Gain-framed Messages and NRT Sampling to Promote Smoking Cessation in Lung Cancer Screening Programs
Phase: PHASE2
Conditions: Lung Cancer Screening, Smoking Cessation
Sponsor: Medical University of South Carolina

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Gain-framed messages and NRT for lung cancer screening patients ( Pro00055397 ) 
PI: Benjamin Toll, PhD 
Version 13 (11/14/2022) 
 
SPECIFIC AIMS 
 
Screening for lung cancer at earlier, more treatable stages has the potential to reduce mortality from the 
US’s most deadly cancer.1 The US Preventive Services Task Force (USPSTF) now recommends annual 
screening for lung cancer with low-dose computed tomography (LDCT) for high risk individuals based on age 
and smoking history.2 The Center for Medicare and Medicaid Services (CMS) recently approved annual lung 
cancer screening for its beneficiaries when conducted   in centers offering comprehensive programs that 
include advice on smoking cessation.3 While it has been suggested that LC screening is a potential teachable 
moment, most current smokers seen for screening have variable motivation to quit, and many are unwilling to 
engage in a formal cessation program. Thus, there is a strong need to address smoking cessation across this 
continuum, catalyzing treatment engagement and cessation among all. The interventions in this study are 
broad and translational – effectively promoting quitting among all smokers and doing so in a way that is easily 
disseminable. In the context of 3 lung cancer screening programs (MUSC, VA and Yale) this project will 
evaluate a more intense yet still feasible intervention to enhance patient motivation to make and succeed in a 
quit attempt.  
 
Our group has established effective tobacco interventions that demonstrate increased quit attempts and 
smoking cessation from: 1) gain-framed messaging, and 2) nicotine replacement therapy (NRT) sampling.  
Based on the tenets of Prospect Theory4 and an accumulating body of evidence from our previous studies, 
messages emphasizing the benefits of smoking cessation (i.e., gain-framed) are more effective than messages 
emphasizing the risks of continued smoking (i.e., loss-framed) for increasing intentions to quit, quit attempts, 
and smoking cessation in general populations of smokers.5-9 Our work also includes several studies showing 
that sampling of cessation medications leads smokers (both motivated and not) to increased cessation.10-12 
Together, gain framed messaging and NRT sampling offer a novel and compelling opportunity to engage 
smokers and catalyze cessation. Our methods, if shown to be successful, can be easily shared with lung 
cancer screening programs across the country. Thus, we plan to conduct a randomized trial of gain-framed 
intervention (yes vs. no) x NRT sampling (2-week supply of both nicotine patch and lozenge vs. not) within a 
high-risk group of smokers (N=367) across 3 study sites (MUSC, VA and Yale). This study is powered to 
examine main effects of our 2 interventions:    
Primary Aim 1: To determine if the rate of smoking cessation among lung screening patients is improved by 
delivering gain-framed smoking cessation messages and delivery of a free starter package of medication (gain-
framed behavioral intervention + 2 weeks of nicotine patches and lozenges vs. unframed behavioral 
intervention + no medication).  
Hypothesis 1: Cessation rates will be significantly higher at 6-months after lung screening for the smoking 
cessation strategy involving a gain-framed intervention + 2 weeks of nicotine patches and lozenges compared 
to a strategy of an unframed behavioral intervention + no medication. We define cessation as 7-day point 
prevalence but will assess multiple definitions of success.   
Exploratory Aim: To examine mediators and moderators of treatment to determine mechanisms of treatment 
effects and which subgroups are most likely to respond to the gain-framed and medication interventions, and to 
explore differential effects of the study factors across treatment groups.  Treatment interactions will also be 
explored secondarily.    
Hypothesis: Changes in self-efficacy, smoking cessation outcome expectancies, familiarization with NRT, 
motivation, and autonomy will act as mechanisms for the smoking cessation effects (i.e., will act as mediators 
of treatment). Lung screening findings (e.g., presence of a nodule, cancer, etc), nicotine dependence, and 
health disparities will modify treatment response (i.e., will act as baseline moderators of treatment).  
Exploratory Aim: To examine additional treatment endpoints: patient reach, intervention fidelity, patient 
acceptance and engagement, cost, and the ease of delivery and feasibility.  
Hypothesis: We hypothesize that this project will be a low-cost feasible intervention that will reach a majority of 
patients who are smokers, with high adherence to and acceptance of the critical intervention elements.  
Our rigorously designed study will be the first to demonstrate the individual and combined effects of gain-
framed messaging and NRT sampling in a lung cancer screening population, which is a high-risk, difficult to 

2 
 
treat group of smokers in need of feasible, easily administered interventions, thus offering strong potential for 
clinical and population impact.     
 

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RESEARCH STRATEGY 
A. Significance: 
 
Cigarette smoking leads to more than 480,000 deaths annually in the United States.13 Smoking causes 
30% of all cancer deaths and nearly 90% of all lung cancer deaths.14 While many of these deaths occur in 
former smokers, continued smoking remains an ongoing public health challenge, despite the remarkable 
progress that has been made in development of effective smoking cessation treatments.15 Lung cancer is now 
the leading cause of cancer death in both men and women in the US.16 In addition to primary prevention 
(tobacco control), secondary prevention through early detection is another strategy to reduce lung cancer 
death rates. More specifically, lung cancer screening with low-dose CT scans (LDCT) identifies lung cancer at 
an earlier, more treatable stage in high-risk patients. Evidence from the National Lung Screening Trial (NLST), 
for which MUSC was a study site, showed that screening with LDCT for high risk individuals (>30 pack years of 
smoking, <15 yr quit-time, and 55-74 yrs of age) conferred a 20% reduction in mortality for those patients who 
received 3 annual low dose CT scans.17 These findings led the USPSTF to recommend annual screening with 
LDCT for lung cancer in persons at high risk based on age and smoking history (grade B),18 with CMS and 
many private insurers now covering screening for this population. With an emphasis on the components 
necessary for a high-quality lung screening program3 which includes smoking cessation efforts, comprehensive 
screening centers are opening across the nation. Tobacco treatment options offer limited success,19 thereby 
increasing the importance of smoking cessation for this population. Much is known about cessation within the 
general population, but less is known for lung screening patients. The proposed study is the first study of a 
smoking cessation intervention specifically for patients enrolled in a clinical lung cancer screening program.  
 
While one might hypothesize that simply having a CT scan may promote cessation, evidence suggests that 
having a scan increases quit rates only slightly, if there is any increase at all.20,21 In a recent study, CT 
scanning prompted smoking cessation shortly following the scan, especially when the results were abnormal. 
However, long-term abstinence rates were similar for those with and without abnormal lung findings.22 
Likewise, referral to a physician for an abnormal scan result may increase initial quit attempts but this is not 
always sustained.23,24 A recent evaluation of qualitative interviews from current smokers offered lung cancer 
screening showed that 49% of participants suggested that screening lowered their motivation for cessation.25 
Misperceptions include the belief that negative screening offers protection from lung cancer; or the perception 
that screening can save lives by catching cancer early when indeterminate findings are identified that can be 
monitored; or a belief that a cancer-free screening test result indicates that they are among “the lucky ones” 
who will avoid the harms of smoking. There is of course no safe level of smoking, even among those who 
screen negative, and the need to effectively address cessation in the context of screening is profound. There is 
limited direction from the CMS memo regarding how to implement smoking cessation, with the option to 
provide very limited advice, which only has small effects.15 The present study is thus timely and novel – we will 
investigate whether we can achieve higher rates of short- and long-term cessation in a high risk population.  
 
Gain-Framed Messages: Prospect Theory4 provides the foundation to assert the influence of health message 
framing for smoking cessation. Prospect Theory suggests that decision makers organize or “frame” information 
relevant to a health decision in terms of potential gains or potential losses, as compared to a present reference 
point (e.g., one’s current level of health). Factually equivalent material can be presented differentially to 
individuals such that they encode it as either a gain or a loss from this reference point.4 Prospect Theory 
summarizes these decision strategies by noting that individuals are, in general, risk-seeking in the domain of 
losses but risk-averse in the domain of gains. When behavioral choices involve risk, individuals will be more 
likely to take these risks when information is framed in terms of the relative disadvantages (losses or costs), 
and they will be more likely to avoid these risks when the information is framed in terms of the relative 
advantages (gains or benefits).26 The type of health behavior also influences the effects of message framing.26 
Gain-framed messages are more effective in promoting physical exercise, sunscreen utilization, and smoking 
cessation, all prevention behaviors (e.g., McCall & Martin Ginis27). In a secondary data analysis of the NLST, 
we demonstrated that former smokers in the control arm abstinent for 7 years had a 20% reduction in lung 
cancer specific mortality compared that of those screened with LDCT. Further, the combination of smoking 
abstinence and LDCT screening resulted in a 38% reduction in lung cancer mortality.28 This novel research will 
be an essential piece of the gain-framed messages specific to lung cancer risk reduction that we use in the 
proposed project. We emphasize, in line with Prospect Theory, that it is the match between a message frame 
(gain or loss) and the required health behavior (prevention or detection) that especially motivates behavior 
change. Gain-framed messages have been shown to be more effective than loss-framed messages for 

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increasing intentions to quit, quit attempts, and smoking cessation in general populations of smokers.5-9  Thus, 
the primary hypothesis for our message framing intervention is that gain-framed messages are especially 
persuasive when promoting cancer prevention behaviors like smoking cessation, and thus can be utilized to 
further improve standard tobacco cessation counseling in the context of lung cancer screening.  We also 
believe that gain-framed messaging will have a particularly salient effect when presented in conjunction with a 
concrete, behaviorally-based cue to action as is offered through NRT sampling.   
 
