
13.3 
Protocol Deviations ................................................................................................................ 53 
13.4 
Publication and Data Sharing Policy ...................................................................................... 54 
14 
PROTOCOL AMENDMENT HISTORY ............................................................................................ 54 
15 
LITERATURE REFERENCES ......................................................................................................... 59 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017 
1 
 
 
 
 
This study will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP) and the following: 
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812) 
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are responsible 
for the conduct, management, or oversight of NIH-funded clinical trials have completed Human Subjects 
Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the Institutional Review Board (IRB) for review and approval. Approval of both the 
protocol and the consent form must be obtained before any participant is enrolled. Any amendment to 
the protocol will require review and approval by the IRB before the changes are implemented to the 
study. In addition, all changes to the consent form will be IRB-approved; a determination will be made 
regarding whether a new consent needs to be obtained from participants who provided consent, using a 
previously approved consent form. 
 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
CAO 
Chronic Airflow Obstruction 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT 
Consolidated Standards of Reporting Trials 
COPD 
Chronic Obstructive Pulmonary Disease 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data and Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
ECOPD 
Exacerbation of Chronic Obstructive Pulmonary Disease 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FEV1 
Forced Expiratory Volume in 1 second 
FFR 
Federal Financial Report 
FVC 
Forced Vital Capacity 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practice 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act 
STATEMENT OF COMPLIANCE 
ABBREVIATIONS 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017 
2 
 
 
 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
LSMEANS 
Least-squares Means 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NCT 
National Clinical Trial 
NIH 
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PBRN 
Practice-Based Research Network 
PI 
Principal Investigator 
PRISm 
Preserved ratio, impaired spirometry 
QA 
Quality Assurance 
QC 
Quality Control 
RE-AIM 
Reach, Effectiveness, Adoption, Implementation, Maintenance 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SNO 
Symptomatic non-obstructed 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
US 
United States 
USPSTF 
United States Preventive Services Task Force 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017 
3 
 
 
 
 
 
 
 
 
Title: 
The CAPTURE Study: Validating a unique Chronic Obstructive Pulmonary 
Disease (COPD) case finding tool in primary care 
Study Description: 
Aims 1 and 3. A prospective, multicenter study including a cross-sectional 
validation to define sensitivity and specificity of CAPTURE and its impact 
on clinical care across a broad range of primary care settings in a cluster 
randomized controlled clinical trial. The CAPTURE tool consists of a 5-item 
self-administered questionnaire and peak expiratory flow (PEF) 
measurement, designed to identify undiagnosed patients with Chronic 
Obstructive Pulmonary Disease (COPD). 
Aim 2. This study delivers a qualitative assessment of clinical practice 
acceptance of and implementation strategy for CAPTURE case finding 
within 10 varied primary care practices across 5 US PBRN regions. We 
evaluate primary care practice attitudes, beliefs and recommendations 
about CAPTURE’s potential to feasibly integrate into clinical practice 
patterns, workflow and quality improvement paradigm planning in a 
variety of primary care clinical settings. 
Definitions: 
CAPTURE+ = Participants with 
• 
CAPTURE score > 5, or 
• 
CAPTURE score of 2, 3, or 4 with a low PEF, defined as <350 L/min 
for males and <250 L/min for females 
CAPTURE- = Participants with CAPTURE score < 2 or scores 2-4 with normal 
PEF, defined as >350 L/min for males and > 250 L/min for females 
Spirometrically defined COPD = Participants with abnormal spirometry, 
defined as post-bronchodilator FEV1/FVC <0.7. If a participant is unable to 
complete a post-bronchodilator spirometry (refusal, technical error on the 
part of coordinator, etc.), and the pre-bronchodilator FEV1/FVC is less 
than 0.65, the participant will be considered to have COPD for the purpose 
of follow-up in this study. 
Clinically significant COPD = Participants with abnormal spirometry, 
defined as post-bronchodilator FEV1/FVC <0.7, plus one of the 
following: 
• 
FEV1 < 60% predicted, or 
• 
> 1 exacerbation-like event within the past 12 months. 
Mild COPD = Participants with abnormal spirometry, defined as post- 
bronchodilator FEV1/FVC<0.7 plus both of the following: 
• 
FEV1 ≥ 60% and 
• 
No prior history of ECOPD 
Preserved ratio, impaired spirometry (PRISm) = Participants without 
spirometrically defined COPD who have post-bronchodilator FEV1 < 80% 
predicted. 
Symptomatic non-obstructed (SNO) = Participants without spirometrically 
defined COPD and without PRISm who have a COPD Assessment Test score 
≥ 10. 
1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017 
4 
 
 
Objectives: 
Aims 1 and 3 Primary Objectives: 
• Aim 1 - Define the sensitivity and specificity of CAPTURE for identifying 
previously undiagnosed patients with clinically significant COPD in a 
broad range of primary care settings. 
 
• Aim 3 – Define the impact of CAPTURE information provided to 
clinicians in identifying and managing CAPTURE+ patients across a 
broad range of primary care settings. 
Aim 2 Primary Objective: 
Explore clinical practice implementation approaches to and acceptance of 
CAPTURE case finding for clinically significant COPD in a range of primary 
care practices. 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
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Aims 1 and 3 Secondary Objectives: 
• 
Aim 1 – 
• 
Define the sensitivity and specificity of CAPTURE for patients with 
COPD across a broad range of racial and ethnic groups in a range 
of primary care settings. 
• 
Determine positive and negative predictive values (PPV and NPV) 
in different practice settings. 
• 
Verify the optimal use (cutoff threshold) of the CAPTURE tool in 
combination with PEF measurements for identifying undiagnosed 
COPD. 
• 
Determine patient and site characteristics that, with the CAPTURE 
assessment, will best identify persons with undiagnosed COPD. 
• 
Determine whether CAPTURE is useful in identifying other 
definitions of undiagnosed COPD including: 
1) spirometry-defined COPD, and 
2) mild COPD 
• 
Determine the potential impact of SARS CoV-2 infection on the 
above operating characteristics of the CAPTURE approach. 
• 
Aim 3 - 
• 
Define the impact of providing CAPTURE education and patient-
level CAPTURE information to clinicians on selected clinician 
interventions for the management of CAPTURE+ patients. 
• 
Assess the impact of CAPTURE education and patient-level 
CAPTURE information on clinician interventions specific to 
smokers who are CAPTURE+. 
• 
Determine the impact of CAPTURE education and patient-level 
CAPTURE information on patient symptoms, exacerbations, 
hospitalizations, and mortality among CAPTURE+ patients. 
• 
Determine the impact of CAPTURE education and receipt of 
patient-level CAPTURE information on identification and 
management of patients with respiratory burden. 
• 
Determine the potential impact of SARS CoV-2 infection on clinical 
actions taken in response to CAPTURE screening. 
Aim 2 Secondary Objectives: 
• 
Qualitatively assess primary care clinical staff COPD practice 
behavior – including COPD screening and diagnostic perceptions, 
beliefs and knowledge – that will inform strategies to improve 
CAPTURE RE-AIM (reach, impact, adoption, implementation and 
maintenance of use) characteristics. 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017 
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• 
Qualitatively assess primary care patient opinion of CAPTURE 
COPD case finding that will inform strategies to improve CAPTURE 
RE-AIM (reach, impact, adoption, implementation and 
maintenance of use) characteristics. 
• 
Determine the potential impact of SARS CoV-2 infection on the 
application of the CAPTURE approach. 
Endpoints: 
Aims 1 and 3 Primary Endpoints: 
• Aim 1 – 
o Sensitivity and specificity of CAPTURE to identify previously 
undiagnosed patients with clinically significant COPD at baseline. 
• Aim 3 – 
o Proportion of CAPTURE+ participants who meet at least one of the 
following within 12 months of study baseline (composite endpoint): 
1) referral for or completion of clinical spirometry testing, 2) new 
diagnosis of COPD, 3) newly prescribed respiratory medication (long 
acting bronchodilator or anti-inflammatory for respiratory 
condition), 4) referral to a specialist for respiratory 
evaluation/treatment, or 5) referral for or completion of pulmonary 
rehabilitation. 
Aim 2 Primary Endpoints: 
• Primary care clinician recommendations that inform CAPTURE RE-AIM 
strategies at both provider and clinical support levels of primary care 
practice. 
• Primary clinician recommendations that inform CAPTURE-associated 
COPD education models for primary care clinicians. 
• Primary care clinician recommendations that inform CAPTURE- 
associated COPD clinical quality improvement designs across a variety 
of primary care practice types. 
Aims 1 and 3 Secondary Endpoints: 
• Aim 1 – 
o Sensitivity and specificity of CAPTURE to identify previously 
undiagnosed patients with COPD across sex, ethnic groups, urban vs 
rural location, and educational level. 
o Positive and negative predictive values (PPV and NPV) in different 
practice settings. 
o Areas under the receiving operator characteristic curve (AUC) for 
various cutpoints of CAPTURE and PEF1 measurements to 
determine the best cutpoint for COPD+ screen. 
o AUC to identify the combination of patient/site characteristics 
which best discriminates those with clinically significant COPD. 
o All primary and secondary endpoints as applied to 1) spirometry- 
defined COPD and 2) mild COPD 
• Aim 3 – 
o Proportion of CAPTURE+ participants who have each of the 
following occur within 12 months of study baseline (separate 
endpoints to be evaluated individually): 1-5) each component of 
the Aim 3 primary endpoint, and 6) recommendation or 
administration of influenza vaccination. 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
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NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017 
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o Proportion of CAPTURE+ participants currently smoking at the 
baseline study visit who have any of the components of the Aim 3 
primary endpoint or any of the following occur within 12 months 
of baseline (evaluated as a composite endpoint and as individual 
endpoints): 1) clinician counseling or recommendation for smoking 
cessation, 2) referral to a smoking cessation program, 3) referral to 
a smoking quit line, and 4) newly prescribed medication for 
smoking cessation. 
o In CAPTURE+ participants, change in CAT score between 
baseline and follow-up at 12 months after baseline, and 
proportion of patients who experience exacerbations, 
hospitalizations, or mortality within 12 months of baseline. 
o All of the above endpoints for Aim 3, in the population of 
participants defined by each of the following instead of 
CAPTURE+ status: 1) clinically significant COPD, 2) spirometric 
COPD, 3) Mild COPD, 4) preserved ratio, impaired spirometry 
(PRISm), and 5) symptomatic non-obstructed (SNO). 
o All of the above endpoints for Aim 3, in all of the analysis 
populations named above, separated into cohorts based on 
enrollment date and the degree to which follow-up may have 
been affected by the SARS-CoV-2 pandemic. 
Aim 2 Secondary Endpoints: 
• Existing COPD screening and diagnostic and case finding processes 
within a variety of primary care practices. 
• Primary care practice belief about capacity to change from existing 
COPD screening and diagnostic assessment strategies. 
• Practice-specific COPD screening and diagnostic continuing education 
preference. 
Study Population: 
Aims 1 and 3. 
Adults 45-80 years old without a prior diagnosis of COPD (total N ~ 5000) 
Aim 2. 
- 10 primary care practices: 2 practices per PBRN with up to 15 clinical staff 
participants per practice; clinician N = up to 150 (up to 30 clinician 
participants per PBRN). 
- Aim 1 patient opinion survey population; patient N = 200 (40 patients 
from each PBRN; adults 45-80 years old, without a prior diagnosis of 
COPD). 
- Total N = up to 350 
Phase: 
N/A 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017 
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Description of 
Sites/Facilities Enrolling 
Participants: 
Aims 1 and 3. Enrollment will occur in approximately 100 primary care 
practices affiliated with 7 primary care based practice networks (PBRN) 
across the United States who exhibit a broad range of gender, ethnic, 
racial, socioeconomic, and regional diversity. 
Aim 2. 
• 
Two primary care practices chosen by each of the same 5 PBRN co- 
investigator teams make up the 10 aim 2 practices from which 
clinician participants are enrolled. These 10 practices are separate 
from the 100 chosen practices in aims 1 and 3. 
• 
Patient participants are a sub-sample of those participants 
enrolled in aims 1 and 3. 
Description of Study 
Intervention: 
Aims 1 and 3. Primary care practices will be randomized to either receive 
basic COPD education and patient-level CAPTURE information with 
CAPTURE education (initially basic then later enhanced based on data 
collected in Aim 2) versus COPD education only. 
Aim 2. Participating primary care clinicians from 10 varied practices are 
surveyed at three different time points and participate in two focus groups 
qualitatively assessing CAPTURE implementation strategy and COPD case 
finding approaches in primary care. Participating patients complete one 
10-minute written opinion survey about CAPTURE. 
Study Duration: 
Aim 1 and 3. 4 years 
Aim 2. 2 years 
Participant Duration: 
Aims 1 and 3. Up to 12 months 
Aim 2. 
• 
Primary care practice clinicians: questionnaires and focus groups 
(total 3 hours/participant) over 16 months. 
• 
Primary care patients: one 10-minute questionnaire/participant 
over 14 months. 
 
 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017 
9 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.2 
SCHEMA 
FIGURE 1. OVERALL STRUCTURE OF AIMS 
FIGURE 2. STRUCTURE OF AIM 2 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017 
10 
 
 
 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017 
11 
 
 
 
 
 
Table 1: Schedule of Activities (Aims 1 and 3) 
 
Pre-Visit 
Contact1 
Baseline 
12 Months3 
Contact (C)/ Visit (V)/Medical 
Record Review (MRR) 
C1 
V1 
C2/MRR5 
Time point, days 
(Visit window) 
Prior to 
outpatient visit 
(≤-1) 
Within 30 days 
of pre-visit 
contact 
365 +30 (C2) 
Contact patient re: interest in study 
visit1 
X 
Informed consent 
X 
Demographics 
X 
Medical history (Co-morbidities)2 
X 
Vaccination status 
X 
X 
CAPTURE 5-item questionnaire 
X 
X 
CAPTURE item additional 
questionnaire 
X 
           X 
Peak Expiratory Flow (PEF) 
X 
Height and weight 
X 
Respiratory medications review 
X 
X 
Spirometry4 
X* 
Respiratory symptoms, 
exacerbation assessment 
X 
X 
Smoking exposure history 
X 
Smoking cessation review6 
X 
COPD Assessment Test (CAT) 
X 
X 
COVID-19 Questionnaire 
X 
X 
Adverse Events 
X 
Medical record review 
Additional COVID-19 items 
X 
X 
1. Optional per site recruitment preferences 
2. Comorbidities including cardiovascular, respiratory and malignant disorders 
3. Recorded for a subset of participants who meet any of the following criteria: 1) 
CAPTURE+ subjects defined as CAPTURE Score > 5 or CAPTURE score of 2, 
3, or 4 with a low PEF, defined as <350 L/min for males and <250 L/min for 
females 2) abnormal spirometry defined as post-bronchodilator FEV1/FVC < 
0.70 or FEV1 < 80% predicted at baseline, or pre-bronchodilator FEV1/FVC < 
0.65 or FEV1 < 70% predicted for patients who do not complete post-
bronchodilator spirometry; and, 3) a random sample of approximately 5% of 
those who do not meet criteria 1 and 2. For participants meeting criteria 1 and 2 
who cannot or choose not to complete the 12-month assessment, medical 
record review will still be completed. For participants meeting criteria 1 and 2 
who 
1.3 
SCHEDULE OF ACTIVITIES (SOA) 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017 
12 
 
 
 
 
 
 
Undiagnosed COPD is a leading cause of morbidity and mortality. Spirometry, the ‘gold standard’ for 
diagnosis, is not recommended for screening in asymptomatic individuals or untargeted case finding and 
remains widely underutilized in primary care settings. Targeted case finding approaches have been 
strongly advocated but currently available approaches generally identify patients across the spectrum of 
mild to severe disease without reference to potential therapeutic benefit or exacerbation risk, thereby 
limiting clinical impact and acceptance in primary care. There is an urgent need to develop and 
implement simple case finding approaches that can identify patients with clinically significant COPD in 
primary care settings. 
Through a multi-stage, iterative process we developed a simple case finding tool using five questions 
combined with selective peak expiratory flow (PEF) measurement that identifies individuals with 1) an 
FEV1 < 60% predicted and/or 2) at risk for ECOPD. We call this tool CAPTURE (COPD Assessment in 
Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk)(1). As clinical trials 
have demonstrated benefit and therapeutic guidelines recommend therapy for these individuals we 
have labeled these patients as suffering from ‘clinically significant’ COPD. The long-term goal of this 
project is to identify these patients so that they can be treated and result in improved health status, 
reduced exacerbations, and decreased morbidity. 
 
The overall objectives of Aims 1 and 3 of this project are to 1) validate the sensitivity, specificity, and 
predictive value of CAPTURE to identify undiagnosed, clinically significant COPD patients in a diverse 
primary care population; and explore whether identifying these patients results in improved COPD 
specific care and health status. Our principal hypothesis is that CAPTURE can effectively and efficiently 
identify primary care patients with undiagnosed, clinically significant COPD. We objectively test our 
principal hypothesis by completing to two separate and linked aims: 
 
Aim 1 – Determine the sensitivity and specificity of CAPTURE in identifying clinically significant 
COPD patients in a broad range of primary care outpatient practices. 
 
Working hypothesis - A simple case finding methodology using a five-item questionnaire with 
selective PEF measurement will identify undiagnosed patients with clinically significant COPD. 
change medical practices and medical record review cannot be completed, 
patients will be contacted for completion of patient reported data.  
4. Pre-bronchodilator spirometry will be done for all participants. Post- bronchodilator 
spirometry will be performed for participants with abnormal spirometry (FEV1/FVC < 
0.70 or FEV1 < 80% predicted) *If the participant has taken a bronchodilator within a 
2-hour window of spirometry the spirometry will be considered post-bronchodilator 
and a pre-bronchodilator spirometry will not be done. 
5. The 12-month assessment consists of patient reported data, collected by the 
COPD Foundation, and medical record review completed by site coordinators. 
6. This will be completed in those that are smoking at V1. 
2 
INTRODUCTION 
2.1 
STUDY RATIONALE 

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We will conduct a cohort study of approximately 5,000 participants in 100 primary care practices 
affiliated with five primary care based research networks (PBRN) that provide access to previously 
undiagnosed patients with clinically significant COPD who exhibit gender, ethnic, racial, 
socioeconomic and regional diversity. 
 
Aim 3 – Define the impact of CAPTURE screening in a broad range of primary care outpatient 
practices and evaluate practice and patient characteristics that are associated with care 
implementation and clinical outcomes for patients with respiratory symptoms (CAPTURE+). 
Working hypothesis – Provision of patient specific CAPTURE data to practicing clinicians will result in 
improved management of patients with respiratory symptoms (CAPTURE+). 
 
We will provide basic COPD education and patient level CAPTURE information and education to site 
clinicians at 50 of the sites and prospectively follow selective, pre-defined subgroups of patients to 
define relevant outcomes. Care at the other 50 clinical sites will follow standard of care with basic 
COPD education to clinicians. 
 
Assessing the potential clinical impact of a novel COPD case finding strategy includes confirmation of 
validity in a diverse primary care patient population and a quantitative research evaluation of its impact 
on clinical decision-making and COPD patient outcomes, as found in aims 1 and 3 above. Equally 
important is exploration through validated implementation methods that the newly designed CAPTURE 
tool, even if valid and impactful, can provide real-world utility within a variety of primary care practice 
settings. While we find no evidence in previous COPD screening studies of such detailed appraisal, 
ascertaining the feasibility of clinical testing is a vital component of assuring that new approaches 
address potential clinical practice need, capacity, knowledge and diagnostic gaps. As much as possible, 
clinical respiratory innovations should align with busy workflow at all practice staff levels to more 
effectively identify primary care patients with undiagnosed, clinically significant COPD. The SARS-CoV-2 
pandemic may potentially alter the approach to COPD Case Finding in the primary care community; the 
protocol has been adapted to investigate this possibility. Similarly, the potential of SARS-CoV-2 infection 
and the COVID-19 clinical syndrome to impact respiratory symptoms in primary care patients will also be 
explored. 
To maximize success of the CAPTURE adoption, education and implementation in this study and in 
future work, Aim 2 is introduced to assess practice experience, need and preference that can inform 
clinical COPD case finding and education in primary care settings: 
 
Aim 2 – Explore clinical practice implementation approaches to and acceptance of CAPTURE case 
finding for clinically significant COPD in a range of primary care practices. 
The overall objective of this aim is to qualitatively explore primary care clinical practice acceptance 
of COPD case finding implementation and define education and feasibility strategies to enhance 
adoption in primary care practice. This assessment includes understanding clinician and clinical 
staff COPD practice and perceptions in addition to the feasibility of case finding integration into 
existent clinical work patterns. To attain this objective, we address one working hypothesis – a 
COPD case finding methodology using a validated one-page, five-item questionnaire with selective 
PEF measurement (CAPTURE) can be incorporated into the clinical practice patterns, clinical 
workflow, communication and practice-based quality improvement paradigms in a variety of 
primary care clinical settings. The rationale for this objective reflects the importance of 
establishing if an innovative approach to COPD case finding (CAPTURE) is considered a pragmatic 
tool with potential utility for primary care clinicians within real-world clinical practice settings. 

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With the completion of this aim we anticipate confirming that future validated approaches to 
COPD case finding can be adopted in a broad variety of clinical care settings thereby providing 
further impetus for the rigorous evaluation of a) case finding guided patient outcomes as part of 
routine primary care clinical practice; b) case finding use in a range of primary care health 
professional COPD-related education approaches, clinical quality improvement models and 
diagnostic guidelines; and c) the capacity of clinical case finding with informed follow-up to 
enhance future COPD clinical care therapeutic paradigms used in primary care practice. 
 
