Impact of Nicotine Reduction on Adolescent Cigarette Use, Alternative Tobacco Use, and Harm From Tobacco
Phase: PHASE1
Conditions: Nicotine Dependence, Cigarettes, Uncomplicated
Sponsor: Brown University

Cover page for Protocol 
NCT03860077 
Grant number: R01DA047356 
Grant Title: Impact of Nicotine Reduction on Adolescent Cigarette Use, Alternative Tobacco Use, and 
Harm From Tobacco 
Includes changes approved as of: 9/28/20 

Impact of nicotine reduction on adolescent cigarette use, alternative tobacco use, and harm from tobacco 
 
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1. Lay Summary:  Adolescents are an important vulnerable population to consider as the FDA moves 
toward a nicotine reduction policy. Such a policy, which would mandate a reduction of nicotine in all 
commercially available cigarettes, has the potential to transform public health and greatly reduce the toll 
of tobacco-related death and disease. Yet, data on the effects of such a policy on cigarette use among 
adolescents are lacking. Further, the advent of e-cigarettes and the popularity of alternative tobacco 
products have fundamentally altered the current landscape of nicotine delivery, and these products are 
widely used by adolescents. Although adolescent cigarette use is at an all-time low in the U.S., this 
reduction has been mirrored by an increase in e-cigarette use, and multiple tobacco product (MTP) use is 
the most common pattern of use in youth. Adolescent MTP users are more likely to be dependent on 
nicotine and to have begun using tobacco earlier than their single-product using peers. Thus, MTP-using 
youth differ from youth who solely smoke cigarettes in meaningful ways that have implications for 
responses to a nicotine reduction regulatory policy. In adults, longer-term studies have demonstrated that 
VLNC cigarette exposure results in fewer cigarettes smoked and reduced toxicant exposure; however, 
increased use of alternative tobacco products has also been reported. No studies to date have examined 
the effects of VLNC cigarettes on MTP use or toxicant exposure in youth. This study will use real-time, 
smartphone-based EMA and laboratory-based assessments to: (1) investigate the effects of cigarette 
nicotine reduction on cigarette and MTP use, (2) assess the influence of cigarette nicotine reduction on 
the harms associated with tobacco use, including nicotine and toxicant exposure, respiratory symptoms, 
perceived health risk and nicotine dependence, and (3) use a combination of laboratory and real-time 
assessment to investigate the effects of nicotine reduction on changes in withdrawal, craving, and the 
reinforcing efficacy of cigarettes to characterize the mechanisms by which VLNC use may affect 
behavior. Overall, this project will help determine the effects of VLNC cigarettes on real-world tobacco 
use behavior and indices of tobacco-related harm in adolescents, and examining the mechanisms through 
which nicotine reduction in cigarettes may effect such changes. Such knowledge will contribute to the 
science base that may inform future policy decisions. 
 
2. Protocol Narrative 
a. Aims & Methodology 
a) Aim 1: To determine the effects of VLNC vs. NNC cigarettes on cigarettes smoked per 
day and frequency of alternative tobacco product use in adolescent cigarette smokers. 
We hypothesize that use of VLNC cigarettes will be associated with a decrease in 
combustible cigarettes smoked per day and an increase in the number of days of 
alternative combustible and noncombustible tobacco product use.  
b) Aim 2: To determine the effects of VLNC cigarettes on nicotine and toxicant exposure, 
perceived health risk of tobacco products, respiratory symptoms and dependence. We 
will test the hypothesis that use of VLNC cigarettes will lead to reduced nicotine and 
toxicant exposure, dependence, and respiratory symptoms in adolescent MTP users. 
c) Aim 3: To leverage real-time EMA assessment to determine the effects of VLNC 
cigarettes on withdrawal and craving, and to determine whether these momentary 
changes influence alternative tobacco use. We hypothesize that VLNC cigarette 
exposure may influence momentary changes in withdrawal and craving; and that these 
will vary both within and across individuals. 

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3. Overall Study Design:  A 2-group randomized between-subjects design will be used. Following a 
phone screening and informed consent procedure, adolescent tobacco users (ages 15-19, N=120) who 
report smoking cigarettes on at least 28 out of the last 30 days and use of one or more alternative 
tobacco products in the past 30 days, will complete their first laboratory session (Baseline Session 1 or 
BL1). After a one-week usual-brand baseline period during which all participants smoke as usual, a 
second laboratory session will be completed (BL2). At the end of that session, participants will be 
randomized to switch to either NNC (15.8 mg/g; n = 60) or VLNC (0.4 mg/g) cigarettes (n=60). During 
the 4-week experimental period, participants will be provided with study cigarettes each week and 
instructed to smoke only those cigarettes. They will also be told that they may choose to use other 
nicotine-containing products, such as e-cigarettes and little cigars, during the study. Daily, we will 
assess all cigarette smoking and use of all other tobacco products (as well as any non-compliant use of 
non-study cigarettes), and craving, withdrawal, and other factors using a smartphone-based app.  
Weekly, participants will come to the laboratory to complete assessments of dependence and respiratory 
symptoms, and behavioral economic assessments. Thirty days after the end of the protocol, participants 
will be contacted via phone and asked about their use of tobacco products and any changes in their 
overall health as a safety check. The flow of the protocol is depicted in Figure 1. All laboratory 
measures are shown in Table 1. 
Figure 1. Protocol Timeline. 
 
a.  Research Cigarettes. All cigarettes tested will be Spectrum research cigarettes (22nd Century 
Group, Inc.), which are produced for the National Institute on Drug Abuse (NIDA; NOT-DA-14-
004). The two cigarette types tested in the current study will contain 15.8 mg nicotine/g tobacco 
(normal nicotine content, NNC) or 0.4 mg nicotine/g tobacco (VLNC), both with tar yields of 9 
± 1.5 mg. Cigarettes are available in both menthol and non-menthol versions and participants 
will be assigned the flavor that they prefer based on their usual menthol preference. 

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b.  Advertising & Recruitment: We will contact schools to receive permission to set up 
informational tables during lunchtime that will provide information about the study. Interested 
adolescents will be read a short script with information about the study and if they remain 
interested will be screened for eligibility. We will also advertise the study on regional buses, in 
local and school newspapers, on Craigslist.org, on Facebook and Instagram, on the Center for 
Alcohol and Addiction Study’s (CAAS) website, other places online and on social media, via 
direct mail, and at local events. To reach adolescents outside of high school, we will also 
promote the study at GED classes and youth job training programs, and/or social service 
agencies such as community action programs, using flyers and information sessions. Interested 
adolescents can self-administer a screening interview via iPad, provide contact information to 
receive a follow up phone call, or call the research office to complete a brief, confidential 
telephone screening interview to establish eligibility.  
c. Phone Screen (Provided as attachment): The screening questionnaire will query past 6-month 
cigarette use, past 30-day frequency of other tobacco/nicotine, alcohol, and other drug use, 
motivation for smoking cessation, and other items required to establish preliminary eligibility 
(see Adolescent Phone Screen). The screening will remain the same whether or not it is 
administered via iPad or over the phone.  The screening questionnaire is used only to determine 
eligibility and will not be used as research data. 
d. Informed consent procedure: Adolescents who meet initial eligibility criteria, and who remain 
interested after hearing a more detailed description of the study, will provide contact information 
for their parent or legal guardian (minors only) so that parental informed consent can be 
obtained; 18-19 year olds can provide their own informed consent (see 18+ Consent 
attachment). Research staff will call the minor’s parent/guardian and provide the study 
information and answer any questions that they have (see Parent Phone Script attachment). If 
parents are willing to consent to their child’s participation, we will mail or email them a consent 
form to sign (and one to keep), which the adolescent participant will bring to the first session 
(see Parental Consent attachment). Eligible interested adolescents (with verbal parental consent 
if minors) will be scheduled for the initial in-person session and transportation arranged if 
necessary (see Adolescent Assent attachment). 
4. Screening 
a. During the initial in-person screening, participants will complete several questionnaires and have 
their CO taken to confirm eligibility to enroll. Female participants will also submit a urine 
sample to test for pregnancy. Urine will be sampled for cotinine levels if necessary. The 
Timeline Follow back, stages of change, and MINI suicide subscale will be used to determine 
eligibility. We estimate that we may need to consent up to 200 adolescents to result in a final 
sample of N=120. 
 
b. Inclusion Criteria 
1) Ages 15-19 20 inclusive 
2) Male and female current daily smokers 
a. Defined as self-reported daily cigarette smoking at phone screening AND 

