Little Cigar and Cigarillo Warnings to Reduce Tobacco-Related Cancers and Disease: Randomized Controlled Trial Among US Adults Who Use LCCs
Phase: NA
Conditions: Tobacco Use
Sponsor: UNC Lineberger Comprehensive Cancer Center

Little Cigar and Cigarillo Warnings to Reduce 
Tobacco-Related Cancers and Disease: 
Randomized Controlled Trial among US Adults 
who use LCCs 
 
Principal Investigator: Adam O. Goldstein, MD MPH 
Version 1, 4/17/2023 
Will be registered at ClinicalTrials.gov, will add registration number here: NCT05849051 
 
 

2 
Contents 
Administrative Information..................................................................................................................................................... 4 
Trial Registration ................................................................................................................................................................. 4 
Roles and Responsibilities ................................................................................................................................................... 4 
Funding Statement and Sponsors ....................................................................................................................................... 5 
Abbreviations and Definitions of Terms ............................................................................................................................. 5 
Introduction ............................................................................................................................................................................ 6 
Background and Rationale .................................................................................................................................................. 6 
Objectives and Hypotheses ................................................................................................................................................. 6 
Hypotheses ..................................................................................................................................................................... 7 
Trial Design .......................................................................................................................................................................... 7 
Methods: Participants, Interventions, and Outcomes ............................................................................................................ 7 
Methods Overview .............................................................................................................................................................. 7 
Participant timeline ............................................................................................................................................................. 8 
Study Setting ....................................................................................................................................................................... 8 
Participants ......................................................................................................................................................................... 8 
Eligibility criteria for participation in this study: ............................................................................................................. 8 
Interventions ....................................................................................................................................................................... 8 
Experimental Conditions ................................................................................................................................................. 8 
Warning Stimuli ............................................................................................................................................................... 9 
Stimuli Order ................................................................................................................................................................. 11 
Additional intervention details ..................................................................................................................................... 13 
Outcomes .......................................................................................................................................................................... 13 
Primary .......................................................................................................................................................................... 13 
Secondary ...................................................................................................................................................................... 13 
Other ............................................................................................................................................................................. 14 
Sample Size ....................................................................................................................................................................... 15 
Recruitment ...................................................................................................................................................................... 15 
Compensation Plan ........................................................................................................................................................... 15 
Methods: Assignment of interventions ................................................................................................................................ 15 
Allocation and Blinding ..................................................................................................................................................... 15 
Methods: Data collection management, and analysis .......................................................................................................... 15 
Data collection methods ................................................................................................................................................... 15 
Screener ........................................................................................................................................................................ 15 
Baseline Survey: Day 0 .................................................................................................................................................. 15 

 
3 
 
Daily Surveys: Days 1-6, 8-13, and 15-20 ...................................................................................................................... 16 
Weekly Surveys: Days 7, 14 ........................................................................................................................................... 16 
Post-Test Survey: Day 21 ............................................................................................................................................... 16 
Data Management ............................................................................................................................................................ 16 
Statistical Methods ........................................................................................................................................................... 16 
Methods: Monitoring ............................................................................................................................................................ 17 
Ethics and dissemination ...................................................................................................................................................... 17 
Consent ............................................................................................................................................................................. 17 
Confidentiality ................................................................................................................................................................... 17 
Declaration of Interests .................................................................................................................................................... 18 
Access to data ................................................................................................................................................................... 18 
Ancillary and post-trial care .............................................................................................................................................. 18 
Dissemination Plan ............................................................................................................................................................ 18 
References ............................................................................................................................................................................ 19 
Appendix A: Trial Consent Form ........................................................................................................................................... 21 
 
 
 

