Development and Testing of an Electronic Visit for COPD Early Detection and Smoking Cessation
Phase: NA
Conditions: Pulmonary Disease, Chronic Obstructive, Cigarette Smoking, Telemedicine
Sponsor: Medical University of South Carolina

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PROTOCOL TITLE: Development and Testing of an Electronic Visit for COPD Early Detection 
and Smoking Cessation  
 
PRINCIPAL INVESTIGATOR: Jennifer Dahne, Ph.D. 
 
 
 

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1.0 
Objectives / Specific Aims 
The goal of this work is to develop, refine, and pilot test an electronic visit (e-visit) to: 1) deliver smoking 
cessation treatment to adults at risk for COPD and 2) to improve rates of COPD early detection and 
accurate diagnosis. We will conduct a pilot RCT (N=100, up to 120 assuming 20% attrition) of the 
COPD/smoking cessation e-visit as compared to treatment as usual (TAU), with primary objective to 
provide effect size estimates for a larger RCT. Specific aims are twofold:  
 
Aim 1: Conduct usability testing of the smoking cessation/COPD e-visit with patients (N=5, up to 10 to 
account for attrition) followed by iterative refinements consistent with participant feedback.  
 
Aim 2: Conduct a pilot, small-scale randomized controlled trial to examine COPD and smoking cessation 
outcomes associated with the E-Visit as compared to treatment as usual (TAU; i.e., no e-visit). Outcomes 
will include those related to: e-visit feasibility (i.e., time to complete e-visit, time for provider to review e-
visit, % completed e-visits, qualitative feedback), COPD (early diagnosis rates as a function of treatment 
condition, emergency department visits for respiratory infection), smoking cessation outcomes (self-
reported quit attempts/quit duration and biochemically verified cessation via carbon monoxide), and 
cessation medication utilization. 
 
We hypothesize that participants randomized to the e-visit condition as compared to those randomized to 
the TAU condition will have higher (numerically, if not statistically significant) rates of COPD early 
diagnosis, cessation treatment utilization (medications, counseling), and superior cessation-related 
outcomes.  
 
2.0 
Background 
More than 16 million Americans have COPD and millions more suffer from COPD but have not yet been 
accurately diagnosed or treated1. Nationwide healthcare costs associated with COPD exceed $36 billion 
annually and are projected to reach $49 billion by 20201. COPD is now concentrated within rural 
communities and those who reside in rural areas as compared to those who reside in large metropolitan 
areas have both higher COPD incidence (8% vs. 5%) and higher COPD-related death rates (55 per 
100,000 vs. 32 per 100,000)2. Telehealth strategies to implement evidence-based best practice for COPD 
may be particularly impactful among rural communities as such treatment modalities can extend the reach 
of traditional COPD prevention, diagnosis, and treatment strategies.   
 
In light of the significant public health impact of COPD, the National Heart Lung and Blood Institute 
(NHLBI) issued a COPD National Action Plan in 2017. A key goal within this national action plan is to 
improve the diagnosis, prevention, treatment, and management of COPD by improving the quality of care 
delivered across the health care continuum. Informed by this federal national action plan, and with the 
guidance of HRSA, our team will undertake a 22-month planning and pilot intervention period to identify 
how telehealth modalities might be optimally leveraged to improve the quality of care and outcomes 
among patients at risk for COPD. Because COPD is most commonly caused by cigarette smoking, we 
will focus our planning and intervention period specifically on COPD early detection among cigarette 
smokers and on leveraging telehealth to extend the reach of evidence-based smoking cessation treatment 
(i.e., medications and counseling for smoking cessation) for those at risk for COPD. This work will build 
upon and extend our team’s ongoing efforts to develop a smoking cessation electronic visit (e-visit) that 
can be proactively delivered to all adult MUSC patients who have been identified via the electronic health 
record as cigarette smokers. E-visits are embedded into the most common electronic health record (EHR) 
systems (e.g., Epic, Allscripts, and others) and offer a secure platform through which patients can 

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remotely supply providers with health information. Providers in turn can deliver personalized instructions 
and/or treatment to the patient. Prior studies of asynchronous e-visits for chronic condition treatment have 
found high satisfaction among both patients and providers and that such e-visits can be delivered 
efficiently (average time for patient to complete e-visit = 8.3 minutes, average time for provider to review 
and respond to e-visit = 3.6 minutes)3.  
 
Our team received a pilot award (PIs: Dahne and Diaz) from the South Carolina Telehealth Alliance in 
July 2018 to begin development of a smoking cessation e-visit for implementation within MUSC primary 
care. Preliminary e-visit development is now complete and a pilot trial to examine smoking cessation 
outcomes associated with e-visit receipt is underway. Herein, we will leverage this proactive, scalable 
platform to: 1) deliver smoking cessation treatment to adults at risk for COPD and 2) to improve rates of 
COPD early detection and accurate diagnosis. The ultimate goal of this line of work is to improve the 
quality of care and associated outcomes among patients at risk for COPD.  
 