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b. a breath carbon monoxide (CO) criterion of 5 ppm or higher; if this is not met, urine 
cotinine levels, detected by a NicAlert cotinine screening device, must indicate recent 
smoking (level 3 or higher) 
3) Current users of alternative tobacco product(s) 
a. Defined as any self-reported use of at least one non-cigarette tobacco product (e.g., e-
cigarettes, little cigars, cigarillos, hookah, etc.) in the past 30 days  
4) Participants must speak and comprehend English well enough to complete study procedures. 
a. Participant will be asked to read aloud first few lines of informed consent and then 
summarize the contents aloud to check for competency 
 
Exclusion Criteria 
1) Unwilling to use research cigarettes as part of the study 
2) Self-reported binge drinking of alcohol (> 4/5 drinks within a 2-hour period for female/male 
participants respectively) or use of illicit or non-prescribed drugs (excluding marijuana) > 10 
days in the past 30 daysdaily use of alcohol 
a. We will ask about daily alcohol and drug use in the phone screen, and we will use the 
Timeline Follow-Back to assess current and recent marijuana and alcohol use. 
3) Currently seeking treatment to quit smoking, and/or intending to quit smoking for good in the 
next 30 days 
a. This information corresponds to questions 2 & 3 of the Stages of Change measure 
which will be administered at the in-person screening. 
b. These participants will be excluded, and provided with referral information for 
cessation services in the community. 
4) Suicidal ideation in the past month or any past-year suicide attempts 
a. Suicidal ideation determined by the MINI suicide subscale at the in-person screening 
(Questions 4 and 5) 
b. Suicide attempt in the past year determined by MINI question 6.a. (If participant has a 
lifetime history of suicide attempt between 1 and 10 years ago, licensed medical 
monitor approval required) 
c. If a participant indicates that he/she currently has suicidal ideation during this or any 
future session, the Emergency Protocol will be followed in which a Licensed 
Clinician will be contacted immediately, and participants will speak with the clinician 
over the phone and the clinician will determine the appropriate action to take to keep 
the child safe. 
5) Pregnant or breastfeeding 
a. Determined by urine test at in-person screening; tested again at each in-person visit; 
participant will be excluded or withdrawn if test indicates pregnancy 
b. Self-reports current breastfeeding at in-person screening 
6) Any medical or psychiatric conditions in which participation is likely to pose a significant 
threat to health or for which the condition could interfere with the ability of the participant to 
fully participate (as determined by LMP). 
7) Having participated in another research study during the past year in which they were 
switched to research cigarettes for longer than one week.  
 
Initial eligibility determination will be made by the RA based on the above criteria. If the 
participant is deemed initially eligible, the BL1 session will immediately being. Eligibility 

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criteria will be reviewed by the medical monitor (Dr. Cioe) and the PI to confirm final eligibility 
for the study prior to randomization (BL2). 
5. Baseline 1 Session  
a. Purpose: If the participant is eligible after screening procedures, the first baseline session (BL1) 
will immediately begin. Participants who are ineligible will be paid $25 and will not complete 
the BL1 procedures. The RA will make the initial determination of eligibility; final eligibility 
will be confirmed by the study clinician and PI prior to BL2 (randomization). 
b. Procedure: BL1 will consist of an initial battery assessing baseline characteristics (see measures 
schedule). After these assessments, participants will be oriented to the EMA procedures. 
Research staff will help participants download the app to their smartphones, and then train them 
on how to complete the assessments. EMA surveys will begin the next day (see Table 2 and 
section on EMA Procedures below). During the 1-week baseline EMA period, participants will 
be instructed to smoke and use other tobacco products as they normally would.  
6. Baseline 2 (BL2) Laboratory Session  
a. Purpose: During this session, participants will be randomized to their study cigarette. Using 
multiple laboratory-based measures, this session establishes the acute effects of study cigarettes 
on craving, withdrawal symptoms, and subjective reinforcement value of the participant’s 
randomly assigned study cigarette.  
b. Procedure: At the beginning of the session, participants will provide a breath CO sample, 
complete a timeline follow-back measure for the interim week (i.e., between BL1 and BL2) 
which will query their use of cigarettes, alcohol, marijuana, and alternative tobacco products, 
complete a delay discounting task, and complete measures of craving (QSU), withdrawal 
(MNWS) and mood (PANAS). They will then smoke one study cigarette in the laboratory (while 
being observed by a research assistant in an adjoining room). Female participants will also 
provide a urine sample for a pregnancy test. Next, they will provide a post-smoking CO sample, 
repeat the QSU, MNWS, and PANAS, and then complete measures of cigarette subjective 
effects (CES), and perceived health risks of smoking. Then, they will complete a cigarette 
purchase task (CPT), a behavioral economics-based measure of cigarette reinforcement, which 
assesses hypothetical demand for cigarettes across a range of prices. They will complete the 
Experimental Tobacco Marketplace task which is described in detail under the Measure section.  
Participants will also complete a Health Changes Questionnaire to assess any adverse events. 
Participants will also complete an objective assessment of respiratory function using a 
Spirometer to measure their breath volume, and then provide urine samples for biomarker 
assessment. 
c. Product Dispensing: Participants will be randomized to switch from smoking their usual brand 
cigarettes to smoking either NNC or VLNC cigarettes over a subsequent four-week experimental 
period.  After all BL2 assessments are completed, study cigarettes will be dispensed to the 
participant at 125% of their weekly (between BL1 and BL2) consumption of cigarettes. Extra 
cigarettes are provided, as is typical in studies of this type (e.g., Donny et al., 2015; Hatsukami et 
al., 2010), to accommodate potential increases in smoking that may occur, and to allow any 
compensatory smoking (e.g., with VLNC cigarettes) to be detected. Participants will be 
instructed to smoke only the research cigarettes provided to them by the study rather than their 
usual brand cigarettes or any other cigarettes. They will also be told that they may choose to use 

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other nicotine-containing products (not provided by the study), such as e-cigarettes and little 
cigars, during the study. This distinguishes the proposed trial from past work with adolescents, 
which excluded most poly-tobacco users and prohibited non-cigarette product use during the 
experimental period. Participants will be dispensed cigarettes for a 714-day period; however; if 
their session is scheduled earlier or later (e.g., due to school holiday or vacation), then the RA 
may dispense up to a 14-day supply.. Participants will also be informed that if they run out of 
study cigarettes prior to their next scheduled visit, they can schedule a time to pick up more at an 
Unanticipated Visit, which will follow the same visit protocol as W1/W3 Check-In Visit. If such 
an Unanticipated Visit occurs, the RA will dispense product for the number of days until their 
next scheduled visit (e.g., if they have two days until their next visit, then the RA will dispense 
two days’ worth of study product). 
d. Product Compliance and Accountability: Participants will be required to keep track of all the 
cigarettes provided to them.  Each week, they will return all unused cigarettes and empty or 
unopened cigarette packs to the research staff, and will receive incentives for doing so. 
Participants will be asked if they have decided to quit smoking at each lab visit. If they wish to 
quit, they will be asked if they still want to receive study cigarettes. If not, no cigarettes will be 
dispensed. The participant will be retained in the study with no penalty and will continue to 
complete all subsequent EMA and other self-report assessments. In an ongoing study 
(IRB#1404001032), we dispense research cigarettes in this manner to 15-19-year-old daily 
smokers with approvals from the FDA, Brown University IRB and permission (waiver) from the 
Rhode Island Attorney General (K01CA189300, PI Cassidy). We are in the process of obtaining 
such a waiver for the current study as well. We will provide incentives for study cigarette 
accountability, which we have found to increase study cigarette compliance in our prior trials. 
The incentive will be a payment at each in-person session, which encourages participants to keep 
track of their study cigarettes, minimizes hoarding of study cigarettes, and discourages sharing of 
study cigarettes with other people. The payment schedule for returning unsmoked cigarettes is as 
follows: 50-74% returned, $5; 25-49% returned, $2.50; and 0-24% returned, $0. Returned empty 
packs will receive $1. At each session, participants will be reminded that if they do not like their 
study cigarettes, they can use alternative products that are not cigarettes, as the goal of the study 
is to model a scenario in which a nicotine reduction policy applies only to cigarettes. Honest 
reporting will be encouraged throughout the study. The total possible incentive for 
cigarette/empty pack return is $5. 
e. Randomization: Using procedures similar to our current study, a double-blind randomization 
procedure will be used. We will stratify on the following four variables to optimally balance 
conditions on factors that might influence responses to study cigarettes:  
a) Gender  
b) Average cigarettes per day in past month (CPD; < 8 cigarettes vs. > 8 cigarettes)  
c) frequency of past-month alternative combustible tobacco product use (< 10 days vs. > 
10 days). 
d) frequency of past-month non-combustible tobacco product use (< 10 days vs. > 10 
days). 