Aims 1 and 3. 
COPD remains a major cause of morbidity and mortality. COPD results in substantial morbidity and 
mortality worldwide.(2-4) Globally, the prevalence of COPD and years lived with disability increased 
from 1990 to 2013.(5) This is particularly evident in older individuals.(6) These well-designed population 
based studies confirm the growing impact of COPD. 
COPD is frequently undiagnosed. We recently documented that only 28% of participants with chronic 
airway obstruction (CAO) had physician diagnosed disease.(7) Importantly, an FEV1 <50% predicted was 
noted in 10% of those with undiagnosed CAO; this is similar to other cohorts or population based 
surveys.(8-11) There is consistency in these well-conducted studies that confirm most COPD patients are 
undiagnosed. 
Spirometry is underutilized. The U.S. Preventive Services Task Force (USPSTF) recently recommended 
against the use of spirometry for routine, general population or practice-based screening in 
asymptomatic individuals.(12) An editorial by the PI of this application highlighted the limitations of this 
conclusion.(13) Within primary care spirometry is often viewed as time consuming and difficult to 
implement and interpret.(14) As such, it is not routinely used.(15-19) Even the availability of less 
expensive and easily used spirometers(20) has not resulted in increased utilization.(21, 22) 
Undiagnosed COPD is associated with a negative clinical impact. In a robust, population based study 
we confirmed that undiagnosed patients experienced impaired health status and a higher risk for all- 
cause mortality compared to those without CAO; this was particularly evident with more severe CAO.(7) 
Others have confirmed increased mortality,(23) health status impairment,(24) exacerbation-like 
respiratory events,(11) and increased health care costs.(25, 26) As such, there are consistent data 
suggesting that undiagnosed COPD patients experience negative clinical events and impaired health 
status. 
Therapeutic interventions improve COPD clinical outcomes. Well designed, randomized controlled 
trials confirm that COPD therapy is effective, particularly in patients with an FEV1 < 60% predicted who 
are symptomatic or at risk for ECOPD.(27, 28) Despite limited data, some have suggested that earlier 
detection of patients with previously undiagnosed, yet clinically significant COPD, in primary care 
settings could improve short- and long-term patient outcomes and may be cost-effective. (29, 30) 
COPD case finding approaches to date have generally been methodologically limited. Several COPD 
case finding tools have been created based on existing epidemiologic literature or expert opinion.(31, 
32) This includes tools created by investigators in this study.(33, 34) In general, current approaches were 
designed to identify COPD patients without reference to disease severity or ECOPD risk, resulting in the 
identification of a high proportion of patients with mild or minimally symptomatic disease.(21, 33-39) 
Several studies have tested the accuracy of handheld flow meters for case identification with varying 
sensitivity and specificity.(40) Although informative in terms of CAO, PEF meters have been unable to 
systematically identify patients at risk of ECOPD. We tested a three-staged approach (risk-factor 
2.2 
BACKGROUND 

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questionnaire, PEF, and spirometry) for identifying moderate to severe COPD (FEV1<60% predicted) in a 
convenience sample of the general population.(41) This study was limited by the nature of the 
population screened and the screening questionnaire used but supported the concept that PEF can 
facilitate COPD case finding. 
A systematic analysis of existing databases provides insight into the best variables for COPD Case 
Identification. To identify potential items that could be useful in the identification of undiagnosed COPD 
we interrogated three robust datasets of populations in which the investigators on this application had 
major roles [COPD Foundation Peak Flow Study Cohort (n=5761); Burden of Obstructive Lung Disease 
Kentucky site (n=508); and COPDGene® (n=10,214)].(42) We utilized the machine learning statistical 
method of random forests to identify and validate variables most important in identifying patients with 
clinically significant COPD. COPD case finding candidate content included items reflecting exposure, 
personal and family history, respiratory symptoms, recent health history, activity limitation and 
demographics. 
A comprehensive, qualitative study identified key constructs for identifying recently diagnosed 
patients with clinically significant COPD. We completed a two phase study that included focus groups 
followed by cognitive interviews to refine the key constructs for identifying patients with clinically 
significant COPD.(43) Fifty participants were recruited including those with mild airflow obstruction, 
diagnosed within the previous six months and without previous ECOPD; those diagnosed within the 
previous six months and with a history of at least one ECOPD within the prior year; those with 2-3 risk 
factors for COPD but without CAO; and those with > 4 risk factors for COPD but without CAO. Using a 
content analysis approach, key themes and constructs were identified and integrated with the content 
of the previous literature review and data mining. We identified 44 candidate items that resonated with 
patients and provided important insights into a case finding instrument. 
A five-item questionnaire exhibits excellent operating characteristics to identify clinically significant 
COPD patients. We completed a prospective, multi-site, case-control study of four groups: cases with 
clinically significant COPD – COPD with > 1 ECOPD in the previous year (n=97) and COPD with no ECOPD 
but an FEV1 < 60% predicted (n=89); controls – no known COPD (n=87) and COPD with an FEV1 > 60% 
predicted and no ECOPD in the previous year (n=74). Using random forest analyses the 44 candidate 
items were reduced to 34-item, 21-item, 8-item and two different five-item sets. Through-out the item 
reduction process, the item sets maintained good performance, consistently misclassifying fewer than 
27% of cases and controls, and with sensitivity greater than 80% and specificity greater than 70%. A five- 
item questionnaire exhibited good operating characteristics for separating COPD cases from controls. 
These characteristics were even better when separating COPD from controls without COPD. 
 
Selective PEF measurement enhances the operating characteristics of a COPD case finding strategy. In 
the above case control study PEF was measured using a mechanical PEF meter with disposable 
mouthpieces. To optimize sensitivity and specificity, the following cut-off scores were selected, based on 
our data, for identifying cases of clinically significant COPD using PEF alone: males: <350 L/min; females: 
<250 L/min. The best method for predicting cases was a combination of the questionnaire and PEF 
(CAPTURE), where PEF is used only for mid-range scores. Under this scoring scenario, patients with 
scores of 0 or 1 are not considered at risk of clinically significant COPD; they would not require further 
evaluation. Those with a score of 5 or 6 are considered to be at high risk of clinically significant COPD 
and should be referred directly for further evaluation, including clinical spirometry. Patients scoring in 
the middle range (2 to 4) would undergo PEF testing, applying the 350/250 interpretation thresholds. In 
our sample, 52% of the participants required PEF to determine if spirometry was indicated. The other 
48% needed only the five-item questionnaire. This approach provided 90% sensitivity, 93% specificity 
and an overall error rate of 9%. 

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CAPTURE exhibits similar operating characteristics in a Spanish speaking population. To broaden our 
target population, the five-item questionnaire was methodically translated to Spanish using previously 
validated, rigorous methods(44) to yield an instrument that is equivalent to the English questionnaire 
and linguistically and culturally applicable to persons of diverse Spanish-speaking backgrounds residing 
in the US. In a subset of Spanish speaking participants CAPTURE exhibited excellent sensitivity (88%), 
specificity (92%) and overall error rate (10%) for identifying patients with clinically significant COPD. 
 
Aim 2. 
Consistent with national criteria for preventive and chronic disease care quality, feasibility science is 
designed to assist clinical and health education evaluators plan for assessing and evaluating specific 
implementation factors essential to the success of new diagnostic, therapeutic and programmatic 
options in real-world clinical practice. This aim’s analysis of primary care clinical practice COPD case 
finding feasibility includes an initial evaluation of existing COPD diagnostic and case finding processes 
within the practices, assessment of practices’ capacity to change from existing respiratory symptom 
assessment strategies and an understanding of practice-specific learning preferences associated with 
new diagnostics in chronic disease diagnosis and management. The aim addresses through the RE-AIM 
feasibility approach how a new tool might a) identify target populations (Reach); b) appraise optimal 
targeted respiratory history and symptoms consistent with clinically significant COPD (Effectiveness or 
Impact); c) integrate into practice workflow (Adoption); d) deliver changes and improvements to COPD 
care within the scope of real-world clinical practice (Implementation); and e) persist in use and quality 
over time (Maintenance) (45-53). 
 
 
Potential risks associated with Aims 1 and 3 of this study are outlined below. 
Spirometry: Participants may become short of breath. Syncope, light-headedness and fainting may 
develop during this test. These are uncommon. 
Albuterol: Tremulousness, feeling of a strong, rapid heartbeat, and palpitations can occur with inhaled 
albuterol. A targeted safety questionnaire will be administered to all participants prior to albuterol to 
exclude those with a previous adverse event with the medication. Note that albuterol is only 
administered to those with abnormal spirometry on the baseline spirometry assessment (defined as 
FEV1/FVC < 0.70 or FEV1 < 80% predicted). 
Peak Expiratory Flow: Participants may become short of breath. Syncope, light-headedness and fainting 
may develop during this test. These are uncommon. 
Other non-physical risks of the study include those from economic loss from participation in the study; 
this will be minimized by scheduling tests and evaluations in a timely manner in the fewest number of 
visits possible. Patient and physician participants will be provided a modest fee to cover their time to 
participate in the study. 
We anticipate few adverse events due to the non-invasive nature of the study procedures and the rarity 
of such events encountered during the initial visits and longitudinal follow-up. Medical care will be 
available at each Clinical Center to treat participants who develop adverse events during in-person study 
visits. 
 
 
2.3 
RISK/BENEFIT ASSESSMENT 
2.3.1 
KNOWN POTENTIAL RISKS 

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Potential risks associated with Aim 2 of this study include: 
 
No more than minimal risk exists for participants within aim 2. 
Confidentiality of information and identification are the risks associated with this project. Based on 
previous research and the protocols that have been developed, we believe that the likelihood of these 
risks to the participants would be minimal, i.e. "rare". 
Potential risks associated with the study (all Aims) include: 
Loss of confidentiality of study data: This is unlikely since data collected will be stored in locked file 
cabinets in locked rooms at the Clinical Centers. In addition, only participant IDs are used to identify 
participants in the secure server at the Data Coordinating Center. 
Poor quality data: If the data collected are of poor quality such that it is not useable to achieve study 
aims, participants will have unnecessarily been exposed to other risks in the study. 
 
 
 
For Aims 1 and 3 of this study, participants could receive direct benefit as a result of their participation 
in this research. Current state-of-the-art COPD education is offered to all clinicians at participating PBRN 
sites (see aim 3 protocol) that could result in improved care for their COPD patients. Health care 
providers at practices randomized to the CAPTURE education arm (arm 1), will receive their participant’s 
CAPTURE Tool scores and peak flow results. This may result in further diagnostic testing leading to a 
diagnosis of COPD or other respiratory disorder. 
Known potential benefits for each participating clinical staff include critical review their clinical 
respiratory practice. In general, aim 2 offers the ability to assess and address CAPTURE-specific primary 
care practice feasibility issues which could augment or hamper clinical communication or 
implementation of COPD case-finding in real-world primary care clinical practice. 
Potential benefits to society include improved understanding of how best to identify individuals with 
COPD in the primary care setting. This could ultimately lead to better treatments and lower morbidity 
and mortality for patients with COPD. 
 
 
 
The demonstrated and potential future benefits to improved understanding of COPD case finding 
outweigh the minimal risks of the procedures performed. 
Increased understanding of how best to diagnose individuals at risk for COPD in the primary care 
population has the potential to benefit both patients with COPD and society at large. The risk to 
individuals associated with this study protocol is small and the knowledge to be gained is substantial. 
 
 
 
 
 
 
 
 
 
 
2.3.2 
KNOWN POTENTIAL BENEFITS 
2.3.3 
ASSESSMENT OF POTENTIAL RISKS AND BENEFITS 

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Aims 1 and 3. 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Aim 1: Define the sensitivity and 
specificity of CAPTURE for 
identifying previously undiagnosed 
patients with clinically significant 
COPD in a broad range of primary 
care settings 
Sensitivity and specificity of CAPTURE 
to identify previously undiagnosed 
patients with clinically significant 
COPD at baseline. 
Standard methodology for 
COPD diagnosis will be 
used (1). 
Aim 3: Define the impact of 
CAPTURE information provided to 
clinicians in identifying and 
managing CAPTURE+ patients across 
a broad range of primary care 
settings. 
Proportion of CAPTURE+ participants 
who meet at least one of the 
following within 12 months of study 
baseline (composite endpoint): 1) 
referral for or completion of clinical 
spirometry testing, 2) new diagnosis 
of COPD, 3) newly prescribed 
respiratory medication (long acting 
bronchodilator or anti-inflammatory 
for respiratory condition), 4) 
referral to a specialist for respiratory 
evaluation/treatment, or 5) referral 
for or completion of pulmonary 
rehabilitation. 
The composite endpoint is 
clinically relevant and 
consistent with published 
data (45). This will test 
the impact of CAPTURE on 
clinician behavior. 
Secondary 
Aim 1: Define the sensitivity and 
specificity of CAPTURE for patients 
with COPD across a broad range of 
racial and ethnic subgroups in a 
range of primary care settings 
Sensitivity and specificity of CAPTURE 
to identify previously undiagnosed 
patients with COPD across sex, ethnic 
groups, urban vs rural location, and 
educational status. 
Patient characteristics will 
be used to assess the 
robustness of CAPTURE. 
Aim 1: Determine positive and 
negative predictive values (PPV and 
NPV) in different practice settings. 
Positive and negative predictive 
values (PPV and NPV) in different 
practice settings. 
PPV and NPV will be used 
to assess the robustness 
and usefulness of 
CAPTURE in various 
settings. 
3 
OBJECTIVES AND ENDPOINTS 

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Aim 1: Verify the optimal use 
(cutoff threshold) of the CAPTURE 
tool in combination with FEV1 
measurements for identifying 
undiagnosed COPD. 
AUC for various cutpoints of 
CAPTURE and PEF measurements to 
determine the best cutpoint for 
clinically significant COPD screen. 
The best discrimination 
for CAPTURE combined 
with FEV1 will indicate the 
optimal usage of the tool. 

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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Aim 1: Determine patient and site 
characteristics that, with the 
CAPTURE assessment, will best 
identify persons with undiagnosed 
COPD. 
AUC to identify the combination of 
patient/site characteristics which 
best discriminates those with 
clinically significant COPD. 
The best discrimination 
will determine which site 
and patient characteristics 
best predicted 
undiagnosed COPD in 
combination with the 
CAPTURE tool. 
Aim 1: Determine whether 
CAPTURE is useful in identifying 
other definitions of undiagnosed 
COPD: 
1) spirometry-defined COPD, and 
2) mild COPD 
All primary and secondary endpoints 
as applied to 1) spirometry-defined 
COPD and 2) mild COPD 
This will determine the 
robustness of the 
CAPTURE tool. 
Aim 3: Define the impact of 
providing CAPTURE education and 
patient-level CAPTURE information 
to clinicians on selected clinician 
interventions for the management 
of CAPTURE+ patients. 
Proportion of CAPTURE+ participants 
who have each of the following occur 
within 12 months of study baseline 
(separate endpoints to be evaluated 
individually): 1-5) each component of 
the Aim 3 primary endpoint, and 6) 
recommendation or administration 
of influenza vaccination. 
Each endpoint is clinically 
relevant and consistent 
with published data. (45) 
This will test the impact of 
CAPTURE on clinician 
behavior. 
Aim 3: Assess the impact of 
CAPTURE education and patient-
level CAPTURE information on 
clinician interventions specific to 
smokers who are CAPTURE+. 
 
 
 
 
 
 
 
 
 
 
Proportion of CAPTURE+ participants 
currently smoking at the baseline 
study visit who have any of the 
components of the Aim 3 primary 
endpoint or any of the following occur 
within 12 months of baseline 
(evaluated as a composite endpoint 
and as individual endpoints): 1) 
clinician counseling or 
recommendation for smoking 
cessation, 2) referral to a smoking 
cessation program, 3) referral to a 
smoking quit line, and 4) newly 
prescribed medication for smoking 
cessation. 
Certain outcomes are 
specific to only smokers 
and should be assessed. 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Aim 3: Determine the impact of 
CAPTURE education and patient-
level CAPTURE information on 
patient symptoms, exacerbations, 
hospitalizations, and mortality 
among CAPTURE+ patients. 
In CAPTURE+ participants, change in 
CAT score between baseline and 
follow-up at 12 months after 
baseline, and proportion of patients 
who experience exacerbations, 
hospitalizations, or mortality within 
These endpoints are 
important for quality of 
life and long-term patient 
outlook. 

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12 months of baseline. 
Aim 3: Determine the impact of 
CAPTURE education and patient-
level CAPTURE information on 
identification and management of 
patients with respiratory burden. 
All of the above endpoints for Aim 3, in 
the population of participants defined 
by each of the following instead of 
CAPTURE+ status: 1) clinically 
significant COPD, 2) spirometric COPD, 
3) Mild COPD, 4) preserved ratio, 
impaired spirometry (PRISm), and 5) 
symptomatic non-obstructed (SNO). 
This will assess the 
overall effect of 
CAPTURE screening in 
clinically relevant 
populations. 
Aim 3: Determine the potential 
impact of SARS CoV-2 infection on 
clinical actions taken in response 
to CAPTURE screening. 
All of the above endpoints for Aim 3, 
in all of the analysis populations 
named above, separated into cohorts 
based on enrollment date and the 
degree to which follow-up may have 
been affected by the SARS-CoV-2 
pandemic. 
Clinician behaviors 
likely were affected by 
the presence of a 
pandemic involving 
respiratory illness. 
 
Aim 2. 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
Explore clinical practice 
implementation approaches to and 
acceptance of CAPTURE case 
finding for clinically significant 
COPD in a range of primary care 
practices. 
 
 
 
 
 
 
 
 
 
 
 
 
Primary care clinician 
recommendations that inform 
CAPTURE RE-AIM strategies at both 
provider and clinical support levels of 
primary care practice. 
Primary clinician recommendations 
that inform CAPTURE-associated 
COPD education models for primary 
care clinicians. 
Primary care clinician 
recommendations that inform 
CAPTURE-associated COPD clinical 
quality improvement designs across a 
variety of primary care practice 
types. 
 
 
 
 
 
 
Clinical improvement 
models that introduce 
new testing must 
investigate practice 
opinion and behavior and 
incorporate clinician 
recommendation. 

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Secondary 
Qualitatively assess primary care 
clinical staff COPD practice 
behavior – including COPD 
screening and diagnostic 
perceptions, beliefs and knowledge 
– that will inform strategies to 
improve CAPTURE RE-AIM (reach, 
impact, adoption, implementation 
and maintenance of use) 
characteristics. 
Existing COPD screening and 
diagnostic and case-finding processes 
within a variety of primary care 
practices. 
Primary care practice beliefs about 
capacity to change from existing 
COPD screening and diagnostic 
assessment strategies. 
Practice-specific COPD screening and 
diagnostic continuing education 
preference. 
Awareness of existing 
clinician knowledge and 
behavior can influence 
workflow implementation 
and overall effectiveness 
of new clinical tools. 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Qualitatively assess primary care 
patient opinion of CAPTURE COPD 
case finding that will inform 
strategies to improve CAPTURE RE- 
AIM (reach, impact, adoption, 
implementation and maintenance 
of use) characteristics. 
CAPTURE opinion survey ascertaining 
participant comprehension of 
CAPTURE instructions and testing and 
ease of completion. 
Patient satisfaction, 
understanding and ease of 
test completion affects 
staff implementation and 
workflow decision. 
Participant opinion survey 
results will seed CAPTURE 
implementation planning 
practice staff focus 
groups. 
 
 
 
A prospective, multicenter study that includes three key aims: 1) cross-sectional validation to define 
sensitivity and specificity of CAPTURE; 2) qualitative research exploration engaging clinical staff at all 
levels from primary care practices serving US patient populations of differing gender, racial, ethnic, 
urban/rural and socio-economic blends, and 3) explore the impact of CAPTURE on clinical care and 
patient outcomes across a broad range of primary care settings in a cluster randomized controlled 
clinical trial. The CAPTURE tool consists of a 5-item self-administered questionnaire and selected use of 
peak expiratory flow (PEF) measurement, designed to identify clinically significant Chronic Obstructive 
Pulmonary Disease (COPD). 
For Aim 1, approximately 5,000 patients will be recruited at the time of their regularly-scheduled 
appointment across 100 participating primary care clinics associated with practice-based research 
networks (PBRNs). Eligible participants will undergo a baseline visit during which the CAPTURE tool and 
spirometry will be obtained, as well as PEF and other participant characteristics. 
For Aim 2, approximately 150 clinicians from 10 participating primary care practices across 5 US PBRNs 
will undergo detailed implementation investigation of the CAPTURE case finding model for clinically 
significant COPD. In addition, 200 primary care patients recruited as part of Aim 1 will complete a 10- 
4 
STUDY DESIGN 
4.1 
OVERALL DESIGN 

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minute written CAPTURE opinion survey. 
To address Aim 3, participating primary care practices will be randomized in a 1:1 fashion to one of the 
following interventions: 
• 
Arm 1: Practice clinicians will receive basic COPD education, and patient-level CAPTURE 
information with CAPTURE interpretation education (CAPTURE+ COPD education). As the 
second aim addresses the optimal format for delivering practice CAPTURE education this will be 
incorporated at the sites randomized to this arm (see Enhanced CAPTURE education in Figure 1). 
• 
Arm 2: Practice clinicians will receive basic COPD education only (COPD education). 
 
Basic COPD and CAPTURE specific education will use an interactive, web-based education program 
which will be provided to all practice personnel, including physicians, nurse practitioners, physician 
assistants, nurses, medical assistants, clerical staff and administrative staff. Practitioners at sites 
randomized to the CAPTURE+COPD education intervention will receive the CAPTURE score from the 
central study coordinators soon after the baseline assessments have been completed. 
Addressing Aims 1 and 3 will include a baseline visit for all participants and for Aim 3 longitudinal follow- 
up over 12 months for a predefined cohort of participants. Determination of the participants included in 
the longitudinal follow-up cohorts will be made after the baseline visit. 
 
 
Baseline Data 
 
Practices and/or study staff will pre-screen patients according to local guidelines to identify potential 
participants based on the following criteria: no prior COPD diagnoses, between 45 and 80 years old, and 
speak and read either English or Spanish. The timing of the pre-screening and the method to approach 
these patients for participation in the study (e.g., at the next outpatient visit, via telephone) will be 
flexible, depending upon site recruitment preferences. Patients who are eligible based on the pre- 
screening questions and agree to participate in the study will sign informed consent. After signing the 
consent, they will complete the CAPTURE questionnaire, PEF testing, spirometry testing, other 
respiratory questionnaires, and provide past medical history and demographic information. Local/PBRN 
study coordinators for each of the 7 PBRNs will perform the study procedures and record baseline 
information into the electronic data capture (EDC) system. 
 
The EDC system will calculate a CAPTURE score for each participant, based on his/her CAPTURE 
questionnaire answers and PEF measurement. A binary score (positive or negative CAPTURE) will be 
emailed to the central study coordinator only for participants randomized to CAPTURE+COPD education 
intervention practices. The coordinator will communicate this information to these practitioners. 
Practitioners at sites randomized to the COPD education only intervention will be blinded to CAPTURE 
scores. Practitioners in both intervention arms will be blinded to research spirometry results. 
 
Analyses will include a comparison of CAPTURE scores with data from spirometry testing and participant 
reported data to determine sensitivity and specificity of the CAPTURE tool. The hypothesis is that a 
simple case finding methodology using a five-item questionnaire with selective PEF measurement will 
identify undiagnosed patients with clinically significant COPD. 
 