3.0 
Intervention to be studied  
We are currently in the process of modifying our existing asynchronous smoking cessation e-visit to 
incorporate COPD early detection with MUSC’s BMIC Epic development team. The smoking cessation 
component of the e-visit is based on USPHS guidelines4 and serves to automate much of the 5As (i.e., 
Ask, Advise, Assess, Assist, Arrange) process. Smokers are proactively invited via electronic message 
(e.g., via MyChart) to initiate an asynchronous smoking cessation e-visit. The e-visit is a questionnaire 
administered via MyChart. The initial asynchronous e-visit gathers information about smoking and quit 
histories, followed by questions to assess motivation to quit and an algorithm to determine the best 
smoking cessation medication to prescribe for each patient by assessing contraindications and preferences 
for FDA-approved first line cessation medications (i.e., nicotine replacement therapy, varenicline, 
bupropion). The e-visit will be sent to an attending physician (study physicians included on the IRB 
protocol), who will review the recommendations, inform study staff of which medication to provide to 
participants, make referrals to additional smoking cessation resources (e.g., state quitline), and schedule a 
follow-up e-visit. Varenicline, a class C medication, may be provided as a result of the e-visit. Because 
risks during pregnancy related to Varenicline are unknown, women under the age of 55 who receive a 
recommendation for Varenicline as a result of the e-visit algorithm will subsequently be asked if they 
would be willing to complete a pregnancy test that will be mailed to them. Women under the age of 55 
who are respond “No” to this item will not be prescribed Varenicline. The follow-up e-visit will assess 
tobacco use, medication adherence, side effects, and determine if further cessation treatment is needed 
(e.g., an additional follow-up e-visit, referral to counseling). All patients will be scheduled for at least one 
follow-up e-visit within a month after the initial e-visit. E-visits will also include a SmartSet (i.e., a group 
of orders and other elements that are commonly used together to document a specific type of visit) to 
streamline provider documentation and treatment plans. E-visits typically delivered for clinical purposes 
via Epic at MUSC cost $25, but this cost will be waived for participants in this study.  
 
For the purpose of this trial, this initial asynchronous e-visit will also include an assessment of COPD 
symptoms via the COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and 
Exacerbation Risk (CAPTURE)5. Those who score > 2 on the CAPTURE will be considered symptomatic 
and will be invited to complete additional COPD screening measures. These individuals will be mailed a 
home spirometer and will be asked to complete an additional e-visit during which they will upload a video 
of themselves completing home spirometry via the device. The home spirometer will measure peak 
expiratory flow (PEF), forced expiratory volume (FEV1 and FEV6), and forced vital capacity (FVC). 
These videos will be reviewed by a study attending physician and follow-up care will be provided 
consistent with best clinical practices. In addition to home spirometry, all patients who screen positive on 

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the CAPTURE during the baseline e-visit will be referred to an in person appointment for 
spirometry/bronchodilation consistent with best practices.  
 
Participants enrolled in the present study who are randomized to the TAU condition will be provided 
information about the state quitline and about the importance of quitting smoking and it will be 
recommended that they contact their PCP to schedule a medical visit to discuss quitting smoking.  
 
4.0 
Study Endpoints (if applicable) 
Primary outcome variables include: 
• Evidence-based cessation treatment utilization will be assessed via participant self-report. At each 
follow-up assessment, participants in both groups will be queried for: 1) use of a smoking 
cessation medication since the last assessment, 2) how the medication was obtained (e.g., via the 
study or another outlet such as MUSC’s existing smoking cessation service), and 3) receipt of the 
5As from their PCP6. 
• Cessation-related outcomes will be assessed via participant self-report. Cigarette smoking, use of 
other tobacco products (e.g., e-cigarettes), and quit attempts/quit duration will be assessed at each 
follow-up using a timeline followback for the last 6-months at baseline and since prior follow-up 
for each subsequent assessment7,8.  
• COPD diagnosis will be assessed both via established metrics captured via home spirometry and 
via chart review.  
Secondary outcome variables include: 
• E-visit acceptability and feasibility will be assessed both by examining the percentage of patients 
who complete the initial and follow-up e-visits, and by participant self-report during follow-up 
assessments. Participants will respond to items assessing ease of use, satisfaction, and pros/cons of 
the e-visit. Analytics data (e.g., amount of time it takes to complete the e-visit, amount of time it 
takes the provider to review the e-visit) will also be collected as will data on provider fidelity to e-
visit recommendations (captured by reviewing within Epic whether the provider administered 
treatment consistent with e-visit recommendations). 
 