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Each participant will be assigned a randomization code which will be associated with blind codes 
for cigarette cartons. The research assistant dispensing the cigarettes to each participant will be 
blind to the cigarette nicotine content, and will dispense cigarettes based on the blind code linked 
to each individual’s randomization code. The randomization schedules and the link between the 
randomization code, blind codes and treatment assignment will be maintained securely by the 
CAAS Data Core (Suzanne Sales and Tim Souza). 
f. EMA Platform: All EMA assessments will be conducted via a smartphone app designed for this 
purpose, PiLR EMA (MEI Research, Edina, Minnesota; http://pilrhealth.com/), which was 
developed and made available by MEI Research, Inc. The app is fully customizable for 
conducting time-based, event-based, contingent and random surveys, and supports logic 
branching to ask follow-up questions only when certain events are noted.  The app uses a cloud-
based infrastructure to store data securely, and this software has been used successfully in other 
smoking studies conducted here in vulnerable populations (Allen, Tosun, Carlson, & Allen, 
2017) and in ongoing research on other health behaviors at our Center (for further information 
about ongoing behavioral health projects using the app, see http://pilrhealth.com/projects/). The 
app uses a mobile-friendly interface to capture data, including options for ‘slider’ visual analog 
scales (VAS) to input Likert scale items, text-based data entry, and check boxes to indicate the 
presence of certain environmental features. The app will be downloaded onto participants’ 
phones at the BL1 session. As we have done in prior EMA studies, if participants do not have a 
smartphone, they will be loaned one for the duration of the study. Further detailed information 
about the security and data transmission of the app are included as an attachment to this protocol. 
During the BL1 session, participants will be given detailed instructions on how to use the app, 
including information on when the app will notify them to complete a survey and when they 
should initiate a survey themselves (e.g, after each cigarette or use of any other tobacco product). 
Participants will be provided with a ‘hotline’ phone number to call for general questions and 
technical support. Further information about app data safety and confidentiality is included as an 
attachment.  
g. EMA Procedures: Each assessment will take approximately 90 seconds to complete.  EMA 
report types will include: 1) Interval-contingent wake-up reports whereby participants will be 
signaled to record the number of cigarettes and other nicotine and tobacco products they used the 
day before; 2) Event-contingent tobacco use reports wherein participants will initiate a report 
each time they smoke a cigarette or use an alternative tobacco product; each such report will 
query social context, withdrawal, mood and other factors; and 3) Signal-contingent random 
prompts whereby adolescents respond to an app-initiated audible signal which will prompt a 
report with the same questions as the event-contingent tobacco use report to determine non-
tobacco levels of mood and other factors for comparison purposes. Random prompts will be 
signaled 4 times per day, once per 3-hour block: 8am-11am; 12pm-3pm; 3-6pm; 4-7pm, 8-11pm] 
The purpose of the random prompts is to assess non-tobacco levels of withdrawal, craving, and 
other variables in order to compare these with the variables reported during tobacco reports. 
Variables such as mood, location sett and peer context will be included as these may also affect 
adolescent smoking and can be explored as potential moderators of effects. Random prompts will 
also ask participants if they smoked cigarettes or used any other tobacco products since their last 

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report, and if so, they will be prompted to record it in order to capture any missed product use. 
The minimum number of surveys to be completed per day is five (one interval-contingent 
morning report and four random prompts). Cigarette reports can be compared directly with 
reports on other forms of tobacco to identify common and unique antecedents, and contextual 
factors for use of each type of product use can be compared to those during random prompts. 
During Weeks 2 and 3, to reduce participant burden, only the morning report will be required. 
The schedule of EMA assessments and question wording is included as an attachment.  
7. Week 1 Safety & Product Dispensation Check-In  
a. Purpose: This check-in visit can occur either at our research lab or in the community at the 
participant’s preference and convenience. The purpose of this check-in is to check on safety/any 
adverse events, check CO level, and dispense product; allowing participants to meet us in the 
community will help reduce the burden of travel time for participants and is designed to reduce 
study attrition, particularly among participants for whom the logistics of scheduling and 
transportation may be challenging.  
b. Procedures: Participants will provide breath CO, complete a timeline follow-back measure for 
the interim week which will query their use of study and non-study cigarettes, alcohol, 
marijuana, and alternative tobacco products. Participants will also complete a Health Changes 
Questionnaire to assess any adverse events, and the RA will follow-up on any ongoing medical 
events. Note: These sessions were conducted virtually post-COVID. 
8. Week 2 Laboratory Session 
a. Purpose: This laboratory session will evaluate mid-point responses to study cigarettes. 
b. Procedures: At the beginning of the session, participants will provide a breath CO sample, 
complete a timeline follow-back measure for the interim week which will query their use of 
study and non-study cigarettes, alcohol, marijuana, and alternative tobacco products, and 
complete measures of craving (QSU), withdrawal (MNWS) and mood (PANAS). Female 
participants will provide a urine sample for a pregnancy test. They will then smoke one of their 
study cigarettes. Next, they will provide a post-smoking CO sample, repeat the QSU, MNWS, 
and PANAS, and then complete measures of cigarette subjective effects (CES). Participants will 
also complete a Health Changes Questionnaire to assess any adverse events, and the RA will 
follow-up on any ongoing medical events. 
9. Week 3 Safety & Product Dispensation Check-In 
a. Purpose: As described above (Week 1 Check-In), this check-in visit can occur either at our 
research lab or in the community; the purpose is to check on safety/any adverse events, check 
CO, and dispense product.  
b. Procedures: Participants will provide breath CO, complete a timeline follow-back measure for 
the interim week which will query their use of study and non-study cigarettes, alcohol, 
marijuana, and alternative tobacco products. Participants will also complete a Health Changes 
Questionnaire to assess any adverse events, and the RA will follow-up on any ongoing medical 
events. Note: These sessions were conducted virtually post-COVID. 
10. Week 4 Session 
a. Purpose: This laboratory session will evaluate end-point responses on behavioral economic 
measures and allow for collection of final biomarkers and cigarette collection. 

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b. Procedures: At the beginning of the session, participants will provide a breath CO sample, 
complete a timeline follow-back measure for the interim week which will query their use of 
study and non-study cigarettes, alcohol, marijuana, and alternative tobacco products. Female 
participants will provide a urine sample for a pregnancy test. Then, they will complete the 
cigarette purchase task (CPT), a behavioral economics-based measure of cigarette reinforcement, 
which assesses hypothetical demand for their usual brand and study cigarettes across a range of 
prices. Finally, they will complete the Experimental Tobacco Marketplace task again. 
Participants will also complete a Health Changes Questionnaire to assess any adverse events, and 
the RA will follow-up on and close any ongoing medical events. Should any adverse events be 
left open at this time, they will be re-assessed at the 30-day call. Participants will also complete 
an assessment of respiratory health and provide urine samples for biomarker assessment. 
Participants will also administer and anonymous debriefing survey which will ask them about the 
honest of their reporting. At the end of the week 4 session, following return of all products, 
participants will be debriefed on products used during the study. Health risk information will be 
presented for combusted cigarettes, e-cigs, and other tobacco products, using a handout drawn 
from CDC Fact Sheet. 
b.c. Post-Session COVID survey and qualitative interview: Following the last sessions, participants 
will be asked if they would like to participate in a short survey and interview. They will first 
complete a brief survey of their COVID-19 experiences. Then, the researchers will conduct a 
recorded qualitative interview about their experiences with the EMA app in order to improve 
future app use.  
11. Outcomes, Measures Justification, Descriptions, and Schedule 
Primary Outcomes 
 
 Cigarettes smoked per day 
 Amount of total alternative product (ATP) use  
 
Secondary Outcomes 
 
 Amount of combustible and amount of noncombustible ATP use 
 Toxicant exposure (total nicotine equivalents and NNAL) 
 FEV outcomes 
 
Exploratory Outcomes 
 
 ATSQ score 
 Perceived Health Risk Questionnaire 
 Nicotine dependence score 
 Differences in craving across time and product type  
 Differences in withdrawal across time and product type  
 Measures of reinforcing efficacy/cigarette demand from the Cigarette Evaluation Scale 
 Hypothetical Purchasing in the Experimental Tobacco Marketplace 
 