Nicotine Replacement Therapy (NRT) Sampling NRT sampling merely refers to providing short, starter packets 
of NRT, which can be easily added to existing counseling (message framing) protocols. Sampling is distinct 
from a full course of NRT treatment, in that the intent is to engage smokers in the process of quitting, but 
without any requirement or expectation to quit immediately and/or abruptly. It is a softer, gradual exposure to 
the quitting process that is conceptually designed to heighten smoker acceptance and enhance motivation and 
self-confidence. It is also rooted in marketing research (businesses have been doing this for years), which 
shows that brief exposure to a product, when provided for free, increases positive opinion and more 
importantly increases further use of that product.29  
There are several mechanisms by 
which gain-framed messages and NRT 
sampling, when offered in conjunction 
with lung cancer screening, could 
promote downstream changes in 
smoking behavior (quit attempts, 
abstinence; see Figure 1). We discuss 
these potential mediators for both 
interventions below. One is through 
improved self-efficacy. As smokers gain 
confidence in controlling smoking, they 
may be more likely to believe that total 
abstinence is possible.9 Changes in 
outcome expectancies have been 
shown to act as a mediator in our 
previous gain-framed messaging research.30 NRT sampling might also heighten motivation. Whereas abrupt 
quitting is often daunting, gradual exposure to cessation, particularly when that experience is made easier 
through NRT, might remove some of the perceived barriers to quitting (e.g., “this isn’t so bad, I can do this”). A 
third mechanism is through increased familiarization with NRT. Many smokers continue to hold misperceptions 
about cessation pharmacotherapy, and particularly NRT. Misperceptions are broad, but typically pertain to 
concerns about 1) safety (e.g., addictive potential, adverse events), and 2) efficacy.31-35 In our prior efficacy 
trial of NRT sampling (discussed below), sampling of NRT yielded direct improvements in each of these 
mechanisms; i.e., increases in motivation, confidence, and knowledge/attitudes of NRT,10 which themselves 
are predictive of eventual cessation.34,36-39 Finally, while not an explicit outgrowth of self-determination 
theory,40,41 NRT sampling is wholly consistent with it; i.e., with the rationale that smokers will be more invested 
in the quitting process if they autonomously decide for themselves the goals and pace for changing tobacco 
use. Uptake of cessation treatment is higher when accessibility is increased,42 as would be the case when NRT 
is proactively provided at the point of lung screening. One older study examined outcomes of smokers in a 
cessation program who either received NRT for free, or paid for it.43 Use of NRT was higher when provided for 
free, as was long-term abstinence. Within tobacco control, the best example of NRT sampling is through 
quitlines. Evidence consistently shows that quitlines that offer free medication result in improved cessation 
rates as compared to quitlines that do not.44-49 Some45,50 but not all46 research suggests that 2-week provision 
of NRT is as cost-effective for promotion of quitting as is extended supply. However, whereas quitlines typically 
exclusively draw smokers who want to quit,47,51,52 we believe that NRT sampling is ideally suited to smokers 
across the motivational continuum, serving as a catalyst for treatment engagement among those who are not 
wanting to quit.  In the context of lung cancer screening, NRT sampling is particularly useful because it can be 
delivered on-the-spot (at the point of screening) and does not require specific training or skill. See below for 
prior and ongoing work within our group in support of NRT sampling. We believe that NRT sampling will have 
additional benefit when presented in concert with gain-framed messaging about quitting. This would be the first 
NRT 
Sampling 
 Self-Efficacy 
  Motivation 
 Familiarization 
w/ NRT 
 Autonomy 
Quit  
Attempts 
Abstinence 
  Treatment Utilization 
Figure 1: Conceptual Model for Gain-Frame Messages and NRT 
Gain-
Framed 
Messages 
 Outcome 
Expectancies 

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such test of this hypothesis, which, when presented in the context of a teachable moment, i.e., lung screening, 
offers additional clinical and public health significance.   
In the proposed study, we integrate these 2 complementary approaches to test a gain-framed intervention 
specifically designed for lung screening patients (vs. unframed messaging), as well as evaluating NRT 
sampling (vs. no medication). These interventions are complementary in that the evidence shows they will both 
lead to higher quit rates. Yet they are functionally somewhat independent. The evidence shows that self-
efficacy may be a mediator for both. However, the other mediators are independent – outcome expectancies is 
specific to gain-framed messaging and familiarization with NRT, motivation, and autonomy are specific to NRT 
sampling. The primary hypothesis is that gain-framed messages designed specifically for lung screening 
patients will be especially persuasive when promoting smoking cessation (a prevention behavior), and thus can 
be utilized to further improve standard counseling for lung screening patients. Further, we hypothesize that 
sampling NRT in the lung screening population of smokers will also promote smoking cessation in addition to 
the standard counseling and gain-framed intervention. While our study is based on a 2x2 design, we are 
appropriately focused on the effect of combined treatment (vs. neither) and main effects (of either treatment); 
interactions are explored but cannot drive our scope as such a study would be wholly infeasible (>5,000 
participants). Our project is designed to be translational (in that it can be transferable from our controlled 
efficacy study to other lung screening programs). 
Our proposed study will also evaluate important moderators of response to the intervention. Several 
framed message intervention studies from our group and other research groups have found that patient 
characteristics can moderate treatment efficacy (e.g., baseline characteristics such as tobacco dependence 
measured by the Fagerström scale, which may be very relevant in this patient population).53-56 We will evaluate 
nicotine dependence as a moderator of treatment outcomes, and anticipate that participants with lower nicotine 
dependence scores will have higher quit rates overall regardless of condition assignment but there will be a 
differential benefit of gain-framed messaging and medication for those with higher nicotine dependence scores. 
Further, very large disparities in tobacco use remain across groups defined by race, ethnicity, educational 
level, and socioeconomic status.13 These groups, plus those with mental illness who smoke, are at an 
increased risk for tobacco-related health disparities.57 Given the disparities in tobacco use and health among 
these groups, we will evaluate these variables and determine if they moderate treatment outcomes. We also 
anticipate that smoking outcomes may be affected by the lung screening findings. That is, perhaps a scan that 
identifies emphysema would motivate a patient to quit smoking. Because research is lacking on how screening 
findings affect the efficacy of personalized, gain-framed messaging and NRT sampling, we will carefully 
evaluate these factors and determine if lung screening findings moderate our intervention. 
 
B. Innovation: 
This study has many important, innovative features: 
1. This research is the first randomized smoking cessation trial conducted within and specifically personalized 
for lung cancer screening patients presenting to a lung screening clinic. Novel tobacco treatments for this 
population is critically needed, given the growing population of lung screening patients, which will grow 
dramatically now that lung screening is an approved CMS benefit. 
2. This is the first study to test both gain-framed messages and delivery of a free starter package of NRT to 
promote smoking cessation among lung cancer screening patients with varying levels of motivation to quit 
smoking.   
3. The model is highly translatable to other lung cancer screening settings. We are proposing translational 
behavioral (gain-framed messaging) and pharmacotherapy (NRT starter packages) interventions that would 
not need a specialized service. This could be easily integrated into other lung cancer screening programs. 
 
C. Approach: 
Preliminary Data 
Message Framing: 
Quitline Message Framing Study. As described above, previous studies from our group showed that the 
framing of messages for smoking cessation (e.g., gain-framed) can substantially affect efficacy.7-9 For 
example, we investigated whether gain-framed messages (i.e., presenting benefits of quitting) would be a more 
persuasive method to encourage smoking cessation than standard-care messages for callers to a telephone 
quitline. Coaches from the New York State Smokers’ Quitline were randomly assigned to provide gain-framed 
or standard-care counseling and print materials. Smokers (n=2032) who called the NY Quitline were exposed 

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to either gain-framed (n=810) or standard-care (n=1222) messages via 2 counseling phone calls and framed 
smoking cessation print materials.  All medically eligible callers received NRT. Gain-framed counseling was 
associated with a 10.7% higher rate of abstinence at the 2-week follow-up (i.e., 23.3% gain-framed vs. 12.6% 
standard-care, p<.001). Three-month follow-up data favored the gain-framed group, but was no longer 
statistically significant. However, this study had only very brief messaging one or two times; whereas the 
present study will engage patients with an in depth longer video intervention to begin with, then personalized 
print materials. This study was published in the JNCI6 with an editorial by the NCI’s Director of the Division of 
Cancer Control and Population Sciences, Dr. Croyle.58  
 
Message Framing with Bupropion Study. We also tested a framed message intervention in a primary care 
model using bupropion SR. This study was a randomized smoking cessation clinical trial comparing 2 framed 
messages (gain or loss) for smoking cessation in combination with 7 weeks of open label bupropion SR (300 
mg/day).5 Participants (N=258) were randomly assigned to receive factually equivalent video and print 
messages encouraging smoking cessation that emphasized either the benefits of quitting (gain-framed) or the 
costs of continued smoking (loss-framed). Participants saw 2 brief framed videos in 2 separate pre-quit 
smoking cessation sessions then received print messages at 3 post-quit sessions. The primary outcome 
measure was biologically verified abstinence 6 weeks after the targeted quit date. There was a significantly 
higher proportion of continuously abstinent participants in the gain-framed (47.6%) as compared to the loss-
framed condition (35.2%; p<.05). At a 6-month follow-up, the 7.3% advantage of gain-framed messages 
(24.4% gain-framed vs. 17.1% loss-framed) was marginally but still clinically significant (p=.07). In the present 
study we will conduct an intervention similar to the gain-framed message intervention in this study, but it will 
involve a significantly higher amount of tailoring and print interventions. Thus, we expect to obtain a slightly 
higher quit rate at 6 months than in this preliminary study. 
 
Yale Lung SPORE. The newly funded Yale SPORE will investigate short and long term smoking cessation in a 
high risk population of lung nodule patients. In the SPORE study that just started in late August 2015, we will 
test gain-framed messaging and biofeedback for smoking cessation in a set of interventions specifically 
designed for lung nodule patients. We will investigate whether smoking quit rates among lung nodule patients 
can be improved by augmenting standard care treatment (counseling + pharmacotherapy) with a novel gain-
framed video and print media intervention that is personalized based on an individual’s lung nodule diagnosis 
and presented in a gain-framed manner emphasizing the benefits of quitting for someone with this diagnosis. 
Messages will also be personalized to other characteristics including name, gender, preferred brand of 
cigarettes, and amount smoked to maximize effectiveness. While there is a body of literature that messages 
personalized to smokers’ characteristics seem to be effective and gain-framed messages are effective, no 
study to date has combined these two approaches and investigated a messaging intervention specifically 
personalized and gain-framed for lung nodule patients. We believe this study will be complementary and not 
competitive with the proposed study for two reasons. First, the primary method of recruitment for this study will 
be searches of patients’ medical records to find smokers who have a nodule. Although some patients enrolled 
in this study will have had their nodule detected through lung screening, this will be a relatively small portion of 
the patients enrolled. Two, this study will allow our research team to be an integrated part of the Yale 
Screening and Nodule Program, which will facilitate subject recruitment and follow-up for the proposed study. 
 
