Clinical trial NCT03137303
Conditions: COPD Asthma
Sponsor: University of Illinois at Chicago
Start date: 2017-07-01; Completion date: 2019-09-30
Enrollment: 402 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the use of spirometry in identifying Diagnostic Error in COPD and Asthma patients.

Detailed description:
Asthma and chronic obstructive pulmonary disease (COPD) are common chronic lung diseases that are diagnosed in more than 30 million adults in the United States. However, diagnostic error (DE), is considered one of the most common and harmful of patient-safety problems by the Institute of Medicine, occur frequently with asthma and/or COPD and disproportionately affect minorities and the under-served. DE leads to lost opportunities to identify other chronic conditions, avoidable morbidity and mortality, unnecessary costs to patients and health systems, and poor quality of care. Shortness of breath or dyspnea, which is a common symptom in asthma and COPD, is also common for many other chronic conditions such as cardiovascular disease and obesity. A better understanding of the impact of DE and interventions to improve diagnostic accuracy in asthma and COPD are of particular importance for minorities and the under-served that are disproportionately affected by conditions leading to dyspnea.

Spirometry is a simple, mobile, and essential test that is recommended by all major national and international guidelines for the diagnosis of asthma and COPD. However it is well known that spirometry is not routinely used in the ambulatory primary care setting and minorities and the underserved population are less likely to have spirometry leading to greater prevalence of DE. It has been estimated that 30-50% of people with an existing diagnosis of asthma and COPD were found to be misdiagnosed. Many of these patients misdiagnosed with asthma and/or COPD receive unnecessary respiratory pharmacotherapy which can pose serious risks including pneumonia, cardiovascular events, and mortality. In the setting of DE, these are considered avoidable and unnecessary respiratory pharmacotherapy use in minorities and the underserved that are already disproportionately affected by cardiovascular disease increases the risk of poorer outcomes. There is also DE in the diagnosis of asthma versus COPD, as these are both clinically distinct respiratory disorders with nuances in treatment recommendations. It is reported that African-Americans are considered to have increasing COPD mortality and are disproportionately affected by asthma death rates. However, as spirometry is not routinely performed and DE is prevalent in asthma and COPD, a component of these poor outcomes may be attributable to missed or delayed diagnoses of other chronic conditions or misdiagnosis within asthma and COPD.

Barriers to the use of spirometry in primary care exist at provider and health systems levels. Previous studies show that primary care providers (PCPs) lack knowledge in existing guidelines and in implementing spirometry into primary care clinics. Beyond these barriers, PCPs struggle with logistical challenges such as time and workflow constraints with clinic visits lasting 15 minutes or less in patients with multiple chronic medical conditions. These predisposing and enabling factors explain why prior studies that included interventions to educate PCPs and incorporate spirometry by training personnel in primary care clinics have had limited results.

A new paradigm to improve guideline based care for asthma and COPD which includes spirometry is needed and can lead to a better understanding of DE and improved patient safety and patient-centered outcomes. Health Promoters or Community health workers (CHWs) have been supplementing medical care by disseminating appropriate health care practices for underserved minority populations. However, studies which include diagnostic evaluations with spirometry for asthma and COPD have not been performed. The REDEFINE program (Reducing Diagnostic Error to Improve PatieNt SafEty in COPD and Asthma) will incorporate health promoters working collaboratively with PCPs to address identified barriers to guideline based care which includes spirometry for the diagnosis of asthma and COPD for patients at risk for DE. We propose a comparative effectiveness study to better understand the epidemiology of DE and to evaluate the effectiveness and economic impact of providing the REDEFINE program to an underserved, predominantly minority population with a diagnosis of asthma and/or COPD at risk for DE.

Arms: arm 1: On the day of the outpatient visit, subjects will be advised to arrive 90 minutes prior to their clinic visit. The following will be performed.

1. Subject demographic and contact information
2. Co-morbid conditions
3. Smoking history
4. Medication history from patient and also from pharmacy used by subjects
5. A respiratory exacerbation history in the past year
6. Modified Medical Research Counsel (mMRC) dyspnea scale
7. Quality of life measures

Subjects will be advised to go to their clinics and be managed by their PCP thereafter.