 
4 
 
Administrative Information 
 
Trial Registration 
Title: Little Cigar and Cigarillo Warnings to Reduce Tobacco-Related Cancers and Disease: Randomized Controlled Trial 
among US Adults who use LCCs 
Short Title: Little Cigar and Cigarillo Warnings 
ClinicalTrials.gov Registration: CT.gov link 
Registration Date: TBD 
Roles and Responsibilities 
The research team below is responsible for the study design, management, analysis and interpretation of data; writing 
any reports or publications; and decision to submit any reports or publications. Participant recruitment and data 
collection will be completed through Qualtrics and their panel provider, with supervision by the study team. 
Name 
Role 
Affiliation 
Adam O. Goldstein 
Principal Investigator 
Department of Family Medicine, University of North Carolina at 
Chapel Hill 
Lineberger Comprehensive Cancer Center, University of North 
Carolina at Chapel Hill 
Kristen L. Jarman 
Project Manager 
Department of Family Medicine, University of North Carolina at 
Chapel Hill  
Tara L. Queen 
Statistician, Co-
Investigator 
Department of Health Behavior, Gillings School of Public Health, 
University of North Carolina at Chapel Hill 
Sarah D. Kowitt 
Co-Investigator 
Department of Family Medicine, University of North Carolina at 
Chapel Hill 
Lineberger Comprehensive Cancer Center, University of North 
Carolina at Chapel Hill 
Leah M. Ranney 
Co-Investigator 
Department of Family Medicine, University of North Carolina at 
Chapel Hill 
Lineberger Comprehensive Cancer Center, University of North 
Carolina at Chapel Hill 
Jennifer Cornacchione 
Ross 
Co-Investigator 
Department of Health Law, Policy, and Management, Boston 
University, School of 
Public Health 
Paschal Sheeran 
Co-Investigator 
Department of Psychology and Neuroscience, University of North 
Carolina at Chapel Hill 
Lineberger Comprehensive Cancer Center, University of North 
Carolina at Chapel Hill 
James Thrasher 
Co-Investigator 
Department of Health Promotion, Education, and Behavior, 
Arnold School of Public Health, University of South Carolina 
Sonia Clark 
Research Staff 
Department of Family Medicine, University of North Carolina at 
Chapel Hill 
Olivia Hodgson 
Graduate Research 
Assistant 
Gillings School of Public Health, University of North Carolina at 
Chapel Hill 
 

 
5 
 
Funding Statement and Sponsors 
Research reported in this publication was supported by grant number R01CA240732 from the National Cancer Institute 
(NCI) and the Food and Drug Administration (FDA) Center for Tobacco Products (CTP). The content is solely the 
responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug 
Administration. 
 
National Cancer Institute, 
National Institutes of Health 
9609 Medical Center Drive 
Rockville, MD 20850 
 
Center for Tobacco Products 
Food and Drug Administration 
Document Control Center 
10903 New Hampshire Avenue 
Building 71, Room G335 
Silver Spring, MD 20993-0002 
 
Abbreviations and Definitions of Terms 
Abbreviation 
Definition 
LCC 
Little cigars and cigarillos 
NIH 
National Institutes of Health 
NCI 
National Cancer Institute 
FDA 
Food and Drug Administration  
CTP 
Center for Tobacco Products 
UNC 
University of North Carolina at Chapel Hill 
HWL 
Health warning labels 
PME 
Perceived message effectiveness 
OTP 
Other tobacco product (products other than little cigars and cigarillos) 
 
 
 
 

 
6 
 
Introduction 
Background and Rationale 
Over 4 million US adults regularly smoke cigars, which causes multiple cancers, including oral, esophageal, pancreatic, 
laryngeal, and lung cancer. (NCI ,1998; Chang, 2015) Even smoking 1-2 cigars per day is associated with elevated cancer 
risk. Though cigarette consumption decreased 39% from 2000 to 2015, cigar consumption increased 85%. (Wang, 2016) 
Of the three major types of cigars—large cigars, little cigars, and cigarillos—little cigars and cigarillos (LCC) are the most 
commonly used in the US. (Delnevo, Giovenco, 2017; Delnevo, Hrywna, 2017) LCC use among adults has increased, in 
part, because LCCs are taxed at a lower rate than cigarettes, are subject to fewer regulations and marketing restrictions, 
can be purchased in small pack sizes, and are exempt from flavor bans that apply to cigarettes. 
In May 2016, the Food and Drug Administration (FDA) required text-only warnings on LCC packs, rotating among six 
statements. Research on cigarettes suggests warnings on packs should have multiple rotating sets, contain images 
illustrating the negative health effects associated with LCC use, and be large. (World Health Organization, 2008; 
Hammond, 2011; Noar, 2016) However, the evidence for cigarette warning labels cannot adequately inform 
implementation of improved LCC warnings for four reasons: 1) The FDA proposed cigar warnings differ from existing 
cigarette warnings; 2) there is no evidence on the effectiveness of the FDA proposed cigar warnings (i.e., behavioral 
intentions or outcomes)(Richardson, 2013; Sterling, 2013; Glasser, 2017) or evidence on efforts that might improve LCC 
warnings (i.e., images, larger warning size, removal of LCC flavor descriptors on packaging); 3) Courts have ruled that one 
type of effective tobacco warning (i.e., for cigarettes) cannot be used to justify other types of tobacco warnings, such as 
those for LCCs; (R.J. Reynolds v. FDA, 2012) and 4) LCC users have different demographic and consumption profiles than 
cigarette users (i.e., LCC users include a higher proportion of young adults (SAMHSA, 2017), and African Americans, 
(Nyman, 2016; SAMHSA, 2017), and LCCs are used on fewer days per month)(Nyman, 2016; Jamal, 2018), which should 
be taken into account when developing improved warnings. 
Gaps exist in understanding which LCC warning characteristics (i.e., content, format, size) are most influential in 
reducing LCC use, and how additional LCC policies, such as removal of flavor descriptors on packaging, influence the 
impact of LCC warnings. Our project will provide new data to fill these evidence gaps. 
Our research on LCC warnings has found that the health effects included in warnings are the most important aspect of 
warning the warning statement text, and including multiple warnings can lead to stronger warnings, (Jarman, 2021) that 
that images paired with our warning statements that depict the internal harm or both internal and external harm of 
smoking LCCs were more effective. (Clark, 2022) In a 2x2 experiment to assess whether warning type (warning 
statement + image vs. warning statement only) and warning size (30% vs. 50%) were associated with perceived message 
effectiveness (PME), we found that the warnings that included images were higher in terms of PME than the warnings 
that were text-only, and that warning size were similar in terms of PME. (Goldstein, 2023) 
Given the lack of research on LCC product warnings, our overarching goal is assess whether LCC warnings developed by 
the study team are more effective than the currently implemented health warnings on LCC products. Given this goal, the 
choice of comparators are: 1) Newly developed warnings (the six most effective warnings developed by the study team), 
2) FDA proposed text-only warnings or 3) No warnings (control condition) in which participants will not see warnings.  
Objectives and Hypotheses 
 