NRT Sampling:  We have completed two and have a third ongoing trial of NRT sampling, each in support of our 
rationale that this approach is a particularly useful clinical strategy to promote treatment engagement and 
abstinence among smokers seen in real world medical settings.   
 
NRT Sampling Study 1: Efficacy Trial among Unmotivated Smokers. We recently completed a randomized 
clinical trial (N=849) testing the concept of NRT sampling to induce cessation behavior among smokers 
unmotivated to quit.10,59 Smokers were recruited nationally via online channels, recruited into a phone-based 
intervention trial, and were assessed for six months. Phone-based treatment consisted either of 1) NRT 
sampling, within the context of a practice quit attempt (PQA), or PQA alone. The PQA intervention was a 
behavioral exercise, within which smokers could (or could not) sample nicotine replacement. The PQA was  
 

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Figure 2: Rates of any quit attempt (QA), 24hr quit attempt, floating abstinence (seven days, no smoking, at 
any point in study), and point prevalence (PP) abstinence at Week 26  
designed to increase motivation, confidence, and coping skills. The added value of NRT samples (nicotine 
lozenges) was hypothesized to familiarize smokers with NRT, promote wider acceptance of it, and ultimately to 
enhance motivation and confidence even further. Uptake of NRT during the sampling period was strong: 73% 
of smokers used the product, for an average of 9 days. Cessation outcomes were very promising, with 
significant increases in quit attempts and some measures of abstinence (Figure 2).10  
 
Important observations from our previous work. First, our efficacy study was based only on unmotivated 
smokers, and was powered on quit attempts (abstinence was secondary). Within the current trial, smokers 
across the motivational continuum are included, and our primary outcome is abstinence. Second, participants 
in the NRT+PQA group displayed significant changes in a) motivation, b) confidence, c) knowledge of NRT, 
and d) both positive and negative attitudes towards NRT (Table 1), all of which are mechanisms by which NRT 
sampling works. Third, while the effect size for abstinence was modest (OR=1.2), we believe this is because 
the control group (PQA) had independent effects on quitting.  We have since stripped NRT sampling down to 
its barest elements, 
most easily 
translated into 
clinical service. 
When implemented 
within the context of 
lung screening, 
sampling could 
have significant 
public health 
impact. Fourth, our trial embeds NRT sampling with message framing, which we believe will both a) 
significantly increase reach, and b) offer added weight and impact over NRT sampling in the absence of 
counseling (increased credibility vs. mailed NRT samples in prior study). Finally, outcomes from our prior trial 
were equal to or greater than those from established but time- and verbally-intensive options for cessation 
induction such as motivational interviewing60-62 and provider-delivered brief advice.63 We believe that NRT 
sampling in conjunction with grain-framed messaging as proposed herein is more conducive to producing 
abstinence-based outcomes. 
 
NRT Sampling Study 2: Evaluation of Motivation to Quit. The 
trial above was based on unmotivated smokers only. We next 
completed a separate pilot trial (N=157), of three groups, 
testing A) smokers motivated to quit, given 2-week samples of 
both nicotine patch and lozenge, vs. B) unmotivated smokers, 
given same treatment, vs. C) unmotivated smokers, no 
treatment.12 Over 85% of participants in Groups A and B used 
medication. Results after three months of follow-up (Figure 3) 
provide even further evidence for the sampling intervention. 
While initial motivation to quit enhances outcomes (A vs. B), it 
is not a necessary precursor to success (B vs. C). Note that 
abstinence outcomes were comparable between smokers 
0
20
40
60
80
100
Any QA
Any 24hr QA
Percent
PQA + NRT
PQA
0
5
10
15
20
25
30
Floating Abstinence
PP Abstinence
Percent
Table 1: Benefits of NRT sampling 
Baseline 
End of Treatment 
   
PQA+ 
NRT 
PQA 
p 
PQA+NR
T 
PQA 
p 
Motivation to Quit: Next Month (0-10) 
2.4 (2.8) 2.7 (2.9) 0.1 
4.0 (3.4) 
3.2 (3.1) 
0.001 
Confidence to Quit (0-10) 
4.0 (3.0) 3.9 (3.0) 0.6 
4.8 (3.2) 
4.0 (3.1) 
0.001 
Positive Attitudes towards NRT (1-4) 
3.0 (0.4) 3.0 (0.4) 0.6 
3.2 (0.4) 
2.9 (0.5) <0.001 
Negative Attitudes towards NRT (1-4) 
2.6 (0.7) 2.6 (0.7) 0.8 
2.1 (0.7) 
2.7 (0.8) <0.001 
Knowledge of NRT (0-10) 
4.5 (2.5) 4.4 (2.5) 0.6 
6.5 (2.0) 
4.6 (2.3) <0.001 
0
10
20
30
40
50
60
70
80
90
100
24hr Quit Attempt
7-day PP Abstinence
(3months)
Percent
Figure 3
Group A
Group B
Group C
p < .05
OR = 1.5 
(95% CI: 1.1 - 1.9) 
OR = 1.5 
(95% CI: 1.1 - 2.0) 
OR = 1.2 
(95% CI: 0.8 - 1.8) 
OR = 1.4 
(95% CI: 1.0 - 2.0) 

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who received NRT samples but who were or were not motivated to quit (Groups A vs B), thus suggesting that 
sampling medication is a valuable option for all smokers.   
 
NRT Sampling Study 3: Real-World Comparative Effectiveness within Primary Care.  We have ongoing a large 
(N=1160) cluster randomized pragmatic clinical trial of NRT Sampling within 20 primary clinics across South 
Carolina. This study is powered on abstinence, tracked through six months of follow-up. Outcomes will focus 
on the individual smoker (additional use of medication, quit attempts, abstinence), provider (satisfaction, 
confidence with cessation counseling) and aggregated across clinics (rates of tobacco screening, counseling).    
Everything (screening, consenting, baseline assessment, and treatment delivery) is done within the clinic, by 
clinic staff; only follow-up assessment is conducted centrally by research staff. Thus, we focus on real world 
implementation throughout. Seven clinics have completed enrollment to date (current N=426), and 3 more 
clinics are currently active. Clinician buy-in has been strong in large part because the “intervention” takes mere 
minutes to deliver.  For the current proposal, we add the extra benefits of gain-framed messaging in 
conjunction with NRT sampling, further enhancing benefit but without any sacrifice of feasibility.   
 
Attitudes toward Pharmacotherapy (2 studies). In addition to Dr. Cummings’ prior work on attitudes and 
perceptions of NRT,32,33,64 Dr. Carpenter locally conducted two complementary studies that document attitudes 
and misperceptions of cessation medication. The first was a qualitative study of perceptions of NRT 
specifically.65 Results highlighted enduring misperceptions about NRT that likely undermine usage. Despite 
apprehensions of cessation medication, there were two themes that offer an opportunity to promote wider NRT 
utilization, and both are highly relevant to the current proposal. First, many smokers expressed trust in 
physicians, with a common view that “I would use it if my doctor said it was ok.” Second, a strong number of 
smokers, particularly African American smokers, expressed willingness to try NRT if free samples were 
available: “If I could go to the doctor, and he could tell me the right amount of dosages to quit smoking, 
I would try it.” Together, these beliefs strongly support the notion that NRT sampling, particularly within the 
context of a lung screening clinic, could significantly promote wider uptake of evidence-based treatment.  
Our second study of attitudes towards cessation pharmacotherapy was a phone-based cross-sectional survey 
of South Carolina ever-smokers.66 Current smokers (N=697), attitudes towards pharmacotherapy are 
presented in Table 2. Even among never users of cessation medication, within whom there was disregard for 
pharmacotherapy, there was strong willingness to try a free sample if a healthcare provider gave it to them. 
 
Table 2: Attitudes towards Cessation Medications: Current Smokers1 
 
Ever User2 Never User2 
How well do medications work to help smokers quit? 
61% 
53% 
How concerned are you about medication safety? 
51% 
63% 
How concerned are you that you might get addicted? 
19% 
50% 
How concerned are you about cost? 
65% 
42% 
How likely would you use a sample of medication if provided by your healthcare provider? 
78% 
61% 
1 percent endorsing >4 on Likert scale of 1 (not at all) to 5 (a lot)   2 ever/never users of any pharmacotherapy 
 
Expertise and Ability of the Research Team  
Our research team has the requisite experience and expertise to conduct this study: 
Principal Investigator (PI): Benjamin Toll, Ph.D. Dr. Toll is an Associate Professor of Public Health Sciences at 
MUSC, a member of the Hollings Cancer Center (HCC), Chief of Tobacco Cessation and Health Behaviors at 
HCC, and Co-Director of the HCC Lung Cancer Screening Program. The Tobacco Treatment Program team at 
HCC (which consists of a full time secretary/patient scheduler, a clinical pharmacist, and Dr. Toll) is tasked with 
assessing all HCC patients with regard to tobacco use and offering all patients smoking cessation treatment. 
He has extensive experience conducting randomized controlled studies of interventions that promote smoking 
cessation, and has completed and published 4 large randomized controlled smoking cessation trials.5,6,67,68 He 
is also the Co-PI of a Yale Lung SPORE project evaluating personalized gain-framed feedback and 
biofeedback for smoking cessation among lung nodule patients. Further, prior to his position at MUSC, Dr. Toll 
was an Associate Professor at Yale and thus has a pre-existing relationship with the cancer programs and lung 
cancer screening program at Yale Cancer Center/Smilow Cancer Hospital at Yale-New Haven (YCC).  
 