At the end of the 1 year followup, the patient will be scheduled for a pre and post BD spirometry and undergo the same spirometry protocol as the intervention group. arm 2: On the day of the outpatient visit, subjects will be advised to arrive 90 minutes prior to their clinic visit in the same building as the clinic site. The following information will be collected and procedures will be performed:

1. Subject demographic and contact information
2. Co-morbid conditions
3. Smoking history
4. Medication history from patient and also from pharmacy used by subjects
5. A respiratory exacerbation history in the past year
6. Modified Medical Research Counsel (mMRC) dyspnea scale
7. Quality of life measures
8. Pre and post-bronchodilator using Albuterol (BD) spirometry
Interventions: intervention 1: Spirometry at initial visit intervention 2: Albuterol intervention 3: Spirometry at 12-month follow-up
Intervention descriptions: intervention 1: Initial visit for the intervention group, an initial demographics form and health questionnaires. To evaluate the breathing, a pre and post broncho dilator will be performed as well as a spirometry test. intervention 2: The post broncho dilator spirometry test will be preformed after a breathing medication called Albuterol. Albuterol is used in standard practice for COPD and is commonly used during spirometry. intervention 3: At the end of the 1 year followup, the patient will be scheduled for a pre and post BD spirometry test and undergo the same spirometry protocol as the intervention group.

Protocol documents:
Prot_SAP_000.pdf: 
Page 1 of 13 
 
RESEARCH PROTOCOL 
 
 
Reducing Diagnostic Error to Improve Patient Safety in COPD and Asthma 
(REDEFINE Study) 
 
 
Version: 1.5 
Date:  1/11/2018 
 
Principal Investigator:  Min Joo MD MPH 
Division of Pulmonary, Critical Care, Sleep, and Allergy, Department of Medicine,  
University of Illinois at Chicago, Chicago, IL  
 
Sponsor: AHRQ 1R01HS024964-01   
 
 
SPECIFIC AIMS AND HYPOTHESIS 
  
Aim 1:  Determine the prevalence of and characteristics associated with diagnostic 
error (DE) in asthma and/or COPD in an underserved population 
Aim 2: Evaluate the effectiveness of the REDEFINE program compared to usual care 
on health care utilization and patient-centered outcomes (including respiratory 
medication use, all-cause emergency room visits, and all-cause hospitlizations) 
Hypothesis: 
The REDEFINE program will reduce health care utilization and improve patien-
centered outcomes compared to  usual care. 
Aim 3: Evaluate the cost impact and cost effectiveness of the REDEFINE program 
versus usual care 
Hypothesis: 
The REDEFINE program will be cost-effective in the management of patients 
with COPD and asthma compared to usual care. 
   
 
BACKGROUND AND SIGNIFICANCE 
 
Asthma and chronic obstructive pulmonary disease (COPD) are common chronic 
lung diseases that are diagnosed in more than 30 million adults in the United States.1,2  
However, diagnostic error (DE), considered one of the most common and harmful of 
patient-safety problems by the Institute of Medicine,3,4 occur frequently with asthma 
and/or COPD and disproportionately affect minorities and the underserved. DE leads to 
lost opportunities to identify other chronic conditions, avoidable morbidity and mortality, 
unnecessary costs to patients and health systems, and poor quality of care.3-6  
Shortness of breath or dyspnea, which is a common symptom in asthma and COPD, is 
also common for many other chronic conditions such as cardiovascular disease and 
obesity.  A better understanding of the impact of DE and interventions to improve 
diagnostic accuracy in asthma and COPD are of particular importance for minorities and 
the underserved that are disproportionately affected by conditions leading to dyspnea. 
 Spirometry is a simple, mobile, and essential test that is recommended by all 
major national and international guidelines for the diagnosis of asthma and COPD. 7-10  