Objectives 
The proposed study will fill critical gaps regarding which characteristics make LCC warning most effective and provide 
needed evidence on how LCC warnings influence LCC behavioral intentions. Our overarching goal is to develop 
effective LCC warnings that reduce cancer and other health risks. 
 

 
7 
 
Hypotheses 
• 
Newly developed warnings with images will increase LCC quit intentions more than FDA proposed text-only 
warnings and more than the control condition in which participants do not see packs or LCC warnings 
• 
The FDA proposed text-only warnings will increase LCC quit intentions more than the control condition 
• 
The warning conditions combined will increase LCC quit intentions more than the control condition 
• 
Newly developed warnings with images will increase self-reported learning more than FDA proposed text-only 
warnings 
Trial Design 
The study is designed to be a parallel group trial, with participants evenly allocated to each study condition, using a 
superiority framework. 
Methods: Participants, Interventions, and Outcomes 
Methods Overview 
We will conduct a 3-week web-based RCT of U.S. adults who currently use LCCs. In this study, LCC warnings on packs will 
be electronically presented to participants over time to determine if newly developed LCC warnings increase quit 
intentions compared to FDA proposed text-only warnings and a control condition (in which participants do not see LCC 
packs or warnings.) We will apply a daily diary methodology to present LCC warnings on packs to participants over time. 
Qualtrics will contact, screen, consent and administer the survey. To enroll participants, Qualtrics will screen participants 
using our inclusion criteria and measures and invite eligible participants to enroll in the study. To collect at least 750 
quality completes we anticipate enrolling up to 3,000 people. 
 
At the beginning of the baseline survey (day 0), participants will first consent to participate in the study and then 
complete a questionnaire about their tobacco use and behaviors (e.g., intentions and quit attempts) and other measures 
of interest. At the end of the baseline questionnaire, survey software will randomly assign participants to one of the 3 
study conditions. The three study conditions are: 1) Newly developed warnings (the six most effective warnings 
developed by the study team), 2) FDA proposed text-only warnings or 3) No warnings (control condition) in which 
participants will not see warnings. Participants will be contacted via email each day (at approximately 6am) to invite 
them to complete the survey for that day of the study protocol. 
 
For subsequent days (days 1-6, 8-13, 15-20) participants will be contacted and asked to complete a daily survey which 
will assess their previous day use of LCCs, as well as cigarettes and e-cigarettes. During these daily surveys, participants 
assigned to condition 1 or 2 (i.e., the warning conditions) will view an image of a little cigar and cigarillo package with a 
warning according to the participant’s condition. Participants within each warning condition will view a total of 6 
different warnings over the course of 6 days each week, this will be repeated 3 times during the study, resulting in a 
total of 18 exposures. Participants will be required to view the warning for at least 5 seconds before answering 
questions.  
 
On days 7 and 14 participants will be asked to complete a slightly longer survey with questions about their LCC behaviors 
including: number of LCCs used in the past week, butted out because they wanted to smoke less, and forgone, other 
tobacco use, blunt use, and quit intentions and attempts. 
 