MUSC Co-Investigators: Dr. Carpenter is an Associate Professor of Psychiatry and Behavioral Sciences. His 
research interests include nicotine dependence, smoking cessation (including harm reduction), and tobacco 

9 
 
control. He has extensive experience in smoking cessation/tobacco research, across the continuum of human-
lab, clinical trial/treatment outcome, and policy-based studies. Dr. Tanner is an Assistant Professor of 
Medicine Pulmonary and Critical Care and the Co-Director of the HCC Lung Cancer Screening Program. She 
was one of 8 site leads for the VA National Lung Cancer Screening demonstration project and is an expert on 
various aspects of lung cancer screening including generalizability and shared decision making. Dr. Tanner is 
also a pulmonologist and member of the Multidisciplinary Thoracic Oncology Clinic at the Charleston VAMC. 
She is the head of the lung cancer screening program at the VA. Dr. Silvestri is a Professor of Medicine in 
Pulmonary and Critical Care, and is the President Designate of the American College of Chest Physicians. He 
is a health services researcher with expertise in all aspects of lung cancer diagnostics, screening and 
pulmonary nodule evaluation. He has written a number of guidelines on the diagnostic approach to lung 
cancer. He has published 3 NEJM articles related to lung cancer screening including risk assessment, patient 
selection and cost-efficacy. Dr. Cummings is a Professor of Psychiatry and Behavioral Sciences at MUSC. 
His research interests are in the field of health related behaviors, especially tobacco use prevention and 
cessation. Over the course of his professional career, he has received more than 50 grants and contracts 
totaling over $60 million. His most recent research is investigating the delivery and success of tobacco 
cessation interventions in oncology patients. Dr. Warren is an Associate Professor of Radiation Oncology and 
conducts research evaluating the epidemiology and health behaviors related to tobacco use and other 
exposures by cancer patients, the clinical effects of exposure to tobacco on therapeutic response as well as 
both cancer-related and non-cancer related health outcomes, and policy considerations for standard clinical 
practice and clinical trials design. Dr. Hughes-Halbert is a Professor of Psychiatry and Behavioral Sciences 
and the Program Leader in Cancer Control at HCC. Her research program focuses on identifying sociocultural, 
psychological, and environmental determinants of cancer prevention and control, translating this information 
into interventions, and disseminating efficacious strategies into clinical and community settings. Dr. Rojewski 
is a Postdoctoral Scholar in the Department of Public Health Sciences at MUSC. Her research interests are 
tobacco treatment, behavioral interventions for cessation (e.g., contingency management), and integrating 
cessation interventions in medical settings. Dr. Rojewski will work under the overall supervision of Dr. Toll to 
act as the Project Coordinator of the study. 
 
Yale Co-Investigators: Dr. Fucito is an Assistant Professor of Psychiatry at Yale and the Program Director of 
the Tobacco Treatment Service at Smilow Cancer Hospital at Yale-New Haven/Yale Cancer Center (YCC). Dr. 
Fucito’s Tobacco Treatment Service team [which consists of a full time secretary/patient scheduler, 2 nurse 
practitioners, and a physician (Dr. Bernstein listed below)] is tasked with assessing all YCC patients with 
regard to tobacco use and offering all patients smoking cessation treatment. Dr. Fucito conducts research on 
novel interventions for smoking and moderators and mechanisms of smoking treatment response. Through a 
NIAAA Career Award, she is currently developing an integrated smoking and alcohol treatment for heavy-
drinking smokers that emphasizes personalized feedback about health biomarkers. Her other research has 
identified nicotine dependence as an important moderator of framed smoking message effects. Dr. Bernstein 
is a Professor in the Department of Emergency Medicine at Yale. He pioneered the delivery of screening and 
treatment interventions for smokers in the emergency department (ED).69-72 His most recently published NCI-
funded study, on which Dr. Toll is a co-investigator, tested the efficacy of a multicomponent intervention for 
smokers in the ED. The 3-month biochemically confirmed quit rates for that study are: Intervention vs. Usual 
Care arms, 12.2% vs. 4.9% (P<0.001).73 In addition, Dr. Toll serves as a co-investigator on Dr. Bernstein’s 
current NHLBI-funded study examining the effectiveness of a novel Integrated Tobacco Order Set (ITOS) in an 
Electronic Medical Record in promoting sustained smoking abstinence in adult inpatients. As noted above, Dr. 
Bernstein works closely with Dr. Fucito on all medical aspects of patient care and smoking cessation treatment 
as part of the Tobacco Treatment Service at YCC. Dr. Tanoue is a Professor in the Department of Medicine 
Section of Pulmonary and Critical Care Medicine, Co-Director of the YCC Thoracic Oncology Program, and 
Director of the Yale Lung Cancer Screening and Nodule Program (see attached letter of support from Dr. 
Tanoue). She also is the Principal Investigator for the Yale Lung Cancer Biorepository. Her research interests 
are focused on early detection and risk stratification for lung cancer, and the development of quality metrics for 
lung cancer evaluation and lung cancer screening. 
 
Statistician: Nathaniel Baker, M.S. Mr. Baker is a statistician and Research Instructor at MUSC. He is an 
expert in methodological issues in the design, conduct, and analysis of clinical studies. As a long-standing 
collaborator of Dr. Carpenter’s, Mr. Baker has assisted our tobacco research group in developing appropriate 

10 
 
research designs, power analyses, randomization lists, analyses of adverse events, and outcome analyses for 
our smoking cessation studies.  
 
We considered a single site study but believe: a) recruitment feasibility is enhanced by more sites, and b) there 
are added benefits of geographic and demographic diversity. All analyses will control for site effects. MUSC 
and Yale have a long history of collaborative work. Dr. Toll has worked with investigators at both Yale and 
MUSC for many years, having published extensively with them,53,54,68,73-79 worked on collaborative projects,80,81 
and submitted grants. We are now working to establish a collaborative relationship with the VA.  
 
Design and Methods: 
General overview:   
We propose a group comparison study (gain-framed intervention vs. unframed intervention, starter package of 
2 weeks of nicotine patches and lozenges vs. no medication) to evaluation methods to boost rates of smoking 
cessation for a high-risk group of smokers (N=367) with varying levels of motivation across 3 study sites 
(MUSC, Ralph H. Johnson Veteran Administration and Yale). All eligible study participants will be randomized 
to receive either: 1) Unframed Messaging (hereafter referred to as UM) with no medication, or 2) Gain-framed 
Messaging + Meds (i.e., 1 gain-framed video and print materials + 2 week starter pack of NRT; hereafter 
referred to as GM+M). 
 
Participants: Our target sample will be 367 lung screening patients who currently smoke at each of 3 study 
sites: MUSC), Ralph Johnson VA, and Yale Cancer Center); Total N=367. The following eligibility criteria will 
ensure that we obtain our study sample of lung screening patients. Inclusion: 1) 50 years or older (we see no 
reason for an upper limit given supportive evidence for cessation among elderly),82 2) at least a 20 pack year 
history of smoking (i.e., the base population of high risk smokers to get screened) as assessed by the patients 
ordering healthcare provider or the research team, 3) current smoker (defined as any smoking in the past 30 
days – this is the criteria our lung cancer screening programs will use to trigger tobacco treatment 
interventions), 4) willing to be randomized, 5) English speaking; Exclusion: 1) unstable psychiatric/medical 
conditions such as suicidal ideation, acute psychosis, severe alcohol dependence, or dementia, and 2) known 
allergy to adhesives, and 3) current participation in another tobacco treatment program (e.g., using medication 
from a primary care doctor, quitline, etc).  
 
Procedures:  
Participants will be identified through the established lung cancer screening programs at all 3 sites (MUSC, VA, 
and Yale). The differences in study procedures for MUSC and VA patients will be the Intake, Consent Process, 
medication dispersal, and location of study visits as described below. All other study procedures will be the 
same for MUSC and VA study participants.  
 
Intake and Consent Process: 
For MUSC Charleston patients:  
If the electronic medical record identifies them as a smoker, or if they report being a smoker at the time of their 
scan, they will meet or speak by phone with one of our study research assistants. Patients who express 
interest in the study will set up an intake appointment with a research staff member within 60 days of the date 
of their shared decision making visit. Patients who decline to participate in the study will be asked why and will 
be asked if we can collect basic demographic data from their medical record (e.g., age, gender, race, ethnicity, 
pack years). All eligible lung cancer screening patients will receive a postcard prior to their appointment 
informing them that they may be eligible to participate in a research study. The study staff will call these 
patients prior to their appointment to gauge interest in the study. If the patient would like more information, a 
study staff member will either meet the patient at the scanner on their proposed scan date, at another agreed 
upon time and place, or speak by phone.  If the patient is interested in enrolling or getting more information 
about the study, a research assistant will speak to them or set a date with the patient to enroll them into the 
study. Study eligibility will be determined in concert with a clinic staff member and the site PI (Dr. Toll at MUSC 
or Dr. Fucito at Yale) following completion of baseline assessments, a review of the electronic medical record 
for health information (if necessary), and the eligibility checklist.  
 
Informed consent will be obtained prior to any other procedures. We will provide participants with the option to 
complete consent and/or baseline session 1) in person, 2) via an MUSC approved HIPAA compliant video 
Commented [TB1]: Chelsea, would you please frame this 
to the IRB like this: 
 
We chose to change our inclusion of potential participants 
from the day of the scan to the day of the shared decision 
making visit because although these 2 events generally occur 
on the same date, it is possible that patients may engage in a 
shared decision making visit and decline participation in the 
scan. We feel this is an important population to include in 
the study.  

11 
 
platform (teleconsent) or via REDCap electronic consent (e-consent) combined with a phone discussion, 3) by 
mail combined with a phone discussion, or 4) a combination of these options. Below is an overview of the 
procedures for each of these options.  
 
1) In person consent – Research staff will meet with the patient at a specified time and place to review the 
consent form and obtain a signature.  
2) Electronic consent - Signatures on the consent form may be obtained electronically via a HIPAA 
compliant secure connection platform (i.e., Doxy.Me, REDCap). Patients will be sent the link to the 
electronic consent form. The research staff will review the consent by phone or video and answer any 
questions before the patient signs the consent form. The patient will be asked if they are in a private 
place where they can discuss personal information. If they are, the research staff will continue with the 
consent process. If they are not, patients will be asked to move to a private place if there is one readily 
available or the call will be rescheduled for a time when the patient has access to a private space. The 
REDCap e-consent form will advise the participant to scroll to the bottom of their screen to input their 
electronic signature. 
3) Mail – If patients are unable or unavailable to complete the consent process by any of the above 
options, they will be sent via mail two copies of the consent, a baseline questionnaire, and a pre-
addressed, pre-stamped return envelope. All mailed materials will include our contact information and 
encourage individuals to call our office with any questions. A member of the research staff will speak 
with the patient over the phone to review the consent form and answer any questions. The person 
obtaining consent will have a copy of the consent, and once the patient has reviewed the consent and 
asked any questions, the person obtaining consent will sign and date their copy and ask the participant 
to sign and date their copy. The consent will be fully executed when the participant mails back their 
copy and the two consents are combined.  
 