Page 2 of 13 
 
However it is well known that spirometry is not routinely used in the ambulatory primary 
care setting11-19 and minorities and the underserved population are less likely to have 
spirometry leading to greater prevalence of DE.20-25  It has been estimated that 30-50% 
of people with an existing diagnosis of asthma and COPD were found to be 
misdiagnosed.11,20,21,26-32  Many of these patients misdiagnosed with asthma and/or 
COPD receive unnecessary respiratory pharmacotherapy which can pose serious risks 
including pneumonia, cardiovascular events, and mortality.33-53  In the setting of DE, 
these are considered avoidable and unnecessary respiratory pharmacotherapy use in 
minorities and the underserved that are already disproportionately affected by 
cardiovascular disease54-56 increases the risk of poorer outcomes.  There is also DE in 
the diagnosis of asthma versus COPD, as these are both clinically distinct respiratory 
disorders with nuances in treatment recommendations.  It is reported that African-
Americans are considered to have increasing COPD mortality and are 
disproportionately affected by asthma death rates.57-60  However, as spirometry is not 
routinely performed and DE is prevalent in asthma and COPD, a component of these 
poor outcomes may be attributable to missed or delayed diagnoses of other chronic 
conditions or misdiagnosis within asthma and COPD. 
Barriers to the use of spirometry in primary care exist at provider and health 
systems levels.  Previous studies show that primary care providers (PCPs) lack 
knowledge in existing guidelines and in implementing spirometry into primary care 
clinics.11,18,61-64 Beyond these barriers, PCPs struggle with logistical challenges such as 
time and workflow constraints with clinic visits lasting 15 minutes or less in patients with 
multiple chronic medical conditions.62,65 These predisposing and enabling factors 
explain why prior studies that included interventions to educate PCPs and incorporate 
spirometry by training personnel in primary care clinics have had limited results.32,63,66-68  
A new paradigm to improve guideline based care for asthma and COPD which 
includes spirometry is needed and can lead to a better understanding of DE and 
improved patient safety and patient-centered outcomes.  Health Promoters or 
Community health workers (CHWs) have been supplementing medical care by 
disseminating appropriate health care practices for underserved minority populations.  
However, studies which include diagnostic evaluations with spirometry for asthma and 
COPD have not been performed.   The REDEFINE program (Reducing Diagnostic Error 
to Improve PatieNt SafEty in COPD and Asthma) will incorporate health promoters 
working collaboratively with PCPs to address identified barriers to guideline based care 
which includes spirometry for the diagnosis of asthma and COPD for patients at risk for 
DE.  We propose a comparative effectiveness study to better understand the 
epidemiology of DE and to evaluate the effectiveness and economic impact of providing 
the REDEFINE program to an underserved, predominantly minority population with a 
diagnosis of asthma and/or COPD at risk for DE. 
  
 
RESEARCH DESIGN AND METHODS 
 
1. RESEARCH DESIGN  
 
This will be a cluster-randomized comparative effectiveness trial conducted of patients 
with a primary care provider (PCP) diagnosis of COPD and/or asthma seen in outpatient 
primary care provider clinics (i.e. Family Medicine, Miles Square Health Center, and 
Academic Internal Medicine) as well as the CRC (Clinical Research Center) at the 
University of Illinois Hospital and General Internal Medicine  and Famly Medicine Clinics 


Page 3 of 13 
 
at Cook County Health and Hospitals Systems (CCHHS).   Providers will be randomized 
and their patients who fulfill the inclusion criteria will receive the intervention or be in the 
usual care group.  Adults with a clinician-diagnosed COPD and/or asthma at high risk 
for diagnostic error due to lack of spirometry will undergo the REDEFINE intervention or 
usual care based on the PCP randomization .  Outcomes will be assessed every 3 
months for up to one year. 
 
 
2. ELIGIBILITY CRITERIA 
 
A.  Primary care provider (PCP) eligibility criteria: 
Primary care providers (PCPs) will include physicians and nurse practitioners.  PCPs 
specializing in internal medicine or family medicine with at least one half day per week 
outpatient clinic session at the following clinics will be eligible for the study: 
• UI Health:  Family  Medicine (FM) clinics, Academic Internal Medicine (AIM) 
clinics 
• Miles Square Health Center (MSHC) 
• Clinical Research Center (CRC) at UIC 
• Cook County Health and Hospitals Systems (CCHHS):  General Internal 
Medicine (GIM) and Family Medicine 
 
B.  Patient eligibility criteria: 
 
Inclusion criteria: 
1. Age ≥40 years of age 
2. Use of a maintenance respiratory medication and one of the following in the past 
year: 
a. diagnosis of asthma  
b. diagnosis of COPD, emphysema, or chronic bronchitis  
3. No spirometry test performed in the past 3 years 
4. Past or current smoker 
  