For the post-test on day 21, participants will be asked to complete a longer questionnaire about their current tobacco 
use and behaviors including current LCC smoking behavior, LCC nicotine dependence, OTP use, LCC and OTP quit 
intentions, and LCC and OTP quit attempts.  
 

 
8 
 
Participant timeline 
Potential participants will be invited to complete the screener, those who are eligible will be invited to participate in the 
study. On Day 0, participants will be asked to complete a baseline survey, then a survey every morning for days 1-6, 8-
13, and 15-20 to deliver an LCC warning (stimuli shown only for conditions 1 and 2) and assess previous day behavior. 
Weekly behavior surveys will be completed on days 7 and 14. There is a final post-test on day 21.   
Process: 
 
 
Study Setting 
The study will be conducted with online surveys, so participants can complete the surveys from wherever they are. As 
part of eligibility criteria, all participants will reside in the United States. 
Participants 
Eligibility criteria for participation in this study: 
1. Members of the recruitment panel (we are partnering with a panel provider for recruitment of all participants) 
2. Agree to provide their honest answers 
3. Current little cigar and/or cigarillo every day or some day users 
4. Over 21 years old 
5. Currently living in US 
6. Inclusion criteria based on the design of the study: 
a. Feel comfortable taking a survey in English without help 
b. Feel comfortable taking an online survey without help 
c. Have an email address that they check regularly  
d. Have access to the internet at work or home 
e. Able to read and respond to surveys delivered to their email 
f. 
Able to complete 2 surveys that take approximately 20 minutes 
g. Able to complete a 5 minute survey each day for 20 days 
7. Inclusion criteria based on verifying real participants: 
a. Able to verify they are not a bot using CAPTCHA 
b. Able to answer a simple, random math question 
 
Interventions 
Experimental Conditions 
1. Newly developed warnings: the six most effective warnings developed in Aim 1 at 30% size 
2. FDA proposed text-only warnings: the six currently proposed warnings at 30% size 
3. Control group: a control condition in which participants will not see warnings, but will be asked to complete 
daily surveys on previous-day LCC behaviors 
 
Baseline 
(Day 0)
20 
minute 
survey
Days 1 - 6
2 - 5 
minute 
surveys 
each day
Day 7
5 - 8 
minute 
survey
Days 8 -
13
2 - 5 
minute 
surveys 
each day
Day 14
5 - 8 
minute 
survey
Days 15 -
20
2 - 5 
minute 
surveys 
each day
Day 21
20 
minute 
survey

 
9 
 
Warning Stimuli  
The stimuli for conditions 1 and 2 will vary based on the day of the protocol. The packages that the study warning labels 
will be shown on is standardized, warning labels will be shown on both a cigarillo and little cigar package (see table 
below: Stimuli Shown by Condition), and the packages will be purple and branded with the fictitious name “Brentfield” 
which has successfully been used in prior research to minimize the influence of brand loyalty and pre-existing brand 
perceptions. The warnings will be shown on the bottom 30% of the front of the package. Warning text for both warning 
conditions will be centered and the marker word “WARNING” was placed on a separate line. In accordance with FDA 
guidelines, warning text will be displayed in an arial bold type font. Across all warnings, the font in little cigar warnings 
was size 12 and in cigarillo packages, the font was size 14. (FDA, 2020) 
For all warning conditions, LCC packages will be centered and placed on either a plain white background or light grey, 
blurred background. When present, background images will be consistent with locations where LCCs could be purchased 
(i.e., at a counter or in a grocery store, or blank). The background is used to give context to the stimuli that may help 
participants focus on it and give a more real world feeling. 
 
Stimuli Shown by Condition:  
Condition 
Six Warning Messages Presented 
Example LCC package depicted on each background 
Transparent 
(White) 
Grocery Store  
Cigar Counter  
 
Newly 
developed 
warnings 
(Condition 
1) 
WARNING: Cigar smoking causes 
pharyngeal and throat cancer. 
 
 
WARNING: Cigar smoking causes stroke 
and blood clots. 
 
 
WARNING: Cigar smoking causes colon 
cancer. 
 
 

 
10 
 
WARNING: Cigar smoking causes 
bladder cancer and blood in urine. 
 
 
 
WARNING: Cigar smoking causes 
esophageal cancer. 
 
 
WARNING: Cigar smoking causes lung 
cancer and lung disease. 
 
 
 
FDA 
proposed 
text-only 
warnings 
(Condition 
2)  
WARNING: Cigar smoking can cause 
cancers of the mouth and throat, even 
if you do not inhale. 
 