 
If a patient, using the remote study visit option, is randomized into a group receiving NRT, the medications will 
be mailed to the participant as soon as possible. If a patient is randomized into the gain-framed group, they will 
be asked to view the gain-framed video via an emailed or texted link and the gain-framed materials will be 
mailed to them as soon as possible. Following the consent process, patients will also be asked to complete the 
baseline assessments during their first meeting. If they are unable to complete these during this appointment, 
research staff will remind them to complete these assessments within a week. Additionally, after consent has 
been obtained and eligibility has been established, we will offer participants the option to complete the baseline 
assessments at another time (including by phone) within a week of the start of the intake session to allow for 
greater flexibility to accommodate participant schedules. The study visit will be done at the clinic, at a public 
location convenient for the participant, or via phone. Participants will be paid $50 for completion of all intake 
assessments. 
 
For MUSC Lancaster, MUSC Chester, MUSC Florence, and MUSC Columbia patients:  
If an eligible patient from either MUSC Lancaster/Chester/Florence/Columbia is interested in enrolling into the 
study, all study procedures will take place remotely. It is not feasible to perform study procedures in person 
due to the far distance from study staff, who are located at MUSC Charleston. Recruitment and all study 
procedures will follow the same procedures as described above for MUSC Charleston sites, with the exception 
of using in-person methods. If the electronic medical record identified the patient as a smoker, or if the patient 
reports being a smoker at the time of their scan, the nurse practitioner will speak with the patient regarding the 
study and/or the patient will speak by phone with one of our study research assistants. The nurse practitioner 
will be given study flyers to hand out to eligible patients. Patients who express interest in the study will set up 
an intake appointment with a research staff member 60 days of the date of their shared decision making visit. 
Patients who decline to participate in the study will be asked why and will be asked if we can collect basic 
demographic data from their medical record (e.g., age, gender, race, ethnicity, pack years). All eligible lung 
cancer screening patients will receive a postcard prior to their appointment informing them that they may be 
eligible to participate in a research study. The study staff will call these patients to gauge interest in the study. 
If the patient would like more information, the study staff will meet with the patient virtually. All study visits from 
the MUSC Lancaster/Chester/Florence/Columbia sites will be conducted remotely. After the patient is 

12 
 
randomized into the study, they will be mailed study intake materials (i.e., wellness bag, written materials, and 
NRT if applicable). Study participants from this site will be paid using Amazon e-gift cards. 
 
For patients at the VA: 
All eligible patients, identified through the CPRS system, will be sent a postcard explaining that they are 
eligible for a research study and the study staff may be in contact with them. Those patients will receive a 
phone call after being sent a postcard from a study team member. The study member will gage the patient’s 
interest in the study, answer any questions the patient may have, and set up a meeting time at the VA or via 
phone. Additionally, the patients will have a phone call shared decision making visit with their Nurse 
Practitioner (NP). During this phone conversation, if the patient is a smoker the VA NP will inform the patient 
about the smoking cessation study we are offering and ask if they are interested in participating. If the patient 
is interested in participating, they will schedule their scan for the Lung Cancer screening clinic at the VA and 
inform us of the patient’s interest via our VA email that is encrypted behind the VA firewall of the date and time 
of the scan. Once a patient is scheduled, the study team member will inform Dr. Tanner, and she we place a 
pending medication order so that the medication will be available at the time of randomization even if Dr. 
Tanner is not available.  A study team member will meet the patient at the VA and give them the flyer and any 
additional information about the study they may need to make a decision and further confirm their willingness 
to participate in the study. If a patient is unavailable to meet at the VA, the study staff will offer to email or mail 
the flyer and discuss the details over the phone. The consent process will take place at the Charleston VAMC 
or via teleconsent (see section below). The initial baseline assessment and follow-up assessments will be 
conducted either face-to-face at the Charleston VAMC or via telehealth per preference of the patient.  
 
 
Study staff will be trained to obtain informed consent and complete the initial (baseline) assessments. They will 
go over the informed consent in detail with each participant and answer any questions the participant may 
have at the time of consent or at any point during the course of the study. Veterans will not participate in the 
research procedures until they have had the study carefully explained to them, have had the opportunity to ask 
questions and demonstrate that they understand the research procedures, and have signed informed consent 
and HIPAA authorization documents. All consent procedures will take place in person at the Charleston VAMC, 
or via teleconsent (see below.). Participants will be given a copy of the informed consent for their records and 
will be able to defer enrollment if they would like to speak with significant others about the study or further 
review the informed consent documents.  
 
We will provide participants with the option to complete consent and/or baseline session 1) in person, 2) by 
mail, or 3) a combination of these options. An additional overview of these procedures is included in the 
previous section about MUSC’s consent process.  
 
1) If the patient agrees to participate in our study in person, we will take them into a private consult room 
where we will thoroughly go over the VA consent and HIPAA form and have them sign these forms.  
Informed consent will be obtained prior to any other procedures in a private setting, then during the 
intake session medical and tobacco use histories and breath CO levels will be obtained. If a patient is 
randomized into a group receiving NRT, a member of the research staff will pick up the prescription 
from the research pharmacy and will give it to the patient.  
2) Mail – If patients are unable or unavailable to complete the consent process by any of the above 
options, they will be sent via mail two copies of the consent, a baseline questionnaire, and a pre-
addressed, pre-stamped return envelope. All mailed materials will include our contact information and 
encourage individuals to call our office with any questions. A member of the research staff will speak 
with the patient over the phone to review the consent form and answer any questions. The person 
obtaining consent will have a copy of the consent, and once the patient has reviewed the consent and 
asked any questions, the person obtaining consent will sign and date their copy and ask the participant 
to sign and date their copy. The consent will be fully executed when the participant mails back their 
copy and the two consents are combined. 
 

13 
 
Participants will be paid $50 for completion of the intake assessments. All follow up visits with the VA patients 
will take place at the VA hospital or over the phone if the patient is unable to attend an appointment at the VA. 
All study activities for participants recruited at the VA will take place at the Ralph H Johnson VA hospital or via 
phone call per patient request. 
 
Medication Dispersal for patients at the VA:  
The research assistant will let the research pharmacist and Dr. Tanner know in advanced when they will be at 
the VA to screen potential research participants. Dr. Tanner will electronically enter the order for the two-week 
supply of Nicotine patches and mini lozenges before randomization because she is not always available to 
enter medication orders at the time of intake. After a patient has been screened and has signed the Informed 
Consent, the ICF will be sent to the research pharmacist via the VA email or taken to the research pharmacy in 
person and copy is made. The research assistant will contact the research pharmacist via phone or Vocera to 
inform them of the randomization. The research pharmacist will fill the order that will then be picked up by the 
research assistant and given to the patient in person. If the patient is using the remote consent option, the 
medications will be mailed to the patient after randomization is confirmed by the research pharmacy.  If the 
patient is unable to complete the intake appointment the same day as their lung cancer screening visit, the 
research assistant will let research pharmacist know when the appointment is scheduled for. Dr. Tanner will 
put the order in for the NRT within a week of the patient’s appointment. If the patient is randomized into a 
group NOT receiving NRT the order will be cancelled. 
 
Standard Care for Smoking Cessation Advice for All Study Participants: 
Upon consent, all participants will be randomized to study group, stratified by study site and level of motivation 
(low: 0-7 on VAS ladder vs. 8-10). Following randomization, all participants will receive a bag with small 
smoking cessation tools (i.e., stress ball) and smoking cessation handouts based on practical counseling 
principles, which is a cognitive-behavioral, evidence-based, smoking cessation treatment modality focused on 
specific strategies to support quitting smoking. If patients are meeting with research staff via tele-consent, e-
consent, or by mail, the wellness bag will be mailed to them with the intervention materials they were 
randomized to receive. All participants will be encouraged to set a quit date.  
 
Study Interventions: 
 
 
Gain-Framed Messaging: We will develop 1 gain-framed video and corresponding printed materials. The 
video will be approximately 4 minutes long and will include individuals of differing racial and ethnic 
backgrounds representative of our study population. The video will be designed specifically for lung screening 
patients, addressing how quitting smoking can be helpful given their present situation. To be clear, we are not 
framing any information to encourage lung screening – the gain-framed intervention will focus on smoking 
cessation in the context of lung screening. It will highlight Dr. Tanner’s recent paper showing that quitting 
smoking will significantly reduce their risk for lung cancer in conjunction with screening.28 For example, a gain-
framed statement in this regard might say: “Attending this lung screening visit and low-dose CT screen is a 
great step toward better health and reducing your risk of lung cancer. Even if you decide not to undergo 
screening, you can still further reduce your risk of developing lung cancer and other diseases by quitting 
smoking. Research of high risk people who did not have a CT scan shows that by quitting smoking and 
maintaining abstinence you continue to reduce your risk for lung cancer.” 
 
For those in the arm that will receive gain-framed materials, we will disseminate the gain-framed print 
media to patients at the time of intake. A research assistant will show participants their assigned video via an 
iPad if they are assigned to the GM+M groups. We chose these procedures for several reasons: a) delivering 
the gain-framed messages by video allows us keep the content consistent, b) videos are easily disseminable, 
c) having our research staff administer the videos is consistent with how the videos would be administered at 
other lung screening programs (i.e., given by support staff and not clinicians), and d) this does not necessitate 
any special training or procedures with the clinical staff.  
 
The most appropriate comparison group for the gain-framed intervention is debatable; we could have used 
a loss-framed or general health video/print intervention as a comparator but we decided against this for several 
reasons: a) it is more translational and more of a "real-world" test to only investigate an intervention that we 
hypothesize may be better than standard care; b) we do not want to waste participants’ time with placebo video 
and handouts that we expect will not help them; and c) notably, our last large smoking cessation trial that 

14 
 
tested message framing was a comparison of standard care to a gain-framed intervention added to standard 
care,6 for similar reasons to those described above. Thus, our control condition for the gain-framed message 
conditions is no message. 
 