 
 
 
 
 
 

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Based on the data collected at baseline, participants will be classified into the following groups for 
analyses: 
Cohort 
Definition 
CAPTURE+ 
Participants with 
• 
CAPTURE score > 5, or 
• 
CAPTURE score of 2, 3, or 4 with a low PEF, defined as <350 L/min for males 
and <250 L/min for females 
CAPTURE- 
Participants with 
• 
CAPTURE score < 2 or scores 2-4 with normal PEF (defined as >350 L/min for 
males and >250 L/min for females) 
Spirometrically 
defined COPD 
Participants with abnormal spirometry, defined as post-bronchodilator FEV1/FVC 
<0.7. If a participant is unable to complete a post-bronchodilator spirometry 
(refusal, technical error on the part of coordinator, etc.), and the pre-bronchodilator 
FEV1/FVC is less than 0.65, the participant will be considered to have COPD for the 
purpose of follow-up in this study. 
Clinically 
significant 
COPD 
Participants with abnormal spirometry, defined as post-bronchodilator FEV1/FVC 
<0.7, plus one of the following: 1) FEV1 < 60% predicted or > 1 exacerbation like 
event within the past 12 months. 
Mild COPD 
Participants with abnormal spirometry, defined as post-bronchodilator 
FEV1/FVC<0.7 plus both of the following: 
• 
FEV1 ≥ 60% and 
• 
No prior history of ECOPD 
Preserved ratio, 
impaired 
spirometry 
(PRISm) 
Participants without spirometrically defined COPD who have post-bronchodilator 
FEV1 < 80% predicted. 
Symptomatic 
non-obstructed 
(SNO) 
Participants without spirometrically defined COPD and without PRISm who have a 
COPD Assessment Test score ≥ 10. 
 
Exploratory analyses to examine the potential impact of SARS CoV-2 infection on the above operating 
characteristics of the CAPTURE approach will include information in the pandemic and post pandemic 
period collected from a simple COVID-19 questionnaire that is based on similar questionnaires from 
other ongoing NHLBI cohort studies. 
 
Longitudinal Follow-up 
A pre-defined subgroup of enrolled participants, who meet any of the below criteria will undergo 
longitudinal follow-up at 12 months, 
1. Participants with a CAPTURE Score ≥ 5 or CAPTURE score of 2, 3, or 4 with a low PEF, defined as 
<350 L/min for males and <250 L/min for females 
2. Participants who have abnormal spirometry results, defined as post-bronchodilator FEV1/FVC < 
0.7 or FEV1 < 80% predicted at baseline. If a participant is unable to complete a post- 
bronchodilator spirometry (refusal, technical error on the part of coordinator, etc.), and the pre- 
bronchodilator FEV1/FVC is less than 0.65 or FEV1 is less than 70% predicted, the participant will 
be considered to have abnormal spirometry for the purpose of follow-up in this study. 
3. A random sample of approximately 5% who do not meet criteria 1 - 2 

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Participants who meet the criteria for follow-up will be sent notification shortly after enrollment, and 
receive reminders at 3, 6, and 9 months. Patient-reported data will be collected by COPD Foundation via 
telephone, secure web-based server, or mail-based methodologies, based on participant preference. 
 
Subject medical data will be collected from the medical record to assess for changes in practice-level 
care. 
 
The hypothesis for Aim 3 is that sites where COPD and CAPTURE education and patient-level CAPTURE 
data are provided to clinicians will exhibit improved COPD diagnosis and COPD-related care compared to 
sites where COPD education is provided to clinicians. 
 
In exploratory analyses to examine the potential impact of SARS CoV-2 infection on the patient 
symptoms and health care utilization a simple COVID-19 questionnaire, based on other ongoing NHLBI 
cohort studies, has been introduced. 
 
Aims 1 and 3 
The totality of the published data confirms the clinical and economic impact of undiagnosed COPD, 
continuing under-diagnosis, and incomplete application of spirometric testing in the primary care 
community. It suggests that there is value in COPD case-finding that targets COPD patients most likely 
to benefit from available therapies. These points identify a pressing health care problem that requires 
an innovative approach to facilitate identifying these individuals. Our preliminary studies enumerated 
in section 2.2 extend these concepts by demonstrating that: 
□ 
Six key domains identify patients with clinically significant COPD. 
□ 
Forty-four distinct items resonate with patients and provide important insights for COPD case- 
finding. 
□ 
Five items exhibit excellent sensitivity and specificity in identifying patients with clinically 
significant COPD. 
□ 
PEF provides incremental value in a case-finding strategy. 
□ 
The combination of a five-item questionnaire and PEF optimizes a COPD case-finding strategy in 
English and Spanish speaking patients. 
Our proposed study will provide crucial data to address the operating characteristics and clinical 
translation to our COPD case-finding strategy into the primary care setting. It will also provide an 
important initial evaluation of the potential clinical impact of the systematic identification of previously 
undiagnosed COPD patients. 
The impact of SARS-CoV-2 infection and its clinical illness, COVID-19, on COPD Case Finding and 
respiratory symptoms in primary care is unknown. In exploratory analyses a simple COVID-19 patient 
questionnaires and additional data elements from medical record review, based on other ongoing NHLBI 
cohort studies, have been introduced. 
 
Aim 2 
The rationale for this aim reflects the importance of establishing if an innovative approach to COPD case 
finding is considered a pragmatic tool with potential utility for primary care clinicians within real-world 
clinical practice settings. With the completion of this aim we anticipate confirming that future validated 
approaches to COPD case finding can be adopted in a broad variety of clinical care settings thereby 
providing further impetus for the rigorous evaluation of a) case finding guided patient outcomes as part 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 

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of routine primary care clinical practice; b) case finding use in a range of primary care health 
professional COPD-related education approaches, clinical quality improvement models and diagnostic 
guidelines; and c) the capacity of clinical case finding and informed follow-up to enhance future COPD 
clinical care therapeutic paradigms used in primary care practice. 
Consistent with Institute of Medicine criteria and US health quality standards for preventive and chronic 
disease care, the feasibility science qualitative research framework is designed to assist clinical and 
health education evaluators prepare, assess and evaluate specific implementation factors essential to 
the success of new diagnostic, therapeutic, educational and programmatic options in real-world clinical 
practice. This aim’s analysis of primary care clinical practice COPD case finding feasibility considerations 
for CAPTURE includes an initial evaluation of existing COPD diagnostic and case finding processes within 
the practices, assessment of practices’ capacity to change from existing respiratory symptom 
assessment strategies and an understanding of practice-specific learning preferences associated with 
new diagnostics and chronic disease diagnosis and management. Patient perceptions of the CAPTURE 
case-finding process are also obtained to provide a holistic perspective of the clinical feasibility of 
CAPTURE implementation in primary care practice. Borrowing from the RE-AIM implementation science 
approach, this aim explores how real-word primary care practices might potentially use CAPTURE to: a) 
identify target populations (Reach); b) refine current practice appraisal of patient respiratory history, 
symptoms and diagnostics used to identify clinically significant COPD (Effectiveness/Impact); c) change 
or integrate COPD case finding into practice workflow (Adoption); d) alter practice communication, 
education and/or care quality improvement planning for COPD diagnosis and management 
(Implementation); and e) use COPD case finding consistently over time (Maintenance). 
Ten primary care practices will undergo detailed implementation investigation of the CAPTURE case 
finding model designed to identify patients with COPD most likely to benefit from available therapeutic 
options. CAPTURE, a one-page questionnaire with selective PEF measurement, is presented to the 
clinicians of ten practices not participating in aims 1 and 3 as a prospective COPD case finding option 
awaiting validation. By representing CAPTURE as a model—and not introducing it into actual practice— 
aim 2 gains recommendation from primary care clinical practice experience with sufficient feasibility 
generality to circumvent interdependence between the operating characteristic exploration (aim 1) and 
qualitative feasibility understanding (aim 2) components of our study. The aim 2 results, that include 
the pooled CAPTURE clinical communication, education and implementation recommendations from 
real-world primary care practice, are analyzed and applied in concert with local and national research 
team expertise to enhance the potential impact of CAPTURE’s introduction into clinical care in aim 3. 
Aim 2 results also provide previously unexplored qualitative information necessary for future long-term 
patient outcome studies of COPD case finding approaches in primary care. 
The impact of SARS-CoV-2 infection and its clinical illness, COVID-19, on COPD Case Finding application 
in primary care is unknown. In a systematic fashion these concepts will be explored during the 
previously planned follow-up interviews and focus groups with clinical practice and regional PBRN 
personnel. 
 
 
Participants that do not meet the criteria for, or are not selected for, longitudinal follow-up will be 
considered to have completed the study after completion of the baseline visit. 
 
Participants included in the longitudinal follow-up phase will be considered to have completed the study 
after completion of the Month 12 Assessment as shown in the Schedule of Activities (SoA), Section 1.3. 
 
Clinician participants in aim 2 will have completed the study after participation on their second focus 
group between months 14 and 16 as shown in the Figure 2, Structure of Aim 2. 
4.3 
END OF STUDY DEFINITION 

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Inclusion criteria for Aims 1 and 3 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
 
1. Provision of signed and dated informed consent form 
2. Stated willingness to comply with all study procedures and availability for the duration of the study 
3. Male or female, aged 45 – 80 years 
4. Able to read and speak English or Spanish 
 
Inclusion criteria for Aim 2 
 
Two Aim 2 practices are selected by each of their 5 affiliated PBRNs based upon willingness to 
participate and variability of primary care practice type within the PBRN. Differences in practice size, 
staffing, ownership, prior quality improvement engagement, geography, patient population 
socioeconomic status (SES) or languages spoken are among the among the selection criteria the PBRNs 
will utilize to choose. 
 
Clinician participants (10 practices with up to 15 clinicians per practice): 
1. Provision of signed and dated informed consent form. 
2. Stated willingness to comply with availability and all study procedures for the duration of aim 2 by 
the 10 practices (through PBRN recruitment) and their up to 15 clinicians within (through informed 
consent). 
 
Patient participants [200 patients (approximately 40 from each PBRN)] for CAPTURE survey: 
1. Provision of signed and dated informed consent form. 
2. Stated willingness to comply with all study procedures and availability for the duration of the study. 
3. Male or female, aged 45 – 80 years. 
 
 
 
Exclusion criteria for Aims 1 and 3 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. Previous clinician provided diagnosis of COPD 
2. Treated respiratory infection (with antibiotics and/or systemic steroids) in the past 30 days of 
baseline 
3. Participants unable to perform spirometry due to any of the following conditions within the past 
30 days of baseline 
a) Chest surgery 
b) Abdominal surgery 
c) Eye surgery 
d) Heart attack 
e) Stroke 
 
5 
STUDY POPULATION 
5.1 
INCLUSION CRITERIA 
5.2 
EXCLUSION CRITERIA 

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Exclusion criteria for Aim 2 
 
1. Clinician participants: current employment at practices participating in aims 1 and/or 3 
2. Clinician participants: from practices providing fewer than 2 clinician participants 
3. Patient participants: meeting the exclusion criteria for aims 1 and 3 (above) 
 
 
PBRN coordinators, in conjunction with clinical study site personnel, will pre-screen individuals who are 
unlikely to be able to complete research spirometry. These individuals will be considered pre-screen 
failures. 
Participants who are consented to participate but have a prior clinician diagnosis of COPD will be 
considered screen failures. 
 
Recruitment and retention strategies for Aims 1 and 3 
Approximately 4800 participants will be recruited from 100 primary care clinics affiliated with six 
PBRNs. Each PBRN has centrally-based research coordinators with a history of success working in PBRN 
practices, documented expertise in previous large diagnostic or therapeutic trials, and personnel 
experienced in recruitment and data collection. 
IRB approval will be obtained at each PBRN for approval for patient contact, informed consent and 
participation in this study. 
All patients who meet all inclusion and no exclusion criteria at the participating PBRN clinical site will be 
eligible for participation. Research coordinators will work with participating practices to identify and 
approach potential participants. Recruitment strategies may vary depending on the practice. 
Enrollment of participants will depend on the gender, ethnic and racial makeup of those that are being 
recruited from the practices included in this trial. No exclusion criteria apply specifically to women or to 
minorities. The Data Coordinating Center (DCC) will track enrollment of participants throughout the 
course of this study. If women and minorities are under-represented in the initial phase of recruitment, 
a commitment exists to develop recruitment strategies that target these populations so the final study 
group is a well-balanced representation of the studied population. 
Recruitment and retention strategies for Aim 2 
Clinician participants: Approximately 150 clinic participants are recruited by: 1) introductory telephone 
contact with the practice leadership by PBRN research coordinators and the aim 2 research team; 2) 
follow up letter, time commitment infographic and informed consent forms sent to interested practices 
outlining aim 2 clinician participant activities and responsibilities; and 3) in-person aim 2 study 
explanation to clinician participants at the committed practices during the introductory baseline study 
site visit. 
Clinician participant recruitment draws from both prescribing (or “provider”) staff and non-prescribing 
(or “clinical support”) staff. The aim 2 research team will attempt to obtain an even mix of both clinician 
staff types from each practice. Retention incentive of clinician participants over 2 years includes 
provision of on-line COPD education to all clinician participants and monetary incentive to practices as 
determined by each individual PBRN. 
Patient participants: 200 participants (40 from each PBRN) are recruited as a sub-set of the aim 1. Each 
5.3 
SCREEN FAILURES 
5.4 
STRATEGIES FOR RECRUITMENT AND RETENTION 

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of the 200 patient participants in aim 2 are asked to complete a one-time 10-minute written opinion 
survey. Their aim 2 participation is concluded at the end of the opinion survey completion. 
The aim 2 research team and DCC will track enrollment and retention of all aim 2 participants 
throughout the course of the 2-year aim 2 study. 
 
 
 
 
The study intervention is applicable to Aims 2 and 3 and consists of healthcare provider education 
modules. 
The practitioners at the 10 sites selected for Aim 2 will receive module 1, Basic COPD education, and 
may elect to take modules 3-5 for supplemental information on COPD. 
For Aim 3, half of the practices will receive Basic COPD education (module 1) and half will receive Basic 
COPD Education and CAPTURE Education (modules 1 and 2). Practitioners at practices randomized to 
COPD only education must take module 1 and may elect to take modules 3-5; however, they will not 
take module 2. Practitioners at practices randomized to COPD+CAPTURE education must take modules 
1 and 2, and may elect to take modules 3-5. 
 
1 - Basic COPD Education will be provided in order for providers to optimally manage patients with 
COPD. The education will incorporate evidence-based recommendations using the 2018 update of the 
Global Obstructive Lung Disease Strategy(45). For practices enrolled in the pandemic and post 
pandemic periods, additional information will be provided regarding COPD management in the 
pandemic era as well as information on steps to maintain patient and staff safety in the clinical sites 
where CAPTURE patients will be enrolled and assessed. 
 
A 40-minute overview will be presented in the most expeditious manner at each practice site, for 
example by webinar for all practice personnel over the lunch hour, or audiovisual presentation available 
on a dedicated CAPTURE web site. The PBRNs have indicated that this module should be no longer than 
40 minutes. Topics will include: CAPTURE study description and rationale, importance of COPD in the 
region of the local practices, COPD definition and diagnosis, patient goals, and management approach. 
Attendance at this mandatory training will be documented and continuing education credits will be 
provided for physicians and nurse practitioners by National Jewish Health, an accredited CME provider. 
 
2 - CAPTURE education. An online audiovisual module will be developed to explain CAPTURE 
interpretation and use in patient evaluation and diagnosis of COPD. This module will only be available to 
practices randomized to receive the results of CAPTURE for clinical use. 
 
With the information provided in Aim 2 about practice preferences for education, the CAPTURE 
education module will be revised and made available to practices enrolled in Aim 1 after the completion 
of Aim 2. 
 
3 - Online advanced COPD education will be available for all practices and continuing education credits 
will be provided to enhance practitioner participation. Practitioner attendance at each online 
audiovisual module will be collected including the amount of time spent on each education module, 
completion of each module with a post-test and evaluation, and CME will be provided. Education will be 
case-based and will include role playing where appropriate. Seven basic modules of 20 minutes or less 
will be available both to practices randomized to receive CAPTURE results for clinician use and to control 
practices that will not receive CAPTURE results and will cover: 
6.1.1 
STUDY INTERVENTION DESCRIPTION 
6 
STUDY INTERVENTION 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 

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1. Diagnosis of COPD: How to diagnose COPD in primary care including medical history, physical 
exam and role of spirometry, severity categorization 
2. Spirometry overview: Basic clinical interpretation 
3. Advanced spirometry: Test performance, evaluating quality, advanced case-based interpretation 
4. Management overview: Patient goals, smoking cessation, vaccination, patient education, shared 
decision-making 
5. Pharmacotherapy: Inhaled bronchodilators, inhaled corticosteroids 
6. Other therapies: Oxygen, pulmonary rehabilitation, surgical approaches 
7. Inhalation devices: Patient education 
 
4 – On-site COPD education. Additional funds will be sought to provide on-site COPD education. We 
have experience in successfully providing half-day on-site education to primary care practices to 
enhance their management of COPD. 
 
5 – Social media and case conferences. We will use social media (Facebook and Twitter) to provide 
ongoing education about COPD. Facebook and Twitter posts will provide tips on managing COPD. Online 
conferences will be scheduled to discuss cases submitted by primary care providers. 
 
 
 
For Aims 1 and 3, this study will use randomization and blinding as two of the cardinal principles of 
clinical trials to minimize bias. 
Randomization. Practices will be randomized into one of the two interventions, COPD education or 
COPD education + CAPTURE education, in a 1:1 manner, stratified by PBRN. Randomization will occur at 
the time of site activation and each site will be assigned a unique randomization number. The DCC will 
prepare the randomization schedule, using computer-generated block randomization with the block 
size(s) known only by the DCC. A secure web-based application will be built that will be used by the 
central study coordinators to enter site information (e.g., site ID, stratification factor) and to obtain the 
randomization number. The information can be printed and sent and/or emailed directly to the study 
coordinator. 
Blinding. This is a single-blind study with the participants blinded to whether their practitioners have 
received CAPTURE education and patient-level CAPTURE results. Practitioners at sites that are 
randomized to the control arm (COPD education alone) will be blinded to the CAPTURE questionnaire 
and PEF results. All practitioners and participants will be blinded to the baseline COPD status of the 
participants (i.e., blinded to spirometry results), except for safety reasons. In this situation, participants 
and their clinician will be notified if a participant’s post-bronchodilator FEV1 is less than 30% predicted. 
For all other participants, they and their practitioners will be blinded to research spirometry results. The 
coordinator should make every effort to conceal the spirometry results from the participants in these 
latter cases. Study coordinators should also make every effort to conceal the administration of a post- 
bronchodilator spirometry test from the practice staff so as not to unblind the physicians to abnormal 
spirometry. 
 
 
In practices randomized to share the CAPTURE results with the clinician, the goal is to share results with 
the clinician at the time of the CAPTURE study visit. Providing results at the time of the clinical visit will 
allow the clinician to act on the CAPTURE results as soon as possible when the participant is in front of 
6.2 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
6.3 
STUDY INTERVENTION COMPLIANCE 

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the clinician. Based on the workflow at each of the practices, this may not always be possible. 
 
Sharing of the CAPTURE results with the participant's primary care clinician will be tracked by the study 
coordinator enrolling patients at sites randomized to receive CAPTURE results. The sharing of CAPTURE 
results will be recorded on the study eCRF form. The eCRF will collect the timing of when the results 
were provided to the practitioner - whether the results were provided to the clinician at the time of the 
enrollment visit prior to the clinician visit with the patient, or were provided at another time. 
 
If results were not shared at the time of the CAPTURE study visit, then the date of sending the CAPTURE 
results will be recorded on the appropriate eCRF by filling in the date (day/month/year) the exact copy 
of the CAPTURE Tool were sent to the clinician through a HIPPA-compliant method and placed in the 
medical record. The goal is to communicate the results to the clinician. The DCC will monitor review all 
participants' eCRFs to assure that all those enrolled from practices randomized to CAPTURE results have 
been shared with clinicians. 
 
 
Practitioners will treat participants using their own clinical judgment. No medications are prohibited. 
This is not an interventional therapeutic trial. 
 
 
 
In this cluster randomized controlled trial (Aim 3), where practices are the recipients of the intervention 
and where the interventions are based upon education and access to CAPTURE and PEF results, it is not 
anticipated that study intervention will be discontinued at the practice level. However, one of the CO- 
PIs will review safety data, especially SAEs related to baseline spirometry and PEF procedures, to ensure 
there are no untoward effects of the study on participants. 
 
 
Participants are free to withdraw from participation in Aims 1 and 3 of the study at any time upon 
request. 
Clinician participants in Aim 2 are free to withdraw from participation in the study at any time upon 
request. If a clinician is no longer working at the participating practice then their involvement in Aim 2 
activities will end and no further attempt will be made to include them in the remaining questionnaires 
or focus groups. 
 
 
If a participant selected for longitudinal follow up does not respond to the 12-month questionnaires, 
coordinators will attempt to contact participants first by the participant’s preferred method of 
communication, either phone or email. At least three attempts will be made. If no response is obtained, 
the participant’s alternate contact method will be attempted three times. Phone calls will be made at 
different times of the day. If there is no response, a letter will be sent to the participant. If the 
participant cannot be reached, the alternate contact will be called and/or emailed. If no response is 
received, a letter will be sent to the alternate contact. If after all of these methods are employed and no 
6.4 
CONCOMITANT THERAPY 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
7.3 
LOST TO FOLLOW-UP 

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contact with the participant results, the participant will be considered lost to follow-up. 
 
 
 
Efficacy data will be collected by patient-reported outcomes and medical record review. 
 
For Aim 1, CAPTURE, PEF results, acute respiratory event history and spirometry will be considered 
efficacy assessments. They are collected at the baseline visit. 
 
CAPTURE. Participants will complete the 5-item self-administered questionnaire and measurement of 
Peak Expiratory Flow (PEF). 
 
Peak Expiratory Flow (PEF). PEF using the Vitalograph® AsmaPlan® mechanical PEF meter with 
SafeTway® disposable mouthpieces (Vitalograph LTD, UK) will be measured for all participants. Ideally, 
PEF should be prior to the participant’s physician appointment. The participant will perform three PEF 
tests. All three measurements will be recorded. 
 