We will also assess: 
• Nicotine dependence will be assessed at baseline via the Fagerstrom Test of Nicotine 
Dependence9. 
• Motivation to quit and confidence in quitting will be assessed via participant self-report using a 
modified Contemplation Ladder10.  
 
 
5.0 
Inclusion and Exclusion Criteria/ Study Population 
Participants will complete a survey within MyChart to be screened for eligibility. Inclusion criteria for 
patients across aims include: 1) current smoking, defined as smoking 5+ cigarettes/day, for 20+ days out 
of the last 30, for the last 6+ months, 2) age 40+, 3) enrolled in Epic’s MyChart program or willing to sign 
up for MyChart, 4) possess a valid e-mail address that is checked daily to access follow-up assessments 
and MyChart messages, 5) English fluency, and 6) owner of an iOS or Android-compatible smartphone 
and a webcam-enabled device (necessary for providing carbon monoxide readings). As an aim of this 
study is to facilitate COPD early diagnosis, participants will be excluded if they have COPD on their 
problem list within Epic. Inclusion criteria for providers for usability testing include: 1) medical provider 
at MUSC and 2) treat adult patients.  
 
6.0 
Number of Subjects 

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We will recruit up to 10 patients for usability testing and 120 subjects for the pilot RCT. 
 
7.0 
Setting 
Research will be conducted remotely via REDCap and MyChart. Participants will be recruited remotely 
and will be MUSC patients.  
 
8.0 
Recruitment Methods 
Participants will be recruited in the following ways: 
1) Via MyChart: MUSC patients who have previously been identified as smokers will be sent a 
secure message via MyChart inviting them to complete a preliminary eligibility screening. These 
patients will have either agreed to research contact within MyChart or their attending 
physician will have agreed to contact their patients who smoke cigarettes via MyChart. 
Within the message, potential participants will be invited to click a link to complete an eligibility 
screening via MyChart. 
2) In Clinic: Participants may be recruited in clinic either after being identified as a smoker by 
research personnel listed on this application. 
3) Via advertisements (e.g., flyers) and online postings  
 
Note, that while we include the options to recruit in clinic and via advertisements, these will be used as 
backup options should recruitment via MyChart be slow and/or result in an insufficient number of 
participants recruited.  
 
Recruitment of Minority Smokers 
Minority smokers will be included in this trial. All participants will be recruited from MUSC practices, 
which primarily serve residents of Charleston County, South Carolina. United States Census data from 
2015 (the most recent Census year available) reveal that the population within Charleston County is 
68.2% White, 28.1% Black, 2.2% American Indian/Alaskan Native, Asian, or Pacific Islander, 1.5% 
reporting two or more races, and 5.0% are Hispanic or Latino. Compared to Charleston County 
demographics, members of racial and/or ethnic minority groups tend to be overrepresented among 
smokers treated via MUSC’s clinics. Roughly half of smokers treated via these clinics are members of a 
racial or ethnic minority group. We will monitor closely our minority recruitment goals on an ongoing 
basis. If the recruitment of minorities is lower than expected (< 10% projected enrollment), efforts will be 
made to improve recruitment of minorities into the study through oversampling.  
 
9.0 Consent Process 
Signed informed consent will be obtained from study participants. The consent process will take place via 
one of the following modalities: 1) Remote or in person electronic consent (e-consent) via REDCap (if 
remote, e-consent will be facilitated with a discussion over the phone or via video), 2) Remote consent via 
doxy.me facilitated with either a discussion over the phone or video connection via doxy.me, 3) Mailed 
(paper) consent facilitated with a discussion over the phone, or 4) in person consent (e.g., in clinic).  
 
All participants will be provided with a hard copy and/or an electronic copy of the consent form. 
Participants will be informed that participation in this research is strictly voluntary. Informed consent will 
include a detailed description of the purpose and the procedure of the study emphasizing our policy 
regarding privacy and confidentiality and an opportunity for the individual to ask any questions or voice 
concerns. Signatures on the consent form may be obtained with paper and pen OR electronically via 
REDCap/doxy.me. Participants who do not have access to the required technology to complete consent 
remotely via REDCap or doxy.me will be given the option to complete consent via mail facilitated with a 

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discussion over the phone. For participants consented via doxy.me, we will track software analytics 
anonymously, while using the platform, for potential future secondary data analysis examining usability 
of remote electronic consent. We have discussed this with doxy.me developers, who have assured us that 
we can get this data for a given protocol in an anonymous way. We are only interested in times it takes 
individuals to accomplish given tasks within doxy.me. For example, track the time it takes them to 
navigate through the online document and time it takes them to sign the consent form electronically. 
 