NRT sampling:  Participants in the medication arm (GM+M) will be given a 2-week long supply of both 
nicotine patch and lozenge. NRT samples will be delivered in addition to all standard care treatment described 
above.  Given the very brief ‘intervention’ time (few minutes), we believe that treatment groups will be 
essentially time-matched.  We will provide a 2-week supply of both 4 mg lozenge and 21mg nicotine patches 
provided in the original packaging. Detailed information on each product, including instructions for use, will be 
provided in the take-home packet, which will include FAQs and related information intended to dispel 
medication misperceptions. Patients who are receiving nicotine patches and lozenges will be given the option 
to try these over-the-counter products (i.e., a patch and a lozenge) at the time of their study visit with aid from 
the research staff and will receive handouts and instructions about proper use of the NRT.  We provide both 
patch and lozenge for four reasons. First, a number of studies demonstrate their efficacy when used 
singularly.84 Second, they are both over the counter, increasing their utility in various populations, particularly 
within lung cancer screening settings where eligibility is minimal and instructions on use require nominal 
discussion. Third, whereas the patch provides a steady dose of nicotine throughout the day, the lozenge is 
used ad libitum and provides acute nicotine administration. These two mechanisms might appeal to smokers 
differently. Fourth, two studies have shown that combined use of patch + lozenge is superior over placebo and 
single NRT products.11,85,86 We neither explicitly advise nor discourage combined use. Thus, this is an 
opportunity for smokers to learn about two NRT products, to be used individually or together (participant 
choice, including none at all). We will caution all participants on signs of receiving too much nicotine (nausea, 
dizziness), and will monitor adverse events, expected to be rare/mild. Given our inclusive study criteria, some 
study participants who have low nicotine dependence will receive the starter package of NRT. However, given 
recent evidence that dual NRT benefits most low dependence smokers, we feel this is appropriate.87 We do not 
offer a placebo comparison because we are interested in the provision of medication vs. not (and not to 
determine if effects are pharmacologic). However, participants not receiving the starter kit of NRT will still be 
advised to use evidence based medications, including NRT, per standard guidelines. The NRT for MUSC 
patients will be stored in a cabinet in the Tobacco Treatment Program offices. The door to the office suite 
locks. The NRT for VA patients will be obtained via the research pharmacy at the Ralph H Johnson VA Medical 
Center. 
 
Follow-up: Participants will complete assessments at a 1, 3,  and 6 month follow-up session. Research 
staff will meet the MUSC Charleston participant in a public location that is convenient to the participant or 
conduct the follow-up via phone call. MUSC Charleston patients will also have the option of coming in to the 
clinic at Hollings Cancer Center for the follow-up meeting. All participants recruited from MUSC Lancaster, 
MUSC Chester, MUSC Florence, and MUSC Columbia will complete all visits remotely. If the participant has 
an in-person meeting, we will complete a breath CO test and a battery of assessments.  If patients elect to 
complete these vists via phone call and report that they continued to smoke, a CO breath test will not be 
obtained. However, if the patient reports having quit smoking during the phone call, the research staff will 
schedule a visit to obtain the CO breath test. CO will be collected using the Bedfont Smokerlyzer for in-person 
visits or the Bedfont iCO smokerlyzer for remote visits. If CO is obtained remotely, we will mail a breath CO 
monitor to the participants with instructions for use. At a prearranged time, participants will be sent a link to a 
HIPAA Compliant video platform. Participants will virtually meet with research staff and will complete the breath 
CO sample live so that we can be sure it was the participant who provided the sample and reduce the chance 
of sample falsification. The CO device will also email a report of the CO sample to research staff. We plan to 
pay participants $10 for completion of the 1-  and 3-month follow up visits and $30 for the completion of the 6-
month visit. If the study participant is not available to meet in person or by phone, we will mail the follow up 
questionnaire to them to fill out and return via mail to us. Additionally, we can also send patients a link to the 
questionnaires via REDCap and contact them over the phone to get their timeline followback. 
Safety protocol: To ensure the safety of the research assistant they will adhere to the following safety 
guidelines: 
Confirm with participants by phone before the visit 
Send meeting information to the Study Coordinator prior to leaving for the meeting 
Meet in public buildings where you feel safe, and not in parking lots, or public parks  

15 
 
Send a message to the Study Coordinator to confirm that the meeting has ended and you are leaving the 
meeting location 
Never meet a participant after dark 
Keep your phone charged and on your person at all times in case of emergency 
To ensure the safety and privacy of the MUSC participant: 
We will try to meet in a public location that has an area that is in clear sight of others but semi-private area 
where we can obtain research data as confidentially as possible. 
We will not use the patient’s name in public at this location. 
We will speak in low volume to communicate with the participant as not to share information with those in 
the surrounding area. 
To ensure the safety and privacy of the VA participant: 
We create a VA REDCap database behind the VA firewall where all participant study data will be collected, 
stored and analyzed. 
 
 
Assessments (Items with an asterisk will be tested as a mediator or moderator): 
 
Demographic and Smoking History Questionnaire: As in our previous studies, this questionnaire will obtain: 
1) basic demographic information and 2) basic smoking status and history.5,67,88 At baseline this will assess 
basic smoking status and history which will allow us to personalize the messages for participants in the study 
groups receiving gain-framed messages.  
Tobacco and Alcohol Use Calendar (Timeline Followback): This standardized, validated, and reliable 
experimenter-administered rating scale89-91 will be used to obtain quantity and frequency estimates of cigarette 
consumption for a 30-day period prior to treatment. As in our previous clinical trials, we will use the calendar to 
record tobacco use on a daily basis throughout the 6 months of the study.5,67,88  
Abstinence: For our primary outcome, consistent with our past clinical trials, abstinence will be defined as 
7-day point prevalence abstinence, meaning no cigarettes (or other tobacco products) for 7 days, confirmed by 
CO breath test less than or equal to 10 ppm.5,67,88  
 
CO levels: Expired breath CO will be monitored at each in-person visit to verify abstinence during 
treatment. Levels of CO will be measured using a Bedfont Micro+ Smokerlyzer Monitor (Innovative Medical 
Marketing, Williamsburg, VA), which is a precision instrument for detecting CO in exhaled breath. Both study 
sites are currently using these devices and have several on hand. If smoking status is verified remotely, 
participants will be mailed a Bedfont iCO Smokerlyzer with instructions for use. They will complete the breath 
test live on a HIPAA compliant video platform and results will be emailed to study staff.  
Evaluation of Framed Intervention: This manipulation check asks participants to report whether the session 
focused on the costs of continuing to smoke or the benefits of smoking cessation.6  
 
 
*Outcome expectancies: Expectancies regarding the benefits of smoking cessation are important 
determinants of quitting.92-94 We anticipate that gain-framed texts will enhance expectations of the benefits of 
quitting smoking; so outcome expectancies will be evaluated as a mediator. We will administer 6 items from 
the Benefits subscale of the Perceived Risks and Benefits Questionnaire (health, well-being, self-esteem, 
finances, physical appeal, social approval).95 Participants will rate their perceptions of the benefits of quitting 
on a 7-point scale from 1 (no chance) to 7 (certain to happen). A similar brief measure of outcome 
expectancies has been shown to be a mediator of our framed message intervention with NY Quitline callers.30  
 
*Fagerström Test for Nicotine Dependence (FTND) and Heaviness of Smoking Index (HSI): The HSI scale, 
which assesses 2 items from the FTND scale about amount smoked and time-to-first-cigarette, is a commonly 
used scale for the measurement of severity of dependence on nicotine.96 The HSI has been shown to predict 
both behavioral and biochemical indices of smoking.96-98 In line with findings from our previous research53,54 
and from other groups,99,100 we plan to test both the FTND and HSI as moderators of treatment.  
 
*Self-efficacy: Tailored messages have been found to increase self-efficacy for smoking cessation;30 thus, 
we will examine self-efficacy as a mediator of treatment. We will measure self-efficacy using a single item. 
Participants will rate their confidence to quit smoking within the next month from 0 (not at all confident) to 10 
(completely confident).101 A similar, single item self-efficacy measure has demonstrated predictive validity in 
smoking cessation studies, and in our previous research with the NY Quitline.9 

16 
 
 
Use of NRT and Other Pharmacotherapy: We will determine the amount and frequency of NRT used (per 
product), and will determine use of products we provide (lozenge + patch) vs. additional purchase of products. 
We will ascertain the context in which the product is used (e.g., places with smoking restrictions vs. other) using 
prior methods.102 We will specifically ask if the NRT is used “not to quit, but to reduce the amount you smoke” or 
“not to quit or reduce smoking, but to get you through times when you cannot smoke.”   
 
*Attitudes Towards NRT: Based largely on prior work in this area,32-34,93,103 we have published10 on 1) 
positive, and 2) negative attitudes towards NRT, as well as 3) general knowledge of NRT. 
 
*Motivation and Confidence to Quit: We will separately assess motivation and confidence to quit smoking. 
We will do so using our modification of the Contemplation Ladder104 to measure readiness to quit in the next 1 
and 6 months. Our ladders have adequate test-retest stability and predictive validity.105 This measure will of 
motivation will be used for stratification, as well as to assess motivation throughout treatment. 
 
Findings from screening: Lung screening findings will be defined as pulmonary findings (nodule, cancer, 
emphysema, enlarged lymph nodes) and coronary findings (calcification).   
 
*Lung Cancer Distress Questionnaire: Higher baseline distress, as measured by the LCDQ has been 
associated short-term smoking cessation.114 We plan to use a single item from this questionnaire.  
Statistical Considerations 
Power and Sample size: 
We propose to test the primary hypothesis that rates of smoking cessation will be significantly higher 6-months 
after lung screening for the smoking cessation strategy involving a gain-framed intervention + 2 weeks of 
nicotine patches and lozenges compared to a strategy of an unframed behavioral intervention + no medication.   
We assume a biologically confirmed 7-day point prevalence abstinence rate at the 6 month follow up visit of 
10-13% for the participants randomized to receive no NRT or gain framed messaging based on USPHS 
guidelines (Table 6.7 and 6.8 of USPHS Guidelines).15 In studies with a similar 2 week NRT exposure, 6 month 
abstinence rates varied from 16-34 %46,107-109 and a conservative estimate of a 20% abstinence rate in those 
receiving NRT only will be assumed. Based on previous work5,6 we estimate that the abstinence rate of in 
those receiving both NRT and gain framed messaging will be 10-11% increased over those with unframed 
messaging. Based on these estimates, we will have 80% power with a type 1 error rate of 5% to detect the 
conservative difference of between those receiving gain framed messaging + NRT (28%) and those receiving 
unframed messaging and no NRT (13%) with 123 participants randomized to each of the 4 treatment groups 
(total n=492 Participants). This assumes that the two treatment sites are moderately correlated (ICC=0.85) and 
randomize equal numbers of patients to each treatment cell.  Additionally, we anticipate that 15-20% of our 
participants will fail to report 6 month follow up outcome data (LTF, death, moved out of area), accounting for a 
20% attrition during the study follow up, we would need to randomize n=367 participants across all sites (179 
randomized at Yale and 179 between MUSC and the VA) to maintain adequate power to detect the clinically 
meaningful difference stated. Assuming an abstinence rate of 14-17% in the group receiving unframed 
messages, we will have >80% power with a type 1 error rate of 5% to detect an 11% increase in abstinence in 
those receiving gain framed messages with the sample size stated for aim 1.  We considered but opted against 
powering our trial on the treatment interaction, as this would require >5,000 participants.   
 