Spirometry. Before spirometry is performed, participants will be asked if they have taken a medicine 
which they breathed into their lungs from any puffer or inhaler within the past two hours. If participant 
answers yes, then spirometry will be performed but considered a post-bronchodilator spirometry test. 
No further spirometry will be needed. If participant answers no, then pre-bronchodilator spirometry 
will be performed for measurement of forced vital capacity (FVC), forced expiratory volume in one- 
second (FEV1), and calculation of FEV1/FVC (using EasyOne® Spirometer, ndd Medical Technologies Inc., 
Andover, MA). Testing will be performed in accordance with established American Thoracic 
Society/European Thoracic Society (ATS/ERS) standards. Local guidelines to minimize risk of SARS-CoV-2 
infection will be adhered to, including a minimum of appropriate PPE and infection control techniques. 
 
A Spirometry post-bronchodilator will only be performed if pre-bronchodilator spirometry FEV1/FVC is 
less than 0.70 or FEV1 is less than 80% predicted. Post-bronchodilator spirometry will be performed 
within 15 to 20 minutes after inhalation of 2 puffs of albuterol 180 mcg HFA using an AeroChamber 
Plus* Flow-Vu® spacer with one minute between the first and the second inhalation. A separate 
AeroChamber or comparable spacer, using a one way valve to minimize infectious risk, will be provided 
for each participant’s testing. A standing order for albuterol administration may be used if necessary. 
 
Spirometry is a valid, reproducible means of documenting the presence and severity of airflow 
limitation. When properly performed with maximum effort and attention to the details of calibration of 
the instrument, spirometry maneuvers are among the most reproducible of biomedical measures. In 
the setting of a highly trained, experienced therapist, a coefficient of variation of 2-3% is not unusual. 
Spirometry will be performed in a standardized manner in accordance with the ATS guidelines, as 
described in the manual of procedures (MOP). Spirometry is the timed-based measurement of the 
amount of air that can be forcefully exhaled from the lungs after a full inspiration. In the forced 
expiratory vital capacity maneuver, a person inhales as big a breath as possible and then blows it out as 
fast and as long as possible until no more air can leave the lungs. The volume of air leaving the lungs is 
recorded continuously throughout the maneuver in order to allow calculation of important measures of 
lung function. 
 
NHANES prediction equations, which are programmed into the Easy On PC spirometers, will be used to 
8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
BASELINE ASSESSMENTS AND DATA COLLECTION 

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calculate the predicted lung function levels. These require the input of age, height, and race/ethnicity 
(White, Black, Hispanic). For people of mixed or unknown race the White prediction equations will be 
used. 
 
PBRN Research Coordinators will be trained and certified in the performance of spirometry testing. 
Spirometry will be sent for central review for quality control assurance. 
 
Adjudication of the Presence of Obstruction on Post-Bronchodilator Spirometry 
 
The presence of obstruction is determined by the presence of an FEV1/FVC ratio less than 0.70 after the 
administration of a bronchodilator. A bronchodilator will be administered to study subjects whose 
baseline FEV1/FVC is less than 0.70 or whose FEV1 is less than 80% of the predicted value. 
 
If a subject is unable to complete a post-bronchodilator spirometry (refusal, technical error on the part 
of coordinator, etc.), and the pre-bronchodilator FEV1/FVC is less than 0.65, the patient will be 
considered to have COPD for the purpose of follow-up in this study. 
 
Height and weight 
Height and weight will be recorded in order to determine appropriate prediction equations for 
spirometry and possible effect of obesity on spirometry. Height will be recorded and weight will be 
measured prior to spirometry testing. 
 
Demographic Data Collection 
Demographic data including date of birth, gender, ethnicity, race, educational level achieved, daily work 
schedule, living arrangement and health insurance will be entered into the EDC system. 
 
Contact information including address, phone numbers and email address will be obtained. Alternate 
contact information will be obtained for two other people, family members not living with the 
participant or close contacts, who may be knowledgeable about the participant in the event that the 
participant cannot be contacted for subsequent longitudinal follow-up. Alternate contact information 
will include name, address, phone numbers and email addresses. All contact information will be stored 
securely at the clinical site or in a database separate from that developed for the clinical data. 
 
Medical History 
Previous medical diagnoses will include comorbidities such as cardiovascular, respiratory and malignant 
disorders. Influenza vaccination history will also be recorded. This questionnaire will be completed 
under supervision of the coordinator. 
 
Concomitant Medication Review 
Respiratory medications will be recorded at baseline for all participants. This questionnaire will be 
completed under supervision of the coordinator. 
 
CAPTURE Additional Items Questionnaire 
Participants will complete the 13-item self-administered questionnaire. 
 
COPD Assessment Test (CAT) 
Participants will complete the 8-item self-administered questionnaire. 
 
Respiratory symptoms, smoke exposure and exacerbation like events 
History of respiratory symptoms and exacerbation like events over the past year as well as smoke 
exposure (including e-cigarette or equivalent) will be recorded. This questionnaire will be completed 

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under supervision of the coordinator. 
 
Whenever possible, informed consent, eligibility review, CAPTURE Questionnaire and PEF will be 
performed prior to the participant’s clinic appointment, so that CAPTURE results may be provided to the 
physician at the time of his/her appointment if the patient is cared for in a clinical center randomized to 
CAPTURE+ education. 
 
COVID-19 Additional Items Questionnaire 
Participants will complete the 18-item self-administered questionnaire. 
 
Adverse events 
Adverse events related to study procedures will be recorded by the coordinator. 
 
 
 
For Aim 3, the follow-up efficacy assessments are collected from the time of baseline to 12 months in 
selected cohorts (as described in section 4.1). Medical record abstractions completed by PBRN 
coordinators and participant questionnaires administered by study team members from the COPD 
Foundation are used. 
 
Data collected from medical record include: 
 
All participants undergoing 12-month follow- 
up as described in section 4.1 
Current Smokers Only 
Clinical spirometry ordered or administered 
Smoking cessation counseling 
New recorded clinical diagnosis of COPD 
Formal smoking cessation program 
referral/completion 
New prescription for respiratory medication 
(long acting bronchodilator, inhaled steroids) 
New prescription for smoking cessation 
medication 
Exacerbation like event assessment (hospital, 
ED, minute clinic, antibiotic/steroid 
prescription/administration) 
Referral to a smoking quit line 
Vaccination status 
Formal pulmonary rehabilitation program 
referral/completion 
Data related to COVID-19 confirmed and 
suspected cases 
 
 
 
 
 
 
 
8.2 
LONGITUDINAL FOLLOW-UP ASSESSMENTS AND DATA COLLECTION 

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Data from clinical visits to be collected at follow-up by telephone, secure web-based server, or mail- 
based methodologies directly from participants and administered by COPD Foundation study personnel 
include: 
 
All participants undergoing 12-month follow-up 
as described in section 4.1 
Current Smokers Only 
Spirometry referral/completion 
Referral to a smoking cessation program 
New diagnosis of COPD 
Referral to a smoking quit line 
Referral to pulmonologist or other respiratory 
specialist 
New prescription for smoking cessation 
medication 
Exacerbation like event assessment 
Over-the-counter patches/gum for smoking 
cessation 
New prescription for respiratory medication 
(long acting bronchodilator, inhaled steroids) 
CAT score 
Attendance of pulmonary rehabilitation 
CAPTURE questions 
CAPTURE Additional Item Questionnaire 
COVID-19 related questions 
 
 
 
Practice study introduction and participation confirmation: After PBRN practice selection, the CAPTURE 
study Aim 2 lead together with the local PBRN Aim 2 coordinator conduct a 15-minute participation 
confirmation and introduction phone call with the key PBRN contact at each of the two selected 
practices. The study specifics and timeline are reviewed. After practice participation is confirmed, the 
on-site practice assessment date is scheduled. Informed consent forms for clinical staff are mailed to 
each confirmed practice. To reduce practice burden, completed clinical staff informed consent forms (up 
to 15 clinical staff per practice) can be returned by mail to the University of Michigan School of Public 
Health office, addressed to Dr. Randall Brown, or saved for completion and picked up at the on-site 
practice assessment site visit. Following the confirmation phone call, the PBRN Aim 2 coordinator 
completes a short (15 minute) qualitative questionnaire detailing the selected and confirmed practice 
demographics and PBRN parameter of practice choice for each of the two practices. The completed 
PBRN Practice Selection Questionnaire is returned to the Aim 2 data team and stored securely. 
 
On-site Practice Assessment (OSPA): The OSPA is an in-person on-site practice workflow assessment. It 
includes 2 practice clinicians per practice choice, the PBRN Aim 2 coordinator (if available), the CAPTURE 
study Aim 2 lead and the CAPTURE Aim 2 research specialist (if the PBRN Aim 2 coordinator is not 
present). The objective of the visit is to detail specifics of practice workflow, practice physical 
characteristics, staff roles, clinical information gathering patterns for respiratory patients, electronic 
health record communication, continuing education structure, and quality improvement structure. The 
assessment takes place in three parts; the pre-observation practice overview (conducted with the 2 
practice clinicians – 60 minutes), the ½ day practice workflow observation (observation by one member 
8.3 
AIM 2 ASSESSMENTS AND DATA COLLECTION 

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of the Aim 2 research team of common and testing areas used for the respiratory patient). There is no 
patient engagement and no collection of patient-specific identification or health information), and the 
post-observation practice summary (conducted with the same 2 practice clinicians – 30 minutes). 
 
The 3 OSPA assessment tools are: 
i) 
The Pre-workflow Observation Practice Assessment Review Questionnaire 
ii) 
Respiratory Workflow Assessment Review 
iii) 
The Post-workflow Observation Practice Assessment Review Questionnaire 
Also at the OSPA, informed consent is obtained from all remaining participating staff (up to 15 clinical 
staff per practice) by the CAPTURE Aim 2 team and returned to the Aim 2 data team for secure storage. 
 
Clinical Staff Questionnaires (Baseline/6/12 months). Written or on-line questionnaires are provided 
to participating and consented staff personnel at two practice levels -- Non-Prescribing clinical (also 
known as “support”) staff and Prescribing (PR) clinical (also known as “provider”) staff. 
 
Non-Prescribing (NPR) clinical staff are clinical practice personnel involved in clinical workflow (including 
registered nurses, licensed practical nurses, medical assistants, medical assistants and receptionists), yet 
not having the role to make final and official medical diagnostic and management disposition plan 
decisions for and with patients. Prescribing (PR) clinical staff are prescribing clinical practice personnel 
involved in clinical workflow (including doctors, nurse practitioners, and physician assistants) who may 
independently make final medical diagnostic and management disposition plan decisions for and with 
patients. 
 
Questionnaire items explore clinician demographics, including past education, duration of current 
employment and currently held clinical position. COPD knowledge, attitudes, beliefs, practice patterns 
and self-efficacy regarding COPD diagnosis, management, spirometry testing and interpretation, 
practice workflow and communication in the clinical primary practice care of adult patients with 
respiratory disease. Additional questions include preferred continuing education method and clinical 
staff quality improvement modalities for respiratory disease management. Specific examples of past 
practice chronic disease diagnostic changes and the individual and practice-wide levers of success and 
challenge associated with those changes are explored. 
 
Each of the 3 (baseline, 6-month and 12-month) questionnaires are completed within 30 minutes. No 
identifying patient data is collected. Online questionnaires are collected and secured by the CAPTURE 
DCC and Aim 2 research team. The participants who complete written questionnaires (per their 
preference) mail completed questionnaires via pre-addressed stamped envelope to the CAPTURE DCC 
and Aim 2 research team. 
 
Patient Opinion Surveys: 
200 patient participants, 40 from each PBRN, are recruited as a sub-sample from Aim 1 practices. 
Patient participants fulfill all inclusion and exclusion criteria and receive informed consent for survey 
participation as part of aim 1. 
 
Eligible participants complete a written one-time 5 to 10 minute CAPTURE opinion survey. Patient 
survey data is collected by Aim 1 research coordinators and is processed with Aim 1 baseline patient 
data. Patients receive a $15 gift card for completion of the survey Aim 2 patient participation ends at the 
completion on the lone opinion survey. 
 
Participants who prefer to complete the 5 to 10-minute survey online via Qualtrics will be sent a secure, 
Qualtrics link via email. The Qualtrics survey will include a brief, introductory screen affirming consent, 
describing the survey and instructions about participation. Once the survey is complete, participants will 

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see a screen with instructions about how to obtain their $15 gift card and how to contact study staff 
with questions regarding the survey. 
 
 
Modular online COPD education. Access to free, COPD on-line, continuing education is provided for all 
clinical staff at each practice. Each module will take 20 minutes or less. Modular components of and 
access to COPD education is described in the protocol. Aim 2 clinician participant access and completion 
of COPD education modules is assessed by clinician questionnaires and focus group item response over 
12 months (between months 2 and 14 of Aim 2 timeline). 
 
COPD in Primary Care/CAPTURE Introduction Focus Groups: 
Two 45 to 60-minute focus group discussions occur at each Aim 2 practice. Focus groups are informed 
by practice demographics, practice assessment data – including respiratory workflow, baseline clinical 
staff questionnaire data regarding respiratory knowledge, attitudes, beliefs and practice preference for 
the diagnosis and care of adult patients with respiratory disease as well as patient opinion from 
CAPTURE surveys and past CAPTURE study (46, 47). Focus group candidate themes and prompts are 
developed for non-prescribing clinical staff (NPR) and prescribing clinical staff (PR) and are presented at 
separate on-site focus group sessions to allow more detailed discussion of role responsibility in the 
context of daily practice workflow, generating a more abundant qualitative data sample. Separation of 
and PR clinical staffing implementation themes into two focus groups also limits potential for 
hierarchical work-related discussion suppression described in other short duration focus group studies 
(48-52). 
 
The focus group moderator introduces the CAPTURE tool utilizing CAPTURE education components 
described in Section 6.1.1. The focus group moderator follows RE-AIM prompts for CAPTURE 
implementation planning discussion throughout the focus group. Targeted COPD self-efficacy limitation 
themes from questionnaire data (including awareness and/or use of validated respiratory assessment 
questionnaires, spirometry, COPD guidelines, inhaled medication patient education, oxygen therapy, 
smoking cessation education, vaccination recommendation, pulmonology specialty care and pulmonary 
rehabilitation referral) are explored. Questions will probe clinicians to identify and explain levers that 
may maximize uptake of CAPTURE use in their practices as well as potential barriers to implementation. 
The Aim 2 research team will record each focus group using audio and written note-taking that will allow 
an abridged yet detailed tape-based micro-interlocutor analysis of focus group emergent themes, 
questions, answers and interactions. Key themes informing consensus discussion, program modifications 
and key elements of the CAPTURE RE-AIM implementation dimensions will be identified. Audio- 
recordings will be professionally transcribed and codes will be generated for the interview topics and 
key research questions. Reviewing the transcripts line-by-line, all substantive information will be 
assigned a priori codes as relevant for CAPTURE RE-AIM implementation planning, COPD diagnosis and 
CAPTURE intra-office clinical communication and COPD/CAPTURE education preference assessment. 
Additional codes will be developed for sub-themes and emergent themes. 
 
Development of Practice-Based CAPTURE Implementation PBL Cases: 
From analyses of the 2 NPR and 2 PR CAPTURE Introduction focus groups per PBRN, baseline clinical 
staff questionnaire data, online CAPTURE opinion surveys, and on-site practice assessments, 1 primary 
care practice CAPTURE implementation case per PBRN (total implementation cases = 5) is created by the 
Aim 2 research team. Given local knowledge of chronic disease management quality improvement 
history, effort, challenge and successes, each PBRN’s participation in case creation will be instrumental. 
The Aim 2 research team will lead case creation using evidence-based problem based learning (PBL) 
techniques (53-57). The Center for Research on Learning and Teaching (CRLT) at the University of 
Michigan will serve as research reference for PBL case development qualification (58). Each local PBRN 
PBL case will be distributed to the Aim 2 clinical staff at the 2 participating PBRN practices 2 weeks prior 

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to the CAPTURE Implementation focus groups, giving Aim 2 participants an opportunity to read the case 
introductions prior to the focus group session. Also, each practice will receive one additional non-PBRN 
case for focus group discussion as selected by the Aim 2 research team. Therein, each of the 5 CAPTURE 
implementation PBL cases will receive 2 comprehensive focus group reviews (see below). 
 
CAPTURE Implementation PBL Case Presentation Focus Groups: 
Each practice participates in a final pooled (NPRs and PRs together) on-site focus group. Two CAPTURE 
implementation cases (described above) are discussed at each focus group. The focus will explore, 
discuss, glean and create optimal 1) CAPTURE implementation, 2) CAPTURE clinical communication, 3) 
CAPTURE/COPD education and 4) CAPTURE primary care quality improvement recommendations pooled 
from all clinical practice levels for each of the 2 presented cases. 
 
The Aim 2 research team will record each focus group using audio and written note-taking that will allow 
an abridged yet detailed tape-based micro-interlocutor analysis of focus group emergent themes, 
questions, answers and interactions. Key themes informing consensus discussion, program 
modifications and key elements of the CAPTURE RE-AIM implementation dimensions will be identified. 
Audio-recordings will be professionally transcribed and codes will be generated for the interview topics 
and key research questions. Reviewing the transcripts line-by-line, all substantive information will be 
assigned a priori codes as relevant for CAPTURE RE-AIM implementation planning, COPD diagnosis, 
CAPTURE intra-office clinical communication, and COPD and CAPTURE education preference, and COPD 
diagnosis quality improvement assessment. Additional codes will be developed for sub-themes and 
emergent themes. 
 
 
 
Adverse event means any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related (21 CFR 312.32 (a)). 
 
 
 
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of either the investigator or 
sponsor, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization 
or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability 
to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not result 
in death, be life threatening, or require hospitalization may be considered serious when, based upon appropriate 
medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. 
 
 
The following guidelines will be used to describe severity of AEs. 
 
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities. 
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
8.4 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.4.1 
DEFINITION OF ADVERSE EVENTS (AE) 
8.4.2 
DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) 
8.4.2.1  SEVERITY OF EVENT 

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• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating. Of note, the term “severe” does not necessarily equate to “serious”. 
 
All AEs must have their relationship to study intervention assessed by the clinician who examines and 
evaluates the participant based on temporal relationship and his/her clinical judgment. The degree of 
certainty about causality will be graded using the categories below. 
 
• 
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. 
• 
Possibly Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the study intervention). However, 
other factors may have contributed to the event (e.g., the participant’s clinical condition, other 
concomitant events). Although an AE may rate only as “possibly related” soon after discovery, it 
can be flagged as requiring more information and later be upgraded to “probably related” or 
“definitely related”, as appropriate. 
• 
Not Related – The AE is completely independent of study intervention administration, and/or 
evidence exists that the event is definitely related to another etiology. There must be an 
alternative, definitive etiology documented by the clinician. 
 
The Principal Investigator will be responsible for determining whether an adverse event (AE) is expected 
or unexpected. An AE will be considered unexpected if the nature, severity, or frequency of the event is 
not consistent with the risk information previously described for the study intervention. 
 
 
Adverse events (AE)s that occur during the baseline visit will be recorded. 
 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate case report form (CRF). Information to be collected includes event description, time of 
onset, clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All AEs 
occurring while on study must be documented appropriately regardless of relationship. All AEs will be 
followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. 
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. 
 
All AEs that occur at baseline visit will be recorded in the case report form and reported to the DCC. We 
anticipate few adverse events due to the non-invasive nature of the study procedures. Participants will 
only be enrolled if they meet the study eligibility criteria, including assessment for contraindications for 
8.4.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
8.4.2.2
RELATIONSHIP TO STUDY INTERVENTION 
8.4.2.3  EXPECTEDNESS 
8.4.4 
ADVERSE EVENT REPORTING 

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spirometry. Targeted safety questions will be asked of all patient participants prior to albuterol to 
exclude those with a previous adverse event with the medication and others at high risk due to cardiac 
abnormalities. 
 
SAEs will be reported to the IRB at the institution where the event occurred and the University of 
Michigan IRB will be notified of any serious adverse experience within 7 calendar days of occurrence. 
These will be reported to the DSMB. 
Follow-up of serious adverse events 
All SAEs will be followed up until resolution or permanent outcome of the event. All follow-up 
information will be included in the case report form. The DSMB will make recommendations to ensure 
data integrity and the safety of study participants. 
 
 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to 
participants or others to include, in general, any incident, experience, or outcome that meets all of the 
following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)- 
approved research protocol and informed consent document; and (b) the characteristics of the 
participant population being studied; 
 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
 
The investigator will report unanticipated problems (UPs) to the reviewing IRB and to the DCC. The UP 
report will include the following information: 
 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number; 
• 
A detailed description of the event, incident, experience, or outcome; 
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP; 
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP. 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline: 
 
• 
UPs that are SAEs will be reported to the IRB and to the DCC within 7 calendar days of the 
investigator becoming aware of the event. 
• 
Any other UP will be reported to the IRB and to the DCC within 14 calendar days of the 
8.4.5 
SERIOUS ADVERSE EVENT REPORTING 
8.5 
UNANTICIPATED PROBLEMS 
8.5.1 
DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
8.5.2 
UNANTICIPATED PROBLEM REPORTING 

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investigator becoming aware of the problem. 
• 
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and the Office for 
Human Research Protections (OHRP) within one month of the IRB’s receipt of the report of the 
problem from the investigator. 
 
Safety oversight will be under the direction of a DSMB (physicians with the appropriate expertise, 
including non-involved pulmonologists, primary care physicians, and independent statisticians with 
clinical experience). Members of the DSMB should be independent from the study conduct and free of 
conflict of interest, or measures should be in place to minimize perceived conflict of interest. The DSMB 
will meet at least semiannually to assess safety and efficacy data on each arm of the study. The DMSB 
will operate under the rules of an approved charter that will be written and reviewed at the 
organizational meeting of the DSMB. At this time, each data element that the DSMB needs to assess will 
be clearly defined. The DSMB will provide its input to the Principal Investigators. 
 
 
 
9.1.1 PRIMARY OBJECTIVES 
 
Define the sensitivity and specificity of CAPTURE for identifying previously undiagnosed patients with 
clinically significant COPD in a broad range of primary care settings. We will also explore clinical practice 
implementation approaches to and acceptance of CAPTURE case finding for clinically significant COPD in 
a range of primary care practices. Further, we will define the impact of CAPTURE information provided 
to clinicians in identifying and managing patients with respiratory symptoms (CAPTURE+) across a broad 
range of primary care settings. 
 