10.0 Study Design / Methods 
 
 
Usability Testing 
Following initial development of the modified e-visit, we will complete usability testing of the e-visit 
with 5 patients (up to 10 to account for attrition). Usability testing participants will complete all study 
procedures as outlined below for the pilot RCT, but will also be asked to provide additional feedback as 
they complete the e-visits so that the investigative team can iteratively refine and improve the e-visits. 
Inclusion/exclusion criteria for usability testing participants will be the same as criteria for pilot RCT 
participants (see section 5.0 above). As participants complete the e-visits remotely, research staff will be 
connected in real time to the participant via audio and/or video. As participants complete the e-visits, we 
will follow the Concurrent Think Aloud method to elicit real-time feedback and research staff will take 
notes on emotional reactions, task completion, task time, and errors11. The compensation schedule for 
participants included in initial usability testing will be the same as for participants enrolled in the RCT. 
Following usability testing, Dr. Dahne will then prioritize refinements which will be implemented by the 
BMIC Epic development team in preparation for the subsequent pilot trial. 
 
Pilot RCT 
A two-arm pilot RCT (N=100, up to 120 assuming 20% attrition) will test cessation treatment utilization, 
smoking cessation outcomes, and COPD diagnosis rates as a function of smoking cessation e-visit vs. 
TAU. Recruitment will primarily occur proactively and remotely via the EMR. We will conduct an 
automated EMR search via established procedures for all patients treated within MUSC DFM clinics 
during the past 12 months who: 1) smoke, 2) are > 40, 3) have MyChart accounts, and 4) do not have 
COPD on their problem list. These patients will be sent a MyChart message from a member of their 
care team inviting them to participate in a research study for cigarette smokers. These messages 
will only be sent to patients of PCPs who have agreed that their patients may be contacted for the 
purpose of this study. This invitation will include clear opt out procedures should the patient not 
wish to be contacted in the future for the purpose of this study. Clinical providers included in the 
Usability Testing phase of the project will not be asked to directly refer their own patients to the 
study. However, their patients may still be recruited via the EMR. After sending these automated e-
mail messages via MyChart, the study team may also call, e-mail, and/or text message potential 
participants to notify them that a message was sent to them via MyChart. Again, such contact will only be 
made to patients of PCPs who have agreed that their patients may be contacted for the purpose of this 
study. If interested, participants will complete a screening online via MyChart to determine study 
eligibility (see above for inclusion criteria). After completing determination of eligibility, if eligible and 
interested in participating in the study, participants will be scheduled for a time to complete informed 
consent (see 9.0 Consent Process). After consent is obtained, participants will be randomized 2:1 to 
receive either the smoking cessation e-visit or TAU. If randomized to the e-visit condition, participants 
will be sent a link to initiate the e-visit. All e-visit medication recommendations will be reviewed by 
physicians included on this IRB protocol. Medications will be e-prescribed to a mail order pharmacy (e.g., 
MUSC’s mail order pharmacy) and then mailed to participants, with all costs covered by the study. Note 

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that only FDA approved cessation medications will be recommended, which include nicotine replacement 
therapy (patch, gum, lozenge), varenicline, or bupropion. Medications will only be recommended if a 
participant does not have a contraindication for that medication. Women who indicate during the e-visit 
that they are currently pregnant or are planning to become pregnant within the next 6 months will not 
receive a medication recommendation/prescription as a result of the e-visit. These women will receive a 
counseling referral. Any woman under the age of 55 who receives a varenicline recommendation as a 
result of the e-visit will subsequently be asked within the e-visit if she is willing to complete a pregnancy 
test that will be mailed to her at no cost to verify that she is not pregnant prior to taking varenicline. 
Women under the age of 55 who respond “Yes” to this item will be mailed a pregnancy test by study staff 
and will be required to verify (with signature) that they completed the test and are not pregnant via 
REDCap. Women under the age of 55 who respond “No” to this item will not receive varenicline as a 
result of the e-visit. These women instead will either receive NRT, bupropion and/or counseling based on 
other contraindications and medication preferences indicated throughout the e-visit. Participants will be 
scheduled for a follow-up e-visit one month following their initial e-visits. The follow-up e-visit may also 
result in a medication recommendation that will be e-prescribed and mailed to the participant as outlined 
above for the baseline e-visit. If randomized to the TAU condition, participants will be provided 
information on quitting smoking, including information about the state quitline, and will be provided a 
recommendation to contact their PCP to schedule a medical visit to discuss quitting smoking.  
For participants randomized to the e-visit condition, the baseline e-visit will include a 5-item 
questionnaire (the CAPTURE) to assess COPD symptoms. Participants who score > 2 on this measure 
will be invited to complete home spirometry. These participants will be mailed a home spirometer and 
will be invited to complete an additional e-visit after receiving the home spirometer at which time they 
will be instructed regarding how to use the device and will upload a video of themselves completing home 
spirometry. Participants will also be asked to enter into the e-visit metrics available via the spirometer 
including FEV1 and peak expiratory flow. These videos will be reviewed by a study attending physician 
and follow-up care will be provided consistent with best clinical practices. In addition to home 
spirometry, all patients who screen positive on the CAPTURE during the baseline e-visit will be referred 
to an in person appointment for spirometry/bronchodilation consistent with best practices. Costs related to 
in person spirometry testing will be paid for by the study for appointments completed by the time of the 3-
month assessment. Although the medical order for spirometry testing may remain active following the 3-
month assessment, any testing completed after the date of the 3-month assessment will not be paid for by 
the study. 
 
