Comparison of the Substitution Between Different Tobacco/Nicotine Products as a Function of Tobacco-user Type
Phase: NA
Conditions: Cigarette Smoking, Nicotine Vaping
Sponsor: Virginia Polytechnic Institute and State University

 
Comparison of the Subs2tu2on Between Diﬀerent Tobacco/Nico2ne Products as a Func2on of 
Tobacco-user Type 
 
Protocol and Sta2s2cal Analysis Plan 
 
NCT05177848 
 
IRB approved: December 9, 2022 
 
Date submiOed: August 28, 2024 

21-1046 Comparison of the substitution between different tobacco/nicotine products as a
function of tobacco-user type
VT Research Protocol version 1.0.1 
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INSTRUCTIONS: 
●
Use this “TEMPLATE PROTOCOL (HRP-503)” to prepare a study protocol
outlining your research plan.
●
Depending on the nature of your study, some major sections might not be
applicable to your research. If so, simply mark as “N/A.” For example, a simple
survey might have many sections with “N/A.”  For subsections (e.g., 1.x or 8.x)
you can mark as “N/A”if you are certain that the subsection is not applicable.
●
Once the IRB/HRPP approves your submission, your latest approved version of
the protocol will be stored in the IRB Protocol Management online system.
●
If your research plan changes and you need to modify the protocol, please submit
an amendment to Protocol Management with the requested modifications.
Download your current protocol from Protocol Management and indicate the
changes/revisions using the track changes feature in order to make review of the
modifications easier to follow. If you are unable to use track changes, please
create a new paragraph wherever you need to make a change, and indicate
“Amendment: Date” before making a change to any section. Protocol
management will store the older versions of your protocol if the IRB or HRPP
staff need to compare them during the review.
PROTOCOL TITLE: 
Include the full protocol title. 
Compare the substitution between different tobacco/nicotine products as a function of 
tobacco-user type. 
PROTOCOL NUMBER:   
Include the number assigned in Protocol Management (verify this has been added 
before submitting protocol to HRPP).  
VT IRB # 21-1046 
PRINCIPAL INVESTIGATOR: 
Full Name and Degrees: Warren K. Bickel, PhD 
Department: Fralin Biomedical Research Institute at VTC 
Telephone Number: 540 526 2088  
Email Address: wkbickel@vtc.vt.edu 
FUNDING: 
Sponsor(s): National Institutes of Health, National Cancer Institute - grant 
5P01CA200512. 
Funded already or in the proposal phase?: Funded 
Is Virginia Tech the primary awardee or the coordinating center of this grant or 
contract? If not, list the primary institution: Medical University of South 
Carolina. This Experiment 1 is part of Project 4 of an NIH P01 Grant awarded to 
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Medical University of South Carolina. Virginia Tech is receiving a subcontract 
for Project 4. All of the human subject research activities for Project 4, including 
this first experiment will be carried out at Virginia Tech. Experiment 1 is a single 
site study.   
 
 
VERSION NUMBER/DATE:  
Include the version number and date of this protocol. Versions should start at 1.0. 
Version 1.0 12/03/2021 
 
REVISION HISTORY:  
Use this table to keep track of changes. Add more rows as needed. 
 
Revision 
# 
Version Date 
Brief Summary of Changes  
(i.e., the different sections) 
Consent 
Change? 
1.0 
06/01/2022 
Software was updated from Qualtrics to 
QuestionPro; Session 3 can now be completed 
in person or remotely; other language was 
added to clarify the procedures. 
Yes 
2.0 
07/12/2022 
Inclusion criteria was changed from "Stable 
tobacco use patterns for at least three months" 
to two months. 
No 
3.0 
1/17/2022 
Supplementary breath and saliva samples were 
added; inclusion criterion was updated. 
Yes 
 
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Table of Contents 
1.0 
Study Summary 
4 
2.0 
Objectives 
4 
3.0 
Background 
5 
4.0 
Study Endpoints 
8 
5.0 
Study Design and Statistical Analysis Plan 
8 
6.0 
Setting 
9 
7.0 
Study Intervention(s)/Investigational Agent(s) 
10 
8.0 
Procedures Involved 
11 
9.0 
Data and Specimen Long Term Storage and Use 
15 
10.0 Sharing of Results with Subjects 
18 
11.0 Study Timelines 
18 
12.0 Inclusion and Exclusion Criteria 
19 
13.0 Vulnerable Populations 
20 
14.0 Number of Subjects 
21 
15.0 Recruitment Methods 
22 
16.0 Withdrawal of Subjects 
24 
17.0 Risks to Subjects 
24 
18.0 Potential Benefits to Subjects 
27 
19.0 Data Management and Confidentiality 
28 
20.0 Provisions to Protect the Privacy Interests of Subjects 
29 
21.0 Provisions to Monitor the Data to Ensure the Safety of Subjects 
31 
22.0 Compensation for Research Related Injury 
31 
23.0 Economic Burden to Subjects 
32 
24.0 Consent Process 
32 
25.0 Process to Document Consent in Writing 
35 
26.0 Resources Available 
36 
27.0 Multi-Site Research 
38 
 
 
 