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a. Background/Descriptive Measures: A modified version of the PATH Demographics and 
Tobacco Use History (Adolescent version) will be used to assess participant characteristics and 
lifetime history of tobacco product use (using a comprehensive list of combusted and non-
combusted products), including ages of initiation and progression through smoking milestones 
such as daily use. The Vaping History Questionnaire will be used to assess lifetime use of e-
cigarettes, including e-cigarette characteristics. Social and Environmental Influences (tobacco 
use by parents and peers; perceived norms for cigarettes and e-cigs) will be assessed using a 
modified Interpersonal Influences Questionnaire (Colby et al., 2005. We will use the reliable and 
valid Smoking Stage of Change (Velicer, Hughes, Fava, Prochaska, & DiClemente, 1995) to 
assess readiness to change at baseline and week 4. The Center for Epidemiological Studies-
Depression Scale (CES-D; Radloff, 1991) is a widely used and validated 20-item questionnaire 
assessing depressive symptoms in the past week.  This measure will be used for sample 
description given the high co-occurrence of smoking and depression. Respiratory symptoms will 
be assessed using the American Thoracic Society Questionnaire (ATSQ; Comstock, Tockman, 
Helsing, & Hennesy, 1979). Participants report the frequency of experiencing each of 8 
respiratory symptoms (e.g., morning cough, wheezing, shortness of breath when walking). We 
recently validated this scale for assessing the severity of respiratory symptoms associated with 
smoking in adolescents (Cassidy, Roberts & Colby, 2015). Nicotine Dependence will be 
assessed using the modified Fagerstrom Tolerance Questionnaire (Heatherton, Kozlowski, 
Frecker, & Fagerström, 1991). Scores on this measure will be evaluated as an outcome at Week 
4 as an index of changes in dependence as a function of VLNC exposure.  
b. Safety: Pregnancy tests will be performed for all female participants at Screening/BL1, BL2, and 
both lab visits (weeks 2 and 4).  The suicide subscale from the Mini International 
Neuropsychiatric Interview (MINI; Sheehan et al., 2010) will be used at Screening to evaluate 
suicide risk. CO level will be obtained at every session to evaluate level of exposure to smoke; a 
large increase in CO (i.e., CO > 80 ppm) can be a reason for withdrawing a participant from the 
study. Brief Medical History (Screening/BL1) assesses physical and emotional health to 
establish eligibility for participation (determined by the medical monitors). In subsequent 
sessions, the Health Changes Questionnaire asks whether the participant experienced any 
changes in his/her physical or emotional health since their last visit, including whether they have 
visited the doctor, the hospital, or whether they have had a change in any of their medications. 
Any endorsement of a negative health change will be tracked as an adverse event.  
c. Frequency of tobacco and other drug use measures: Past 30-day tobacco product use will be 
comprehensively assessed using a Timeline Follow-Back (TLFB), a reliable calendar-assisted 
interview validated for estimating daily use of tobacco and other substances in adolescents 
(Lewis-Esquerre et al., 2005). The TLFB will determine: # cigarettes per day; frequency of e-cig 
use (including nicotine concentration in e-liquid) and use of all other tobacco products; use of 
alcohol (# standard drinks/day); and frequency of marijuana use and other illicit or recreational 
drug use. The TLFB will also be used to assess tobacco, alcohol, marijuana and other drug use 
between sessions to evaluate use over the course of the study.  
d. Biomarkers. Expired breath CO level is a reliable and valid assessment of recent smoking and 
will be measured using a Vitalograph CO Monitor. CO will be assessed at BL to confirm 

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smoking status and for sample description. CO will be evaluated pre- and post-cigarette in each 
labs session, and as an outcome at Week 4 as a biomarker of changes in effects of changes in 
combustible product use.  Urine samples will be analyzed for the tobacco-specific nitrosamine 4-
methylnitrosamineo-1-(3-pyridyl)-1-butanol (NNAL), a biomarker of tobacco smoke carcinogen 
that decreases upon combustible tobacco cessation or reduction (Benowitz et al., 2012; Hecht et 
al., 2014) and total nicotine equivalents (TNEs), which is a measure of total nicotine exposure 
(i.e., from all nicotine-containing products). Both TNEs and NNAL will be analyzed from 
samples collected at baseline (BL2) and at the end of the product use period (W4). Samples will 
be shipped twice per year for analysis to the University of Minnesota and will be analyzed by 
Sharon Murphy, Ph.D. (see letter of support included in grant application). Scores on this 
measure will be evaluated as an outcome at Week 4. Forced Expiratory Volume (FEV) is a 
measure of how much air a person can exhale during a forced breath. Cigarette smoking is 
associated with reduced lung function in adolescents, indicating mild airway obstruction, and 
with slowed lung growth during adolescence (Gold et al., 1996) whereas quitting smoking leads 
to improvement in lung function and slows reductions in lung function associated with aging in 
later adulthood (Kohansal et al., 2009). Forced vital capacity (FVC) is the total volume of breath 
exhaled during the test; FEV1 is the volume exhaled within the first second. FEV will be 
measured with a water-filled recording spirometer. Research assistants will be trained by Co-
Investigator Cioe, who has experience measuring FEV in clinical settings, to take these 
measurements. Each participant will perform three forced expirations; FVC and FEV1 means 
will be calculated for each expiration judged acceptable by the RA.  
e. Assessments of Potential Mechanisms. The Brief Questionnaire on Smoking Urges (Brief 
QSU; (Cox, Tiffany, & Christen, 2001) assesses craving for cigarettes. Factor 1 assesses desire 
to smoke/positive reinforcing aspects of smoking, and Factor 2 assesses relief from 
withdrawal/negative reinforcing aspects of smoking.  The Minnesota Nicotine Withdrawal 
Scale (MNWS; Hughes & Hatsukami, 1986) asks individuals to rate their experience of 
withdrawal from nicotine using a four-point scale across 7 items reflecting DSM-IV criteria for 
nicotine withdrawal syndrome. The Positive and Negative Affect Scale (PANAS; Watson, 
Clark, & Tellegen, 1988) asks participants to rate how they are feeling at the moment, using a 
series of adjectives, on a 5-point scale (from “not at all” to “extremely”); its items form two 
factors tapping positive affect and negative affect.  All of these measures have been validated for 
use in adolescent smokers and shown to be sensitive to smoking abstinence effects (Colby et al., 
2010) and effects of VLNC cigarettes (Kassel, Evatt, et al., 2007). Each participant will rate how 
much he/she enjoyed the cigarette they just smoked using the Cigarette Evaluation Scale, 
which assesses subjective characteristics such as enjoyment on a 7-point Likert scale (CES; 
(Arger et al., 2017; Cappelleri et al., 2007). Participants will report their perceptions of the health 
risks associated with both their usual brand and their study cigarette brand using the Perceived 
Health Risks Assessment (Hatsukami et al., 2010).  
f. Behavioral Economic Assessments of Reinforcing Efficacy. The Cigarette Purchase Task 
(Jacobs & Bickel, 1999; MacKillop et al., 2008) will be used to assess demand for both their 
usual brand cigarette which may change as a function of VLNC exposure (Smith, et al., 2016). 
Participants will be asked how many cigarettes of their usual brand and their study cigarette they 

Impact of nicotine reduction on adolescent cigarette use, alternative tobacco use, and harm from tobacco 
 