9.1.1.1 SENSITIVITY AND SPECIFICITY OF THE CAPTURE TOOL 
 
Primary Hypothesis 1. The CAPTURE tool will exhibit excellent sensitivity and specificity in diagnosing 
clinically significant COPD as defined by post-bronchodilator FEV1/FVC < 0.70 in addition to either >1 
exacerbation-like event (ECOPD) within the past 12 months or an FEV1 < 60% predicted. Approximately 
5000 patients will be enrolled in the study with the expectation that 300-800 of these will have 
previously undiagnosed clinically significant COPD, identified through research spirometry and 
documentation of prior respiratory events. Amongst cases, we will calculate the proportion of 
individuals who are at high risk for clinically significant COPD based on CAPTURE (sensitivity). Similarly, 
amongst non-cases, we will calculate the proportion of individuals not classified as having clinically 
significant COPD based on CAPTURE (specificity). Corresponding 95% confidence intervals will be 
calculated. 
 
Based on our preliminary data drawn from a research setting, we noted 89.7% sensitivity and 93.1% 
specificity for CAPTURE. Table 9-1 shows the range of sensitivity and specificity 95% confidence interval 
widths that would result if the true sensitivity or specificity is 85%, 90% or 95% across a range of sample 
sizes. For instance, if we find 500 individuals with confirmed clinically significant COPD and CAPTURE has 
90% sensitivity, then the 95% confidence interval for sensitivity would be 90% ± 2.6%. Similarly, if 4,000 
individuals are confirmed to have no evidence of clinically significant COPD and CAPTURE has 90% 
specificity, then the 95% confidence interval for specificity would be 90% ± 0.9%. 
8.6 
SAFETY OVERSIGHT 
9 
STATISTICAL AND ANALYTICAL PLANS 
9.1 
SAMPLE SIZE AND POWER 

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Table 9-1 Projected Confidence Interval Widths for Various Sensitivity/Specificity Percentages (Columns) 
and Sample Sizes (Rows). 
Sensitivity or Specificity 
Sample Size 
85% 
90% 
95% 
5000 
± 1.0% 
± 0.8% 
± 0.6% 
4000 
± 1.1% 
± 0.9% 
± 0.7% 
1000 
± 2.2% 
± 1.9% 
± 1.4% 
500 
± 3.1% 
± 2.6% 
± 1.9% 
250 
± 4.4% 
± 3.7% 
± 2.7% 
100 
± 7.0% 
± 5.9% 
± 4.3% 
50 
± 9.9% 
± 8.3% 
± 6.0% 
 
9.1.1.2 ADOPTION AND IMPLEMENTATION OF THE CAPTURE TOOL IN PRIMARY CARE 
PRACTICE 
 
Primary Hypothesis 2: A COPD case finding methodology using a validated one-page, five-item 
questionnaire with selective PEF measurement (CAPTURE) can be incorporated into the clinical practice 
patterns, clinical workflow, communication and practice-based quality improvement paradigms of a 
variety of primary care clinical settings. 
 
Aim 2 is a qualitative study to determine the efficacy of workflow integration of the CAPTURE tool. 
Statistical analysis of the clinician questionnaire will involve simple sums of each item and reviewing 
answers across practices and region. Standard frequencies for questions will be developed to examine 
patterns in responses. 
 
The clinician focus groups will be conducted on-site at each practice at a time convenient for the 
participating clinicians. The number of prescribing and non-prescribing clinicians will equal 15 per 
practice and is based on interest with a maximum of 8 prescribing clinicians/practice. The sample size 
will follow a basic qualitative sampling standard of interviewing to redundancy or saturation. The 
number of clinicians to be interviewed (up to n=15 in each practice) is estimated based on achieving 
concept saturation. Reflecting regional primary care practice norms and to bolster concept saturation, 
PBRN Aim 2 coordinator focus group discussion participation is encouraged for very small practices 
where the participating prescribing and non-prescribing clinician total is less than or equal to 4. For all 
practice focus groups questions will explore the described Aim 2 CAPTURE RE-AIM concepts, barriers to 
implementation of the CAPTURE tool at other practice sites, standard processes for COPD and 
respiratory care diagnosis and management for each clinical role within the practice, and perception of 
quality improvement methods at each practice. Clinician focus groups are conducted on-site at each of 
the 10 practices. 
 
Transcripts of clinician focus groups will all be digital and entered into a qualitative data analysis 
program, NVivo for Mac. This program allows for an investigation of the salience, patterning, and 
contexts of key discourse items. Grounded theory methods will be used to identify and label recurrent 
themes and concepts within textual materials. Texts will be examined line-by-line, key phrases assigned 
tentative category labels, and coded passages grouped under the themes of feasibility, barrier and 
utility. The analyses will look for “traces” in dialogue, including repetitions, key words, evaluation 
statements, and metaphors. Change in salience, patterning, or content of key themes will provide 
further empirical evidence regarding the efficacy of our program’s efforts to impact community norms 
and behaviors. An audit trail will be maintained to document the position of text material from which 
codes and themes are developed. We will use word/code counts of repetitive themes and concepts to 
indicate patterns. By allowing for open-ended responses, the narratives and notes will allow us to 

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capture significant changes in participants’ attitudes or behaviors. Codes and themes will be discussed 
iteratively with the research team members to hone definitions and assure consistency of 
interpretation. We will establish a coding dictionary and all interviews will be coded using the complete 
set of themes. Two independent coders will code each document to assure inter-coder reliability. 
Preliminary results will be shared with our Aim 2 research team and will inform the development of the 
case studies for the latter part of the project. 
 
9.1.1.3 PRACTICE BEHAVIOR IN SITES WITH VERSUS WITHOUT CAPTURE EDUCATION AND 
PATIENT LEVEL CAPTURE DATA PROVIDED 
 
Primary Hypothesis 3: Sites where basic COPD and CAPTURE education are provided to clinicians, along 
with patient level CAPTURE data, will have a higher probability than control sites (i.e., those receiving 
only basic COPD education) of meeting the composite endpoint in their CAPTURE+ patients within 12 
months of baseline. From medical record review and follow-up patient survey responses, the composite 
endpoint is met if one of the following is recorded: (1) referral for or completion of clinical spirometry 
testing, 2) new clinical diagnosis of COPD, 3) newly prescribed respiratory medication (long acting 
bronchodilator or anti-inflammatory for respiratory condition), 4) referral to a specialist for respiratory 
evaluation/ treatment, or 5) referral for or completion of pulmonary rehabilitation. 
 
The study will enroll 50 CAPTURE practices and 50 control practices; each practice will enroll 50 patients 
(for a total of approximately 5,000 patients). We project that within each practice, there will be at least 
5 patients previously undiagnosed with COPD who have a CAPTURE+ screening result. The primary 
analysis will be to compare the average proportion of CAPTURE+ patients per practice that meet the 
composite endpoint in the two intervention arms. For power and sample sizes computations, this is a 
cluster randomized trial of n=50 clusters (practices) per intervention arm with 5 CAPTURE+ patients per 
cluster (practice). The primary power calculation is based on comparing the average cluster sample 
proportion (average proportion of CAPTURE+ patients per practice meeting composite endpoint) 
between intervention arms. Table 9-2 displays power for a two-sample test comparing average cluster 
sample proportions, accounting for possible intra-cluster correlation coefficient (ICC) values of 0.05, 
0.10 and 0.15 that are typically seen in cluster randomized trials of behavioral interventions 
(https://www.abdn.ac.uk/hsru/research/research-tools/study-design/). These calculations assume a 
type I error of 5% and that the control arm meets the composite endpoint in 5% of CAPTURE+ patients 
and the CAPTURE arm meets the composite endpoint in higher percentages (columns of Table 9-2). 
There will be variability in the actual number of CAPTURE+ patients per practice. It is standard practice 
to inflate the number of needed clusters by 12% to account for this extra source of variability. 
Therefore, our power calculations are based on 44 clusters per intervention arm. 
 
Table 9-2. Overall power to detect a difference in rate of meeting primary endpoint in 
CAPTURE group (50 practices/clusters) vs usual care (50 practices/clusters), 
assuming 5% performance rate in usual care; 50 patients total / practice; assuming 10% 
prevalence gives 5 CAPTURE+/practice 
Improvement 
over usual care 
+7.5% 
+10% 
+15% 
+25% 
+50% 
ICC=0.05 
0.72 
0.89 
0.99 
>0.99 
>0.99 
ICC=0.10 
0.65 
0.84 
0.98 
>0.99 
>0.99 
ICC=0.15 
0.59 
0.79 
0.97 
>0.99 
>0.99 
 
 
 
 

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9.1.2 SECONDARY OBJECTIVES 
 
9.1.2.1 SENSITIVITY AND SPECIFICITY IN PREDEFINED SUBGROUPS 
 
Table 9-3. Projected numbers of clinically significant COPD cases and non-cases we expect by subgroup of interest assuming 
prevalence of obstructed individuals is between 6-16%. (*Non-Hispanic) This table assumes prevalence of non-clinically 
significant COPD similar to clinically significant COPD (not included in this table). 
Total 
Men 
(50%) 
Women 
(50%) 
White* 
(62%) 
Black* 
(15%) 
Hispanic 
(18%) 
Rural 
(46%) 
Urban 
(54%) 
Ever- 
Smokers 
(40%) 
Never- 
smokers 
(60%) 
Projected # 
confirmed 
clinically 
significant 
COPD by 
subgroup 
300- 
800 
150-400 
150- 
400 
186- 
496 
45- 
120 
54-144 
138- 
368 
162- 
432 
120-320 
180-480 
Projected # 
confirmed no 
COPD by 
subgroup 
3,400- 
4,400 
1,700- 
2,200 
1,700- 
2,200 
2,108- 
2,728 
510- 
660 
612-792 
1,564- 
2,024 
1,836- 
2,376 
1,360- 
1,760 
2,040- 
2,640 
 
We will also examine several subgroups of interest that are key to addressing our overall goal of defining 
the value of CAPTURE across a broad range on individuals. These will include sex, ethnic groups, rural 
and urban location, and educational level, among individuals with clinically significant COPD, 
spirometrically defined COPD and individuals with “mild” COPD as defined in this protocol. We have 
specifically chosen clinical sites with a diverse gender, racial and ethnic mix, and rural and urban mix 
with the expected prevalence of clinically significant COPD cases and controls by subgroup outlined in 
Table 9-3, again with corresponding sensitivity and specificity confidence interval widths in Table 9-1. 
For example, if sensitivity of CAPTURE in Hispanic individuals is 90%, then a sample size of approximately 
100 would give a confidence interval of 90% ± 5.9%. We believe that with an overall sample size of 5,000 
recruited patients we will have adequately sized subgroups to assess the operating characteristics of 
CAPTURE in the subgroups of interest. 
 
9.1.2.2 FURTHER ANALYSIS OF ASSOCIATIONS BETWEEN MEETING COMPOSITE ENDPOINT 
AND INDIVIDUAL AND PRACTICE LEVEL OUTCOMES 
 
Secondary analyses for evaluating practice behavior are exploratory, and therefore not included in a 
formal power and sample size analysis. These analyses are described further in Section 9.3.2. 
 
 
Aim 1 
Population used for sensitivity calculations are all enrolled patients with clinically significant COPD as 
defined by post-bronchodilator FEV1/FVC < 0.70 in addition to either >1 exacerbation-like event (ECOPD) 
within the past 12 months or an FEV1 < 60% predicted. 
 
Population used for specificity calculations are all enrolled patients with no demonstrable COPD as 
determined by research spirometry conducted upon study entry, FEV1/FVC ≥ 0.70. 
 
Aim 2 
Clinician participants: enrolled clinicians are from 2 primary care practices in each of five US PBRN 
regions that do not engage in Aims 1 or 3 investigation. Eligible clinicians include primary care providers 
and primary care clinical non-provider support personnel. 
9.2 
POPULATIONS FOR ANALYSES 

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Patient participants: enrolled as a sub-sample of Aim 1 participants at baseline. One CAPTURE patient 
opinion survey is administered at baseline. Aim 2 participants fulfill the inclusion, exclusion and 
population analysis criteria of aim 1. 
 
Aim 3 
Populations used in 2-sample comparisons of outcomes between the two intervention arms will be 
based on randomization group (intent-to-treat analysis). 
 
For primary analysis of each Aim 3 outcome, the analysis population will consist of all patients with 
follow-up data for that outcome from both the medical record review and the patient survey 
administered by the COPD Foundation (section 8.2). 
 
Secondary analyses will be performed using alternative analysis populations, including 
1. All patients with outcome data from the medical record review, and 
2. All patients selected for follow-up. 
 
 
 
 
 
SAS version 9.4 PROC LOGISTIC will be used for computations. Calculations of sensitivity and specificity 
along with their corresponding 95% confidence intervals assume independent Bernoulli outcomes for 
each patient. Clinically significant COPD+ and COPD- populations selected for these analyses are 
described in Section 9.2. CAPTURE+ patients are those with a baseline CAPTURE score > 5 or with a 
baseline CAPTURE score of 2, 3, or 4 with a low PEF (defined as <350 L/min for males, <250 L/min for 
females). 
 
In addition to the primary sensitivity/specificity calculations, sensitivity/specificity and associated 95% 
confidence intervals will be calculated in predefined subgroups: sex, ethnic subgroups, rural and urban 
location, and educational status. As part of secondary analyses, receiver operating characteristic (ROC) 
curve analyses will evaluate different thresholds of the CAPTURE questionnaire score in defining a 
positive clinically significant + COPD screen, separately and in combination with low PEF characteristics, 
and the additional CAPTURE questions. As part of this exploration, participant and practice level data 
as well as interactions with the CAPTURE tool results, will be considered as predictors of clinically 
significant COPD using multivariable logistic regression. Corresponding positive and negative predictive 
values will be estimated across the range of prevalence percentages seen at the enrolled practices. 
Model selection in secondary logistic regression analyses will be based on forward selection using 
maximum likelihood theory, with entry into the model dependent on statistical significance at the 0.05 
level. Exploration of this nature has the potential to produce artificially high operating characteristics 
(area under the curve [AUC], sensitivity and specificity) based on overfitting the data. SAS 9.4 PROC 
LOGISTIC includes a cross-validation approach to ROC curve analysis [ROCOPTIONS(CROSSVALIDATE) 
] that we will use when assessing operating characteristics for any new prediction tool that goes beyond 
the original CAPTURE metric considered in primary analyses. Once a final logistic regression model has 
been selected, classification thresholds for predicting clinically significant COPD will be described by the 
investigative team from the cross-validated ROC curve. Calibration plots of observed versus predicted 
sensitivity, and observed versus predicted specificity, will be conducted across previously specified 
subgroups of interest (sex, ethnic subgroups, rural and urban location, and educational status). 
9.3 
STATISTICAL ANALYSES 
9.3.1 
SENSITIVITY AND SPECIFICITY (AIM 1) 

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All of the above analyses will be applied to these additional populations: (1) patients with 
spirometrically defined COPD and (2) patients with mild COPD. 
 
 
 
 
 
The primary analysis of the Aim 3 primary endpoint will be to compare the average cluster sample 
proportion (average proportion of CAPTURE+ patients per practice meeting composite endpoint) 
between intervention arms. Practices that do not identify any CAPTURE+ subjects will not contribute to 
the primary analysis.  The primary analysis is a two-sample test comparing average cluster sample 
proportions that explicitly takes into account correlation between individuals treated within the same 
practice. A two-sided p-value < 0.05 will be considered statistically significant. This analysis corresponds 
to a generalized estimating equation (GEE) regression analysis with (1) individual-level binary composite 
outcome data, (2) CAPTURE intervention group as a covariate, (3) practice id used to identify correlated 
outcomes, (4) exchangeable correlation matrix that assumes similar correlation between all composite 
outcome results for patients within the same practice, and (5) an identity link function so that the 
coefficient parameter corresponding to CAPTURE intervention group represents a difference in outcome 
probability. The primary analysis would then correspond to a test for whether the CAPTURE 
intervention group parameter is non-zero. There are no planned interim analyses for the primary 
endpoint, the rationale being that this is not a pharmaceutical or device trial that would benefit from 
standard stopping rules for efficacy. A DSMB will be monitoring the study for safety and study integrity. 
 
Secondary analyses on meeting the composite outcome for participants who are CAPTURE+ will employ 
the GEE analysis framework with individual and practice level predictors in addition to the CAPTURE 
intervention group. Interactions will be assessed. We will also use the GEE framework to study and 
describe each of the individual components of the composite outcome as they relate to individual and 
practice level outcomes. In the subset of smoking patients, we will use GEE regression analysis to study 
additional binary outcomes, such as incidence of physician counselling/recommendation to stop 
smoking, physician referral to a formal smoking cessation program, newly prescribed smoking cessation 
medication, and referral to a smoking quit line. 
 
For each Aim 3 outcome that is collected via both medical record review and patient survey, the primary 
analysis will be among patients with complete outcome data from both the medical record and patient 
survey. Sensitivity analyses will be conducted by imputing missing outcome data using different 
assumptions and applying the primary analysis method to the resulting data sets. Sensitivity analyses 
will include (1) imputation of negative responses (i.e., responses indicating that the outcome has not 
occurred) for all missing patient survey responses, followed by analysis of all patients with medical 
record review data; (2) imputation of positive responses (i.e., responses indicating that the outcome has 
occurred) for all missing patient survey responses, followed by analysis of all patients with medical 
record review data; and (3) multiple imputation of all missing outcome data using the observed 
outcomes and covariates, followed by analysis of all patients selected for follow-up. 
 
In participants who are CAPTURE+, change in CAT score will be analyzed using mixed models with a 
random effect for practice. The average cluster sample proportion of patients who experience 
exacerbations will be compared between intervention groups using methodology similar to that used for 
the primary endpoint. Subject to having sufficient mortality events, survival analysis allowing for 
correlation of endpoints within cluster (practice) will be used to compare mortality between 
9.3.2 
PRACTICE BEHAVIOR (AIM 3) 

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intervention groups and perform multivariable analysis. We will explore differences between 
intervention groups in the average cluster sample rate of hospitalizations again using GEE. All additional 
secondary analyses will also be applied to patients with clinically significant and spirometrically defined 
COPD, Mild COPD, PRISm, and symptomatic non-obstruction. Practices that do not have any patients 
with these conditions will not contribute to analyses of these secondary endpoints, respectively. 
 
Model selection in GEE secondary analyses will be based on statistical significance at the 0.05 level using 
robust sandwich estimation of variability within clusters. Model fit will be checked by comparing 
observed versus predicted values within predefined subgroups of interest (sex, ethnic subgroups, rural 
and urban location, and educational status). 
 
Analyses will be repeated in populations separated into cohorts based on enrollment date and the 
degree to which follow-up may have been affected by the SARS-CoV-2 pandemic. 
 
 
Site-specific practice information, clinician knowledge and behavioral questionnaires, as well as patient opinion 
survey responses are recorded primarily to populate focus group themes for qualitative analysis. Secondary analyses 
of individual clinician and patient response using frequencies, means, ranking and dispersion by clinician type, 
practice and PBRN is accomplished using SAS version 9.4. Correlation with implementation recommendation is 
determined using GEE variance models. 
 
Audio transcripts of clinician focus groups will all be digital and entered into a qualitative data analysis 
program, NVivo for Mac. This program allows for an investigation of the salience, patterning, and 
contexts of key discourse items. Grounded theory methods will be used to identify and label recurrent 
themes and concepts within textual materials. Texts will be examined line-by-line, key phrases assigned 
tentative category labels, and coded passages grouped under the themes of feasibility, barrier and 
utility. The analyses will look for “traces” in dialogue, including repetitions, key words, evaluation 
statements, and metaphors. Micro-interlocutor analysis of focus group emergent themes, questions, 
answers and interactions will account for individual gaps in focus group participation. Change in 
salience, patterning, or content of key themes will provide further empirical evidence regarding the 
efficacy of our program’s efforts to impact clinician community norms and behaviors. An audit trail will 
be maintained to document the position of text material from which codes and themes are developed. 
We will use word/code counts of repetitive themes and concepts to indicate patterns. By allowing for 
open-ended responses, the narratives and notes will allow us to capture significant changes in 
participants’ attitudes or behaviors. Codes and themes will be discussed iteratively with the research 
team members to hone definitions and assure consistency of interpretation. We will establish a coding 
dictionary and all interviews will be coded using the complete set of themes. Reviewing the transcripts 
line-by-line, all substantive information will be assigned a priori codes as relevant for CAPTURE RE-AIM 
implementation planning, COPD diagnosis, CAPTURE intra-office clinical communication, and COPD and 
CAPTURE education preference, and COPD diagnosis quality improvement assessment. Two 
independent coders will code each document to assure inter-coder reliability. Preliminary results will be 
shared with the Aim 2 data team and will inform the development of the CAPTURE case studies and 
primary care practice implementation recommendations. 
 
 
 
 
 
 
9.3.3 
CAPTURE IMPLEMENTATION RECOMMENDATIONS (AIM 2) 

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Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent forms will be Institutional 
Review Board (IRB)-approved and the participant will be asked to read and review the document. The 
investigator will explain the research study to the participant and answer any questions that may arise. 
 
A HIPPA waiver will be submitted to each IRB to prescreen clinic schedules and patient panels for 
recruitment purposes. The PHI reviewed by the coordinator in the electronic health record (EHR) will 
include age, date of birth, diagnosis of COPD, respiratory medications, and other medical conditions that 
are contraindicated for spirometry. A waiver of written consent will be submitted to each IRB to pre- 
screen potential participants for eligibility criteria prior to informed consent. The pre-screening will 
either be by telephone prior to an upcoming clinic visit, or in person at the time of the visit. An IRB- 
approved telephone/in-person screening script will be submitted to each IRB. 
 
A verbal explanation will be provided in terms suited to the participant’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research participants. 
Participants will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. Participants will additionally have the opportunity to review the study and informed 
consent prior to providing consent for the study. Participants must be informed that participation is 
voluntary and that they may withdraw from the study at any time, without prejudice. A copy of the 
informed consent document will be given to the participants for their records. The informed consent 
process will be conducted and documented in the source document (including the date), and the form 
signed, before the participant undergoes any study-specific procedures. The rights and welfare of the 
participants will be protected by emphasizing to them that the quality of their medical care will not be 
adversely affected if they decline to participate in this study. 
 
All PBRN research coordinators, COPD Foundation study staff and other clinical investigators will be 
certified by their local IRB in informed consent and human studies research. 
 
Clinicians interested in participating in the qualitative, minimal risk study for Aim 2, will be given the 
opportunity to review the consent form below and sign it. This can happen once their practice agrees to 
participate in Aim 2 activities or during the first in person site visit with Dr. Brown. 
 