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1.0 
Study Summary 
 
Study Title 
Compare the substitution between different tobacco/nicotine 
products as a function of tobacco-user type. 
Study Design 
In a within-subject repeated measures design, participants 
will complete seven ETM conditions, which include five 
trials assessing different cigarette prices: a) all products at 
market price (control), b) nicotine vaping products at 1/2 
market price, c) nicotine vaping products at 2x market price, 
d) heated tobacco products at 1/2 market price, e) heated 
tobacco products at 2x market price, f) nicotine pouches at 
1/2 market price, and g) nicotine pouches at 2x market price. 
Primary Objective 
To compare the effects of different tobacco/nicotine products 
(i.e., conventional cigarettes, NVPs, HTPs, and NPPs) on 
tobacco/nicotine purchasing and substitution in the 
Experimental Tobacco Marketplace, as a function of tobacco 
user type.  
Secondary 
Objective(s) 
N/A 
Study Population 
Cigarette smokers and dual cigarette/NVP users 
Sample Size 
N = 52 completers 
Research 
Intervention(s)/ 
Investigational 
Agent(s)  
A survey consisting of questionnaires and behavioral tasks.   
Study Duration for 
Individual 
Participants 
Session 1: Consent, Assessments and In-laboratory flavor 
assessment (approximately 2h00). 
Session 2: Experimental Tobacco Marketplace 
(approximately 1h30) 
Session 3: Follow-up (approximately 1h00) 
Acronyms and 
Definitions  
NVPs: Nicotine Vaping Products 
HTPs: Heated Tobacco Products 
NPPs: Nicotine Pouch Products 
ETM: Experimental Tobacco Marketplace 
FBRI: Fralin Biomedical Research Institute  
VTCRC: Virginia Tech Corporate Research Center  
 
 
2.0 
Objectives 
2.1 Describe the purpose, specific aims, or objectives of this study: 
 
Purpose: To compare the effects of different tobacco/nicotine products (i.e., 
conventional cigarettes, NVPs, HTPs, and NPPs) on tobacco/nicotine 
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purchasing and substitution in the Experimental Tobacco Marketplace, as a 
function of tobacco user type. 
 
2.2 State the hypotheses to be tested:  
The primary hypotheses are: 1) purchasing of NVPs, HTPs, and NPPs will increase as the 
price of conventional cigarettes is increased (i.e., they will all serve as substitutes), 2) the 
effect will be largest when those alternative products are at a reduced price, and 3) dual 
cigarette/NVP users, because they are multi-tobacco users, will show greater substitution 
than exclusive cigarette smokers. 
3.0 
Background 
3.1 Summarize the relevant prior research on this topic and gaps in current 
knowledge within the field of study: 
 
Cigarettes have long been the dominant tobacco product, and the vast majority of the 
tobacco-related harm comes from their combustion.[1] In recent years, alternative 
nicotine delivery systems have developed. These products deliver nicotine without 
combusting tobacco and are marketed as alternative products for addicted smokers.[2] In 
the previous funding period, we focused on the emergence of NVPs. In this project, we 
add two additional product classes: HTPs and NPPs. 
HTPs (sometimes called Heat Not Burn) are different from NVPs. HTPs heat 
reconstituted tobacco (tobacco not present within NVPs) at a temperature below the one 
required for combustion. Because the tobacco is not burned, exposure to harmful 
chemicals generated by cigarette smoke is substantially lower for HTPs.[3] The 
prevalence of HTP use in 2020 among current smokers and recent ex-smokers is 
estimated to be 2.7% in the US. [4] In Tokyo, where it has had the greatest success, IQOS 
captured 2.4% of the market share for tobacco, with >50% of smokers who tried the 
product switching entirely from cigarettes.[5] The limited data available on HTPS 
suggest that they are likely to serve as a substitute for conventional cigarettes.[6]Their 
role for dual cigarette/NVP users is unknown. 
NPPs contain nicotine, but no tobacco,[7] and as a result, may present reduced harm 
compared to combustible and non-combustible tobacco products, such as smokeless 
tobacco and snus. A recent pharmacokinetic study showed that the two highest doses of 
NPP (Zyn) deliver nicotine quickly and at levels similar to traditional smokeless tobacco 
products.[8] In 2020, the prevalence of NPP use among current smokers and ex-smokers 
was estimated to be 0.7% in the US. [4] The most recent Nielsen data show that sales 
from these products are sharply on the rise. However, given that NPPs are oral nicotine 
products, rather than inhaled products like NVPs and HTPs, whether NPPs would 
effectively substitute for cigarettes or NVPs among cigarette smokers or dual users is 
unknown. Further, the strength of substitution for NPPs relative to NVPs and HTPs is 
unknown. Thus, utilization of NPPs in the ETM may provide data about substitutability 
that is prescient for understanding the implications of these products for tobacco control. 
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1. National Center for Chronic Disease Prevention and Health Promotion (US) Office on 
Smoking and Health. The Health Consequences of Smoking—50 Years of Progress: A 
Report of the Surgeon General. Atlanta (GA): : Centers for Disease Control and 
Prevention (US) 2014. https://www.ncbi.nlm.nih.gov/pubmed/24455788 
2. Zeller M, Hatsukami D, Strategic Dialogue on Tobacco Harm Reduction Group. The 
Strategic Dialogue on Tobacco Harm Reduction: a vision and blueprint for action in the 
US. Tob Control 2009;18:324–32. doi:10.1136/tc.2008.027318 
3. IQOS. https://www.pmi.com/smoke-free-products/iqos-our-tobacco-heating-system 
(accessed 23 Jun 2020). 
4. Li L, Borland R, Cummings KM, et al. Patterns of non-cigarette tobacco and nicotine 
use among current cigarette smokers and recent quitters: Findings from the 2020 ITC 
Four Country Smoking and Vaping Survey. Nicotine Tob Res Published Online First: 8 
March 2021. doi:10.1093/ntr/ntab040 
5. Caputi TL. Industry watch: heat-not-burn tobacco products are about to reach their 
boiling point. Tob Control 2016;26:609–10. doi:10.1136/tobaccocontrol-2016-053264 
6. Adriaens K, Van Gucht D, Baeyens F. IQOSTM vs. e-Cigarette vs. Tobacco Cigarette: 
A Direct Comparison of Short-Term Effects after Overnight-Abstinence. Int J Environ 
Res Public Health 2018;15. doi:10.3390/ijerph15122902 
7. Robichaud MO, Seidenberg AB, Byron MJ. Tobacco companies introduce ‘tobacco-
free’ nicotine pouches. Tob Control Published Online First: 21 November 2019. 
doi:10.1136/tobaccocontrol-2019-055321 
8. Lunell E, Fagerström K, Hughes J, et al. Pharmacokinetic comparison of a novel non-
tobacco-based nicotine pouch (ZYN®) with conventional, tobacco-based Swedish snus 
and American moist snuff. Nicotine Tob Res Published Online First: 22 April 2020. 
doi:10.1093/ntr/ntaa068 
3.2 Describe any relevant preliminary data: 
 