PIs: Cassidy & Colby 
 
12 
 
would purchase per day at increasing costs per pack, starting with how many they would 
consume when cigarettes are free (zero price). This measure has been validated for use in 
adolescents in a study directed by primary mentor Colby (Murphy, MacKillop, Tidey, Brazil, & 
Colby, 2011). Participants will also complete the CPT for their study cigarette. Similarly, the 
Juul Purchase task will be administered to those participants who report past 30-day Juul use.. 
Delay discounting is a measure of impulsivity which asks participants to make hypothetical 
choices between a fixed amount of money now and larger amount of money after a delay. This 
measure has been widely used in substance abuse research, and correlates with smoking status in 
adolescent smokers (Quisenberry et al., 2016) and is included for descriptive and exploratory 
purposes.  The Experimental Tobacco Marketplace (Bickel et al., 2018) will be used to assess 
effects of cigarette price on consumption of cigarettes and alternative products. In the task, 
participants are shown a virtual marketplace of tobacco products, including both noncombustible 
and combustible alternative products, as well as cigarettes. Participants are instructed to make 
hypothetical purchases of tobacco products that they would use for the week. Participants are 
given an experimental budget of money which can be used in the marketplace and are instructed 
that they can ‘save’ unspent money. The costs for the other products will reflect average prices in 
RI and will not change across conditions. For each iteration of the task, participants will receive 
account balances approximately equal to the money they would spend on three days’ worth of 
tobacco. They can purchase as many or few tobacco products as their account balance allows 
(only packaged products, e.g., whole cigarette packages, can be purchased). For example, if a 
participant smokes a pack of cigarettes each day, then she is spending ~$10.00 per day on 
tobacco, as this is the price of a pack of cigarettes in RI. During each iteration of the ETM task, 
she will have an account balance of $30.00 to spend on tobacco for a 3-day period. The 
hypothetical cigarette available will be their study cigarette. Across trials, the price of cigarettes 
increases while the prices of alternative products remain the same. On each trial, participants can 
choose to purchase any combination of tobacco products that they choose, as long as they stay 
within their experimental budget. Across four trials, the price of cigarettes will increase ($0.12, 
$0.25, $0.50, and $1.00, $2.00, $4.00, $8.00, and $16.00 per cigarette). The following 
tobacco/nicotine products will be available on the ETM: 
a) Study cigarettes – menthol OR non-menthol flavors depending preference; 
b) Little cigars (e.g., Winchester, Cheyenne) – menthol and tobacco flavors; 
c) Cigarillos (e.g., Black and Mild; Swisher Sweets) – menthol and tobacco flavors; 
d) E-cigarettes (e.g., cigarette-like systems such as Juul and tank-like systems such as 
NJOY prefilled tanks) – menthol and tobacco flavors;  
e) Snus (e.g., Camel and Marlboro snus) – menthol and tobacco flavors; 
f) Conventional smokeless tobacco products (e.g., Copenhagen) – menthol and tobacco 
flavors; 
g) Non-prescription medicinal nicotine (e.g., 2mg and 4mg nicotine gum; 7, 14 and 21 mg 
nicotine patch) – menthol and regular flavors; 
This task will first be administered at Baseline 2 following acute cigarette exposure to assess 
intentions to purchase alternative products following initial exposure to study cigarettes, and at 
Week 4 to assess effects of extended exposure to study cigarettes on intentions to purchase 

Impact of nicotine reduction on adolescent cigarette use, alternative tobacco use, and harm from tobacco 
 
PIs: Cassidy & Colby 
 
13 
 
alternative products across groups. This measure will be compared with patterns of product use 
generated from EMA assessment in the field.  
g. Laboratory Measures schedule (Table 1) 
 
 
Measure 
Screening 
Baseline 1 
Baseline 2 Week 1 
Week 2 
Week 3 
Week 4 
Demographics/Tobacco Use 
History and Exposure 
X 
 
  
  
  
  
 
Brief Medical History  
X 
 
 
  
  
 
 
Smoking Stages of Change 
X 
 
 
 
 
 
X 
MINI Suicide Subscale 
X 
 
 
 
 
 
 
Pregnancy Test 
X 
X 
X 
X 
X 
X 
X 
Timeline Follow Back (TLFB) 
X 
 
 X 
X 
X  
X 
X 
Breath Carbon Monoxide  
X 
 
X 
X 
X 
X 
X 
Dependence (mFTQ) 
 
X 
 
 
X 
 
X 
ASTQ Respiratory Questionnaire 
 
 
X 
 
X 
 
X 
Delay Discounting 
 
X 
 
 
 
 
X 
Environmental Tobacco 
Smoke/Social Influences 
 
X 
 
 
 
 
 
Depressive Symptoms (CESD) 
 
X 
 
 
 
 
 
Quit Intentions Questionnaire 
 
 
X 
X 
X 
X 
X 
Health Changes Questionnaire 
 
X 
X 
X 
X 
X 
Craving (Brief QSU) (pre/post cig) 
 
X 
 
X 
 
 
Withdrawal (MNWS) (pre/post 
cig) 
 
X 
 
X 
 
 
Affect (PANAS) (pre/post cig) 
 
X 
 
X 
 
 
Cigarette Evaluation Scale (post 
cig) 
 
X 
 
X 
 
 

Impact of nicotine reduction on adolescent cigarette use, alternative tobacco use, and harm from tobacco 
 
PIs: Cassidy & Colby 
 
14 
 
Perceived Health Risks (UB) 
 
X 
 
 
 
 
Perceived Health Risks (Study) 
 
X 
 
 
 
X 
Cigarette Purchase Task (UB) 
 
X 
 
X 
 
X 
Cigarette Purchase Task (Study) 
 
X 
 
X 
 
X 
Juul Purchase Task 
 
X 
 
X 
 
X 
Experimental Tobacco 
Marketplace 
 
X 
 
 
 
X 
Respiratory Health Outcomes 
(FEV) 
 
X 
 
 
 
X 
Urine NNAL/TNEs 
 
  
X 
  
  
 
X 
Debriefing Questionnaire 
 
 
 
 
 
 
X 
 
 
12. 30-Day Follow Up Call: Participants will be contacted after 30 days by telephone to assess current 
tobacco use, quit status, and to assess overall safety. Participants who have not quit will be advised to do 
so. 
13. Compensation: The following payment schedule for in-person session attendance will be used: 
a.  $25 for BL1; $50 for BL2; $15 each for W1 and W3, $50 each for W2 and W4. If a participant 
comes in for the in-person screening but is ineligible, they will still be paid $25 for their time 
provided they meet the CO or NicAlert inclusion criteria. Participants will be paid $25.00 per 
day that they ineracted with the phone accorign to the intrsucrions given in Weeks 1, , and 5; in 
Weeks 3 and 4, they that theycan  complete at least one EMA assessment for $2.00 daily for a 
possible maximum total of $17370. A completion bonus of $75 will be given to participants who 
attend all laboratory sessions. A bonus payment of $50 will be paid to participants who complete 
80% or more of their EMA surveys. Participants will be eligible to earn up to $40 in random 
bonuses if they interact with the app  A completion bonus of $75 will be given to participants 
who attend all laboratory sessions. A maximum of $20 possible compensation is available for 
returned cigarettes. Bonus payments are included because study procedures involve considerable 
time commitments and five sessions, thus attrition is a potential issue. Participants are free to 
discontinue at any time and will receive full compensation for the sessions they complete. The 
total possible compensation will be $523420. Participants will be paid using ClinCard.  
 
14. Risks and Benefits. Potential risks and benefits for participants 
a. Subjective discomfort (survey questionnaires): The protocol includes survey questions about medical 
history, drug and alcohol use, and questionnaires about mood.  Answering these personal questions 
could make the participant feel uncomfortable.  However, the questions we ask are commonly used 
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Impact of nicotine reduction on adolescent cigarette use, alternative tobacco use, and harm from tobacco 
 
PIs: Cassidy & Colby 
 
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in research and clinical practice and the participant will not be required to answer any question 
he/she is not comfortable answering. Answers to these questions will be kept confidential. 
b. Subjective discomfort (biological samples): The participant may feel some discomfort about 
providing breath and/or urine samples for analysis. This probability of this risk is low, based on our 
past experience using these measures.  Interactions with participants will be conducted in private 
rooms. Urine sample collection is private (i.e., unsupervised); the participant will provide the sample 
in a private bathroom within the laboratory suite. Discomfort will be further minimized by 
employing trained staff to conduct all procedures and emphasizing that study participation is 
voluntary.  
c. Breach of Confidentiality: A risk of the interview is loss of privacy if other people find out the 
results. We will work to ensure that the participant’s confidentiality is kept. Research data without 
identifiers will be maintained in a locked file cabinet and on password-protected computers in the 
research staff workplace, with only code numbers identifying participants. Study consent forms and 
the linkage between the participants’ names and codes will be stored in a locked file cabinet in the 
Contact PI’s office, on a separate floor of the building. 
d. Smoking Cigarettes: The participant will smoke a single cigarette in the laboratory on 2 separate 
occasions.  Study participation is restricted to established daily smokers so that this limited exposure 
will present no increased risk of harm than their current smoking status incurs.   
e. Smoking Withdrawal: The participant may experience some discomfort related to nicotine 
withdrawal as a function of switching to VLNC cigarettes over an extended period.  Symptoms can 
include irritability, frustration, anxiety, depressed mood or sadness, desire or craving to smoke, 
difficulty concentrating, and increased appetite or hunger. These feelings can be uncomfortable but 
they are normal, temporary, and usually mild. Participants are not prohibited from using other 
nicotine-containing products, which would prevent or reduce these symptoms. 
f. Coercion: Coercion is a possible risk due to monetary compensation for participation; however, the 
likelihood of this risk is low because the compensation is commensurate with time and effort 
required for this study.   
g. Compensatory smoking: The possibility exists that use of VLNC cigarettes over an extended period 
may lead to compensatory smoking (i.e., more intense or frequent smoking in an attempt to derive 
more nicotine from study cigarettes). However, research to date indicates that this outcome is 
unlikely. We will monitor the participant’s weekly cigarette use and CO levels to evaluate the extent 
to which compensatory smoking is occurring, and will make changes to the protocol to reduce this as 
necessary. 
h. Lower perceived risk of harm: The possibility exists that use of VLNC cigarettes over an extended 
period may lead to perceiving a reduced risk associated with VLNC cigarettes; we will debrief the 
participant post-study on risks associated with smoking. All cigarettes are harmful to a person’s 
health. Smoking can lead to severe or fatal medical problems including heart disease, respiratory 
(breathing) problems and diseases, cancer, diabetes, and other health risks.  The study cigarettes do 
not provide less risk than the participant’s usual brand cigarette. 
 