 
WARNING: Cigar smoking can cause 
lung cancer and heart disease. 
 
 
WARNING: Cigars are not a safe 
alternative to cigarettes. 
 
 

 
11 
 
WARNING: Tobacco smoke increases 
the risk of lung cancer and heart 
disease, even  in nonsmokers. 
 
 
 
WARNING: Cigar use while pregnant 
can harm you and your baby. 
 
 
WARNING: This product contains 
nicotine. Nicotine is an addictive 
chemical. 
 
 
No stimuli: 
Control 
(Condition 
3) 
For condition 3, the control, 
participants were not presented any 
stimuli. 
N/A 
N/A 
N/A 
 
Stimuli Order  
 

 
13 
 
Message Letter Condition 1: Text + Image Warning 
Condition 2: FDA Text Only Warning 
F 
WARNING: Cigar smoking causes 
stroke and blood clots. 
(Stroke1) 
WARNING: This product contains nicotine. 
Nicotine is an addictive chemical. 
(Nicotine2) 
 
Background Order (based on Latin Square Design) 
We will have 3 background options (A=Plain, B=Counter, C=Grocery), they will be counterbalanced in order based on day 
• 
Message A will have background sequence: A, B, C (Sequence 1) 
• 
Message B will have background sequence: C, A, B (Sequence 3) 
• 
Message C will have background sequence: A, C, B (Sequence 2) 
• 
Message D will have background sequence: C, B, A (Sequence 4) 
• 
Message E will have background sequence: B, A, C (Sequence 6) 
• 
Message F will have background sequence: B, C, A (Sequence 5) 
 
Additional intervention details 
Participants can withdraw from the study if they choose by no longer responding to the survey links and may withdraw 
their data by contacting the UNC study team. 
Multiple strategies have been implemented to maximize adherence to the trial protocol, including reaching out to 
participants via email with invitations and reminders each day, compensating them based on completion of the most 
important questionnaires. 
There is no relevant concomitant care or interventions that are permitted or prohibited during the trial. 
Outcomes 
Primary 
- 
LCC quit intentions at post test (day 21) 
o Average quit intention score measured by survey, Quit intention measured with 3 questions, the final 
quit intention score is a mean of the response to the 3 questions, on a scale of 1 to 4, where 1 indicates 
low intention to quit, and 4 indicates a high intention to quit. 
 
Secondary 
- 
Number of LCCs smoked in past day (each day) 
o Measured daily by survey 
- 
Number of days smoked LCCs in past week (days 7, 14, and 21) 
o Measured weekly by survey 
- 
Number of LCCs smoked in the past week (days 7, 14, and 21) 
o Measured weekly by survey 
- 
Butting out LCCs (days 7, 14, and 21) 
o Measured weekly by survey 
- 
Forgoing LCCs (days 7, 14, and 21) 
o Measured weekly by survey 
- 
LCC quit attempts (days 7, 14, and 21) 
o Measured weekly by survey 
- 
LCC quit intentions (days 7 and 14) 

 
15 
 
Sample Size 
The sample size is based on quit intentions effect sizes from an RCT comparing graphic cigarette warnings to text only 
warnings (Brewer, 2016). Based on the effect size observed in that study, we would have 80% power at α=0.05 to detect 
a small change in differences between our groups (f=0.12). 
Recruitment 
We are working with Qualtrics research services to conduct this study and enroll participants from one of the panel 
providers that they work with. Qualtrics has access to high quality research panels across the US. They are able to 
leverage these panels to provide timely and reliable data collection to UNC and other research universities. We have 
high confidence that Qualtrics will be able to meet our recruitment goals. 
Compensation Plan 
Qualtrics will manage participant incentives. Participants in studies conducted by Qualtrics receive an incentive based on 
the length of the survey and their specific profile. The types of rewards vary and may include cash, airline miles, gift 
cards, redeemable points, sweepstakes entrance and vouchers. Participants who complete only the screening survey will 
receive a small incentive. For this study, participants who complete the baseline, 6 of the daily message surveys, at least 
one of the weekly surveys (day 7 or day 14), and day 21 will receive an incentive. Participants who complete only a few 
of the surveys but do not satisfy the criteria above will not receive an incentive. 
 
Methods: Assignment of interventions 
Allocation and Blinding 
Participants will not be informed specifically about the possible interventions that they may be assigned to. Researchers 
will not be blinded to the condition that participants had been assigned to, however all outcome measures will be 
assessed via online survey. At the end of the baseline survey, survey software will randomly assign participants to one of 
the three study arms. Participants will have an equal chance of being randomized to each study arm. 
 