The Experimental Tobacco Marketplace (ETM) [1], a novel method recently developed, 
permits estimates of the effects of new policies and products on consumption and 
substitution in the tobacco marketplace. This methodology places the mix of products, 
prices, and specific policies under experimental control so as to provide estimates of 
novel policies obtained under conditions that simulate “real world” circumstances. This 
approach provides insight into how a given policy may alter consumption, preferences, 
and substitution among tobacco products. Different policies have been examined with 
this methodology in adult smokers, as part of the previous funding period. Study 1 
examined the impact of e-liquid nicotine strength and showed that the substitutability 
between cigarettes and NVPs increased as a function of e-liquid strength. The 24mg/mL 
strength resulted in the greatest substitutability  (p<0.001; f=1.05).[2] Study 2 examined 
cigarette taxes and e-liquid subsidies. It showed that cigarette taxes decreased cigarette 
purchases (p=0.005; f=0.45).[3] Interestingly, e-liquid subsidies had no effects on 
cigarette purchases, but increased e-liquid purchases (p=0.013; f=0.44). Study 3 used a 
hypothetical ETM and replicated the taxes and subsidies conditions from Study 2 among 
exclusive cigarette smokers and dual cigarette/NVP users in an international context as 
part of the ITC survey. Analysis of country-specific differences have yet to be explored, 
however, the US cohort replicates the findings of the lab-based ETM. Note, the effects of 
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taxes on cigarette purchases observed in Studies 2 and 3 replicate and demonstrate the 
generality of our findings as related to prior econometric analysis of the impact of 
national and state taxes.[4] This replication provides an example of reverse translational 
research demonstrating that the ETM can reflect effects observed in larger 
populations.[5] Study 4 investigated the effects of NVP use in smoke-free environments 
on product choice. The results suggest that permitting NVP use in the workplace 
increased e-liquid purchase on average (p<0.001; f=0.56), but nicotine concentration had 
no effect on e-liquid demand intensity. Cigarette demand was unaltered across 
conditions.[6] This study suggests that allowing NVP use in the workplace may increase 
the demand for e-liquid without affecting purchases of conventional cigarettes.  
Collectively, and importantly for the proposed study, our ETM work shows that the 
substitution between products is dependent upon several factors (nicotine strength, price 
of the substitutable product, and the type and number of products in the marketplace). In 
these studies, we change the price as an expeditious, effective, and quantifiable method to 
promote change. With that change, we can ascertain the likelihood that smokers will 
defend their consumption or substitute it for another product. In doing so, we can 
estimate the consequences of a policy constraint before implementation. 
  
 
1. Bickel WK, Pope DA, Kaplan BA, et al. Electronic cigarette substitution in the 
experimental tobacco marketplace: A review. Prev Med 2018;117:98–106. 
doi:10.1016/j.ypmed.2018.04.026 
2. Pope DA, Poe L, Stein JS, et al. Experimental tobacco marketplace: substitutability of 
e-cigarette liquid for cigarettes as a function of nicotine strength. Tob Control Published 
Online First: 18 April 2018. doi:10.1136/tobaccocontrol-2017-054024 
3. Pope DA, Poe L, Stein JS, et al. The Experimental Tobacco Marketplace: Demand and 
Substitutability as a Function of Cigarette Taxes and E-Liquid Subsidies. Nicotine Tob 
Res under review. 
4. Chaloupka FJ, Grossman M, Bickel WK, et al. The Economic Analysis of Substance 
Use and Abuse: An Integration of Econometric and Behavioral Economic Research. 
Published Online First: 1 January 1999.https://www.nber.org/books/chal99-1.pdf 
(accessed 7 Aug 2020). 
5. Shakhnovich V. It’s Time to Reverse our Thinking: The Reverse Translation Research 
Paradigm. Clin Transl Sci 2018;11:98–9. doi:10.1111/cts.12538 
6. Freitas Lemos R, Stein JS, Pope DA, Brown J, Feinstein M, Stamborski KM, Tegge 
AN, Heckman BW, Bickel WK. E-liquid Purchase as a Function of Workplace 
Restriction in the Experimental Tobacco Marketplace. Exp Clin Psychopharmacol; 
Advance online publication. https://doi.org/10.1037/pha0000444 
 