Exclusion criteria: 
• Unable to perform adequate spirometry 
• Non-English speaking 
• Pregnancy  
• Plans to move from the Chicago area within the next year 
• Seen by pulmonary or allergy specialist in the past 3 years 
• Any terminal illness with a life expectancy of <6 months  
• Life threatening (e.g. Intensive care admission and/or use of mechanical 
ventilation ) respiratory failure event in the past year  
 
 
3. SUBJECT SELECTION, RECRUITMENT, AND INFORMED CONSENT 
 
PCP Selection, Recruitment, and Informed consent 
 
Primary care providers (PCPs) specializing in internal medicine or family medicine with 
at least one half day per week outpatient clinic will be included in the study.  We 


Page 4 of 13 
 
estimate a total maximum recruitment of 80 eligible PCPs from all sites (approximately 
50 PCPs from UI Health and MSHC sites and approximately 30 PCPs from CCHHS).  
The recruitment will include a combination of paper letter and email invitations with 
endorsement from the clinic directors and other supervisors. A list of eligible PCPs will 
be obtained from each site from the clinic directors.  A research introduction letter will 
be mailed to the qualifying practitioners as well as an email invitation sent to their email 
accounts.  The letter and email will be sent simultaneously to ensure contact and will 
include a short introduction to why the research is being performed and a description of 
participants’ roles in the study.  Also included will be a contact number for those who 
would like to volunteer or who would like additional information.  The letter will include a 
statement that there will be no penalty for not participating.  The letter will also contain a 
postcard with a stamp, where the eligible PCP checks to agree to participate or decline 
to participate. The email will instruct them to reply by email to the same choices.  If a 
response is not received in 2 weeks, a second recruitment letter and email will be sent 
followed by a postcard 2 weeks later. Once a PCP agrees to participate, informed 
consent will be obtained prior to initiation of any study procedures. 
 
Patient Selection, Recruitment, and Informed consent 
 
Approximately 500 patients will be recruited for this study from the FM, AIM, MSHC and 
GIM sites (A total of 250 from UI Health and MSHC sites and a total of 250 from 
CCHHS site).  All sites use the same electronic medical record (EMR) system which is 
Cerner Powerchart.  An Information Systems Specialists (ISS) from UI Health (including 
MSHC) and CCHHS will search the administrative data of their respective sites to 
provide a list of patients meeting the first three of the inclusion criteria listed above and 
are scheduled to be seen in PCP clinics or the CRC (Clinical Research Center at UIC),  
two weeks in the future.  More specifically, using electronic health records, within the 
past 12 months, the following patients will initially be identified:  age ≥ 40 years and 
using at least one maintenance respiratory medication (e.g. long acting beta agonists 
(LABA), long acting anticholinergics (LAA),inhaled corticosteroids (ICS), 
phosphodiesterase-4 inhibitors (PDE-4i), and at least one of the following 1) diagnosis 
of asthma (ICD-9 493.xx or ICD 10 J45.xx), 2) diagnosis of COPD, emphysema, or 
chronic bronchitis (ICD-9 491.xx, 492.xx, 496 or ICD 10 J41.xx, J42.xx, J43.xx, J44.xx). 
.In addition, our ISS will also only include those who have not had a current procedural 
testing (CPT) codes for spirometry (CPT codes:  94010, 94014, 94015, 94016, 94060, 
94070, 94620) or completed order for spirometry testing in the past 3 years.  
 
Medical charts of patients will be reviewed to prescreen for eligibility for the study.  
Participants who meet preliminary eligibility criteria will be mailed a patient recruitment 
letter informing them of the study and our intent to contact them by telephone to 
complete a phone screen approximately one week before the participants’ scheduled 
primary care visit.  The letter will be sent 2 weeks before the planned phone screen and 
will have a phone number to call to opt out of the study.  A patient phone screen is 
conducted to confirm eligibility criteria and the participants’ verbal consent to participate 
in the study is obtained. During the call, we will confirm their scheduled appointment 
date, go over the study, answer any questions, and if the subject agrees, conduct the 
phone screen to verify eligibility criteria.  If eligible, they will be asked to participate in 
the study and if agreeable will be asked to come in 90 minutes before the clinic visit.  
Once a subject agrees to participate, informed consent will be obtained prior to initiation 
of any study procedures.  