 
When a study is prematurely terminated, refer to Section 7, Study Intervention Discontinuation and 
Participant Discontinuation/Withdrawal, for handling of enrolled study participants. 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to study participants, investigator, funding agency, and 
regulatory authorities. If the study is prematurely terminated or suspended, the Principal Investigator 
10  SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 INFORMED CONSENT PROCESS 
10.1.1.1 CONSENT PROCEDURES AND DOCUMENTATION 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 

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(PI) will promptly inform study participants, the Institutional Review Board (IRB), and sponsor and will 
provide the reason(s) for the termination or suspension. Study participants will be contacted, as 
applicable. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, and the sponsor(s) and their interventions. Therefore, the study protocol, documentation, data, 
and all other information generated will be held in strict confidence. No information concerning the 
study or the data will be released to any unauthorized third party without prior written approval of the 
sponsor. 
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the Institutional 
Review Board (IRB), regulatory agencies may inspect all documents and records required to be 
maintained by the investigator, including but not limited to, medical records (office, clinic, or hospital) 
and pharmacy records for the participants in this study. The clinical study site will permit access to such 
records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. In addition, it may be transmitted and stored at the DCC in a database separate from 
the clinical database (used for statistical analysis and scientific reporting) and with COPD Foundation 
study team access to aid in contacting participants at the 12-month follow-up. At the end of the study, 
all records will continue to be kept in a secure location for as long a period as dictated by the reviewing 
IRB, Institutional policies, or sponsor requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored at the DCC. This will not include the participant’s contact or identifying 
information. Rather, individual participants and their research data will be identified by a unique study 
identification number. The study data entry and study management systems used by clinical sites and by 
DCC research staff will be secured and password protected. At the end of the study, all study databases 
will be de-identified and archived at the DCC. 
 
For the online Aim 2 patient opinion survey, Qualtrics is used. Qualtrics is a secure University of 
Michigan (U-M) contracted-for cloud service that can be used to maintain or share the university's 
sensitive unregulated data, as well as some kinds of sensitive regulated data. 
 
U-M's agreement with Qualtrics includes a Business Associate Agreement. This means individuals may 
use this service to maintain Protected Health Information (PHI) regulated by HIPAA. Complying with 
HIPAA's requirements is a shared responsibility. Users sharing and storing PHI in Qualtrics are 
responsible for complying with HIPAA safeguards, including: 
 
• 
Using and disclosing only the minimum necessary PHI for the intended purpose. 
• 
Obtaining all required authorizations for using and disclosing PHI. 
• 
Ensuring that PHI is seen only by those who are authorized to see it. 
10.1.3 CONFIDENTIALITY AND PRIVACY 

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• 
Obtaining all necessary data-sharing agreements and Business Associate Agreements for using 
and disclosing PHI. 
• 
Following any additional steps required by your unit to comply with HIPAA. 
 
Sensitive data, including PHI, may be collected and stored in Qualtrics for non-clinical, academic 
purposes only (for example, research and hospital quality improvement initiatives). Qualtrics cannot be 
used for any clinical applications, no matter the sensitivity level of the data 
 
 
 
 
The principal investigators are responsible for providing direction and oversight of all study activities. 
 
Principal Investigators 
Fernando Martinez, MD, MS 
MeiLan Han, MD, MS 
Weill Cornell Medicine 
University of Michigan 
1305 York Avenue, 
1500 E. Medical Center Dr. 
Box 96, Room Y-1059 
3916 Taubman Center 
New York NY 10021 
Ann Arbor, MI 48109 
646-962-2748 
734-936-5201 
Fjm2003@med.cornell.edu 
mrking@med.umich.edu 
 
 
PBRNs will have the following roles and responsibilities: 
 
CAPTURE Study Preparation 
 
1. Review protocol to help identify operational details 
2. Submit final protocol and informed consents to all IRBs necessary for the participating sites 
3. Complete and maintain current human participants training for all main study personnel as required 
by the IRB 
4. Attendance of PBRN coordinators at in person training, spirometry certification for all coordinators, 
update of spirometry quality assessments and training 
5. Identify and recruit local practice sites to participate in the study 
CAPTURE Study Implementation 
1. Facilitate COPD and when appropriate CAPTURE education 
2. Maintain regular contact with participating PBRN practice sites during their period of patient 
enrollment 
3. Supervise and send PBRN Research Coordinators to enroll patients, perform study visits including 
completion of the CAPTURE questions, peak flow, spirometry, and collect other information on all 
enrolled patients 
4. Complete pre bronchodilator spirometry on all participants 
5. Complete post bronchodilator spirometry on participants with abnormal pre-bronchodilator 
spirometry as defined by study algorithm (e.g. those with pre bronchodilator results consistent with 
11  STUDY ADMINISTRATION AND OVERSIGHT 
11.1 STUDY LEADERSHIP 
11.1.1 PRINCIPAL INVESTIGATORS 
11.1.2 PRACTICE BASED RESEARCH NETWORKS (PBRN) 

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obstruction) 
6. Facilitate completion of data entry to the data coordinating center 
7. Follow up by research coordinator for patients failing to respond to the follow up questionnaires 
8. Collect practice outcome data related to enrolled patients at close of study from either electronic 
medical records or if practice does not have EMR, by manual record review 
 
Patient participants and staff participants will be recruited from the PBRNs. 
 
PBRN 
Location 
Director 
Atrium Health 
North Carolina 
Hazel Tapp, PhD 
LA Net Community Health Network 
Southern California 
Lyndee Knox, PhD 
High Plains Network 
Colorado 
Linda Zittleman, MD 
Duke Primary Care Research Consortium 
Oregon Rural Practice-Based Research Network 
North Carolina 
Oregon 
Rowena Dolor, 
MD  
Nancy Elder, 
MD  
University of Illinois, Chicago 
Illinois 
Min Joo, MD 
Circuit Clinical, Buffalo 
New York 
Irfan Khan, MD 
 
 
 
 
 
 
Led by Dr. David Mannino, the Spirometry Core will maintain quality of the research spirometry that is 
integral to the success of the study. The work will be done in conjunction with a research assistant. This 
includes the following functions: 
 
1. Development of the operation manual for the sites 
2. Training of the site staff in the use of the spirometry equipment (including travel to training and 
sites as needed) 
3. Certification of staff in spirometry 
4. Assessing staff adherence to protocols for the use of bronchodilators 
5. Grading and adjudication of spirometry 
6. Importing processed spirometry into spreadsheets 
7. Uploading processed data to data coordinating center 
8. Working with data coordinating center to verify and clean data 
 
In addition, Dr. Mannino will be a critical part of the team that evaluates the data both from spirometry 
and the other components of this study (the CAPTURE tool, quality of life measures, etc.), in addition to 
being part of the writing team that analyzes data and disseminates the findings from this study. 
 
 
 
 
 
11.1.3 SPIROMETRY CORE 

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Dr. Randall Brown will lead the qualitative Aim 2 activities which assess the implementation strategy and 
acceptance recommendations for CAPTURE use in primary care practice. His team includes an Aim 2 
project manager and dedicated research assistant. Led by Dr. Brown the Aim 2 team coordinates with 
PBRNs and their selected Aim 2 practices and will conduct qualitative site visits and focus groups in 
addition to administering clinical practice behavioral questionnaires. Drs. Barbara Yawn, Barry Make, 
Bruce Bender and Julia Houfek will contribute to the development of the web based educational 
modules and the qualitative efforts on this project. 
 
Dr. Cathie Spino directs the DCC, housed at the University of Michigan within the Statistical Analysis of 
Biomedical & Educational Research (SABER) Unit of the Department of Biostatistics in the School of 
Public Health. The DCC staff will include a Database programmer, Data manager, Senior Unblinded 
Statistician, Statistical Analyst, Project Manager, Clinical Monitor, Web Programmer/Designer, and a 
Research Administrator. In addition, the blinded senior statistician, Dr. Susan Murray, is located at the 
University of Michigan. The DCC plays a pivotal role in the design, implementation, execution and 
administration of the study. The DCC will be responsible for randomization, eCRFs and online reporting 
systems, preparation of the manual of operations for data entry, addressing questions regarding entry 
and analysis, monitoring recruitment, follow-up and adherence to protocol, and scheduling and 
arranging meetings of the Executive Committee, Steering Committee, and Medical Monitor. The DCC 
will prepare all of the routine study reports for the Executive Committee, Operations Committee, and 
Medical Monitor. The DCC will interact with all of the Cores and other Committees, as needed. The DCC 
will compile data tables and listing for DSMB reports. 
 
 
 
The Clinical Coordinating Center (CCC) will be led by Principal Investigators Fernando Martinez, MD, MS 
at Weill Cornell Medicine, and MeiLan Han, MD, MS at the University of Michigan. Dr. Martinez will be 
responsible for overall study oversight as well as fiscal management of the overall project and capitation 
payments to sites for work performed. He will also be responsible for communication with NIH and 
submission of annual reports. Dr. Han will work with the Data Coordinating Center to oversee clinical 
trial enrollment and, along with her statistical team, be responsible for coordinating statistical analysis. 
The process for making decisions on scientific direction and allocation of resources will be made by both 
Drs. Martinez and Han, with input from the rest of the investigative team as needed. 
 
Additional Clinical Coordinating Center (CCC) responsibilities: 
• 
Establish subcontracts with enrolling sites, central laboratories, imaging service providers, and 
others as appropriate 
• 
Protocol development and scientific design oversight 
• 
Statistical analysis 
• 
Participating study site selection 
• 
Review of serious adverse events and unanticipated problems involving risk to participants or 
others, reporting to participating centers and regulatory reporting 
• 
Prepare and maintain Clinical Coordinating Center IRB submissions 
• 
Analyze and present data to DSMB 
11.1.4 IMPLEMENTATION CORE 
11.1.5 DATA COORDINATING CENTER (DCC) 
11.1.6 CLINICAL COORDINATING CENTER 

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Clinical Coordinating Center Personnel 
Fernando Martinez, MD, MS 
Co-Principal Investigator 
Weill Cornell Medicine 
1305 York Avenue 
Box 96, Rm Y-1059 
New York, NY 10021 
T: 646-962-2748 
E: fjm2003@med.cornell.edu 
 
MeiLan Han, MD, MS 
Co-Principal Investigator 
University of Michigan 
3916 Taubman Center 
1500 E. Medical Center Dr. 
Ann Arbor, MI 48109-5361 
T: 734-936-5201 
E: mrking@med.umich.edu 
 
Barry Make, MD 
National Jewish 
1400 Jackson St., K729 
Denver, CO 80206 
T: 303-398-1993 
E: makeb@njhealth.org 
 
Barbara Yawn, MD, MSc 
Chief Medical Officer 
COPD Foundation 
Washington, DC 20002 
University of Minnesota 
1963 112th Circle NE 
Blaine, MN 55449 
T: 507-261-3096 
E: yawnx002@umn.edu 
 
Randall Brown, MD, MPH 
University of Michigan 
2822 SPH I 
1415 Washington Hts. 
Ann Arbor, MI 48109-2029 
T: 734-763-1549 
E: rbrownmd@umich.edu 
 
Anna Smyth, M.A.  
Grants Administrator 
Weill Cornell Medicine 
1305 York Avenue, Y-1054 
New York, NY 10021 
T: 646-962-2743 
E: ans2104@med.cornell.edu 

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Catherine Meldrum, PhD, RN, MS 
Project Manager 
University of Michigan 
Taubman Center Floor 3 Reception C 
1500 E. Medical Center Dr. SPC 5360 
Ann Arbor, MI 48109 
T: 734-647-7840 
E: cathymel@umich.edu 
 
Betsy Peters, BSN 
Project Manager 
Weill Cornell Medicine 
1305 York Avenue, Y-1054 
New York, NY 10021 
T: 646-962-2742 
E: elp2018@med.cornell.edu 
https://umich.app.box.com/folder/0 
 
 
The 12 month Survey Coordinating Center will be led by Co-Investigator Barbara Yawn, MD MSc, Chief 
Science Officer at the COPD Foundation. Dr. Yawn will be responsible for oversight of the development 
and implementation of the reminder notices and 12 month survey administration by COPD Foundation 
study personnel for participants selected to complete the 12 month follow up survey. 
 
 
 
The Executive Committee will be led by the Principal Investigators and will consist of the 2 elected PBRN 
Directors, 1 representative of the COPD Foundation, Co-Investigators, Data Coordinating Center PI and 
Project Manager, NIH official and Clinical Coordinating Center Project Managers. The Executive 
Committee will meet every one-to-two weeks to administratively direct and monitor the progress of the 
study and to respond to any design, implementation or administrative issues that arise during the study. 
 
The Operations Committee will consist of Overall Principal Investigators, PBRN Directors and lead 
coordinators, DCC Project Managers, and Co-Investigators. It will address implemental and 
administration faced by the PBRN practices that arise during the study. 
 
Other subcommittees, such as the Publications and Ancillary Studies Subcommittees, will be constituted 
to support maximizing the utility of the CAPTURE study to the scientific community. 
 
 
11.1.7 12 MONTH SURVEY COORDINATING CENTER 
11.2 ORGANIZATIONAL STRUCTURE 

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Each clinical site will perform internal quality management of study conduct, data, documentation and 
completion. An individualized quality management plan will be developed. 
 
Quality control (QC) procedures will be implemented beginning with the data entry system and data QC 
checks that will be run on the database will be generated. Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution. 
 
 
 
 
 
Comprehensive data coordinating center (DCC) functions for this clinical trial, including clinical 
monitoring, database development, web-based data entry and management, as well as the creation and 
export of study reports for the DSMB will be provided by the University of Michigan Statistical Analysis 
of Biomedical and Education Research (SABER) group. Housed in the top nationally ranked Department 
of Biostatistics, SABER, in its 17-year existence, has served as the DCC for over 50 studies, including 
multiple NIH-sponsored networks. 
The DCC will use OpenClinica® (OpenClinica Clinical Trial Software; OpenClinica, LLC, Waltham, MA), a 
clinical trial software platform for electronic remote (i.e., site-based entry) data capture and clinical data 
management, as the basis for our custom-designed data entry and management system. The majority of 
data will be collected via electronic Case Report Forms (CRFs); however, other data sources, such as 
laboratory data from the central laboratory, may be used. In these circumstances, the DCC will also 
13.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
12  QUALITY ASSURANCE AND QUALITY CONTROL 
13  DATA HANDLING AND RECORD KEEPING 

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utilize electronic data transfer. Protocols for the transfer of data, with careful attention to data integrity, 
will be written by experienced programmers and stored in the OpenClinica database or data mart. 
The DCC has established a set of standard operating procedures (SOPs) governing the processes used to 
ensure patient privacy and data confidentiality, including the use of anonymous participant IDs on CRFs 
and in reports. OpenClinica® enables compliance with Good Clinical Practice (GCP) and regulatory 
requirements by providing differentiated user roles and privileges, password and user authentication 
security, electronic signatures, SSL encryption, and comprehensive auditing to record and monitor 
access and data changes. 
Data collection is the responsibility of the central study staff at the PBRN under the supervision of the 
PBRN Director (investigator). The investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. In addition to the protocol, the DCC will prepare a 
Manual of Procedures which provides additional detail on data collection procedures, including source 
documentation, eCRF completion guidelines, data handling procedures and procedures for data 
monitoring and quality control that ensure these data are accurate, consistent, complete and reliable 
and in accordance with ICH 36. 
 
 
Study documents should be retained as required by local regulations. No records will be destroyed 
without the written consent of the sponsor, if applicable. It is the responsibility of the sponsor to inform 
the investigator when these documents no longer need to be retained. 
 
 
A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), or Manual of Procedures (MOP) requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly. 
These practices are consistent with ICH GCP: 
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
• 
5.1 Quality Assurance and Quality Control, section 5.1.1 
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2. 
 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within 5 working days of identification of the protocol deviation or scheduled protocol- 
required activity. Protocol deviations must be sent to the reviewing Institutional Review Board (IRB) per 
their policies. The site investigator is responsible for knowing and adhering to the reviewing IRB 
requirements. Further details about the handling of protocol deviations will be included in the MOP. 
 
 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
13.2 STUDY RECORDS RETENTION 
13.3 PROTOCOL DEVIATIONS 
13.4 PUBLICATION AND DATA SHARING POLICY 

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This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As 
such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer- 
reviewed journals. Data from this study may be requested from other researchers after the completion 
of the primary endpoint by contacting Drs. Martinez and Han. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Protocol Amendment 2.0 - Summary of Changes 
Location 
Page 
Number 
Type of 
Change 
Description 
Rationale 
Cover Page 
--- 
Administrative 
Update Protocol Version to 2.0 
and update version date to 
Amendment version and date 
Cover Page 
--- 
Administrative 
Add NCT # for each AIM 
Add all 3 numbers to protocol since each 
AIM is registered in clinicaltrials.gov 
Table of Contents 
--- 
Administrative 
Corrected page numbers for new 
version 
Updating Table of Contents to reflect any 
page number shifts due to reformat 
Multiple Sections 
Multiple 
Administrative 
Changed Medical Chart Review to 
Medical Record Review 
throughout the protocol 
Changed Medical Chart Review to Medical 
Record Review throughout the protocol 
1.2 Schema Table 
1 
9 
Clarification 
Concomitant medications revised 
to read Respiratory Medications 
Further clarification since these are limited 
to respiratory medication not all 
medications 
14  PROTOCOL AMENDMENT HISTORY 

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1.2 Schema Table 
1 
9 
Clarification 
Foot note 3 moved to 12 month to 
reflect the data that will be 
collected for subjects who qualify 
for 12 month follow-up w 
Clarification that 12 month column is for 
indicating what data will be collected for 
subjects who meet 12 month follow-up 
criteria 
1.2 Schema Table 
1 
9 
Clarification 
X in last column for 12 month 
spirometry was deleted. This was 
originally meant to be footnote 
that post bronchodilator 
spirometry would be performed at 
baseline for those subjects that 
qualified 
Further clarification that spirometry will 
not be done at 12 month follow-up, the 
footnote was meant to reflect post 
bronchodilator spirometry at baseline for 
those subjects who qualify 
Section 2.3.1 
Known Potential 
Risks 
14 
Revision 
For Albuterol: A targeted safety 
questionnaire will be administered 
to all participants prior to albuterol 
to exclude those with a previous 
adverse event with the medication 
and others at high risk due to 
cardiac abnormalities. 
Subjects are excluded who have had MI 
and therefore not necessary 
Section 4.1 
Overall Study 
Design 
21 
Clarification 
Patient-reported data will be 
collected by telephone, secure 
web-based server, and mail-based 
methodologies based on 
participant preference and 
completed by the COPD 
Foundation., as well as medical 
record abstraction, depending 
upon practice site preferences and 
feasibility. 
The COPD Foundation will be collecting 
participant 12 month follow-up subject 
questionnaires 
Section 4.1 
Overall Study 
Design 
21 
Clarification 
Clinic site data will also be 
collected from the Subject medical 
record data will be collected from 
the medical record to assess for 
changes in practice-level care. 
Further clarification that this data will be 
collected from medical record 
Section 6.3 Study 
Intervention 
Compliance 
27 
New 
If results were not shared at the 
time of the CAPTURE study visit, 
then the date of sending the 
CAPTURE results will be recorded 
on the appropriate eCRF by filling 
in the date (day/month/year) the 
exact copy of the CAPTURE 
Toolresults were sent to the 
clinician through a inter–clinic 
email or other HIPPA-compliant 
method and placed in the medical 
record. The goal is to 
communicate the results to the 
clinician in a timely manner within 
3 business days. The DCC will 
monitor review all participants' 
eCRFs to assure that all those 
enrolled from practices 
randomized to CAPTURE results 
have been shared with clinicians. 
in the specified timeframe. 
The study team wanted to clarify that the 
exact copy of the CAPTURE tool should be 
shared with clinician. Also wanted to make 
timing of sharing less restrictive and the 
team recognized that restrictive 
parameters cannot always be realized in 
clinical practice setting 

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Section 8.2 
Longitudinal 
Follow-up 
Assessment and 
Data Collection 
30 
Clarification 
Medical chart abstractions 
completed by PBRN coordinators 
and participant questionnaires 
administered by study team 
members from the COPD 
Foundation are used. 
Clarification that medical chart reviews will 
be done by PBRN coordinators and COPD 
Foundation will administer participant 
questionnaires at 12 months 
Section 8.2 
Longitudinal 
Follow-up 
Assessment and 
Data Collection 
30 
Clarification 
Data from clinical visits to be 
collected at follow-up by 
telephone, secure web-based 
server, or mail-based 
methodologies directly from 
participants and administered by 
COPD Foundation study personnel 
Clarification that COPD Foundation will 
administer participant questionnaires at 12 
months 
Section 10.1.1 
Informed 
Consent Process 
45 
New 
All PBRN research coordinators, 
COPD Foundation study staff and 
other clinical investigators will be 
certified by their local IRB in 
informed consent and human 
studies research. 
The COPD Foundation has attained IRB 
approval as their team will be interacting 
with participants 
Section 10.1.3 
Confidentiality 
and Privacy 
46 
Clarification 
In addition, it may be transmitted 
and stored at the DCC in a 
database separate from the clinical 
database (used for statistical 
analysis and scientific reporting) 
and with COPD Foundation study 
team study coordinator access to 
aid in contacting participants at 
the 12-month follow-up. 
COPD Foundation will have access to 
participant contact information from a 
separate database in order to contact 
participants for follow-up questionnaire 
completion 
Section 11.1.2 
Practice Based 
Research 
Networks (PBRN) 
47 
Administrative 
Moved Roles and Responsibilities 
to section 11.1.2 
Moved Roles and Responsibilities to section 
11.1.2 
Section 11.1.2 
Practice Based 
Research 
Networks (PBRN) 
47 
Revision 
Change Carolinas HealthCare 
System to Atrium Health and add 
new PI for Oregon Rural Practice- 
Based Research Network 
Carolinas HealthCare System is now Atrium 
Health and the new PI at Oregon, Dr. Lyle 
Fagnan is retiring and Dr. Nancy Elder will 
take his place as director and site PI for 
CAPTURE 
Section 11.1.7 
Clinical 
Coordinating 
Center 
49 
Clarification 
Update titles for COPD Foundation 
study members 
Administrative change to include titles for 
Dr. Yawn 
Section 11.1.8 12 
Month Survey 
Coordinating 
Center 
50 
New 
Add 12 Month Survey 
Coordinating Center to Study 
Leadership, Section 11. 
The COPD Foundation study team will be 
coordinating outreach to 12 month follow- 
up subjects and administering surveys 
Section 11.2 
Organizational 
Structure 
51 
Clarification 
Includes 1 representative of the 
COPD Foundation in the Executive 
Committee Organization 
description. 
COPD Foundation representatives are part 
of the Executive Committee currently 
Section 4.1 
Overall Study 
Design 
9, 10, 21 
New 
Deletion of CAT Score ≥ 10 and 
CAPTURE Score ≥ 2 and return to 
CAPTURE+ and abnormal 
spirometry as longitudinal follow- 
up criteria 
The study team proposes to defer 
longitudinal follow-up based solely on an 
isolated, baseline CAT or CAPTURE scores 
as it is outside the scope of the current 
CAPTURE program. The study team is also 
proposing to return to the original scientific 
approach to follow CAPTURE+ (as defined 
in the protocol) subjects along with 
abnormal post-BD spirometry and 5% 