3.3 Based on the existing literature, provide the scientific or scholarly 
rationale for and significance of your research and how will it add to 
existing knowledge: 
 
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An important aim of tobacco control is to reduce demand for the most harmful products. 
No study to date has experimentally compared the effects of conventional cigarettes, 
NVPs, HTPs, and NPPs on tobacco/nicotine purchasing and substitution. A priori 
knowledge of substitutability across novel and widely used tobacco products may 
forecast the impact of policies on product switching.  
4.0 
Study Endpoints 
4.1 Describe the primary and secondary study endpoints. See links below for 
discussion of study endpoints and how they may differ from study 
objectives. These are most common in clinical trials but are sometimes 
applicable to other types of biomedical research, as well as social, 
behavioral, or educational research. See link below for a discussion. 
https://docs.google.com/document/d/1Wocz7K7a0hCQJPPO_khh5l1
SQQjhGDDGHzcOPRHR5Tw/edit?usp=sharing  
 
Substitutability: cigarettes, NVPs, HTPs, and NPPs will be compared to assess 
substitutability as a function of tobacco user type. 
 
4.2 Describe any primary or secondary safety endpoints. These should be 
included for all studies that are greater than minimal risk. (Minimal risk: 
The probability and magnitude of harm or discomfort anticipated in the 
research that are not greater in and of themselves than those ordinarily 
encountered in daily life or during the performance of routine physical or 
psychological examinations or tests.): 
 
This study will recruit adults who regularly smoke cigarettes and who regularly smoke 
cigarettes and use NVPs. This study’s procedures are not designed to increase daily 
nicotine use and we do not anticipate any increased risk to participants directly from this 
study, although there are risks of nicotine use and these are included in the risk section of 
this protocol and consent. 
 
5.0 
Study Design and Statistical Analysis Plan 
5.1 Describe the basic study design/approach (e.g., qualitative study using five 
focus groups of first year students to describe assimilation into the 
university community; randomized controlled trial of a behavioral change 
intervention to increase dietary intake of whole grains; pre- post-test 
evaluation of new pedagogical techniques to improve adult literacy): 
 
In a within-subject repeated measures design, participants will complete seven ETM 
conditions, which include five trials assessing different cigarette prices: a) all products at 
market price (control), b) nicotine vaping products at 1/2 market price, c) nicotine vaping 
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products at 2x market price, d) heated tobacco products at 1/2 market price, e) heated 
tobacco products at 2x market price, f) nicotine pouches at 1/2 market price, g) nicotine 
pouches at 2x market price. 
 
 
5.2 Describe corresponding data analysis plan/approach (e.g., content analysis 
of focus group transcripts; descriptive analysis followed by linear 
regression modeling; nonparametric analysis of pre- and post-test 
measures): 
 
A within-between subject analysis of variance (ANOVA) will test for differences in 
substitution and demand measures between user types (exclusive cigarette smokers and 
dual cigarette/NVP users) and relative price scenario (e.g., ½ market price for HTPs). We 
will test for the interaction between the relative price scenarios and each user type, 
suggesting a difference in how each user type responds to price scenarios. Order effects 
will be included in all models to account for the balanced Latin square design for 
counterbalancing the ETM conditions within the session. We will perform post-hoc 
contrasts to compare user types, based on our hypotheses. 
 
Additional analyses might be conducted.   
 
 
6.0 
Setting 
6.1 Describe the sites or locations where your research team will conduct the 
research.  Consider each of the items listed below: 
● 
Identify where your research team will identify and recruit potential 
subjects. 
● 
Identify where the team will perform the research procedures. 
● 
Describe the composition and involvement of any community 
advisory board(s). 
● 
For research conducted in other locations, describe: 
o 
Site-specific regulations or customs affecting the research at 
those locations. 
o 
Local scientific and ethical review structure at those locations.  
Examples include work in other cultures or ethnic groups 
(within or outside of the U.S.) and work with churches. The 
HRPP will provide additional guidance for international 
research. 
 
Location of Recruitment:  
Participants will be recruited from the Roanoke-Blacksburg community via flyers, word 
of mouth referrals, and electronic advertisements (e.g., Craigslist, Facebook). To the 
extent possible, we will attempt to minimize obstacles to participation. For example, 
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travel barriers will be addressed by providing transportation or parking costs to 
participants, and scheduling barriers will be minimized by offering a flexible session 
schedule. 
 
Location of study: 
All methods and measures will be conducted using standard operating procedures at the 
Fralin Biomedical Research Institute (FBRI) at VTC, the Virginia Tech Corporate 
Research Center (VTCRC) or a designated site. All staff (including recruitment staff) will 
have completed human subjects' protection and research training. We have a history of 
successful recruitment of cigarette smokers and NVP users. All participants will enroll on 
a voluntary basis and sign an IRB-approved consent form prior to study participation. 
 
 
7.0 
Study Intervention(s)/Investigational Agent(s) 
7.1 Describe the study interventions (including behavioral interventions) and/or 
investigational agents (e.g., drugs or devices) to be used in this study.  Consider 
each of the items listed below:  
● 
Drug/Device Handling: If the research involves drugs or devices, 
describe your plans to store, handle, and administer the drugs or 
devices so that they will be used only on subjects, and only by 
authorized investigators. 
● 
Describe whether any of the following will be used: microwaves, X-
rays, DEXA scans, general anesthesia, or sedation 
● 
If control of the drugs or devices used in this protocol will be 
accomplished by following an established, approved organizational 
SOP (e.g., Research Pharmacy SOP for the Control of 
Investigational Drugs, etc.), please reference the SOP in this section. 
 