Anticipated abstinence rates – 6 months 
Gain-framed 
Intervention 
No Message 
Intervention 
 
2 week starter pack NRT 
28-30% 
18-20% 
23-25% 
No Medication 
20-23% 
10-13% 
15-18% 
 
24-27% 
14-17% 
 
 
Statistical Analysis: 
Categorical clinical and demographic variables will be assessed by chi-square tests of independence, while 
continuous variables will be assessed using Student’s t-test. In addition to baseline group differences, preliminary 
analysis of baseline characteristics with outcomes of interest will examine significant correlates of abstinence in 
the study population. Characteristics found to be significantly associated with smoking outcomes will be included 
as covariates in the initial stages of model development. Our primary aim is to determine if the rate of smoking 
cessation among lung screening patients may be improved by delivering gain-framed smoking cessation 
messages and delivery of a free starter package of medication (gain-framed behavioral intervention + 2 weeks 
of nicotine patches and lozenges vs. unframed behavioral intervention + no medication). We hypothesize that 
rates of smoking cessation will be significantly higher at 6-months after lung screening for the smoking cessation 

17 
 
strategy involving a gain-framed intervention + 2 weeks of nicotine patches and lozenges compared to a strategy 
of an unframed behavioral intervention + no medication.  Primary and secondary models will be developed 
including the effects of both randomized conditions; gain framed vs. unframed messaging and NRT vs. no 
medication, and a cluster effect of study site.  Models will be computed both unadjusted and adjusted for 
significant covariates found in the preliminary analysis.  For these efficacy analyses, 7-day point prevalence 
abstinence will be defined as having no cigarettes (or other tobacco products) for 7 days, confirmed by CO breath 
test less than or equal to 10 ppm.  All randomized participants will be included in the analyses (intent-to-treat 
approach), and participants will be considered non-abstinent at any missed visit (drop-out/lost-to-follow-up 
included). To comprehensively analyze the longitudinal efficacy of gain framed messages and NRT sampling, 
the entire study time course will be analyzed with repeated measures logistic regression using a Generalized 
Estimating Equation framework. Continuous abstinence (CA) from the time of lung screening to the 1 and 3 
month follow-ups (Weeks 4 and 12) and to final follow-up visit (Week 26) will be assessed using logistic 
regression analysis.  Time to first lapse (puff) and time to relapse (first of 3 consecutive days smoking ≥1 
cigarette) will be analyzed using Cox Proportional Hazard models with effects of both randomized conditions in 
a 2x2 design; gain framed vs. unframed messaging and NRT vs. no medication, and a cluster effect of study 
site.  In addition to the primary intent-to-treat analyses, additional exploratory approaches (e.g., modified intent-
to-treat models, per protocol analysis, and completer analysis) will be undertaken as indicated and a sensitivity 
analysis comparing these models to the ITT model will be completed.   
 
We have an exploratory aim in which we plan to examine moderators of treatment to determine which 
subgroups are most likely to respond to the gain-framed and medication interventions, and we will explore 
differential effects of the study factors across treatment groups. Procedures from MacKinnon et al110 will be 
used to test mediators. We hypothesize that changes in self-efficacy, smoking cessation outcome expectancy, 
familiarization with NRT, motivation, and autonomy will act as mechanisms for the smoking cessation effects 
(i.e., will act as mediators of treatment). Variables that predict the outcome variable (smoking cessation) 
differently between treatments will be considered to be moderators using the model outlined by Kraemer et al.111 
In order to be considered a moderator, the variable must be present prior to randomization and must not be 
related to the independent variable. We hypothesize that lung screening findings (e.g., presence of a nodule, 
cancer, etc.), nicotine dependence, and health disparities will modify treatment response (i.e., will act as 
baseline moderators of treatment). Variables that predict the outcome variable but do not significantly interact 
with treatment condition (i.e., influence outcome regardless of treatment condition) will be classified as 
nonspecific pre-randomization predictors.  
 
Our other exploratory aim will examine additional treatment endpoints: patient reach, intervention fidelity, 
patient acceptance and engagement, cost, and the ease of delivery and feasibility. We hypothesize that we will 
reach a majority of qualified patients who are current smokers, adherence to the critical elements of the 
intervention design and delivery methods will be successfully met, patient acceptance and engagement will be 
greater in the gain-framed messaging and NRT arms, the cost will be higher in the NRT arms, and both the 
gain-framed messages and dispensing of the 2-week starter pack of NRT will be easily delivered and feasible 
as part of the lung screening clinic work flow.  Patient adherence, exposure to study content, 
acceptance/responsiveness to content and noted distinguishing factors will be assessed within the study and 
across study groups.112,113  Associations between treatment status and these exploratory endpoints will be 
assessed using general linear mixed models with data appropriate residual distribution assumptions 
(Gaussian, Poisson, etc.) and transformations where necessary.   
 
Adverse Events (AE) and Serious Adverse Events (SAE) will be recorded during the duration of the 
treatment period.  All cause treatment emergent adverse event and serious adverse event frequencies will be 
compared through the use of analysis of variance models. Of particular interest will be (S)AEs that lead to 
treatment suspension or study discontinuation. Study retention will be assessed by two methods; total number 
of treatment visits attended will be compared using Poisson regression for count data, while the number of 
days retained will be assessed using Cox Proportional Hazards regression models. 
 
Recruitment, Feasibility, and Timeline  
Patients eligible for this study come from our lung cancer screening programs at our 3 study sites (MUSC, VA 
and Yale). Because the smoking cessation treatment programs led by Dr. Toll and Dr. Fucito are clinical 
services, we have access to any and all of these patients for recruitment and are able to easily identify them 
through the Epic Medical Record (which is used at both study sites). Moreover, because Dr. Toll is the Co-
Director of the Lung Cancer Screening Program at MUSC and with the support of Dr. Tanoue (see attached 

18 
 
letter), who is the Director of the Lung Screening and Nodule Program at Yale, we have full access to all lung 
screening patients at those study sites. Dr. Tanner is the director of the lung cancer screening program at the 
VA and will be able to assist us in identifying all eligible participants that come through the lung cancer 
screening program. Because the USPTF recently recommended lung cancer screening for high-risk individuals 
and CMS covered lung screening as a benefit, many insurers are now covering lung cancer screening for high-
risk patients, so these numbers should continue to grow rapidly. At HCC, Between March 1, 2015 and 
September 1, 2015, we have had 50 patients screened under physician referral to the screening program 
(approximately 8 per month). We have engaged the primary care physicians at MUSC (University Internal 
Medicine) and are conducting outreach with these physicians to increase referrals for lung cancer screening at 
MUSC. Dr. Toll’s Co-Director of the Lung Cancer Screening Program at MUSC, Dr. Nichole Tanner (a co-
investigator on this grant), conducted similar outreach activities this past year at the Charleston VA and was 
able to screen 400 patients in the first year the program was open. Thus, we anticipate that our number of 
patients we are able to recruit will grow rapidly in the coming year. At YCC, there are 100 patients scheduled 
for screening over the next 4 months. Given the start date of this grant project and the time needed to prepare 
for the trial after the grant is awarded, we are highly confident that we will easily be able to meet our 
recruitment goal of approximately 1 participants per month (7 patients per month per site, VA/MUSC and Yale). 
This seems quite feasible given the large (and quickly growing) pool of patients available. The study timeline is 
described below: 
 
Months 1–6: 
Create gain-framed intervention materials, obtain study medication, train staff on study 
procedures, and finalize IRB approval. 
Months 7–51: 
Actively recruit 367 participants (approximately 14/month) and follow for 6 months.  
Months 50–60:  
Complete follow-up interviews, data analyses, prepare presentations and publications. 
 
Strengths and Overall Impact 
The proposed research has numerous strengths including: a) an experienced multi-disciplinary team; b) a timely 
research question, namely how to optimally enhance smoking cessation in growing populations of current 
smokers who are receiving lung cancer screening; c) gain-framed smoking cessation messages specifically 
developed for lung screening patients; d) an innovative pharmacotherapy strategy for all smokers; and e) ability 
to easily translate our findings to the growing number of lung cancer screening programs across the country. 
The findings from this research will have high overall impact by filling gaps in our knowledge of tobacco cessation 
in this high-risk population of smokers. These findings and the sharing of materials developed as part of this 
research will assist cancer centers and other healthcare organizations to maximize management of lung cancer 
screening patients with proven interventions for cessation, to have the greatest possible impact on lung cancer 
incidence and mortality.  
 
PROTECTION OF HUMAN SUBJECTS  
 
RISKS TO THE SUBJECTS  
 
Human Subjects Involvement and Characteristics  
In this experiment, participants will be recruited to participate in a smoking cessation study in the context of lung 
cancer screening. For the randomized controlled study, we will use the following inclusion and exclusion criteria. 
Inclusion: 1) 50 years or older (we see no reason for upper limit given supportive evidence for cessation among 
elderly), 2) 20 pack year history of smoking (i.e., the base population of high risk smokers to get screened), 3) 
current smoker (defined as any smoking in the past 30 days – this is the criteria our lung cancer screening 
programs will use to trigger tobacco treatment interventions), 4) willing to be randomized, 5) English speaking; 
Exclusion: 1) unstable psychiatric/medical conditions such as suicidal ideation, acute psychosis, severe alcohol 
dependence, or dementia, and 2) contraindications to NRT. We intend to enroll 616 participants across 3 sites 
(MUSC, VA and Yale).  
 