Page 5 of 13 
 
 
 
4.  DESCRIPTION OF PROCEDURES 
 
A) PCP Education and Randomization:  
After obtaining PCP informed consent and prior to patient recruitment, a one hour 
educational session will be held for PCPs participating in the study. The purpose 
of this session is to provide education to PCPs about COPD, asthma, spirometry, 
and GOLD and GINA guidelines (GOLD=Global Initiative for Chronic Obstructive 
Lung Disease, GINA=Global Initiative for Asthma). The educational session will 
provide continuing medical education credit to those who attend.  The learning 
objectives will be the following: 1) Review COPD and asthma disease definition, 
presentation, diagnosis and testing including spirometry, 2) be familiar with the 
GOLD and GINA guidelines and recommendations for therapy.   
 
PCPs who consented to participate in the study and completed the education 
session will be randomized to have their patients who meet the study criteria 
receive the intervention or usual care. 
     
B) Patient subject- Intervention:   
On the day of the outpatient visit, subjects will be advised to arrive 90 minutes 
prior to their clinic visit in the same building as the clinic site or the CRC (Clinical 
Research Center at UIC).  The following information will be collected and 
procedures will be performed: 
 
1. Subject demographic and contact information 
2. Co-morbid conditions 
3. Smoking history 
4. Medication history from patient and also from pharmacy used by subjects 
5. A respiratory exacerbation history in the past year  
6. Modified Medical Research Counsel (mMRC) dyspnea scale and  COPD 
Assessment Test 
7. Quality of life measures 
8. Pre and post-bronchodilator (BD) spirometry 
9. De-Escalation Spirometry Screener for patients de-escalating based on 
spirometry (See Based on spirometry findings) 
10. De-Escalation Phone Script  
 
Based on spirometry findings: 
1. If the spirometry findings are consistent with COPD and/or asthma, the 
following will be provided to the provider and patient to have available during 
the clinic visit:  a letter summarizing the interpretation of the findings using 
GOLD/GINA criteria with recommendations for initial guideline driven therapy 
based on GOLD/GINA guidelines.  Subjects will be managed by their PCP 
thereafter. 
2. If the spirometry findings are normal, with approval from the PCP, will de-
escalate respiratory medication therapy via a stepwise process and schedule 
patient back for a repeat pre and post bronchodilator spirometry within 1-2 
weeks at the same time and place as the PCP clinic session or the CRC 
(Clinical Research Center at UIC).  Again with the PCP approval, this 


Page 6 of 13 
 
deescalation and repeat spiromety can occur in 1-2 week intervals until all 
maintenance medications are discontinued as long as the pre and post 
spirometry continues to be normal. After each visit, the following will be 
provided to the provider and patient:  a letter summarizing the interpretation of 
the findings using GOLD/GINA criteria with recommendations for initial 
guideline driven therapy based on GOLD/GINA guidelines, if appropriate.  
Subjects will be managed by their PCP thereafter.    
3. All spirometry test results and the subject’s assessment at the time of the test 
will be uploaded into the subject’s electronic health record for future reference. 
 
 
C) Patient subject- Usual Care:  
On the day of the outpatient visit, subjects will be advised to arrive 60 minutes 
prior to their clinic visit in the same building as the clinic site or the CRC (Clinical 
Research Center).  The following will be performed.  
 
1. Subject demographic and contact information 
2. Co-morbid conditions 
3. Smoking history 
4. Medication history from patient and also from pharmacy used by subjects 
5. A respiratory exacerbation history in the past year  
6. Modified Medical Research Counsel (mMRC) dyspnea scale and COPD 
assessment test 
7. Quality of life measures 
 
Subjects will be advised to go to their clinics and be managed by their PCP 
thereafter. 
 