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random sample of those subjects that meet 
neither of these criteria. Those subjects 
already selected under the current 
algorithm would still be followed 
longitudinally (and noted as selected under 
the initial follow-up selection criteria) and 
would use data as appropriate. 
Importantly, the primary care clinician 
colleagues within the CAPTURE program do 
not feel there is a safety issue in not 
following this population as there are no 
data defining a negative impact of an 
isolated, elevated CAT score in primary 
care patients. 
Section 1.1 
Synopsis, Section 
4.1 Overall Study 
Design, Section 
8.1 Baseline 
Assessments and 
Data Collection 
3, 20, 29 
New 
Addition of adjudication of the 
presence of obstruction on post- 
bronchodilator spirometry 
As the study commenced, several instances 
of the faulty spirometry software reading 
incomplete or participant refusal of post- 
bronchodilator occurred and led to the 
need for spirometry core to determine 
review process in these instances and 
validity of pre-bronchodilator spirometry. 
The rationale for this is that in other 
databases where all patients had both pre 
and post-bronchodilator spirometry, those 
who had a pre-bronchodilator FEV1/FVC 
less than 0.65 had a post-bronchodilator 
FEV1/FVC less than 0.70 more than 95% of 
the time. 
8.1 Baseline 
Assessments and 
Data Collection 
28 
New 
Addition of spirometry instructions 
if participant has taken a medicine 
they breathed into lungs from 
puffer or inhaler within two hours 
of spirometry test 
Since study start, one participant reported 
taking albuterol shortly before the visit. 
The study clinicians confirmed this scenario 
would constitute the participant being in a 
post-bronchodilator state already with no 
further need to proceed after initial 
spirometry. The data collection process 
has been updated to assure these values 
would be placed in post-bronchodilator 
data. Coordinators are instructed to ask 
this question before spirometry should this 
scenario occur again during the study. 
Protocol Amendment 3.0 - Summary of Changes 
Location 
Page 
Number 
Type of 
Change 
Description 
Rationale 
Cover Page 
--- 
Administrative 
Update Protocol Version to 3.0 
and update version date to 24 
September 2019 
Amendment version and date updated 
Cover Page 
--- 
Administrative 
Add NCT # for each AIM 
Add all 3 numbers to protocol since each 
AIM is registered in clinicaltrials.gov 
Multiple Sections 
Multiple 
Revision 
Number of PBRNs participating in 
aims 1 and 2 revised to 6 PBRNs 
throughout protocol. 
Additional PBRN added 
1.2 Schema Table 
1 
9 
Revision 
CAPTURE 12 additional items 
questionnaire 
The CAPTURE 12 item additional 
questionnaire was renamed. 
Section 8.1 
Baseline 
30 
Clarification 
CAPTURE Additional Items 
Questionnaire administration 
Further instruction for administration of 
CAPTURE Additional Items Questionnaire, 

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Assessments and 
Data Collection 
instruction added to Study 
Assessments. 
as described in Section 1.2 Schema table, 
was added. 
Section 11.1.2 
Practice Based 
Research 
Networks (PBRN) 
48 
Revision 
University of Illinois, Chicago 
added as a participating PBRN. 
University of Illinois, Chicago added as an 
enrolling site in aims 1 and 3. 
Protocol Amendment 4.0 - Summary of Changes 
Location 
Page 
Number 
Type of 
Change 
Description 
Rationale 
Protocol 
Amendment 
Summary of 
Changes Table 
--- 
Administrative 
Protocol Amendment 2.0 – 
Summary of Changes was added to 
the Summary of Protocol 
Amendments Table. 
Amendment 2.0 – Summary of Changes 
was added to provide a comprehensive list 
of changes across all protocol 
amendments. 
Protocol Amendment 5.0 - Summary of Changes 
Location 
Page 
Number 
Type of 
Change 
Description 
Rationale 
1.2 Schema Table 
1, 8.2 
Longitudinal 
follow-up 
assessment 
9, 32 
New 
A COVID-19 questionnaire was 
added to the 12-month follow-up 
visit, performed by the COPD 
Foundation. 
A COVID-19 questionnaire was added to 
collect information about the COVID-19 
prevalence in primary care, impact on 
symptoms, relation to comorbidities, and 
impact on provider outcomes. 
2.1 Study 
Rationale, 4.1 
Overall Design, 
4.2 Scientific 
Rationale for 
Study Design 
11, 22, 
23 
New 
Rationale for collecting COVID-19 
information from participants was 
added. 
The impact of COVID-19 on COPD Case 
Finding and respiratory symptoms in 
primary care is unknown. COVID-19 
information will be used to investigate this. 
4.1 Overall Study 
Design 
21 
Revision 
The following change was made: 
Participants who meet the criteria 
for follow-up will be sent 
notification/reminder letters 
within the first 3 weeks of  shortly 
after enrollment and receive at 3, 
6, and 9 months 
Language was updated for flexibility in 
notification of participants in order to allow 
time to confirm follow-up criteria. 
8.1 Baseline 
Assessments and 
Data Collection 
29 
Revision 
Additional guidance for sites to 
follow their local institutional 
guidelines for spirometry was 
added. 
Institutional guidance for minimizing the 
risk of COVID-19 spread during spirometry 
varies across sites. Sites should ensure they 
are following local guidance. 
8.3 Aim 2 
Assessments 
34 
Revision 
Participants will receive a $15 gift 
card for completion of the opinion 
survey, instead of $10. 
This was a typo in the prior version of the 
protocol. 
8.2 Longitudinal 
follow-up 
assessment 
31 
New 
Extraction of data related to 
COVID-19 confirmed and 
suspected cases will be added to 
the 12 month medical record 
review. 
A COVID-19 questionnaire was added to 
collect information about the COVID-19 
prevalence in primary care, impact on 
symptoms, relation to comorbidities, and 
impact on provider outcomes. 
Protocol 
Amendment 
Summary of 
Changes Table 
--- 
Administrative 
Protocol Amendment 2.0 – 
Summary of Changes was added to 
the Summary of Protocol 
Amendments Table. 
Summary of Changes for protocol versions 
2.0 and 3.0 –were added to Section 14 to 
provide a comprehensive list of changes 
across all protocol amendments. 
Protocol Amendment 6.0 - Summary of Changes 
Location 
Page 
Number 
Type of Change 
Description 
Rationale 

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Cover page 
--- 
Administrative 
Update Protocol Version to 6.0 and 
update version date to 10 JAN 2022 
Amendment version and date 
1.1 Synopsis 
Definitions 
3 
Revision 
Language related to normal PEF has 
been changed to greater than or 
equal to the measurement ranges 
for males and females. 
“…defined as >350 L/min for males and 
> 250 L/min for females” 
The previous sentence stated that the PEF 
scores needed to be greater to 350 L/min or 
250 L/min and not inclusive of these values.  
1.1 Synopsis 
Definitions 
3 
Revision 
Language related to exacerbations 
been changed to greater than or 
equal 1.  
“> 1 exacerbation-like event within the 
past 12 months.” 
The previous sentence stated that the 
number of exacerbations need to be greater 
than 1 but was not inclusive of 1. The new 
statement is to clarify that clinically 
significant COPD includes 1 or more 
exacerbations. 
1.1 Study 
Population 
6 
Revision  
The overall N has been changed to 
approximately 5000.  
(total N =~ 5000) 
The DSMB approved the reduction of 
enrollment from 5000 but the study will aim 
to enroll as many participants as possible. 
This has been reflected throughout the 
document.  
2.1 Study Rationale 11 
Revision  
We will conduct a 5,000 participant 
cohort study of approximately 5,000 
participants  
The DSMB approved the reduction of 
enrollment from 5000 but the study will 
aim to enroll as many participants as 
possible. This has been reflected 
throughout the document.  
2.2 Background  
13 
Revision  
Language related to exacerbations 
been changed to greater than or 
equal 1.  
“…COPD with > 1 ECOPD” 
The previous sentence stated that the 
number of exacerbations need to be 
greater than 1 but was not inclusive of 1. 
The new statement is to clarify that 
clinically significant COPD includes 1 or 
more exacerbations. 
4.1 Overall Design 20 
Revision  
Language related to normal PEF has 
been changed to greater than or 
equal to the measurement ranges 
for females. 
“>250 L/min for females” 
The previous sentence stated that the PEF 
scores needed to be greater to 350 L/min 
or 250 L/min and not inclusive of these 
values. Participants with PEF values 
greater than or equal to 350 L/min (males) 
or 250 L/min (females) are CAPTURE 
Negative.  
4.1 Overall Design 20 
Revision  
Language related to exacerbations 
been changed to greater than or 
equal 1.  
“…> 1 exacerbation like event within 
the past 12 months.” 
The previous sentence stated that the 
number of exacerbations need to be 
greater than 1 but was not inclusive of 1. 
The new statement is to clarify that 
clinically significant COPD includes 1 or 
more exacerbations. 
9.1.1.1 Sensitivity 
and Specificity of 
the CAPTURE Tool 
39 
Revision 
Language related to exacerbations 
been changed to greater than or 
equal 1.  
“... either >1 exacerbation-like 
event (ECOPD) within the past 12 
months” 
The previous sentence stated that the 
number of exacerbations need to be 
greater than 1 but was not inclusive of 1. 
The new statement is to clarify that 
clinically significant COPD includes 1 or 
more exacerbations. 
9.1.1.3  
Sensitivity and 
Specificity of the 
CAPTURE Tool 
41 
Revision  
 
“(for a total of approximately 5,000 
patients).” 
The DSMB approved the reduction of 
enrollment from 5000 but the study will aim 
to enroll as many participants as possible. 
This has been reflected throughout the 
document.  

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9.2 
Population 
for Analyses  
42 
Revision 
Language related to exacerbations 
been changed to greater than or 
equal 1. 
“…>1 exacerbation-like event 
(ECOPD)” 
The previous sentence stated that the 
number of exacerbations need to be greater 
than 1 but was not inclusive of 1. The new 
statement is to clarify that clinically 
significant COPD includes 1 or more 
exacerbations. 
Protocol Amendment 7.0 - Summary of Changes 
Location 
Page 
Number 
Type of Change 
Description 
Rationale 
Cover page 
--- 
Administrative 
Update Protocol Version to 7.0 and 
update version date to 25JUN2023 
Amendment version and date 
Abbreviations 
2 
Administrative 
PRISm- Preserved ratio, impaired 
spirometry  
SNO- Symptomatic non-obstructed 
2 new abbreviations have been added to this 
table.  
1.1 Synopsis 
3 
Addition 
Definitions: 
Preserved ratio, impaired spirometry 
(PRISm) = Participants without 
spirometrically defined COPD who 
have post-bronchodilator FEV1 < 80% 
predicted. 
• Symptomatic non-obstructed (SNO) = 
Participants without spirometrically 
defined COPD and without PRISm who 
have a COPD Assessment Test score ≥ 
10. 
2 new Definitions have been added to define 
the following terms: 
PRISm- Preser4ved ratio, impaired spirometry 
SNO- Symptomatic non-obstructed 
1.1 Synopsis 
4 
Edit 
Objectives: 
• Aim 3 – Define the impact of 
CAPTURE information provided to 
clinicians in identifying and managing 
CAPTURE+ patients with respiratory 
symptoms (CAPTURE+) across a broad 
range of primary care settings. 
Under Objectives, Aim3 has been edited to 
properly describe CAPTURE+ patients 
1.1 Synopsis 
5 
Clarification 
Objectives: 
• Aim 3 - 
• Define the impact of providing 
CAPTURE clinician education, and 
patient- level CAPTURE information to 
clinicians (“CAPTURE education”) on 
selected clinician additional 
therapeutic interventions in previously 
undiagnosed patients with clinically 
significant COPD for the management 
of CAPTURE+ patients. 
• Assess the impact of CAPTURE 
education and patient-level CAPTURE 
information on clinician interventions 
specific to smokers who are 
CAPTURE+. 
• Determine the impact of CAPTURE 
education and patient-level CAPTURE 
information on patient symptoms, 
exacerbations, hospitalizations, and 
This amendment clarifies Aim 3 and the 
analyses that are being conducted.  

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mortality among CAPTURE+ patients. 
• Determine the impact of CAPTURE 
education on patient symptoms, 
exacerbations, hospitalizations, and 
mortality. 
• Determine the impact of CAPTURE 
education and receipt of patient-level 
CAPTURE information on when COPD is 
defined spirometrically identification 
and management of patients with 
respiratory burden. 
1.1 Synopsis 
6 
Addition 
Endpoints: 
• Aim 3 – 
O Proportion of CAPTURE+ participants 
who meet at least one of the following 
within 12 months of study baseline 
(composite endpoint): 1) 
referral for or completion of clinical 
spirometry testing, 2) new diagnosis of 
COPD, 3) newly prescribed respiratory 
medication (long acting bronchodilator 
or anti-inflammatory for respiratory 
condition), or 4) referral to a specialist 
for respiratory evaluation/treatment, 
or 5) referral for or completion of 
pulmonary rehabilitation. 
Aim 3 Endpoints now includes the analysis of 
referral or completion of pulmonary rehab at 
the 12 month follow up.  
1.1 Synopsis 
6,7 
Clarification  
Secondary Endpoints 
• Aim 3 – 
Proportion of CAPTURE+ participants 
who have each of the following occur 
within 12 months of study baseline 
(separate endpoints to be evaluated 
individually): 1-5) each component of 
the Aim 3 primary endpoint, and 6) 
recommendation or administration of 
influenza vaccination. patients who 
meet the components of the 
composite endpoint. 
o 
Proportion of patients with 
clinically significant COPD who meet 
the 
o 
composite endpoint. 
O Proportion of CAPTURE+ participants 
currently smoking at the baseline study 
visit who have any of the components 
of the Aim 3 primary endpoint or any 
of the following occur within 12 
months of baseline (evaluated as a 
composite endpoint and as individual 
endpoints): 1) clinician counseling or 
recommendation for smoking 
cessation, 2) referral to a smoking 
cessation program, 3) referral to a 
smoking quit line, and 4) newly 
prescribed medication for smoking 
cessation. In participants with clinically 
significant COPD who are current 
smokers, the incidence of physician 
referral to a formal smoking cessation 
program, prescribed smoking cessation 
medication, and referral to pulmonary 
Clarification of the secondary endpoints and 
what participants will be analyzed.  

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rehabilitation program. 
O In CAPTURE+ participants, change in 
CAT score between baseline and 
follow-up at 12 months after baseline, 
and proportion of patients who 
experience exacerbations, 
hospitalizations, or mortality within 12 
months of baseline. In participants 
with clinically significant COPD, change 
in CAT score, and proportion of 
patients who experience 
exacerbations, hospitalizations, or 
mortality. 
O All of the above endpoints for Aim 3, 
in the population of participants 
defined by each of the following 
instead of CAPTURE+ status: 1) 
clinically significant COPD, 2) 
spirometric COPD, 3) preserved ratio, 
impaired spirometry (PRISm), and 5) 
symptomatic non-obstructed (SNO) All 
of the above endpoints for Aim 3, with 
the patient population defined as 
those who have COPD defined 
spirometrically. 
O All of the above endpoints for Aim 3, 
in all of the analysis populations 
named above, separated into cohorts 
based on enrollment date and the 
degree to which follow-up may have 
been affected by the SARS-CoV-2 
pandemic. 
1.3 Schedule of 
Assessments 
11 
Edit 
Footnote 3: 
3. Recorded for a subset of participants 
who meet any of the following criteria: 
1) CAPTURE+ subjects defined as 
CAPTURE Score > 5 or CAPTURE score 
of 2, 3, or 4 with a low PEF, defined as 
<350 L/min for males and <250 L/min 
for females 2) abnormal spirometry 
defined as post-bronchodilator 
FEV1/FVC < 0.70 or FEV1 < 80% 
predicted at baseline, or pre-
bronchodilator FEV1/FVC < 0.65 or 
FEV1 < 70% predicted for patients who 
do not complete post-bronchodilator 
spirometry; 
The footnote was edited to include more 
information regarding the spirometry testing 
and what is defined as abnormal.  
3.0 Objectives and 
Endpoints 
18 
Edit 
Aim 3 Objectives and Endpoints have 
been updated to reflect changes 
throughout the study. Aim 3 changes 
for Objectives, Endpoints, and 
Justifications have been made in this 
table  
The Aim 3 clarifications noted above, are 
reflected in the edits of this table.  
4.1 Overall Design 24 
Addition 
PRISm and SNO have been added to 
the Cohort Table.  
PRISm- Participants without 
spirometrically defined COPD who 
have post-bronchodilator FEV1 < 80% 
PRISm and SNO Cohorts have been added to 
reflect the changes in the protocol.  

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predicted. 
SNO- Participants without 
spirometrically defined COPD and 
without PRISm who have a COPD 
Assessment Test score ≥ 10. 
4.1 Overall Design 24 
Clarification 
Longitudinal Follow Up 
2. Participants who have abnormal 
spirometry results, defined as post-
bronchodilator FEV1/FVC < 
0.7 or FEV1 < 80% predicted at 
baseline. If a participant is unable to 
complete a post- bronchodilator 
spirometry (refusal, technical error on 
the part of coordinator, etc.), and the 
pre- bronchodilator FEV1/FVC is less 
than 0.65 or FEV1 is less than 70% 
predicted, the participant will be 
considered to have COPD abnormal 
spirometry for the purpose of follow-
up in this study. 
This clarifies what constitutes as an Abnormal 
Spirometry in CAPTURE which would lead to a 
follow up 12 months after the initial visit.  
8.2 Longitudinal 
Follow-Up 
Assessments and 
Data Collection 
34 
Addition  
Medical Record Data Collection  
Current Smokers Only: 
New prescription for smoking 
cessation medication 
Referral to a smoking quit line 
Medical record review will now collect data 
about new prescriptions for smoking 
cessation medication and referrals to a 
smoking quit line for current smokers.  
8.2 Longitudinal 
Follow-Up 
Assessments and 
Data Collection 
35 
Addition  
Data Collection by the COPD 
Foundation 
Current Smokers Only: 
Smoking cessation counseling Referral 
to a smoking cessation program 
Smoking cessation medications 
(including OTC) Referral to a smoking 
quit line 
New prescription for smoking 
cessation medication 
Over-the-counter patches/gum for 
smoking cessation 
All participants undergoing 12-month 
follow-up as described in section 4.1: 
Spirometry referral/completion 
Deleted * and footnote for * 
Data collected by the COPD Foundation will 
now include information referrals to a 
smoking cessation program and a smoking 
quit line as well as medications, including 
over the counter medications, for current 
smokers. 
9.1.1.3 Practice 
Behavior in Sites 
With Versus 
Without Capture 
Education and 
Patient Level 
43 
Clarification  
From medical record review and 
follow-up patient survey responses, 
the composite endpoint is met if one 
of the following is recorded: (1) 
referral for or completion of clinical 
spirometry testing, 2) new clinical 
Clarification about what is collected during 
the medical record review for hypothesis 3 
has been included in this paragraph. The 
addition of referral or completion of 
pulmonary rehab was also included for 
analysis.  

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Capture Data 
Provided 
diagnosis of COPD, 3) newly prescribed 
respiratory medication (long acting 
bronchodilator or anti-inflammatory 
for respiratory condition), or 4) referral 
to a specialist for respiratory 
evaluation/ treatment, or 5) referral 
for or completion of pulmonary 
rehabilitation. 
9.2 Populations for 
Analyses 
Clarification 
Aim 3:  
Populations used in 2-sample 
comparisons of the average proportion 
of CAPTURE+ patients per practice that 
meet the composite endpoint in 
outcomes between the two 
intervention arms will be based on 
randomization group (intent-to-treat 
analysis). 
This change clarifies how the samples will be 
analyzed for Aim 3.  
9.2 Populations for 
Analyses 
45 
Addition 
Aim 3:  
For primary analysis of each Aim 3 
outcome, the analysis population will 
consist of all patients with follow-up 
data for that outcome from both the 
medical record review and the patient 
survey administered by the COPD 
Foundation (section 8.2). 
Secondary analyses will be performed 
using alternative analysis populations, 
including 
1.All patients with outcome data from 
the medical record review, and 
2.All patients selected for follow-up. 
Additional information regarding the primary 
analysis of Aim 3 outcomes is now included in 
this section.  
9.3.2 Practice 
Behavior (Aim 3) 
46 
Clarification 
Additional language regarding how the 
Aim 3 primary endpoint and analysis is 
included in this section.  
9.3.2 Practice 
Behavior (Aim 3) 
46 
Edit 
5) an identity link function so that the 
coefficient parameter corresponding to 
CAPTURE intervention group 
represents a difference in outcome 
probability a logistic link function 
This was edited to provide more information 
about the link function analysis.  
9.3.2 Practice 
Behavior (Aim 3) 
46 
Addition  
For each Aim 3 outcome that is 
collected via both medical record 
review and patient survey, the primary 
analysis will be among patients with 
complete outcome data from both the 
medical record and patient survey. 
Sensitivity analyses will be conducted 
by imputing missing outcome data 
using different assumptions and 
applying the primary analysis method 
to the resulting data sets. Sensitivity 
analyses will include (1) imputation of 
negative responses (i.e., responses 
indicating that the outcome has not 
occurred) for all missing patient survey 
responses, followed by analysis of all 
patients with medical record review 
This paragraph was added to provide 
additional information surrounding the 
analyses of Aim 3.  