This study does not involve any smoking cessation interventions. This study does 
involve experimental manipulation of tobacco/nicotine product price to understand 
consumer's behavior. Participants will be provided with a FDA approved NVP and 
HTP to use during the study.  
 
7.2 List the name of all drugs (including any vitamins, supplements, herbs, or 
nicotine) to be used in the study.  Indicate whether they have FDA 
approval, and list any limitations for their use:  
 
The range of products available to sample and purchase includes: cigarettes, chewing 
tobacco, HTPs, nicotine gum, nicotine lozenges, nicotine patches, NPPs, NVPs, and snus. 
All the products that will be available to sample and purchase are FDA approved and 
available in the real world. Note that as of November 29, 2021, IQOS Devices and 
Heatsticks were removed from all stores, due to an order issued by the International 
Trade Commission regarding an ongoing patent dispute. These products are no longer 
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available for sale in the U.S. However, the ITC order does not impact products that 
researchers/consumers already have in their inventory. 
 
7.3 List all devices, how they will be used, their purpose in the study, and if 
they will be used in a manner consistent with their approved uses. If they 
will be used in ways that are not yet FDA approved, indicate whether they 
need an IDE or a determination that they are exempt from the IDE 
Determination. If a determination of significant risk or non-significant risk 
is needed for any of the devices, include the researcher’s recommendation 
for each of those devices:  
 
Participants will be provided with a NVP and a HTP and instructed how to use 
according to the manufacturer specifications. Both products are FDA approved. 
 
7.4 If the drug is investigational (has an IND) or the device has an IDE or a 
claim of abbreviated IDE (non-significant risk device), include the 
following information: 
● 
Identify the holder of the IND/IDE/abbreviated IDE. 
● 
Explain procedures followed to comply with sponsor requirements 
for FDA regulated research for the following: 
 
Applicable to: 
FDA Regulation 
IND Studies 
IDE studies 
Abbreviated 
IDE studies 
21 CFR 11 
X 
X 
 
21 CFR 54 
X 
X 
 
21 CFR 210 
X 
 
 
21 CFR 211 
X 
 
 
21 CFR 312 
X 
 
 
21 CFR 812 
 
X 
X 
21 CFR 820 
 
X 
 
 
 
N/A 
 
 
 
8.0 
Procedures Involved 
8.1 Describe and explain the study design: 
In a within-subject repeated measures design, participants will complete questionnaires 
on a computer, sample a range of tobacco products, and complete ETM conditions. 
Specifically, participants will purchase tobacco products in an online store under seven 
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ETM conditions, which include five trials assessing different cigarette prices: a) all 
products at market price (control), b) nicotine vaping products at 1/2 market price, c) 
nicotine vaping products at 2x market price, d) heated tobacco products at 1/2 market 
price, e) heated tobacco products at 2x market price, f) nicotine pouches at 1/2 market 
price, g) nicotine pouches at 2x market price. 
8.2 Provide a description of: 
● 
All research procedures being performed  
● 
If the study has more than one procedure, session, and/or subject 
population, describe each procedure, session, and/or study 
population separately. For complex studies, you are encouraged to 
include a figure or chart. 
 
 
Participants will complete a 1) informed consent, assessment session, and an in-
laboratory flavor assessment, 2) an ETM session, and a 3) follow-up session. Session 1 
and 2 will be separated by an at home sampling phase and Session 2 and 3 will be 
separated by an at home product use phase. 
1) In the consent and initial assessment session, participants will go through standard 
consent procedures and then provide a breath to confirm recent levels of smoking. 
Participants will complete a timeline follow back (TLFB) to assess previous month recent 
smoking, and consumption of nicotine products, and to determine ETM budget. A survey 
will administer demographics questions and nicotine/tobacco-related assessments 
(Questionnaire on Smoking Urges-Brief, Heaviness of Smoking Index, Perceived Health 
Risk, Product Evaluation Scale, Intention to transition and/or quit, Tobacco awareness 
and Hypothetical Purchase Task for a range of products). At the end of the session, 
participants will experience a trial of the ETM that will be used in the next session. For 
the NVP, HTP and NPP flavor assessment, participants will rank order flavors from a list 
of available flavors and choose two flavors to try. During the in-laboratory flavor 
assessment, participants will be provided single-user/individual NVP and HTP devices. A 
research assistant will read through the manufacturer instructions on how to use the 
products with the participant. Sampling will occur in our negative air pressure ventilated 
smoking laboratory, specifically designed for these types of studies. The smoking 
laboratory is a custom-built laboratory space in ARRC, which was approved as part of 
the opening of the Virginia Tech Carilion Institute. This laboratory is enclosed to 
minimize harm to other participants and laboratory personnel. Participants may use the 
devices throughout the study and won't be asked to return them.  
If needed, the informed consent and initial assessment session and flavor assessment can 
be in different days. 
For the sampling phase, participants will be provided with the most preferred flavor of 
NVP, HTP and NPP to sample during the sampling period. Participants may also be 
provided with a sample of any other commercially available tobacco product they wish to 
examine and try.  
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2) In the ETM session, participants will buy tobacco products to use throughout the next 
5 days. Participants will complete a total of 35 purchasing trials each for 5 days' worth of 
products. They will be exposed to 7 conditions with cigarettes increasing in price. A 
balanced Latin square design will be used to present the following conditions: a) all 
products at market price (control), b) nicotine vaping products at 1/2 market price, c) 
nicotine vaping products at 2x market price, d) heated tobacco products at 1/2 market 
price, e) heated tobacco products at 2x market price, f) nicotine pouches at 1/2 market 
price, g) nicotine pouches at 2x market price. Additionally, participants will complete the 
Questionnaire on Smoking Urges-Brief.   
 