At the end of the 1 year followup, the patient will be scheduled for a pre and post 
BD spirometry and undergo the same spirometry protocol  (de-escalation 
protocol) as the intervention group. 
Based on spirometry findings: 
1. If the spirometry findings are consistent with COPD and/or asthma, the 
following will be provided to the provider and patient:  a letter summarizing the 
interpretation of the findings using GOLD/GINA criteria with recommendations 
for initial guideline driven therapy based on GOLD/GINA guidelines.  Subjects 
will be managed by their PCP thereafter. 
2. If the spirometry findings are normal, with approval from the PCP, will de-
escalate respiratory medication therapy via a stepwise process and schedule 
patient back for a repeat pre and post bronchodilator spirometry within 1-2 
weeks at the same time and place as the PCP clinic session.  Again with the 
PCP approval, this deescalation and repeat spiromety can occur in 1-2 week 
intervals until all maintenance medications are discontinued as long as the pre 
and post spirometry continues to be normal. After each visit, the following will 
be provided to the provider and patient:  a letter summarizing the interpretation 
of the findings using GOLD/GINA criteria with recommendations for initial 
guideline driven therapy based on GOLD/GINA guidelines, if appropriate.  
Subjects will be managed by their PCP thereafter.   
3. All spirometry test results and the subject’s assessment at the time of the test 
will be uploaded into the subject’s electronic health record for future reference. 


Page 7 of 13 
 
   
D) Outcome Measures:  
1. Primary outcome:   
(i) Accurate classification of patient as having COPD and/or asthma 
(ii) All-cause and respiratory related, acute care outpatient visits, ED visits, 
and hospitalizations 
2. Secondary outcome:  
(i) Appropriate use of respiratory medications based on guidelines 
(ii) Use of other diagnostic testing:  ECG, echocardiograms, CT/CXR, stress 
testing, cardiac catheterization, other pulmonary function tests 
(iii)Initiation of guideline based therapy 
(iv)Quality of life measures 
 
E)  Data collection and follow-up 
1) Baseline data collection obtained at visit zero (V0), in addition to those listed 
under intervention and usual care: 
1. Demographic data (gender, age, self-reported race) 
2. SES related measures:  median household income 
3. Level of education 
4. Type of health insurance or self-pay 
5. Up to two emergency contacts information 
6. List of current respiratory medications from subject’s pharmacy and 
verification with patient 
7. Co-morbidities 
8. History of prior ED visits or hospitalizations in the past one year with 
associated cause  
9.  EQ-5D 5L +B Bolt-on 
10.  SF-36 short form 
11.  Social support survey 
 
2) All subjects will have their medical charts reviewed every 3 months after the 
initial visit (MR1, MR2, MR3, MR4) up to one year.  These electronic medical 
chart reviews will be used to obtain follow-up data since last study contact. 
1. Change in type of health insurance or self-pay 
2. List of current respiratory medications from subject’s pharmacy and 
verification with patient 
3. Use of diagnostic testing:  ECG, echocardiograms, CT/CXR, stress 
testing, cardiac catheterization, other pulmonary function tests 
4. Any ED visits or hospitalizations or acute outpatient care visit and 
associated cause. 
5. Healthcare utilization outside of U of I system (e.g. testing such as 
spirometry, ED and hospitalizations) if available through scanned records 
 
3) All subjects will be contacted every 3 months after the initial visit via 
telephone (T1, T2, T3, T4) up to one year; or they will be given the option to 
complete in person based on subject’s convenience, for example they have a 
doctor appointment near time of study follow-up.  These phone calls will be 
used to obtain follow-up data since last study contact. A reminder post-card 
will be mailed to the subjects a month before the next telephone contact. 
1. Change in type of health insurance or self-pay 


Page 8 of 13 
 
2. List of current respiratory medications from subject’s pharmacy and 
verification with patient 
3. Use of diagnostic testing:  ECG, echocardiograms, CT/CXR, stress 
testing, cardiac catheterization, other pulmonary function tests 
4. Any ED visits or hospitalizations or acute outpatient care visit and 
associated cause. 
5. Healthcare utilization outside of U of I system (e.g. testing such as 
ancillary testing, ED and hospitalizations)  
6. mMRC 
7. A respiratory exacerbation history  
8. EQ-5D 5L +B Bolt-on 
9. SF-36 short form (at 3, 6 and 12 months) 
10. Social support survey (at 6 months and 12 months) 
 
F) Monetary compensation of subjects  
1. PCP compensation: 
UI Health and MSHC PCPs will receive $95 in cash after completion of the 
education session. For CCHHS PCPs, the Division  or Department with receive a 
total of $95 per participant to be part of the divisional fund to be used by the PCP 
at their discretion as allowed by their institution.   
 