 
All participants will subsequently be text messaged and/or emailed a REDCap link, accessible via 
smartphone, tablet, or computer to complete study assessments. These assessments will occur at baseline 
(following consent), 1-month following study enrollment, and 3-months following study enrollment. 
Assessments are estimated at 20 minutes each and will be administered remotely via REDCap through our 
established procedures. Participants will be compensated via electronic gift cards (e.g., Amazon) which 
will be emailed or texted to participants. Participants will receive $30 for completion of the baseline 
assessment questionnaire. After completing each follow-up questionnaire within 72 hours of being 
emailed the link, participants will be compensated $30. Participants will be compensated $30 for each 
completed carbon monoxide recording. They will be compensated an additional $100 for completion of 
all three sets of questionnaires and both carbon monoxide samples. E-visit acceptability and feasibility 
will be assessed both by examining the percentage of patients who complete the initial and follow-up e-
visits, and by participant self-report during follow-up assessments. Participants will respond to items 
assessing ease of use, satisfaction, and pros/cons of the e-visit. Analytics data (e.g., amount of time it 
takes to complete the e-visit, amount of time it takes the provider to review the e-visit) will also be 
collected as will data on provider fidelity to e-visit recommendations (captured by reviewing within Epic 

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whether the provider administered treatment consistent with e-visit recommendations). Cigarette smoking, 
use of other tobacco products (e.g., e-cigarettes), and quit attempts/quit duration will be assessed at each 
follow-up using a timeline followback for the last 6-months at baseline and since prior follow-up for each 
subsequent assessment7,8. Nicotine dependence will be assessed at baseline via the Fagerstrom Test of 
Nicotine Dependence9. Participants will report motivation to quit and confidence in quitting using a 
modified Contemplation Ladder10. Expired air carbon monoxide will also be captured. Treatment 
utilization will be assessed via participant self-report. At each follow-up assessment, participants in both 
groups will be queried for: 1) use of a smoking cessation medication since the last assessment, 2) how the 
medication was obtained (e.g., via the study or another outlet such as MUSC’s existing smoking cessation 
service), and 3) receipt of the 5As from their PCP6. COPD diagnosis will be assessed via participant self-
report and via medical records review. At each follow-up time point, participants will be asked whether a 
clinical provider has given them a COPD diagnosis. Medical records will be reviewed for up to 12-
months following completion of the 3-month follow-up survey to identify: 1) whether the participant was 
referred for in person spirometry, 2) whether the participant attended that appointment, and 3) whether the 
participant was given a diagnosis of COPD.  
 
11.0 Data Analysis and Data Management  
 
Data Analysis 
 
As this is a pilot trial, our primary goal is to estimate an intervention effect size and out secondary goal is 
to examine the feasibility/acceptability of the e-visit. Precise parameter estimation can be achieved with 
25-30 participants per group12. To estimate an effect size for the smoking cessation e-visit intervention, 
we will randomize participants 2:1 (active:control), with 67 participants in the active condition and 33 in 
the control condition. Primary smoking-related outcomes for this trial include cessation treatment 
utilization (e.g., medication) and quit attempts. Assuming a cessation treatment utilization rate of 48% in 
the active condition and 11% in the control condition, with 2:1 randomization we will have 95% power to 
detect an effect. For quit attempts, assuming a quit attempt rate of 24% in the e-visit condition and 6% in 
the TAU condition, we will have 60% power to detect an effect. Our intent here is not a fully powered 
trial for cessation, but is rather to collect preliminary data to inform future trials.   
 