For the five days following the ETM session, participants will be asked not to use or 
purchase any outside tobacco/nicotine products and not to sell or give away any of their 
purchases.  
3) In the follow-up session, participants will complete a timeline follow back to assess 
previous week recent smoking, and consumption of nicotine products. A survey will 
administer nicotine/tobacco-related assessments (Perceived Health Risk, Product 
Evaluation Scale, and Hypothetical Purchase Task for a range of products). Session 3 will 
be in laboratory unless participants are having difficulty returning to the lab. If 
participants are unable to complete the study in person, a Zoom session will be scheduled 
and participants will interact with study personnel to complete the session. The same 
computerized assessments will be administered in person and using Zoom. 
 
In all three sessions, participants may be asked to provide breath and saliva to test for 
recent nicotine/tobacco use. The intent is to compare the two methods of detecting 
current tobacco and nicotine use. Participants who are available to complete the third 
session in-lab will be considered for this procedure.  Approximately the next six 
exclusive smokers will be invited to complete this procedure, which will help inform the 
most appropriate methods for future research.  
To collect breath sample, we will use the Icoquit, which is a single-user commercially 
available device. To collect saliva, we will use the iScreen Saliva Nicotine Test, which is 
a single-use test also commercially available. Procedures will be conducted following the 
manufacturers' instructions. 
Additionally, participants will complete a TLFB to describe the quantities and times of 
tobacco and nicotine use in the past 24 hours.  
 
 
8.3 Describe: 
● 
Procedures or safeguards intended to reduce the probability and 
magnitude of risks. (For example: Reducing the risk of injury in a 
virtual reality study either by having the subjects sit during the study 
or by providing an obstacle-free space for walking.) 
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● 
Be sure to describe all drugs and devices used in the research, when 
they will be administered or used, and their purpose.  
● 
Methods used to collect data about subjects. Please upload all data 
collection forms to Protocol Management. Some common examples 
are: 
● Screening questionnaires  
● Survey(s), including online surveys 
● Demographic questionnaire(s) 
● Interview guide(s), e.g., questions or pool of questions for semi-
structured interviews  
● Focus group guide(s) 
● Other documents used to collect data  
 
 
Participation in this study is completely voluntary and participants may choose not to 
participate at any time.  
Participants will be given an FDA approved NVP and HTP to sample/use during the 
course of this study. Research personnel will provide detailed instructions and 
demonstration to assure proper use according to the manufacturer specifications. 
 
Information and data from participants will be collected from research staff and from 
self-reported surveys. Examples of the assessments described in section 8.2 are attached. 
 
8.4 What data will you collect during the study and how you will obtain them? 
Please include descriptions of electronic data collection, database 
matching, and app-based data collection: 
 
All of the survey and questionnaire data will be collected using QuestionPro, an online 
survey platform used to develop, administer, and collect participant data in a secure 
password protected database.  
ETM data will be collected using an experimental online store custom-built by a 
programmer and used in previous studies.  
All tasks will be performed on a computer. Only study personnel will have access to the 
collected data. 
 
8.5 Who will transcribe or code audio and/or video recordings?: 
 
N/A 
 
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8.6 Include a description of any deception to be used in the study. Include 
justification for the use of deception (why the deception is necessary), 
describe the debriefing process, and describe how the study meets all the 
following criteria  for alteration of consent (deception is considered an 
alteration of informed consent): 
• The research involves no more than minimal risk to the subjects 
• The alteration will not adversely affect the rights and welfare of the 
subjects 
• The research could not practicably be carried out without the 
alteration/deception 
• (Optional but encouraged in most cases) Subjects will be provided with 
additional pertinent information after participation (i.e., debriefing for 
studies involving deception)  
 
 
N/A 
 
 
8.7 If the study involves long-term follow-up (once all research related 
procedures are complete), describe what data will be collected during the 
follow up period and when it will occur:  
 
N/A 
 
 
9.0 
Data and Specimen Long Term Storage and Use 
9.1 If you will store data or specimens for future use, describe where you will 
store the data or specimens, how long they will be stored, and how and by 
whom the data or specimens will be accessed: 
 
All participant data, including electronic data, will be stored in secure places to protect 
confidential participant information. Secured places will include locked filing cabinets, 
locked rooms accessible only to study personnel, and/or password-protected databases. 
Moreover, all data will be quality controlled in preparation for data analyses. All 
discrepancies in data entry will be checked against the raw data source, and the correct 
data entry will be used. All data entered into spreadsheets and databases will be coded by 
participant ID number and not by name (i.e., first and last name). Additionally, all 
entered data will be backed up on secure password-protected servers. Computers used in 
the studies will also be password protected, accessible only by study personnel. IRB 
regulations will be strictly adhered to in the conduct of the proposed research. 
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Specifically, prior to implementation of any protocol changes, amendments will be 
submitted to the IRB for approval. 
 