Sources of Materials. The sources of data for participants in this project is open-ended questions through 
interviewer-administered self-report questionnaires of background, behavior (eg, smoking), and cognitions (eg, 
motivation). Questionnaires will be administered at the time of intake (i.e., the lung cancer screening 
appointment), and at 1, 3, and 6 months for follow-up. All responses will be collected on a secure, password-

19 
 
protected, electronic Web-based form. The data will be sent to a secure database in REDCap. Only research 
staff members have access to the database. The data obtained from VA participants will be house in the VA 
REDCap database.  
We will collect demographic information, as well as diagnostic medical information related to their screening. 
Identifiable information will be collected and used to enroll, treat, and contact participants. It will only be used for 
this purpose.  
 
Research data will be collected using in-person interviews and self-reports. All identifiable information will be 
stored in a locked file cabinet. All identifiable information collected from VA patients will be stored in a locked 
cabinet in Dr. Tanner’s office room C405 at the Ralph H Johnson VA Hospital. All participants will be assigned 
a study participant ID made up of numbers and letters. Subsequently, participants will be identified in the Case 
Report Forms (CRFs) only by that number (e.g., CM24). A list of MUSC IDs and the corresponding names will 
be maintained by the Principal Investigator and stored on the MUSC BOX.Com site. Digital data with PHI will be 
stored on a secured server. A list of VA IDs and the corresponding names will be maintained by the site Principal 
Investigator, Dr. Tanner, and stored on the V drive behind the VA firewall. Digital data without PHI may be stored 
and analyzed on a laptop or desktop computer. 
 
Potential Risks. The risks to participating in these studies are minimal. Participants are informed in advance 
about the content of the educational materials that they will receive and the kinds of questions that they will be 
asked. They are also informed that they may terminate participation without penalty. Moreover, they are informed 
that, if any pre- or post-intervention question seems too personal or if they prefer not to respond for any reason, 
they can skip the question without penalty. There is also the risk of loss of confidentiality and privacy. Some 
participants will be offered nicotine replacement therapy (NRT), and there are risks in taking NRT. The NRT used 
in this study (patch and lozenge) is a standard smoking cessation intervention and is available over-the-counter. 
The most common adverse effect of nicotine transdermal delivery is topical skin irritation, ranging from mild 
erythema to a more generalized skin reaction, frequently in subjects with a history of eczematous dermatitis. The 
most common adverse effects of nicotine replacement lozenges are upset stomach and heartburn.  
 
ADEQUACY OF PROTECTIONAGAINST RISKS  
 
Recruitment and Informed Consent  
Participants will be recruited through the lung cancer screening programs at Hollings Cancer Center and Yale 
Cancer Center/Smilow Cancer Hospital at Yale-New Haven and the Ralph H. Johnson Veteran Administration. 
Informed consent will be obtained prior to beginning the study. 
 
Protection Against Risk. We will take the following steps to reduce the direct risk of participating in the study:  
 
(a) If offended in any way, participants can terminate any part of participation without penalty. In all of the 
preliminary experiments reported in this proposal, no participant reported being unduly distressed or upset about 
his or her participation, although occasionally participants do drop out because they are no longer interested in 
the study or because it is taking too long and they have other obligations. To date, no one has expressed 
significant regret about having participated.  
 
(b) If a participant or potential participant appears extremely distraught or clearly preoccupied, investigators will 
use their discretion as to whether or not to attempt to enroll the individual into the study or suggest that their 
participation stop. 
 
(c) If a participant reports an adverse effect of the NRT, we will work with them to ensure that they are using the 
medication properly. If it is determined that they have been using the medication properly and are still 
experiencing an adverse effect, they will be encouraged to discontinue use of the NRT.  
 
d) Several steps will be taken to safeguard the confidentiality of subjects and their data. All research data that is 
collected will be assigned a study participant number and that number will only identify participants in digital 
databases. The names of participants will not be associated with this data and assessments will be maintained 

20 
 
according to participant study number. A master list connecting participant study numbers to participant names 
will be kept online on the Box MUSC approved encrypted website where only senior level project staff will have 
access to the information. Any information published as a result of the study will be such that it will not permit 
identification of any participant. For VA patients, their consent forms will be stored in a locked cabinet in Dr. 
Tanner’s space on VA premises and their MUSC consent and HIPAA will be stored in a locked cabinet on MUSC 
premises.  
Medical records are maintained under the person’s name, but the study number is not entered anywhere into 
that record. Right to privacy for participation in this research will be protected through coding of data and proper 
storage of research records. The Principal Investigator will maintain a list of IDs and the corresponding names 
online on the BOX MUSC approved encrypted website. Consistent with mandated reporting requirements for 
health providers, we advise participants that in the case of child abuse or neglect, threat of injury to self or others, 
or intention to destroy property, that we may need to intervene and report that information to the proper 
authorities. Subjects will be informed of this limit to confidentiality as it is stated in the informed consent 
document. For VA patients, there will be a note entered in the CPRS system that they have been consented to 
participate in an MUSC study but no other notations of study procedures will appear in their medical records.  
The data will be stored in a locked room for 7 years after the final data is collected. The PI and the research staff 
will have access to PHI. Organizations that have a responsibility for protecting human participants, including the 
MUSC IRB, may have access to subjects’ medical records containing PHI. Additionally, the funding agency 
(National Cancer Institute) may have access to subjects’ medical records containing PHI. 
 
 
POTENTIAL BENEFITS OF THE PROPOSED RESEARCH TO THE SUBJECTS AND OTHERS  
 
Participants will receive advice about quitting smoking. Subjects participating in this study may benefit from the 
information provided to them the counselor by having their motivation to quit smoking bolstered and by receiving 
advice that helps them to quit smoking. Although the investigators cannot know for sure whether this study will 
be of any direct benefit to participants, the results of the study will facilitate the development of more effective 
smoking cessation intervention materials, which will promote tobacco and cancer control. 
 
IMPORTANTCE OF THE KNOWLEDGE TO BE GAINED  
 
Although the proposed research poses minimal risks to participants, it has high potential for advancing 
knowledge in the field of smoking cessation. The proposed research will augment current knowledge on the 
efficacy of interventions administered in the context of lung cancer screening. Administering a sample of NRT 
and gain-framed messages may help to identify a low-cost method for increasing the effectiveness of a 
moderate-intensity intervention for smoking cessation that has the potential to reach smokers at high risk of lung 
cancer, thereby bolstering tobacco and cancer control efforts across the United States. Given the minimal risks 
in the study and the potentially great benefit to science, the risk/benefit ratio in this study appears quite favorable. 
 
DATA AND SAFETY MONITORING PLAN  
 
Monitoring for data integrity and safety will be the responsibility of the investigators, the MUSC Institutional 
Review Board, and the Yale University Human Investigation Committee.  
 
Data Monitoring. For this review process, we evaluate a semiannual report of aggregate data that contains 
screening data, baseline demographics, retention data, adverse events data, accrual status including 
projections, times to milestones, and any other data that will help in the assessment of the experiments. Based 
on this report, we will decide whether we will: 1) continue recruitment unchanged; 2) continue with a protocol 
amendment; 3) stop the study pending further investigation. If after assessment, we feel that a protocol 
amendment is needed, the MUSC IRB and the Yale HIC will be immediately informed by the site PIs. 
 
Safety Monitoring. This protocol presents minimal risks to participants. The study involves receiving gain-
framed messages and/or a 2-week sample of NRT, and to complete follow-up interviews. The only risk that can 
be anticipated from this study is loss of confidentiality, and this will be protected using the procedures described 

21 
 
in the “Sources of Materials” section above. Nonetheless, because we anticipate that behavior change (which 
will pose minimal risk to participants) will be a product of participating, we have developed a safety monitoring 
plan to report adverse events resulting from behavioral changes.  
 
Monitoring to identify adverse events. Prior to implementing the randomized study, research staff will be 
trained to identify adverse events. Research staff will be instructed to provide the Project Coordinator a detailed 
description of the event. The Project Coordinator will grade the event in conjunction with the PI within 24 hours. 
The following additional individuals will be informed immediately of serious adverse events: (a) all Co-
investigators; (b) the National Cancer Institute; (c) the MUSC Institutional Review Board; and (d) the Yale 
University Human Investigation Committee. All of these individuals and committees will receive a copy of an SAE 
Form within 48 hours. 
 
Plan for grading adverse events. Serious Adverse Events (SAE). The FDA’s definition of serious adverse 
events (21 CFR 312) will be used. Serious Adverse Events include any untoward medical occurrence that at any 
dose results in death or the immediate risk of death, hospitalization or the prolonging of an existing 
hospitalization, persistent or significant disability/incapacity or a congenital anomaly/birth defect, new cancer, or 
medication overdose. Adverse events will be defined and graded for risk as follows:  
 
Coding of Severity:  
0 = No adverse event or within normal limits  
1 = Mild adverse event  
2 = Moderate adverse event  
3 = Severe, resulting in psychiatric or medical hospitalization  
4 = Life-threatening adverse event  
5 = Fatal adverse event  
 
Coding of Attribution will be made for adverse events grade 3 and above (ie, serious adverse events):  
1 = Unrelated to study interventions  
2 = Unlikely relationship to study interventions  
3 = Possible relationship to study interventions  
4 = Probable relationship to study interventions  
5 = Definite relationship to study interventions 
 
Plans for reporting serious unanticipated and anticipated adverse events. Serious adverse events, whether 
unanticipated or anticipated, will be reported immediately (within 24 hours) to the MUSC Institutional Review 
Board, the Yale University Human Investigation Committee, and to the National Cancer Institute, and a written 
report will be submitted within 48 hours. The PI will evaluate the adverse event and determine whether the 
adverse event affects the Risk/Benefit ratio of the study and whether modifications to the protocol or the consent 
procedures are required.  
 
Plans for reviewing and reporting nonserious anticipated or unanticipated adverse events. Any 
participants' experiences of anticipated and unanticipated adverse events will be reported on an annual basis to 
the MUSC Institutional Review Board, the Yale University Human Investigation Committee, and the National 
Cancer Institute as part of an annual progress report (NCI) and annual re-approval (MUSC Institutional Review 
Board and the Yale University Human Investigation Committee). 
 

22 
 
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