Data analysis for the primary objective will focus on descriptive analysis of primary smoking-related 
outcomes. Descriptive statistics (e.g., frequencies, percentages) will be calculated for the primary 
smoking-related outcomes (treatment utilization, quit attempts). Because rates of these primary outcomes 
are expected to be low in control group, we will utilize Fisher’s exact tests to compare rates between the 
e-visit and TAU groups. Secondary exploratory analyses for this primary objective will examine changes 
in these outcomes over time by treatment condition. We will utilize Generalized Estimating Equations 
(GEEs) with log link functions, which will allow us to account for correlated repeated measures within 
study participants. Planned covariates include sex and the main effect of time.   
 
Data analysis for the secondary objective to examine treatment feasibility specifically for the smoking 
cessation e-visit will focus on descriptive analysis of: 1) % of those initiate the baseline e-visit who 
complete it, 2) % of those who complete the baseline e-visit who subsequently complete the follow-up e-
visit, 3) average time to complete the e-visit (for patients), 4) average time to review the e-visit (for 
providers), 5) provider fidelity to e-visit recommendations, and 6) participant self-report of e-visit ease of 
use, interest in using an e-visit again in the future, benefits of using the e-visit, and strengths/challenges of 
completing the e-visit. The e-visit will be considered feasible and acceptable if: 1) >90% of those who 
initiate the baseline e-visit complete it, 2) >75% of those who complete the baseline e-visit complete the 

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follow-up e-visit, 3) providers are faithful to e-visit recommendations >80% of the time, and 4) self-report 
data indicate participant benefits and ease of use (average score for each > 4 on 5-point scale).  
 
Data Management 
 
Regarding questionnaire data, data will be obtained for research purposes only. All data will be collected, 
stored, and managed via REDCap, which is a secure, web-based application designed exclusively to support 
data capture for research studies. REDCap provides secure, web-based flexible applications, including real 
time validation rules with automated data type and range checks at the time of entry. The underlying 
database is hosted in a secure data center at MUSC, a secure environment for data systems and servers on 
campus, and includes redundancy, failover capability, backups and extensive security checks. The system 
has several layers of protection including user/group account management, "Data Access Groups" which 
allow data to be entered by multiple groups in one database with segmented user rights for entered data, 
audit trails for all changes, queries and reports, and Secure Sockets Layer (SSL) encryption. Name and 
relevant contact information will be obtained to provide compensation and every effort will be made to 
maintain subject confidentiality, in accordance with HIPAA. All data will be identified only by code 
numbers (participant IDs). Participant IDs will be linked to participants’ names in a password-protected file 
that is accessible only to the PI and trained research staff.  
 
12.0 Provisions to Monitor the Data to Ensure the Safety of Subjects (if applicable) 
 
This section is based on the recommendations in NIDA’s “Guidelines for developing a Data and Safety 
Monitoring Plan” as well as NCI’s “Essential Elements of a Data and Safety Monitoring Plan for Clinical 
Trials Funded by the National Cancer Institute.”  
 
Summary of the Protocol 
We will develop and iteratively test a comprehensive e-visit for delivery to smokers treated via primary 
care. Through an established partnership with MUSC Epic developers, we will develop the e-visit consistent 
with USPHS best practice guidelines for smoking cessation treatment via primary care. Those who self-
report symptoms of COPD will be invited to complete home spirometry. We will then complete a 
randomized pilot trial of 1) e-visit vs. 2) TAU.  
 
Trial Management 
The study will be managed from the Addiction Sciences Division within the Department of Psychiatry and 
Behavioral Sciences at the Medical University of South Carolina (MUSC). Recruitment, data collection, 
data management, and treatment provision will be coordinated and centrally managed at our research lab at 
MUSC and will be implemented within local MUSC clinics.  
 
Data Management and Analysis 
Participants will enter data in REDCap, a secure, web-based application designed exclusively to support 
data capture for research studies. REDCap provides: 1) an intuitive interface for data entry (with data 
validation); 2) audit trails for tracking data manipulation and export procedures; 3) automated export 
procedures for seamless data downloads to common statistical packages (SPSS, SAS, Stata, R); 4) 
procedures for importing data from external sources; and 5) advanced features, such as branching logic and 
calculated fields. These procedures are effective in minimizing data entry errors (e.g., missing or errant 
data). The data analysis plan is outlined above. 
 
Quality Assurance 

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Accuracy and completeness of the data collected will be ensured by weekly review. The REDCap system 
does not accept outliers, illogical response patterns, etc. The PI and research assistants will have weekly 
meetings to discuss any qualitative comments received during data collection and any problems in data 
collection. The PI will examine the database for potential irregularities monthly. Initial data analyses will 
examine distributions of variable scores and comparability of baseline characteristics across conditions in 
case analyses need to be adjusted for these. Confidentiality procedures are outlined above.  
 