Methods: Data collection management, and analysis 
Data collection methods 
Data collection will be conducted using Qualtrics web survey platform, questionnaires and references for measures can 
be found in the study measures document. Where possible, the measures used are previously developed and validated 
measures. Multiple strategies have been implemented to maximize adherence to the trial protocol, including reaching 
out to participants via email with invitations and reminders each day, and compensating them based on completion of 
the most important questionnaires. 
Screener 
Qualtrics will use invite potential participants to complete the screening survey and people who are eligible will be 
invited to complete the baseline survey. The screener is used to assess participant eligibility and collect demographic 
data. 
 
Baseline Survey: Day 0 
• 
Eligible participants will be invited to participate in the study and complete the baseline survey to enroll 
• 
The first part of the baseline survey will be a consent form with an agreement to participate in the study 
• 
The baseline survey contains baseline tobacco use questions (e.g., motivation to quit, previous year LCC quit 
attempts, nicotine dependence, etc.).  

 
16 
 
• 
At the end of the baseline questionnaire, survey software will randomly assign participants to one of the 3 study 
conditions 
Daily Surveys: Days 1-6, 8-13, and 15-20 
• 
There are 18 daily surveys, which align with each participant’s condition. Participants in conditions 1 and 2 will 
be shown stimuli (in accordance with their assigned condition) and condition 3 will not see any stimuli. 
Participants will stay in their condition throughout the study. Depending on the day, participants will see a 
different message 
• 
Daily surveys will be sent out at 6am EST and will close at 2am EST (gives west coast until 11pm to complete 
surveys). There will be a reminder email sent in the afternoon. 
Weekly Surveys: Days 7, 14 
• 
Weekly behavior surveys will include questions about LCC behaviors including: number of LCCs used in the past 
week, butted out because they wanted to smoke less, and forgone), other tobacco use (OTP), blunt use, and quit 
intentions and attempts.)  
• 
The weekly surveys will be sent out at 6am EST and will close 48 hours later.  There will be a reminder email sent 
in the afternoon, and the next day. 
Post-Test Survey: Day 21 
• 
For the post-test on day 21, participants will be asked to complete a longer questionnaire about their current 
tobacco use and behaviors including current LCC smoking behavior, LCC nicotine dependence, OTP use, LCC and 
OTP quit intentions, and LCC and OTP quit attempts. 
• 
Participants in conditions 1 and 2 will be asked recognition questions to assess whether they can recognize 
warnings shown to them in their condition  
• 
Participants will also be asked about their study experience 
• 
The post-test surveys will be sent out at 6am EST and will close 48 hours later.  There will be a reminder email 
sent in the afternoon, and the next day. 
Data Management 
Data management will be conducted by the study team. Multiple processes have been implemented to ensure high data 
quality, including internal pilots to test the protocol and ensure that data collection instruments are working properly, 
and ongoing data monitoring will be conducted during data collection to ensure that any issues with data quality are 
caught early and fixed. A pilot of the protocol with actual participants will be conducted before the full study is launched 
and participants will be asked about their experience in the study at the end of the pilot to further ensure that the 
protocol is working as intended and ensure a high quality data collection. 
Statistical Methods 
We will analyze the data using intention-to-treat analyses. Our primary outcome is LCC quit intention at post-test. We 
will model LCC quit intentions with message condition (warnings with images, FDA proposed text-only warnings, and a 
no warning control) as the between-participant predictor. 
Analysis methods will depend on the time point that the outcome was measured. Post-test measures will be analyzed 
differently than repeated measures from the daily survey and weekly surveys, as outlined below. All models will include 
a categorical indicator of day to control for the durable linear effect of time. 
Analysis methods for post-test measures will use linear regression for continuous outcomes, including the primary 
outcome of quit intentions, and logistic regression for dichotomous outcomes. Imputation will be used so that all 
participants who were randomized to an intervention and completed at least one daily survey will be included in the 
analysis, consistent with intention to treat practices. 