15. Adverse Events 
a. Collection and reporting of AEs and SAEs 
While participating in the trial, adverse events and changes in medications will be assessed at 
every study visit and carbon monoxide will be obtained.  Medical events will typically be 

Impact of nicotine reduction on adolescent cigarette use, alternative tobacco use, and harm from tobacco 
 
PIs: Cassidy & Colby 
 
16 
 
identified during the administration of the Health Changes Questionnaire. Other events may be 
identified by spontaneous reports during non-scheduled assessments.  
b. Questionnaire items that will be reviewed: 
Health Changes Questionnaire  
1) Have you noticed that your physical health or mental health have gotten worse since your 
last visit? If Yes, please describe. 
2) Have you had any changes in medication since your last visit? If Yes, please describe:  
3) Since your last visit, have you gone to the doctor? If Yes, please describe:  
4) Since your last visit, have you gone to the hospital? If Yes, please describe: 
No new AE required if one or more conditions below are met and the description does not 
otherwise meet the definition of an AE. 
1) Existing AE already open for reported symptom 
2) Pre-existing condition without increase in severity or frequency of symptoms (brief 
medical history will be updated if not previously reported). 
3) Received preventative or follow-up medical care. 
4) Other (explain). 
For the participant’s protection, participants will be withdrawn immediately from the 
study if any of the following occur: 
1) Cardiovascular disease (CVD) event: Typically includes MI (heart attack), PTCA 
(angioplasty/stenting), bypass surgery, stroke, peripheral vascular disease (arterial 
blockages in arms or legs leading to procedure or surgery).  Less common CVD problems 
would be new cardiac arrhythmias (e.g., new atrial fibrillation) or new valvular disease 
(e.g., mitral or aortic regurgitation). 
2) DVT/PE (deep vein thrombosis/pulmonary embolism, i.e., blood clots in the venous 
system). 
3) Suicide Attempt:  A participant will be withdrawn if he/she attempts suicide at any time 
during participation in the study. 
4) Psychiatric Hospitalization: A participant will be withdrawn if he/she is hospitalized for 
psychiatric reasons at any time during participation in the study. 
5) Pregnancy: If a participant indicates she is pregnant or has a positive pregnancy test at 
any session, she will be withdrawn from the study, and this event will remain open until 
delivery.  At that time the license medical monitor will contact the participant to ask a 
few questions about the baby’s health and will update the open ‘Adverse Event Form’.   
The following will be monitored and can lead to the participant being withdrawn by the PI 
or Licensed Medical Monitor: 
1) Expired breath Carbon Monoxide >80 ppm 
2) Any hospitalization or debilitation in which participation in the study could be 
detrimental to the recovery process. This will be self-reported by the participant and will 

Impact of nicotine reduction on adolescent cigarette use, alternative tobacco use, and harm from tobacco 
 
PIs: Cassidy & Colby 
 
17 
 
be reviewed by the MPIs and medical monitor to determine whether continued 
participation in the study is appropriate.   
3) If a participant is behaving in an inappropriate or threatening manner, admits to lying 
about eligibility criteria, including omitting previous medical diagnoses and medications, 
is participating in other smoking research studies that could affect the primary outcome 
measures, does not follow study instructions, etc., then an MPI can withdraw him/her 
from the study at her discretion.  
Serious adverse events (SAEs): Information about all serious adverse events will be collected 
and recorded on a standard Serious Adverse Event Report Form. To ensure participant safety, 
each study-related serious adverse event will also be reported to the IRB office within 72 hours 
of learning of its occurrence. A serious adverse event is an undesirable sign, symptom or medical 
condition which: 
1.is fatal or life-threatening 
2. requires or prolongs hospitalization 
3. results in persistent or significant disability/incapacity 
4. constitutes a congenital anomaly or a birth defect 
5. is medically significant, in that it may jeopardize the subject and may require medical 
or surgical intervention to prevent one of the outcomes listed above. 
A hospitalization would not be considered to be a serious adverse event if it was elective, pre-
planned, or for a pre-existing condition that did not worsen since starting the study; or for 
treatment on an outpatient basis for an event not fulfilling any of the definitions of serious given 
above and not resulting in hospital admission.  
Any SAE occurring after the participant has signed the informed consent and until the participant 
has stopped study participation must be reported. Investigator responsibilities for notification of 
SAEs are described above. 
c. Management of SAEs and Other Study Risks 
The medical monitor will review all AEs. A study participant may be discontinued from the 
study if a medical monitor and/or an MPI determines it is the best decision in order to protect the 
safety of a participant. In the event that a participant either withdraws from the study or the 
investigator decides to discontinue a participant due to an AE/SAE, the participant will have 
appropriate follow-up medical monitoring. The participant experiencing an AE/SAE will be 
followed until the problem resolves, stabilizes, or is clearly unrelated to the study cigarettes. Any 
AE that remains open will be reviewed and closed during the 30-day follow-up phone call.   
d.  Medical Monitor Contact information: 
Robert Swift, M.D., Ph.D. 
Email: robert_swift_md@brown.edu  

Impact of nicotine reduction on adolescent cigarette use, alternative tobacco use, and harm from tobacco 
 
PIs: Cassidy & Colby 
 
18 
 
Phone: 401-863-6643  
Patricia Cioe, Ph.D., R.N.P. 
Email: patricia_cioe@brown.edu 
Phone: 401-863-6638 
16. Research Involving Minors. Adolescents who meet initial eligibility criteria during the phone screen, 
and who remain interested after hearing a more detailed study description, will provide contact 
information for their parent/guardian (minors only) so that parental informed consent can be obtained; 
18-19 year olds can provide their own consent. Minors will not be scheduled without research staff first 
talking directly to a parent/guardian. Research staff will call the parent or guardian, describe the study, 
and answer any questions. Consent forms will be mailed or emailed to the parent (with a copy to 
keep/option to print for their records). Adolescents will then be scheduled for the initial in-person 
session and transportation arranged if necessary. The adolescent (if a minor) will bring the signed 
consent form to the in-person screening session, or the RA will ensure that the participants’ parent has 
electronically signed the consent form. Participants will complete informed assent (minors)/consent at 
the in-person screening session. A researcher will review the assent/consent form in detail, review all 
study procedures, and answer questions. Participants will receive a copy of their consent/assent form. 
Participants over 18 will need to provide an ID that indicates their age in order to participate. 
 
 

H:\Project SIREN\Clinical Trials Results Reporting\OTHER DOCS\Codebook_Highlighted.Changes.docx 
 
Morning Report 
First Random Prompt 
Report of the Day (FR) 
Random Prompt Report 
(RR) 
Usual Brand Smoke 
Report (UR) 
Study Cig Smoke 
Report (SR.) 
Alternative Product 
Report (AR) 
Item 
Response Format 
Logic 
MR1 
 
 
 
 
 
What time did you go to bed last night? 
Enter hour (text entry) 
 
MR1A 
 
 
 
 
 
What time did you wake up today? 
Enter hour (text entry) 
 
MR1B 
 
 
 
 
 
Please rate how well you slept. 
1 Not well at all  
to  
10 Very well 
(categorical) 
 
MR2 
 
 
 
 
 
Think about the time since the last report 
you completed yesterday and when you 
went to sleep. Did you forget to enter 
any smoke reports? 
0=No 
1=Yes 
If “Yes”, proceed 
to MR2B. If 
“No”, skip to 
MR3. 
MR2A 
 
 
 
 
 
What time did you last use tobacco? 
1=15 mins ago 
2=30 mins ago 
3=45 mins ago 
4=1 hour ago 
5=2 hours ago 
6=3 or more hours ago 
 
MR2B 
 
 
 
 
 