2. Patient subject compensation: 
Baseline visit (Vo):  
Same for Intervention and usual care groups:   Subjects will be provided 
$75 in cash for completing the initial study visit.   
Telephone contact (T1-T3):  
Same for Intervention and usual care groups.  Subjects who choose to 
complete the follow-up in person or via telephone will receive $20 in cash 
at the time of the visit or at a later specified time that is convenient for the 
subject. 
Final contact (T4):  
Intervention:   Subjects will receive $95 in cash at the time of the their last 
visit in-person. 
Usual Care Group:   Subjects will receive $95 in cash  at the completion of 
the 1 year spirometry and follow-up. 
Additional spirometry visits after de-escalation of therapy: 
Same for Intervention and usual care groups (except the intervention 
group will receive this near the beginning of the study and usual care 
group will receive this near the end of the study):   Subjects will be 
provided a $50 in cash for each additional spirometry visit.   
 
2.A. Provision to compensation:  If human subject receives over $200.00 
within one (1) calendar year, it is incumbent for the study staff to obtain the 
subjects social security number based on the OBFS guidelines.  However, if 
human subject receives a total under $200.00 within the calendar there is no 
need to obtain social security number from the human subject. 
 
5. STATISTICAL ANALYSES 
All data will be stored in a secure, locked location. Data will be entered and managed 
through the Research Electronic Data Capture (REDCap). REDCap is a secure web-
based application for building and managing online databases.  REDCap is provided by 


Page 9 of 13 
 
the CCTS Design Analysis Core.  Data will be analyzed for clinical effectiveness using 
intention-to-treat principles.69-71 For Aim 1, we will evaluate the misdiagnosis rates of 
the intervened and usual care groups separately at the first visit. Then compare rates 
between groups by using a generalized linear mixed model for binary outcome with two 
cluster levels, PCP and hospital, to account for the dependence within clusters. For the 
Aim 2, to investigate the impact of the misdiagnosis over time (4 time points: 0, 3, 6, 9, 
12 months) on the quality of life and healthcare utilization, we will fit generalized linear 
mixed models with time, group, and their interaction as the main predictors.  Two cluster 
levels, PCP and hospital, will be specified in the model to account for the dependence 
within clusters72,73 and an appropriate link function will be used for each outcome. 
Clinical important confounders will also be adjusted in the models. Before these 
analyses we will use descriptive statistics to describe the sample, and any assumption 
behind each statistical method will be examined during the analysis. A two-sided p-
value less than 0.05 would be considered as statistical significance. All the analyses will 
be conducted by using SAS 9.2 (SAS Inst., Cary, NC). 
 
For Aim 3: Costs:  The intervention costs for the study include the cost of the 
spirometry test, the time of the CHW/health promoter, and time of pulmonologist to 
provide periodic oversight of spirometry validity.  In addition to estimating the costs 
associated with the intervention it will be important to measure the healthcare utilization 
for participants included in the study.  It is possible that the intervention leads to use of 
other healthcare resources, particularly if the patient is determined to be free of 
respiratory disease.  Therefore, we will measure both respiratory-related and overall 
healthcare costs.  To measure these costs, we will determine overall healthcare 
utilization and apply unit costs to each of the events. Using chart reviews, we will 
examine healthcare utilization during the follow-up period.  We will categorize 
healthcare utilization into either respiratory-related or all other healthcare use.  We will 
apply standardized prices to each of the utilization components to estimate the overall 
and respiratory-related healthcare resource use during the study period. The 
standardize prices will be based on either the National Committee for Quality Assurance 
standardize price list for their relative resource use measure or Medicare 
reimbursement rates.  For medications, we will rely on average wholesale price of 
medications to assign an average price to each of the COPD and asthma-related 
medications.  
 Cost-Effectiveness:  The secondary outcome measures included in the study will be 
used to estimate the effectiveness to be used in the cost-utility analysis. We will use 
responses to the EQ5D to estimate patient utility and use that in calculation of quality-
adjusted life-years (QALY).  The area under the curve will be compared between the 
two groups and the difference will be the incremental effect used in the cost-utility 
analysis.  
Cost-utility analyses:  We will evaluate the cost-utility of the intervention compared to 
usual care over the study period using recommended methods for cost-effectiveness 
analysis.74  To compare the cost-effectiveness of the intervention to usual care, the 
findings are summarized into a ratio that provides the results in terms of the costs per 
unit of effect.  We will calculate the difference in intervention costs and respiratory-
related healthcare resource use between groups to determine the numerator of the ratio 
and the denominator will be the difference in QALYs in the cost-utility analysis.  These 
incremental cost-effectiveness ratios (ICERs) will represent the cost per gain in QALYs 
for the intervention compared to standard care.  As part of the cost-utility analysis we 
will evaluate the uncertainty associated with the ICERs.  We will use bootstrapping 