 
17 
 
Secondary models will examine differences between groups for items measured multiple times in either daily or weekly 
surveys (ex., LCC behavior measures). For these models, we will use linear mixed modeling to account for the repeated 
measure design. Mixed models are appropriate to use and robust to missing data, so we will be able to include everyone 
who completed at least 1 daily questionnaire, consistent with intention to treat practices. 
Secondary models will also be run for the primary outcome as well as secondary outcomes that include the number of 
daily surveys completed (This is a measure that is equivalent to the dose of the stimuli for the active condition and also 
applies to the control condition) 
LCC behavior is collected separately for cigarillos and little cigars and will be combined in the main analyses for these 
outcomes (ex. Number of cigarillos in past day and number of little cigars in past day combined for number of LCCs in 
past day). We also plan to run separate analyses for cigarillo behavior and little cigar behavior. 
Additional information about the statistical analysis can be found in the Statistical Analysis Plan. 
Methods: Monitoring 
To ensure maximum protection of human subjects, we submitted our research project information to the School of 
Medicine Data Safety and Monitoring Board at the University of North Carolina at Chapel Hill and asked them to make the 
final decision regarding risk to participants and whether or not our studies should receive their supervision. A 
representative of the board agreed that given that the study involves a low risk behavioral intervention in a healthy 
population, that oversight by the board was not necessary. 
Adverse events are not expected in this trial due to the minimal risks to participants, and no threat to participant health, 
so plans for collecting, assessing and reporting adverse events are not necessary. 
We have no plans for auditing trial conduct. 
Ethics and dissemination  
This trial was granted an exemption by UNC’s IRB under IRB # 22-2531.  
All protocol changes will be communicated to the study team, and any change in participant interaction will be approved 
by UNC’s IRB. Protocol changes will be tracked in an appendix table with new versions after initial approval including the 
date, version number, and a summary of changes. 
 
Consent 
Consent will be collected electronically as part of the baseline survey at the beginning of the study. At the beginning of 
the baseline survey, participants will view the consent form with an agreement to participate in the study. Participants 
will only be able to proceed with the study if they agree to participate in the study. 
Confidentiality 
We will take the following steps to minimize the risk to a breach of confidentiality via unauthorized access, use, 
disclosure, modification, loss or theft of participants’ information: We will use and enforce appropriate security 
measures including physical, technical and administrative safeguards. Data will be stored on a university secure server 
that is password accessed and is only accessible to key research personnel. All study personnel are required to have valid 
training on ethics of research on human subjects and to complete confidentiality certification procedures upon 
employment. The research team will not have access to personal identifying information. 
This study proposes research that has been determined to include Security Level 1 data security requirements. The PI 
has agreed to accept responsibility for managing these risks appropriately in consultation with departmental and/or 

 
18 
 
campus security personnel. The Data Security Requirements addendum can be reviewed here: 
https://guides.lib.unc.edu/datasecurity/irbis 
 
Declaration of Interests  
The study team declare that they have no competing interests.  
 
Access to data 
We will make data collection instruments available for public use after data collection and analyses are complete. On 
request, we will also make data sets available, stripped of individual identifiers, following publication of the relevant 
study’s main findings. We may submit deidentified data collected in this study to a data repository, such as UNC Odum 
Institute's Dataverse (https://dataverse.unc.edu/dataverse/unc) to make our deidentified data publicly available. As part 
of submitting the data to a repository we will provide basic information about how the data was collected and upload a 
deidentified dataset to the repository. 
 
Ancillary and post-trial care 
This trial presents no more than minimal risk to participants, does not collect data on harms to participants or assess 
interim data during the trial. There is no need for ancillary or post-trail care. 
 
Dissemination Plan  
The study team plans to disseminate study findings via conference presentation and peer reviewed manuscripts in 
scientific journals. The study team will also share findings via ClinicalTrials.gov registration. We will follow authorship 
guidelines depending on the journal to which manuscripts are submitted. There are currently no plans to make a 
participant level dataset public. 
 
 
 

 
19 
 
References 
Brewer NT, Hall MG, Noar SM, et al. Effect of pictorial cigarette pack warnings on changes in smoking behavior: A 
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20 
 
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22 
 
person to another. Personnel of a government agency sponsoring the study may also be provided information 
about your involvement in the research study. 
 
The de-identified data collected as part of this study may be used for additional research or included as part of a 
study data registry without additional consent. 
 
If you complete this study, you will be given an incentive from the panel provider. To complete this study, you 
must complete the survey today, the surveys on day 7, 14, and on or within 48 hours after day 21, and at least 6 
of the surveys on the other days. 
 
If you have any questions about this research, please contact the study team by calling (919)966-3016 or 
emailing JKristen@email.unc.edu. If you have questions or concerns about your rights as a research subject, 
you may contact the UNC Institutional Review Board at 919-966-3113 or by email to IRB_subjects@unc.edu. 
 