What did you use? Select all that apply 
 
 
1=Non-study cigarette 
2=Study cigarette 
3= E-cigarette/vape 
4= Cigar/cigarillo (Black & 
Mild, Swisher Sweets) 
5= Smokeless tobacco (chew, 
dip, snuff, snus) 
6=Hookah 
7=Pipe (tobacco) 
 
MR3 
 
 
 
 
 
How many study cigarettes did you 
smoke yesterday? 
Numeric (integer) entry (0-
200) 
 
MR4 
 
 
 
 
 
How many non-study cigarettes did you 
smoke yesterday? 
Numeric (integer) entry (0-
200) 
 

H:\Project SIREN\Clinical Trials Results Reporting\OTHER DOCS\Codebook_Highlighted.Changes.docx 
 
Morning Report 
First Random Prompt 
Report of the Day (FR) 
Random Prompt Report 
(RR) 
Usual Brand Smoke 
Report (UR) 
Study Cig Smoke 
Report (SR.) 
Alternative Product 
Report (AR) 
Item 
Response Format 
Logic 
MR5 
 
 
 
 
 
Select all alternative tobacco products 
you used yesterday. 
0=None 
1= E-cigarette/vape 
2= Cigar/cigarillo  (Black & 
Mild, Swisher Sweets) 
3=Smokeless tobacco (chew, 
dip, snuff, snus) 
4=Hookah 
5=Pipe (tobacco) 
Each endorsed 
choice brings up 
data entry for 
quantity (6A-6E) 
MR6A 
 
 
 
 
 
About how many puffs of E-
cigarette/vape do you think you took? 
Numeric (integer) entry (0-
200) 
Show only if “E-
cigarette/vape” is 
selected in MR5 
MR6A1 
 
 
 
 
 
Did you finish a Juul pod or refill your 
vape tank? 
0=No 
1=Yes 
Show only if “E-
cigarette/vape” is 
selected in MR5 
MR6B 
 
 
 
 
 
About how many cigars did you smoke? 
Numeric (integer) entry (0-
200) 
Show only if 
“Cigar/cigarillo) 
is selected in 
MR5 
MR6C 
 
 
 
 
 
About how much smokeless tobacco did 
you use? 
Text entry 
Show only if 
“smokeless 
tobacco” is 
selected in MR5 
MR6D 
 
 
 
 
 
About how much hookah did you use? 
Text entry 
Show only if 
“hookah” is 
selected in MR5 
MR6E 
 
 
 
 
 
About how much pipe (tobacco) did you 
use? 
Text entry 
Show only if 
“pipe (tobacco)” 
is selected in 
MR5 
 
 
 
 
 
 
 
 
 

H:\Project SIREN\Clinical Trials Results Reporting\OTHER DOCS\Codebook_Highlighted.Changes.docx 
 
Morning Report 
First Random Prompt 
Report of the Day (FR) 
Random Prompt Report 
(RR) 
Usual Brand Smoke 
Report (UR) 
Study Cig Smoke 
Report (SR.) 
Alternative Product 
Report (AR) 
Item 
Response Format 
Logic 
 
FR0A 
RR0A 
 
 
 
Have you used tobacco in the last 30 
minutes? 
0=No 
1=Yes 
If “Yes”, proceed 
to R0B. If “No”, 
proceed to R1. 
 
FR0B 
RR0B 
 
 
 
Did you do a smoke report? 
0=No 
1=Yes 
If “Yes”, proceed 
to R1. If “No”, 
proceed to R0C. 
 
FR0C 
RR0C 
 
 
 
Please do a smoke report now. 
(Instruction) 
All – random 
survey end. 
 
FR1 
 
 
 
 
Think about the time since you woke up 
this morning. Did you forget to enter any 
smoke reports? 
0=No 
1=Yes 
If “Yes”, proceed 
to FR1B. If 
“No”, proceed to 
FR2. 
 
 
RR1 
 
 
 
Think about the time since you last 
completed a report. Did you forget to 
enter any cigarette or tobacco reports? 
0=No 
1=Yes 
If “Yes”, proceed 
to R1B. If “No”, 
proceed to R2. 
 
FR1A 
RR1A 
 
 
 
What time did you last use tobacco? 
1=15 mins ago 
2=30 mins ago 
3=45 mins ago 
4=1 hour ago 
5=2 hours ago 
6=3 or more hours ago 
 
 
FR1B 
RR1B 
 
 
 
What did you use? (Select all that apply) 
1=Non-study cigarette 
2=Study cigarette 
3= E-cigarette/vape 
4= Cigar/cigarillo (Black & 
Mild, Swisher Sweets) 
5= Smokeless tobacco (chew, 
dip, snuff, snus) 
6=Hookah 
7=Pipe (tobacco) 
IF 3,4 OR 5 show 
FR1C/R1C 
(flavor Q) 

H:\Project SIREN\Clinical Trials Results Reporting\OTHER DOCS\Codebook_Highlighted.Changes.docx 
 
Morning Report 
First Random Prompt 
Report of the Day (FR) 
Random Prompt Report 
(RR) 
Usual Brand Smoke 
Report (UR) 
Study Cig Smoke 
Report (SR.) 
Alternative Product 
Report (AR) 
Item 
Response Format 
Logic 
 
FR1C 
RR1C 
 
 
 
What flavor was your product? 
1=Tobacco 
2=Menthol/Mint 
3=Fruit 
4=Candy 
5=Vanilla 
6=Desserts/Sweets 
9=Other 
 
 
 
 
 
 
 
Think about how you are feeling right 
now. Do you feel… 
 (NWQ header) 
 
 
FR2 
RR2 
 
 
 
Desire or craving to smoke a cigarette? 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
FR3 
RR3 
 
 
 
Angry, irritable, or frustrated? 
 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
FR4 
RR4 
 
 
 
Anxious or nervous? 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
FR5 
RR5 
 
 
 
Difficulty concentrating? 
 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 

H:\Project SIREN\Clinical Trials Results Reporting\OTHER DOCS\Codebook_Highlighted.Changes.docx 
 
Morning Report 
First Random Prompt 
Report of the Day (FR) 
Random Prompt Report 
(RR) 
Usual Brand Smoke 
Report (UR) 
Study Cig Smoke 
Report (SR.) 
Alternative Product 
Report (AR) 
Item 
Response Format 
Logic 
 
FR6 
RR6 
 
 
 
Impatient or restless? 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
FR7 
RR7 
 
 
 
Hungrier than usual? 
 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
FR8 
RR8 
 
 
 
 Depressed? 
 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
FR9 
RR9 
 
 
 
Happy? 
 
 
0=Not at all 
1=A little 
2=Moderately 
3=Quite a bit 
4=Extremely 
 
 
FR10 
RR10 
 
 
 
Stressed? 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
FR11 
RR11 
 
 
 
Bored? 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
 
 
 
 

H:\Project SIREN\Clinical Trials Results Reporting\OTHER DOCS\Codebook_Highlighted.Changes.docx 
 
Morning Report 
First Random Prompt 
Report of the Day (FR) 
Random Prompt Report 
(RR) 
Usual Brand Smoke 
Report (UR) 
Study Cig Smoke 
Report (SR.) 
Alternative Product 
Report (AR) 
Item 
Response Format 
Logic 
 
FR12 
RR12 
 
 
 
Where are you now? 
0 Home/Dorm 
1 Other's Home/Dorm 
2 Work/School 
3 Party/Bar/Club 
4 Public Place (Outside) 
5 Public Place (Inside) 
6 Car/Bus/Other 
Transportation 
99 Elsewhere 
 
 
FR12O RR12O 
 
 
 
You chose other location.  Please 
describe where you are now: 
Text entry 
Show if 
‘Elsewhere’ is 
selected in R12 
 
FR13 
RR13 
 
 
 
Who are you with? (Select all that apply) 
1 Friend(s)  
2 Parent(s) 
3 Sibling(s) 
4 Boy/girlfriend 
5 Teacher 
6 Co-workers 
7 Other persons 
0 No one, I was alone 
 
 
FR14 
RR14 
 
 
 
Are any of these people using tobacco 
products? (Select all that apply) 
1=Cigarettes 
3=E-cigarette/vape 
4=Cigar/cigarillo 
5=Smokeless tobacco 
6=Hookah 
7=Pipe (tobacco) 
0=No other people are using 
tobacco 
Do not show if 
only ‘No One’ is 
selected in R13 
 
(code 2 
intentionally 
skipped “study 
cig” to keep 
values consistent 
with similar 
fields) 