Regulatory Issues 
All serious AEs will be reported to the MUSC Committee on Human Research within 48 hrs. Follow-up of 
all unexpected and serious AEs will also be reported. All AEs will be reviewed weekly by the PI and yearly 
by the IRB. Any significant actions taken by the local IRB, and protocol changes will be relayed to the 
funding agency. We estimate the significant AE rate to be 5% or less. Potential conflicts of interest (COI) 
will be reported using the SRNT rules for disclosure as well as the rules of MUSC’s COI committee. 
 
Trial Safety 
The potential risks and benefits and methods to minimize these risks are outlined in the “Risks to Subjects” 
section. AEs will be tracked and rated as mild, moderate or severe and as related to medication by the 
participant. We will determine if any AEs result in dropouts, or are serious according to FDA guidelines. 
The PI (Dr. Dahne) will serve as the Program Manager for AEs. All unexpected AEs will be monitored 
while they are active to determine if treatment is needed. Risk profiles for smoking cessation medications 
that may be prescribed as an outcome of the e-visit are minimal, with the most common side effects being 
nausea, headache, and dry mouth. All patients will be active MUSC. As such, we expect AEs will be rare. 
Nonetheless, they will be coded on a weekly basis using the FDA’s COSTART rules13 and entered into a 
database. For each weekly study meeting, the research assistant(s) will prepare a summary of all AEs, 
including their severity, whether they caused a dropout, required treatment and presumed relation to drug 
intake. The PI will review this at the weekly study meeting (or before if more urgent). Drs. Diaz and Player, 
board-certified Family Medicine physicians, will be available for on-site medical supervision for any issues 
that cannot be resolved by Dr. Dahne.  
 
Study procedures will follow as much as possible the FDA’s Good Clinical Practice Guidelines and our 
research team has found Spilker’s comprehensive text on conducting clinical trials to be useful14. The 
research assistants will be instructed not to reveal whether a person is a participant in the study and will 
report to the PI any outside requests for information about a participant or any breaches in confidentiality. 
All requests by participant’s physicians and other medical providers will be referred directly to the PI.  
 
Data and Safety Monitoring Plan Administration 
The PI will be responsible for monitoring the trial. The PI will examine monthly the outcomes database for 
missing data, unexpected distributions or responses, and outliers. The PI will check weekly the AE database 
prepared by the research assistant(s) immediately prior to the lab meeting a) to see if any particular 
COSTART categories are being endorsed more frequently than normal and b) to determine if any side-
effect symptom checklist scores are higher than expected. A DSM report will be filed with the IRB and 
funding agency on a yearly basis, unless greater than expected problems occur. The report will include 
participant characteristics, retention and disposition of study participants, quality assurance issues and 
reports of AEs, significant/unexpected AEs and serious AEs. We will report efficacy at the end of the trial. 
 
13.0 Risks to Subjects 
 

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This is considered a minimal risk study. Minimal risk means the probability and magnitude of harm or 
discomfort anticipated in the research are not greater in and of themselves other than those ordinarily 
encountered in daily life or during performance of routine physical or psychological examinations or tests. 
The potential risks in this study include those related to: a) smoking cessation medications, b) 
confidentiality, and c) frustration.  
 
a) Smoking cessation medications: Participants in both treatment arms may receive an FDA-approved 
smoking cessation medication. Participants in the e-visit condition may receive a prescription as an 
outcome of the e-visit and participants in the TAU condition may receive a prescription if they contact 
their PCP to discuss quitting smoking. These medications include: nicotine replacement therapy (NRT), 
varenicline, and/or bupropion. Participants will be educated about their smoking cessation medication 
as part of the e-visit or during their normally scheduled medical appointment if randomized to the TAU 
condition. Pregnancy or intention to become pregnant will be assessed during the e-visit. Medication 
will only be prescribed if a participant does not have contraindications for that medication. Participants 
will be provided with our study phone number and instructed to call our study personnel should they 
experience AEs or if they have questions/concerns about medication use. Given the relatively benign 
risk profiles of these medications, we expect AEs, which will be assessed across follow-up timepoints 
via REDCap, to be rare and mild. Participants will be encouraged to contact Dr. Dahne as soon as 
possible for serious AEs and for those conditions that labeling suggests seeing a provider. We will 
withdraw participants who have a serious AE. For other AEs, if the participant wishes it, the participant 
will be withdrawn from the study. 
 
b) Confidentiality: Participants will be made aware of limits to confidentiality at the beginning of 
screening and when reviewing study procedures/during informed consent which include report of 
suicidal or homicidal intent or report of abuse or neglect. If the participant reports suicidal or homicidal 
intent or abuse/neglect, Dr. Dahne will take appropriate action as outlined by the MUSC IRB, NIH, and 
the State of South Carolina, which may include contacting the authorities and/or pursuing involuntary 
commitment at a mental health facility. If participants present no imminent danger but also need more 
extensive treatment of mental health concerns, they will be given appropriate referrals and instructed to 
contact their physician.  
 
c) Frustration: Participants may become frustrated while completing study assessments. Participants 
will be informed that they may refuse to answer any question(s) that they do not wish to answer and 
that they may discontinue study participation at any time. 
 