9.2 For specimens, list the data to be stored or associated with each 
specimen: 
 
N/A 
 
9.3 Describe the procedures to release data or specimens outside of the 
research team, including the process to request a release, approvals 
required for release, who can obtain data or specimens, and what data 
will be provided with specimens: 
 
Investigators will adhere to all NIH requirements regarding data sharing. Participant data 
collected in this project will be de-identified before sharing for analysis outside of the 
study team. As part of this process, all investigators will be required to agree to the 
following conditions: 1) will adhere to the reporting responsibilities; 2) will not 
redistribute the data beyond the requesting individual and named collaborators; 3) will 
give appropriate acknowledgement; 4) will not use the data for commercial purposes; and 
5) will obtain appropriate ethical approvals. 
Results from research conducted will be shared and disseminated, including: regular 
project meetings, annual meetings, symposia, workshops, and/or conferences for related 
groups. Manuscripts will be written and submitted for publication in peer-reviewed 
journals/conferences, following the NIH Public Access Policy guidelines. All necessary 
ethical approvals will be obtained. 
 
 
Data requests will be reviewed by the principal investigator and data will be shared with 
the expectation of acknowledgment of funding source and primary study team. 
 
9.4 Describe the identifiers to be included with stored data or specimens, as 
well as any key or code that could be used to make them identifiable. 
Describe where the code will be stored, who will have access to it, and 
when it will be destroyed: 
 
Original signed consent forms will be stored in a study specific binder for this protocol, 
separate from all other study documents, identifying information, and data collection.  
All screened participants are assigned study IDs that are thereafter associated with all 
collected data, whether paper or electronic. The electronic de-identified data is stored on 
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the shared servers which are password protected. Non-electronic data that is collected is 
stored in study-specific binders identified only by study ID. These binders are stored in a 
locked room within ARRC. 
Study ID and full name are available together electronically only in REDCap [1], a 
widely used secure web-based application that enables us to build and maintain a 
participant database. Specifically, we use REDCap to collect demographic and other 
screening criteria for eligibility for study enrollment. This service is password protected 
and has been approved by Virginia Tech IRB.  
 
1. Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap)--a 
metadata-driven methodology and workflow process for providing translational research 
informatics support. J Biomed Inform 2009;42:377–81. doi:10.1016/j.jbi.2008.08.010 
 
 
9.5 Please select the identifiers you will obtain (whether directly from 
participants or from another source), including but not limited to: 
 
☒ 
Name 
☒ 
Geographical subdivisions smaller than a state, including street address, 
city, county, precinct, zip code, and equivalent geocodes (note, the initial 
three digits of a zip code are not considered identifiable) 
☒ 
Elements of dates (except year) for dates directly related to an individual, 
including birth date, admission date, discharge date, date of death, and 
single year of age over 89 and all elements of dates (including year) 
indicative of such age (note, such ages and elements may be aggregated 
into a single category of age 90+) 
☒ 
Phone numbers 
☐ 
Fax numbers 
☒ 
Electronic mail addresses (e-mail) 
☒ 
Social Security numbers 
☐ 
Medical record numbers 
☐ 
Health plan beneficiary numbers 
☐ 
Account numbers 
☐ 
Certificate/license numbers 
☐ 
Vehicle identifiers and serial numbers, including license plate numbers 
☐ 
Device identifiers and serial numbers 
☐ 
Web Universal Resource Locators (URLs) 
☐ 
Internet protocol (IP) address numbers 
☐ 
Biometric identifiers, including finger and voice prints (audio recording) 
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☐ 
Full face photographic images and any comparable images (including 
video recording) 
☐ 
Student record number or identification number   
☐ 
User name for online or computer accounts 
☐ 
Any other unique identifying number, characteristic, or code (note this 
does not mean the unique code assigned by the investigator to code the 
data): Click here to explain.   
 
10.0 Sharing of Results with Subjects 
10.1 Describe whether you will share results (study results or individual subject 
results, such as results of investigational diagnostic tests, genetic tests, or 
incidental findings) with subjects or others (e.g., the subject’s primary care 
physician). If so, describe how you will share the results and include this 
information as part of the consent document. Upload materials you will use 
to explain the results to subjects: 
 
We will not share study results or individual results directly with the study participants or 
others. 
 
11.0 Study Timelines 
11.1 Describe: 
● 
The duration of an individual subject’s participation in the study (for 
example, 1 hour, 2-4 weeks, 3-5 years). 
● 
The amount of time expected to enroll all study subjects (weeks, 
months, years, etc.) 
● 
The amount of time expected for the investigators to complete this 
study including primary data analyses. 
 
1) Participant's schedule 
 
The participation of one subject is expected to take approximately 2 weeks.  Session 1 
(Consent, Assessments and in-laboratory flavors assessment) is estimated to take 
approximately 2h. Session 2 (Experimental Tobacco Marketplace) is expected to take 
approximately 1h30. Session 3 (follow-up) is estimated to take approximately 1h00.  
*Note that participants will sample/use products between sessions 1 and 3.  
 
2) Study timeline 
 
Enrollment and data collection are expected to take 1 year.  
 