Do you agree to participate? 
[ ] Yes, I agree to participate 
 
 

 
23 
 
Appendix B. List of Measures by Timeframe 
Screener 
Baseline 
Daily (with messages) 
Day 7 and 14 - Weekly 
Behavior Assessment 
Post 
Quality Participants 
• 
Quality Control 
• 
Captcha 
• 
Simple Math Problem 
Assess LCC use 
• 
Ever Cigarillo 
• 
Days per month smoked 
cigarillo 
• 
Every/some days cigarillo 
• 
Cigarillo brand 
• 
Ever little cigar 
• 
Days per month smoked 
little cigar 
• 
Every/some days little 
cigar 
• 
Little cigar brand 
Demographics 
• 
Age 
• 
Hispanic/Latino origin 
• 
Race 
• 
Gender 
• 
State 
Other inclusion criteria: 
• 
Comfort with survey in 
English 
• 
Comfort with survey on 
computer 
• 
Email access 
• 
Access to internet 
• 
Ability to complete 
emailed surveys 
Consent Form 
Weekly Behavior 
Assessment 
Other tobacco use questions 
(14-28 items) 
• 
Cigarette use (2 items) 
• 
Motivation to quit 
smoking 
• 
Previous year LCC quit 
attempts 
• 
Nicotine Dependence (5 
items) 
• 
Tripartite Risk (3 items) 
• 
Self-Efficacy 
• 
Response Efficacy 
• 
Open Mindedness 
• 
OTP Quit Intentions (0-7 
items) 
• 
OTP Quit Attempts (0-7 
items) 
Additional Demographics 
• 
Sexual orientation 
• 
Education 
• 
Household size 
• 
Income 
• 
Subjective Financial 
Status 
• 
Zip code 
 
 
• 
Past day cigarillos 
• 
Past day little cigars 
• 
Past day cigarettes 
• 
Past day e-cigarettes 
• 
Warning/Study Stimuli 
• 
Attention to stimuli 
 
 
LCC Behavior (5 – 9 items) 
• 
Memory Cue 
• 
Past week Cigarillos 
• 
Days smoked 
• 
Number smoked 
• 
Butting out cigarillos 
• 
Forgoing cigarillos 
• 
Past week little cigars 
• 
Days smoked 
• 
Number smoked 
• 
Butting out little 
cigars 
• 
Forgoing little cigars 
OTP (2-9 items) 
• 
Tobacco products used 
in past week 
• 
Past week large cigars 
• 
Past week cigarettes 
• 
Past week smokeless 
• 
Past week e-cigarettes 
• 
Past week hookah 
• 
Past week oral nicotine 
• 
Past week something 
else 
• 
Past week NRT 
Past day items (4 items) 
• 
Past day cigarillos 
• 
Past day little cigars 
• 
Past day cigarettes 
• 
Past day e-cigarettes 
Intentions, etc. (14 items) 
Weekly Behavior 
Assessment 
Other tobacco use questions 
(12-26 items) 
• 
Motivation to quit 
smoking 
• 
Nicotine Dependence (5 
items) 
• 
Tripartite Risk (3 items) 
• 
Self-Efficacy 
• 
Response Efficacy 
• 
OTP Quit Intentions (0-7 
items) 
• 
OTP Quit Attempts (0-7 
items) 
Stimuli Responses (11 items) 
• 
Reactance (3 items) 
• 
Self-reported learning 
• 
Recall 
• 
Recognition (6 items) 
Quality Control Questions (8-
11 items) 
• 
See stimuli (+follow up) 
• 
Read text (+follow up) 
• 
Understand questions 
(+follow up) 
• 
Do study again 
• 
Recommend study to 
friend 
• 
Annoyed by study 
• 
Anything to share 

 
24 
 
• 
Ability to complete 
longer surveys 
• 
Ability to complete daily 
surveys 
• 
Past week blunts (2 
items) 
• 
LCC quit intentions (3 
items) 
• 
LCC Quit attempts 
• 
Conversations (2 items) 
• 
Other LCC warnings 
• 
Cognitive elaboration (2 
items) 
• 
Perceptions of recent 
LCCs smoked (3 items) 
 
• 
Difficulty with behavior 
recall 
Between 18 and 22 items – 
estimate about 5 – 6 minutes 
Between 20 and 34 items + 
consent, + 25-36 from 
weekly behavior assessment. 
 
Estimate it will take 14 – 20 
minutes when combined 
with screener and weekly 
behavior assessment 
3 items or stimuli and 5 items 
– estimate about 2 minutes 
to complete 
Between 25 and 36 items – 
estimate about 5 – 8 min 
Between 31 and 48 items, 
plus 25-36 from weekly 
behavior assessment. 
 
Estimate it will take 15 – 22 
minutes when combined 
with weekly behavior 
assessment