Since patients will all currently be receiving medical care at MUSC, there are no additional risks associated 
with participation in this study. 
 
Adequacy of Protection Against Risks 
 
Recruitment and Informed Consent 
Study participants will be recruited from local MUSC clinics. Smoking status is assessed for every patient, 
consistent with MUSC’s best practice guidelines. Patients identified as smokers via the EMR will be sent a 
message inviting them to participate in a research study. Interested patients will complete determination of 
eligibility via MUSC’s REDCap system, a secure, HIPAA-compliant data management system. All 
participants will review consent documents and will provide informed consent consistent with procedures 
outlined above. Participants will be given the opportunity to ask questions about their participation 
throughout the course of the study. A copy of the informed consent will be kept centrally at our study office 

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within locked filing cabinets, and a copy will be given to each study participant as well. Participants will 
be given a study phone number and e-mail address to contact for questions. 
 
Protections Against Risk 
All screening information will be kept in a password protected REDCap database. Only key study personnel 
will have access to the database. If an individual is not eligible to participate, his/her screener will include 
his/her first name and last initial and the reason for disqualification. Eligible participants’ full name, 
telephone number and e-mail address will be recorded in the database. This is the only place where 
participants’ names and subject identification numbers appear together. Eligible participants will be 
assigned a subject number, will complete informed consent, will be randomized, will complete baseline 
assessments, and subsequently will receive their randomized intervention. 
 
Upon completing eligibility screening, if study eligible, individuals will be provided with an overview of 
the study, asked to review study procedures via a consent form, and asked to provide signed consent. 
Participants will be informed of limitations of confidentiality (i.e., abuse or neglect, intention to harm self 
or someone else) both verbally and/or in writing during the informed consent process. The consent form 
will include the participant’s name, but not his/her subject number. Consent forms will be provided in 
English. As utilization of the smoking cessation e-visit requires that participants are able to read, 
participants unable to read the consent form on their own will not be included. 
 
Regarding questionnaire data, data will be obtained for research purposes only. All data will be collected, 
stored, and managed via REDCap, which is a secure, web-based application designed exclusively to support 
data capture for research studies. REDCap provides secure, web-based flexible applications, including real 
time validation rules with automated data type and range checks at the time of entry. The underlying 
database is hosted in a secure data center at MUSC, a secure environment for data systems and servers on 
campus, and includes redundancy, failover capability, backups and extensive security checks. The system 
has several layers of protection including user/group account management, "Data Access Groups" which 
allow data to be entered by multiple groups in one database with segmented user rights for entered data, 
audit trails for all changes, queries and reports, and Secure Sockets Layer (SSL) encryption. Name and 
relevant contact information will be obtained to provide compensation and every effort will be made to 
maintain subject confidentiality, in accordance with HIPAA. All data will be identified only by code 
numbers (participant IDs). Participant IDs will be linked to participants’ names in a password-protected file 
that is accessible only to the PI and trained research staff.  
 
Protection against risks associated with smoking cessation medications include a Data and Safety 
Monitoring Plan that includes monitoring of AEs. FDA contraindications for each smoking cessation 
medication will be factored into the smoking cessation e-visit. Through informational material provided via 
the e-visit and with standard medication packaging, participants will be educated about potential AEs and 
nicotine intoxication symptoms (for NRT medications). We anticipate very few AEs. AE’s will be discussed 
with Drs. Diaz and/or Player.  
 
14.0 Potential Benefits to Subjects or Others 
 
All smokers in this trial will receive at minimum standard smoking cessation care and evidence-based 
educational information about quitting smoking. We will not augment standard smoking cessation care as 
provided by each patient’s primary care physician. The majority of participants will also receive an 
invitation to complete a smoking cessation e-visit. The major benefit to society will be whether this smoking 
cessation e-visit will improve cessation outcomes relative to TAU. Potential issues of medication risks, 

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confidentiality, and frustration are a high priority and will be closely monitored throughout the study. 
Consequently, the risk to benefit ratio in the proposed study appears to be acceptable. 
 
 
15.0 Sharing of Results with Subjects 
 
Study enrollment and study outcomes will not be shared with medical staff, including the participant’s 
physician. 
 
 
 

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