H:\Project SIREN\Clinical Trials Results Reporting\OTHER DOCS\Codebook_Highlighted.Changes.docx 
 
Morning Report 
First Random Prompt 
Report of the Day (FR) 
Random Prompt Report 
(RR) 
Usual Brand Smoke 
Report (UR) 
Study Cig Smoke 
Report (SR.) 
Alternative Product 
Report (AR) 
Item 
Response Format 
Logic 
 
FR15 
RR15 
 
 
 
What are you doing? (Select all that 
apply) 
 
 
1 Drinking Alcohol 
2 Using Marijuana 
3 Using other Drugs 
4 Socializing 
5 Exercising/Walking/Sports 
6 Studying/Reading/Working 
7 
Game/Movie/Video/TV/Music 
8 Social Media/Texting/On 
Phone 
9 Resting 
10 Eating/Drinking 
99 Other 
 
 
FR15A RR15A 
 
 
 
You chose Eating/Drinking.  What are 
you eating or drinking? Select all that 
apply. 
1 Meal 
2 Snack 
3 Caffeine drink 
9 Other beverage 
Show if 
‘Eating/drinking’ 
is selected in R15 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AR0 
What type of product did you use 
1= E-cigarette/vape 
2=Cigar/cigarillo (Black & 
Mild, Swisher Sweets) 
3=Smokeless tobacco (chew, 
dip, snuff, snus) 
4=Hookah 
5=Pipe (tobacco) 
IF 1,2 OR 3 show 
AR1B (flavor Q) 
 
 
 
UR1 
SR1 
AR1 
What time did you last use 
[PRODUCT]? 
1=15 mins ago 
2=30 mins ago 
3=45 mins ago 
4=1 hour ago 
5=2 hours ago 
6=3 or more hours ago  
Should be piped 
text 
To replace 
[PRODUCT] 
from item AR0. 

H:\Project SIREN\Clinical Trials Results Reporting\OTHER DOCS\Codebook_Highlighted.Changes.docx 
 
Morning Report 
First Random Prompt 
Report of the Day (FR) 
Random Prompt Report 
(RR) 
Usual Brand Smoke 
Report (UR) 
Study Cig Smoke 
Report (SR.) 
Alternative Product 
Report (AR) 
Item 
Response Format 
Logic 
 
 
 
 
 
AR1A 
What flavor was your product? 
1=Tobacco 
2=Menthol/Mint 
3=Fruit 
4=Candy 
5=Vanilla 
6=Desserts/Sweets 
9=Other 
 
 
 
 
 
 
 
Think about how you felt just before 
[SMOKED/VAPED/you used tobacco]. 
Did you feel… 
IF FIRST REPORT WITHIN 
A 2 HOUR BLOCK (i.e. the 
long survey); ELSE go to 
UT1/ST1/AT1 
Should be piped 
text 
for [tobacco 
PRODUCT] 
from item AR0. 
 
 
 
UR2 
SR2 
AR2 
Desire or craving to smoke a cigarette? 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
 
 
UR3 
SR3 
AR3 
Angry, irritable, or frustrated? 
 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
 
 
UR4 
SR4 
AR4 
Anxious or nervous? 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
 
 
UR5 
SR5 
AR5 
Difficulty concentrating? 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 

H:\Project SIREN\Clinical Trials Results Reporting\OTHER DOCS\Codebook_Highlighted.Changes.docx 
 
Morning Report 
First Random Prompt 
Report of the Day (FR) 
Random Prompt Report 
(RR) 
Usual Brand Smoke 
Report (UR) 
Study Cig Smoke 
Report (SR.) 
Alternative Product 
Report (AR) 
Item 
Response Format 
Logic 
 
 
 
UR6 
SR6 
AR6 
Impatient or restless 
 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
 
 
UR7 
SR7 
AR7 
Hungrier than usual? 
 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
 
 
UR8 
SR8 
AR8 
 Depressed? 
 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
 
 
UR9 
SR9 
AR9 
Happy? 
 
0=Not at all 
1=A little 
2=Moderately 
3=Quite a bit 
4=Extremely 
 
 
 
 
UR10 
SR10 
AR10 
Stressed? 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
 
 
UR11 
SR11 
AR11 
Bored? 
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
 
 
UR12 
SR12 
AR12 
Where were you when you used 
tobacco? 
0 Home/Dorm 
1 Other's Home/Dorm 
 

H:\Project SIREN\Clinical Trials Results Reporting\OTHER DOCS\Codebook_Highlighted.Changes.docx 
 
Morning Report 
First Random Prompt 
Report of the Day (FR) 
Random Prompt Report 
(RR) 
Usual Brand Smoke 
Report (UR) 
Study Cig Smoke 
Report (SR.) 
Alternative Product 
Report (AR) 
Item 
Response Format 
Logic 
2 Work/School 
3 Party/Bar/Club 
4 Public Place (Outside) 
5 Public Place (Inside) 
6 Car/Bus/Other 
Transportation 
99 Elsewhere 
 
 
 
UR12O 
SR12O 
AR12O 
You chose other location.  Please 
describe where you were: 
Text entry 
Show if 
_R12=Elsewhere 
 
 
 
UR13 
SR13 
AR13 
Who were you with when you used 
tobacco? Select all that apply. 
1 Friend(s)  
2 Parent(s) 
3 Sibling(s) 
4 Boy/girlfriend 
5 Teacher 
6 Co-workers 
7 Other persons 
0 No one, I was alone 
 
 
 
 
UR14 
SR14 
AR14 
Were any of these people using tobacco 
products? (Select all that apply) 
1=Cigarettes 
3=E-cigarette/vape 
4=Cigar/cigarillo 
5=Smokeless tobacco 
6=Hookah 
7=Pipe (tobacco) 
0=No other people were using 
tobacco 
Do not show if 
‘No one’ is 
selected in _R13 
 
 
 
UR15 
SR15 
AR15 
What were you doing just before you 
used tobacco? Select all that apply. 
 
1 Drinking Alcohol 
2 Using Marijuana 
3 Using other Drugs 
4 Socializing 
5 Exercising/Walking/Sports 
6 Studying/Reading/Working 
 
 
 
 

H:\Project SIREN\Clinical Trials Results Reporting\OTHER DOCS\Codebook_Highlighted.Changes.docx 
 
Morning Report 
First Random Prompt 
Report of the Day (FR) 
Random Prompt Report 
(RR) 
Usual Brand Smoke 
Report (UR) 
Study Cig Smoke 
Report (SR.) 
Alternative Product 
Report (AR) 
Item 
Response Format 
Logic 
7 
Game/Movie/Video/TV/Music 
8 Social Media/Texting/On 
Phone 
9 Sleeping 
10 Eating/Drinking 
11 Other 
 
 
 
UR15A 
SR15A 
AR15A 
You chose Eating/Drinking.  What were 
you eating or drinking? Select all that 
apply. 
 
1 Meal 
2 Snack 
3 Caffeine drink 
9 Other beverage 
Show if 
‘Eating/drinking’ 
is selected in 
_R15 
 
 
 
 
 
 
Think about how you felt just after you 
used [tobacco]. 
 
Should be piped 
text 
for [tobacco 
PRODUCT] 
from item AR0. 
 
 
 
UR16 
SR16 
AR16 
Did you feel a desire or craving to smoke 
a cigarette?  
0=None 
1=Slight 
2=Mild 
3=Moderate 
4=Severe 
 
 
 
 
UR17 
SR17 
AR17 
Thinking about the [product] you just 
used. 
 
How pleasurable was your [product]? 
 
0=Not at all 
1=A little 
2=Moderately 
3=Quite a bit 
4=Extremely 
Pipe in text to 
replace [product] 
from item AR0. 
depending on 
product used. 
 
 
 
UR18 
SR18 
AR18 
Thinking about the [product] you just 
used. 
 
How satisfying was your [product]? 
 
0=Not at all 
1=A little 
2=Moderately 
3=Quite a bit 
4=Extremely  
Pipe in text to 
replace [product] 
from item AR0. 
depending on 
product used. 

H:\Project SIREN\Clinical Trials Results Reporting\OTHER DOCS\Codebook_Highlighted.Changes.docx 
 
Morning Report 
First Random Prompt 
Report of the Day (FR) 
Random Prompt Report 
(RR) 
Usual Brand Smoke 
Report (UR) 
Study Cig Smoke 
Report (SR.) 
Alternative Product 
Report (AR) 
Item 
Response Format 
Logic 
MRT1 
FRT1 
RRT1 
URT1 
SRT1 
ART1 
Thank you for reporting this! 
(Instruction) 
 
End of all reports