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data; (2) imputation of positive 
responses (i.e., responses indicating 
that the outcome has occurred) for all 
missing patient survey responses, 
followed by analysis of all patients with 
medical record review data; and (3) 
multiple imputation of all missing 
outcome data using the observed 
outcomes and covariates, followed by 
analysis of all patients selected for 
follow-up. 
9.3.2 Practice 
Behavior (Aim 3) 
47 
Clarification  
Subject to having sufficient mortality 
events, survival 
This statement clarifies that how the survival 
analysis and mortality events will be 
analyzed.  
9.3.2 Practice 
Behavior (Aim 3) 
47 
Addition 
All additional secondary analyses will 
also be applied to patients with 
clinically significant and spirometrically 
defined COPD, PRISm, and 
symptomatic non-obstruction. 
Secondary analyses include PRISm and SNO 
as reflected throughout the protocol.  
9.3.2 Practice 
Behavior (Aim 3) 
47 
Clarification 
Practices that do not have any clinically 
significant COPD or spirometrically 
defined COPD patients with these 
conditions 
Practices that do not have conditions defined 
in the cohorts will not be used in secondary 
analyses.  
9.3.2 Practice 
Behavior (Aim 3) 
47 
Addition 
Analyses will be repeated in 
populations separated into cohorts 
based on enrollment date and the 
degree to which follow-up may have 
been affected by the SARS-CoV-2 
pandemic. 
There may be additional analyses due to 
SARS-CoV-2 and its effects on follow up data.  

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1. 
Martinez FJ, Mannino D, Leidy NK, Malley KG, Bacci ED, Barr RG, Bowler RP, Han MK, Houfek JF, 
Make B, Meldrum CA, Rennard S, Thomashow B, Walsh J, Yawn BP, High-Risk CSSG. A New Approach for 
Identifying Patients with Undiagnosed Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care 
Med. 2017;195(6):748-56. doi: 10.1164/rccm.201603-0622OC. PubMed PMID: 27783539; PMCID: 
PMC5363964. 
 
2. 
Brown DW, Croft JB, Greenlund KJ, Giles WH. Trends in hospitalization with chronic obstructive 
pulmonary disease-United States, 1990-2005. Copd. 2010;7(1):59-62. doi: 
10.3109/15412550903499548. PubMed PMID: 20214464. 
 
3. 
Centers for Disease Control and Prevention. Deaths from chronic obstructive pulmonary disease 
– United States 2000–2005. Morbidity and Mortality Weekly Report. 2008;57(45):1229-32. 
 
4. 
Kochanek KD, Xu J, Murphy SL, Minino AM, Kung HC. Deaths: final data for 2009. Natl Vital Stat 
Rep. 2011;60(3):1-117. 
 
5. 
Global Burden of Disease Study C. Global, regional, and national incidence, prevalence, and 
years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a 
systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386(9995):743-800. doi: 
10.1016/S0140-6736(15)60692-4. PubMed PMID: 26063472; PMCID: PMC4561509. 
 
6. 
Prince MJ, Wu F, Guo Y, Gutierrez Robledo LM, O'Donnell M, Sullivan R, Yusuf S. The burden of 
disease in older people and implications for health policy and practice. Lancet. 2015;385(9967):549-62. 
doi: 10.1016/S0140-6736(14)61347-7. PubMed PMID: 25468153. 
 
7. 
Martinez CH, Mannino DM, Jaimes FA, Curtis JL, Han MK, Hansel NN, Diaz AA. Undiagnosed 
Obstructive Lung Disease in the United States. Associated Factors and Long-term Mortality. Ann Am 
Thorac Soc. 2015;12(12):1788-95. doi: 10.1513/AnnalsATS.201506-388OC. PubMed PMID: 26524488; 
PMCID: PMC4722830. 
 
8. 
Lindberg A, Jonsson AC, Ronmark E, Lundgren R, Larsson LG, Lundback B. Prevalence of chronic 
obstructive pulmonary disease according to BTS, ERS, GOLD and ATS criteria in relation to doctor's 
diagnosis, symptoms, age, gender, and smoking habits. Respiration; international review of thoracic 
diseases. 2005;72(5):471-9. doi: 10.1159/000087670. PubMed PMID: 16210885. 
 
9. 
Lamprecht B, Soriano JB, Studnicka M, Kaiser B, Vanfleteren LE, Gnatiuc L, Burney P, Miravitlles 
M, Garcia-Rio F, Akbari K, Ancochea J, Menezes AM, Perez-Padilla R, Montes de Oca M, Torres-Duque 
CA, Caballero A, Gonzalez-Garcia M, Buist S, Bold Collaborative Research Group tEPISTtPT, the PSG, 
Team BCRGtE-STtP, the PSG. Determinants of underdiagnosis of COPD in national and international 
surveys. Chest. 2015;148(4):971-85. doi: 10.1378/chest.14-2535. PubMed PMID: 25950276. 
 
10. 
Hill K, Goldstein RS, Guyatt GH, Blouin M, Tan WC, Davis LL, Heels-Ansdell DM, Erak M, Bragaglia 
PJ, Tamari IE, Hodder R, Stanbrook MB. Prevalence and underdiagnosis of chronic obstructive pulmonary 
disease among patients at risk in primary care. CMAJ. 2010;182(7):673-8. doi: 10.1503/cmaj.091784. 
PubMed PMID: 20371646; PMCID: PMC2855915. 
 
11. 
Labonte LE, Tan WC, Li PZ, Mancino P, Aaron SD, Benedetti A, Chapman KR, Cowie R, FitzGerald 
JM, Hernandez P, Maltais F, Marciniuk DD, O'Donnell D, Sin D, Bourbeau J, Canadian Respiratory 
15  LITERATURE REFERENCES 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
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71 
 
 
 
Research N, Can CCRG. Undiagnosed Chronic Obstructive Pulmonary Disease Contributes to the Burden 
of Health Care Use. Data from the CanCOLD Study. Am J Respir Crit Care Med. 2016;194(3):285-98. doi: 
10.1164/rccm.201509-1795OC. PubMed PMID: 26836958. 
 
12. 
Guiguis-Blake J, Senger C, Webber E, Mularski R, Whitlock E. Screening for Chronic Obstructive 
Pulmonary Disease: A Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence 
Synthesis No. 130. Publication No. 14-0525-EF-1. Rockville, MD: Agency for Healthcare Research and 
Quality; 2015. 
 
13. 
Martinez FJ, O'Connor GT. Screening, Case-Finding, and Outcomes for Adults With Unrecognized 
COPD. JAMA. 2016;315(13):1343-4. doi: 10.1001/jama.2016.3274. PubMed PMID: 27046363. 
 
14. 
Joo MJ, Sharp LK, Au DH, Lee TA, Fitzgibbon ML. Use of spirometry in the diagnosis of COPD: a 
qualitative study in primary care. Copd. 2013;10(4):444-9. doi: 10.3109/15412555.2013.766683. 
PubMed PMID: 23537230; PMCID: PMC3938329. 
 
15. 
Ferguson GT, Enright PL, Buist AS, Higgins MW. Office spirometry for lung health assessment in 
adults: A consensus statement from the National Lung Health Education Program. Chest. 
2000;117(4):1146-61. doi: 10.1378/chest.117.4.1146 PubMed PMID: 10767253. 
 
16. 
Han MK, Kim MG, Mardon R, Renner P, Sullivan S, Diette GB, Martinez FJ. Spirometry utilization 
for COPD: how do we measure up? Chest. 2007;132(2):403-9. doi: 10.1378/chest.06-2846. PubMed 
PMID: 17550936. 
 
17. 
Joo MJ, Lee TA, Weiss KB. Geographic variation of spirometry use in newly diagnosed COPD. 
Chest. 2008;134(1):38-45. doi: 10.1378/chest.08-0013. PubMed PMID: 18347201. 
 
18. 
Volkova NB, Kodani A, Hilario D, Munyaradzi SM, Peterson MW. Spirometry utilization after 
hospitalization for patients with chronic obstructive pulmonary disease exacerbations. Am J Med Qual. 
2009;24(1):61-6. doi: 10.1177/1062860608326417. PubMed PMID: 19139465. 
 
19. 
Nishi SP, Wang Y, Kuo YF, Goodwin JS, Sharma G. Spirometry use among older adults with 
chronic obstructive pulmonary disease: 1999-2008. Ann Am Thorac Soc. 2013;10(6):565-73. doi: 
10.1513/AnnalsATS.201302-037OC. PubMed PMID: 24053440; PMCID: PMC3960963. 
 
20. 
Buist AS, McBurnie MA, Vollmer WM, Gillespie S, Burney P, Mannino DM, Menezes AM, Sullivan 
SD, Lee TA, Weiss KB, Jensen RL, Marks GB, Gulsvik A, Nizankowska-Mogilnicka E, Bold Collaborative 
Research Group. International variation in the prevalence of COPD (the BOLD Study): a population-based 
prevalence study. Lancet. 2007;370(9589):741-50. doi: 10.1016/S0140-6736(07)61377-4. PubMed PMID: 
17765523. 
 
21. 
Freeman D, Nordyke RJ, Isonaka S, Nonikov DV, Maroni JM, Price D, Halbert RJ. Questions for 
COPD diagnostic screening in a primary care setting. Respiratory medicine. 2005;99(10):1311-8. doi: 
10.1016/j.rmed.2005.02.037. PubMed PMID: 16140231. 
 
22. 
Enright PL. Should we keep pushing for a spirometer in every doctor's office? Respir Care. 
2012;57(1):146-51;discussion 51-3. doi: 10.4187/respcare.01504. PubMed PMID: 22222133. 
 
23. 
Murphy DE, Panos RJ. Diagnosis of COPD and clinical course in patients with unrecognized 
airflow limitation. International journal of chronic obstructive pulmonary disease. 2013;8:199-208. doi: 
10.2147/COPD.S39555. PubMed PMID: 23637527; PMCID: PMC3634319. 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017 
72 
 
 
 
24. 
Miravitlles M, Soriano J, Garcia-Rio F, Munoz L, Duran-Tauleria E, Sanchez G, Sobradillo V, 
Ancochea J. Prevalence of COPD in Spain: impact of undiagnosed COPD on quality of life and daily life 
activities. Thorax. 2009;64:863-8. 
 
25. 
Mapel DW, Robinson SB, Dastani HB, Shah H, Phillips AL, Lydick E. The direct medical costs of 
undiagnosed chronic obstructive pulmonary disease. Value Health. 2008;11(4):628-36. doi: 
10.1111/j.1524-4733.2007.00305.x. PubMed PMID: 18194402. 
 
26. 
Akazawa M, Halpern R, Riedel AA, Stanford RH, Dalal A, Blanchette CM. Economic burden prior 
to COPD diagnosis: a matched case-control study in the United States. Respiratory medicine. 
2008;102(12):1744-52. doi: 10.1016/j.rmed.2008.07.009. PubMed PMID: 18760581. 
 
27. 
Qaseem A, Snow V, Shekelle P, Sherif K, Wilt TJ, Weinberger S, Owens DK, Clinical Efficacy 
Assessment Subcommittee of the American College of Physicians. Diagnosis and management of stable 
chronic obstructive pulmonary disease: a clinical practice guideline from the American College of 
Physicians. Annals of internal medicine. 2007;147(9):633-8. PubMed PMID: 17975186. 
 
28. 
Criner GJ, Bourbeau J, Diekemper RL, Ouellette DR, Goodridge D, Hernandez P, Curren K, Balter 
MS, Bhutani M, Camp PG, Celli BR, Dechman G, Dransfield MT, Fiel SB, Foreman MG, Hanania NA, 
Ireland BK, Marchetti N, Marciniuk DD, Mularski RA, Ornelas J, Road JD, Stickland MK. Executive 
summary: prevention of acute exacerbation of COPD: American College of Chest Physicians and 
Canadian Thoracic Society Guideline. Chest. 2015;147(4):883-93. doi: 10.1378/chest.14-1677. PubMed 
PMID: 25320966; PMCID: PMC4388123. 
 
29. 
Rennard SI, Drummond MB. Early chronic obstructive pulmonary disease: definition, 
assessment, and prevention. Lancet. 2015;385(9979):1778-88. doi: 10.1016/S0140-6736(15)60647-X. 
PubMed PMID: 25943942; PMCID: 4819246. 
 
30. 
Decramer M, Miravitlles M, Price D, Roman-Rodriguez M, Llor C, Welte T, Buhl R, Dusser D, 
Samara K, Siafakas N. New horizons in early stage COPD--improving knowledge, detection and 
treatment. Respiratory medicine. 2011;105(11):1576-87. doi: 10.1016/j.rmed.2010.12.015. PubMed 
PMID: 21239156. 
 
31. 
Calverley PM, Nordyke RJ, Halbert RJ, Isonaka S, Nonikov D. Development of a population-based 
screening questionnaire for COPD. Copd. 2005;2(2):225-32. PubMed PMID: 17136949. 
 
32. 
van Schayck CP, Halbert RJ, Nordyke RJ, Isonaka S, Maroni J, Nonikov D. Comparison of existing 
symptom-based questionnaires for identifying COPD in the general practice setting. Respirology. 
2005;10(3):323-33. doi: 10.1111/j.1440-1843.2005.00720.x. PubMed PMID: 15955145. 
 
33. 
Yawn BP, Mapel DW, Mannino DM, Martinez FJ, Donohue JF, Hanania NA, Kosinski M, Rendas- 
Baum R, Mintz M, Samuels S, Dalal AA, Lung Function Questionnaire Working Group. Development of 
the Lung Function Questionnaire (LFQ) to identify airflow obstruction. International journal of chronic 
obstructive pulmonary disease. 2010;5:1-10. doi: 10.2147/COPD.S7683. PubMed PMID: 20368906; 
PMCID: 2846155. 
 
34. 
Martinez FJ, Raczek AE, Seifer FD, Conoscenti CS, Curtice TG, D'Eletto T, Cote C, Hawkins C, 
Phillips AL, Group C-PCW. Development and initial validation of a self-scored COPD Population Screener 
Questionnaire (COPD-PS). Copd. 2008;5(2):85-95. doi: 10.1080/15412550801940721. PubMed PMID: 
18415807; PMCID: 2430173. 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017 
73 
 
 
 
35. 
Price DB, Tinkelman DG, Halbert RJ, Nordyke RJ, Isonaka S, Nonikov D, Juniper EF, Freeman D, 
Hausen T, Levy ML, Ostrem A, van der Molen T, van Schayck CP. Symptom-based questionnaire for 
identifying COPD in smokers. Respiration; international review of thoracic diseases. 2006;73(3):285-95. 
doi: 10.1159/000090142. PubMed PMID: 16330875. 
 
36. 
Price DB, Tinkelman DG, Nordyke RJ, Isonaka S, Halbert RJ, Group CQS. Scoring system and 
clinical application of COPD diagnostic questionnaires. Chest. 2006;129(6):1531-9. doi: 
10.1378/chest.129.6.1531. PubMed PMID: 16778271. 
 
37. 
Raghavan N, Lam YM, Webb KA, Guenette JA, Amornputtisathaporn N, Raghavan R, Tan WC, 
Bourbeau J, O'Donnell DE. Components of the COPD Assessment Test (CAT) associated with a diagnosis 
of COPD in a random population sample. Copd. 2012;9(2):175-83. doi: 10.3109/15412555.2011.650802. 
PubMed PMID: 22409441. 
 
38. 
Kotz D, Nelemans P, van Schayck CP, Wesseling GJ. External validation of a COPD diagnostic 
questionnaire. The European respiratory journal. 2008;31(2):298-303. doi: 
10.1183/09031936.00074307. PubMed PMID: 17959636. 
 
39. 
Haroon S, Jordan R, Takwoingi Y, Adab P. Diagnostic accuracy of screening tests for COPD: a 
systematic review and meta-analysis. BMJ Open. 2015;5(10):e008133. doi: 10.1136/bmjopen-2015- 
008133. PubMed PMID: 26450427; PMCID: PMC4606431. 
 
40. 
Haroon S, Jordan RE, Fitzmaurice DA, Adab P. Case finding for COPD in primary care: a 
qualitative study of the views of health professionals. International journal of chronic obstructive 
pulmonary disease. 2015;10:1711-8. doi: 10.2147/COPD.S84247. PubMed PMID: 26357469; PMCID: 
PMC4559237. 
 
41. 
Nelson SB, LaVange LM, Nie Y, Walsh JW, Enright PL, Martinez FJ, Mannino DM, Thomashow 
BM. Questionnaires and pocket spirometers provide an alternative approach for COPD screening in the 
general population. Chest. 2012;142(2):358-66. doi: 10.1378/chest.11-1474. PubMed PMID: 22194590. 
 
42. 
Leidy NK, Malley KG, Steenrod AW, Mannino DM, Make BJ, Bowler RP, Thomashow BM, Barr RG, 
Rennard SI, Houfek JF, Yawn BP, Han MK, Meldrum CA, Bacci ED, Walsh JW, Martinez F. Insight into Best 
Variables for COPD Case Identification: A Random Forests Analysis. Chronic Obstr Pulm Dis (Miami). 
2016;3(1):406-18. doi: 10.15326/jcopdf.3.1.2015.0144. PubMed PMID: 26835508; PMCID: PMC4729451. 
 
43. 
Leidy NK, Kim K, Bacci ED, Yawn BP, Mannino DM, Thomashow BM, Barr RG, Rennard SI, Houfek 
JF, Han MK, Meldrum CA, Make BJ, Bowler RP, Steenrod AW, Murray LT, Walsh JW, Martinez F, High- 
Risk CSSG. Identifying cases of undiagnosed, clinically significant COPD in primary care: qualitative 
insight from patients in the target population. NPJ Prim Care Respir Med. 2015;25:15024. doi: 
10.1038/npjpcrm.2015.24. PubMed PMID: 26028486; PMCID: PMC4532157. 
 
44. 
Eremenco SL, Cella D, Arnold BJ. A comprehensive method for the translation and cross-cultural 
validation of health status questionnaires. Eval Health Prof. 2005;28(2):212-32. doi: 
10.1177/0163278705275342. PubMed PMID: 15851774. 
 
45. 
Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, Chen R, 
Decramer M, Fabbri LM, Frith P, Halpin DM, Lopez Varela MV, Nishimura M, Roche N, Rodriguez-Roisin 
R, Sin DD, Singh D, Stockley R, Vestbo J, Wedzicha JA, Agusti A. Global Strategy for the Diagnosis, 
Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017 
74 
 
 
 
Summary. Am J Respir Crit Care Med. 2017;195(5):557-82. doi: 10.1164/rccm.201701-0218PP. PubMed 
PMID: 28128970. 
 
46. 
Johnson K, Tuzzio L, Renz A, Baldwin LM, Parchman M. Decision-to-Implement Worksheet for 
Evidence-based Interventions: From the WWAMI Region Practice and Research Network. J Am Board 
Fam Med. 2016;29(5):553-62. doi: 10.3122/jabfm.2016.05.150327. PubMed PMID: 27613788; PMCID: 
PMC5065058. 
 
47. 
Practice Facilitation Handbook: Module 5. Mapping and Redesigning Workflow.: Agency for 
Healthcare Research and Quality Website.; Updated May 2013 [cited 2018 January 23]. Available from: 
https://www.ahrq.gov/professionals/prevention-chronic-care/improve/system/pfhandbook/mod5.html. 
 
48. 
Onwuegbuzie A, Dickinson W, Leech N, Zoran A. A qualitative framework for collecting ana 
analyzing data in focus group research. Int J Qual Meth. 2009;8(3):1-21. 
 
49. 
Wong SS, Abdullah N, Abdullah A, Liew SM, Ching SM, Khoo EM, Jiwa M, Chia YC. Unmet needs 
of patients with chronic obstructive pulmonary disease (COPD): a qualitative study on patients and 
doctors. BMC Fam Pract. 2014;15:67. doi: 10.1186/1471-2296-15-67. PubMed PMID: 24739595; PMCID: 
PMC3996170. 
 
50. 
Laue J, Melbye H, Halvorsen PA, Andreeva EA, Godycki-Cwirko M, Wollny A, Francis NA, Spigt M, 
Kung K, Risor MB. How do general practitioners implement decision-making regarding COPD patients 
with exacerbations? An international focus group study. International journal of chronic obstructive 
pulmonary disease. 2016;11:3109-19. doi: 10.2147/COPD.S118856. PubMed PMID: 27994450; PMCID: 
PMC5153277. 
 
51. 
Davies F, Risor MB, Melbye H, Spigt M, Brookes-Howell L, O'Neill C, Godycki-Cwirko M, Wollny A, 
Andreeva E, Butler C, Francis N. Primary and secondary care clinicians' views on self-treatment of COPD 
exacerbations: a multinational qualitative study. Patient education and counseling. 2014;96(2):256-63. 
doi: 10.1016/j.pec.2014.05.011. PubMed PMID: 24910421. 
 
52. 
Aggarwal NK, Cedeno K, Guarnaccia P, Kleinman A, Lewis-Fernandez R. The meanings of cultural 
competence in mental health: an exploratory focus group study with patients, clinicians, and 
administrators. Springerplus. 2016;5:384. doi: 10.1186/s40064-016-2037-4. PubMed PMID: 27065092; 
PMCID: PMC4814393. 
 
53. 
Zeitz HJ. Problem based learning: development of a new strategy for effective continuing 
medical education. Allergy Asthma Proc. 1999;20(5):317-21. PubMed PMID: 10566102. 
 
54. 
Onyon C. Problem-based learning: a review of the educational and psychological theory. Clin 
Teach. 2012;9(1):22-6. doi: 10.1111/j.1743-498X.2011.00501.x. PubMed PMID: 22225888. 
 
55. 
Azer SA, Peterson R, Guerrero AP, Edgren G. Twelve tips for constructing problem-based 
learning cases. Med Teach. 2012;34(5):361-7. doi: 10.3109/0142159X.2011.613500. PubMed PMID: 
22452277. 
 
56. 
Idowu Y, Muir E, Easton G. Problem-based learning case writing by students based on early years 
clinical attachments: a focus group evaluation. JRSM Open. 2016;7(3):2054270415622776. doi: 
10.1177/2054270415622776. PubMed PMID: 26981255; PMCID: PMC4776248. 

The CAPTURE Study 
Protocol #: 1R01HL136682 
Version 8.0 
July 17, 2023 
NIH-FDA Clinical Trial Protocol Template – v1.0 7 Apr 2017 
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57. 
Chan ZC. Exploring creativity and critical thinking in traditional and innovative problem-based 
learning groups. J Clin Nurs. 2013;22(15-16):2298-307. doi: 10.1111/jocn.12186. PubMed PMID: 
23452036. 
 
58. 
Case-based Teaching and Problem-based Learning.: Center for Research on Learning and 
Teaching. Available from: http://www.crlt.umich.edu/tstrategies/tscbt. 
59. 
Rubin DB. Multiple Imputation for Nonresponse in Surveys. John Wiley and Sons; 1987.