Page 10 of 13 
 
methods to generate confidence limits for the ICERs.75,76  We will display the results 
graphically on a cost-effectiveness plane and generate cost-effectiveness acceptability 
curves for the intervention compared to usual care.77,78  Cost-effectiveness acceptability 
curves display the probability of the intervention being cost-effective given various 
threshold values.78 Thus decision-makers can identify a threshold value appropriate for 
their setting and determine the probability that the intervention will be cost-effective.  We 
will also conduct sensitivity analyses that use the measure of overall healthcare 
utilization in calculation of the costs, as there may not be perfect specificity in identifying 
respiratory-related costs during the follow-up assessments and the intervention may 
lead to differences in non-respiratory costs. 
 
6. SAFETY MONITORING AND ASSESSMENT 
 
Risks of intervention study 
Spirometry is a breathing test commonly utilized in the outpatient primary care setting.  
Risks and discomforts associated with spirometry are possible. The risks include 
shortness of breath and on rare occasion, the subject might experience dizziness, 
cough, or light-headedness. A medication that can open subjects’ airways may be used 
during spirometry testing. This medication, albuterol, is in a class of medications (i.e. 
short acting beta agonist) that is often used to treat subjects suspected with COPD 
and/or asthma as part of usual care. Albuterol may sometimes cause tremors/shaking, 
nervousness, dizziness, difficulty sleeping, headache, irregular heartbeats, drying or 
irritation of mouth, sore throat, upset stomach, and coughing. These effects usually 
disappear within a short time and do not require treatment.  
 
Data Safety Monitoring Plan 
The PI will review monthly data reports reviewing recruitment, consent, intervention 
activities, adverse events, and follow-up.  Although few, if any, intervention-related 
adverse events are anticipated in this study, the study population is at risk for poor 
outcomes, including life-threatening exacerbations and death not caused by the study 
itself.  The PI will comply with prompt reporting of any adverse event to the IRB  
 
 
7. DATA MANAGEMENT 
 
Confidentiality 
To help ensure that patients’ health information remains private, we will restrict access 
to data collected for our study to study personnel only (via use of password-protection 
and locked cabinets for study documents).  Study ID numbers will be generated and will 
be used when discussing and/or reviewing data at study meetings.  Also, study reports 
will report results in aggregate and not contain information that can be used to identify 
individual patients. 
 
Storage of Data 
Data will be collected from participants in the form of questionnaires and will be 
documented in the secure, password protected, web-based Research Electronic Data 
Capture (REDCap) database available only to members of the research team.  The 
research data will be stored securely using subject ID numbers and kept for 6 years 
after the end of the study.    
 


Page 11 of 13 
 
UI Health electronic medical records(EMR) (inpatient and outpatient) will be reviewed by 
staff from UI Health and CCHHS EMR (inpatient and outpatient) will be reviewed by 
staff from CCHHS . Data collected from both institutions will be input into REDCap.  The 
crosswalk file with direct identifiers to the coded data will be created, encrypted, and 
kept on Dr. Joo’s office computer at 840 S. Wood St. Chicago, Il and stored such that 
only authorized inviduals will have access to patient identifying information.  Hardcopies 
of the data will not be made. 
 
 
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