The study team has projected this study to take approximately 1.5 years to complete 
enrollment, data collection and data analysis.  
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12.0 Inclusion and Exclusion Criteria 
12.1 Describe how you will screen individuals for eligibility. When will 
screening occur and what procedures will you use? Upload any screening 
scripts or surveys to Protocol Management:  
We currently use a master screening, which occurs prior to enrolling participants into our 
research protocols, to effectively decrease attrition in our studies by ensuring that 
participants meet all inclusion/exclusion criteria prior to enrolling into a study.  
12.2 Describe the eligibility criteria that define who will be included and who 
will be excluded from enrollment for each procedure of your study. 
Include any geographic criteria (e.g., Virginia Tech undergraduate 
students, a national sample of adults with engineering degrees, minors 
aged 8-12 in the New River Valley, university faculty in Virginia and 
Paris, France): 
 
Inclusion criteria:  
- Provide informed consent 
- Be at least 21 years of age or older 
- Provide a breath sample for measuring carbon monoxide (CO ≥ 8 ppm) 
- Stable tobacco use patterns for at least two months 
- Be willing to sample NVPs, HTPs, and NPPs. 
For exclusive cigarette smokers:  
- Smoke at least 10 cigarettes daily and do not use NVPs regularly (no more than 9 times 
in the last month). 
For dual cigarette/NVP users 
- Smoke at least 10 cigarettes daily and use NVPs for at least 3 times in a week (report 
use of closed nicotine salt system) 
 
 
Exclusion criteria: 
- Have plans to move out of the area 
- Have a serious or unstable physical or mental health condition 
- Taking a tobacco cessation medication or medication that interferes with nicotine 
metabolism, motivation or reinforcement 
- Report concrete, immediate plans to alter/quit using their usual nicotine products at the 
beginning of the study  
 
12.3 Indicate specifically whether you will include or exclude each of the 
following special populations: (You may not include members of these 
populations as subjects in your research unless you indicate them in the 
description of your subject population.) 
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● 
Minors, as defined by state law where the study is performed 
(infants, children, teenagers) 
● 
Pregnant women (can be included in minimal risk studies by 
mentioning in section 13.1) 
● 
Prisoners (including all incarcerated individuals) 
● 
Adults not capable to consent on their own behalf 
 
This study will focus on cigarette smokers and dual cigarette/NVP users. We will not 
include individuals under the age of 21 in compliance with Virginia state law. Minors, 
pregnant women, prisoners, and adults not capable to consent on their own behalf will be 
excluded from this study. 
 
13.0 Vulnerable Populations 
13.1 If the research involves individuals who are vulnerable to coercion or 
undue influence, please describe additional safeguards you will include to 
protect their rights and welfare. Consider the applicable items listed 
below: 
● 
If the research involves Virginia Tech students, indicate whether 
these are students of any of the investigators. If so, describe whether 
the activities will take place during class time as part of the 
curriculum and the steps you will take to reduce the possibility that 
students feel obliged to participate in order to improve their course 
grade. The HRPP can provide further guidance as needed. Describe 
whether you will request access to student records (e.g., SAT, GPA, 
GRE scores). 
● 
If the research involves employees of Virginia Tech or the research 
sponsor, describe steps you will take to ensure that the employees 
are freely participating and describe how their data will be 
protected from inspection by their supervisors.  
● 
If the research involves Virginia Tech NCAA athletes, you must 
obtain approval from the athletic department.  
● 
For research involving Montgomery County Public Schools, you 
must obtain county approval (after obtaining contingent Virginia 
Tech approval). Other locales have different requirements; please 
check on these and describe here. Approval is typically granted by 
the superintendent, principal, and classroom teacher (in that order). 
Approval by an individual teacher is insufficient. School approval, in 
the form of a letter or a memorandum should be uploaded as a 
supporting document. 
● 
If the research involves pregnant women, review “CHECKLIST: 
Pregnant Women (HRP-412)” to ensure that you have provided 
sufficient information in this protocol. 
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● 
If the research involves prisoners, review “CHECKLIST: Prisoners 
(HRP-415)” to ensure that you have provided sufficient information 
in this protocol. 
● 
If the research involves persons who have not attained the legal age 
for consent to treatments or procedures involved in the research 
(minors), review the “CHECKLIST: Minors (HRP-416)” to ensure 
that you have provided sufficient information in this protocol. 
● 
If the research involves cognitively impaired adults, review 
“CHECKLIST: Cognitively Impaired Adults (HRP-417)” to ensure 
that you have provided sufficient information in this protocol. 
 
 
Virginia Tech Students might participate in the study if they meet the inclusion 
criteria, although students will not be directly recruited because of their status. 
However, no students that have had or have any relationship with this lab will be 
included.  
 
 
14.0 Number of Subjects 
14.1 Indicate the total number of subjects to be enrolled and how this number 
was determined (e.g., sample size calculation [show], number of available 
subjects in a finite pool, number of tests funding award would allow):  
 
In this study, we require n=52 (N=78 accounting for 33% attrition) participants to 
complete the study when using repeated measures with two groups and two 
measurements per participant.  
Our sample sizes are based on a repeated-measures within-between interaction ANOVA 
design using medium effect size (f=0.25) and 80% power. Note the effect sizes observed 
in preliminary data ranged from f=0.29 to f=1.05. Given that the products used in these 
experiments are untested  (i.e., NPPs and HTPs), we conservatively selected a medium 
effect size of f=0.25. To account for multiple testing, we will control for five 
comparisons in each experiment; therefore, we use an alpha of 0.01.  
 
We have been successfully recruiting cigarette smokers and e-cigarette users in our 
community for the past 10 years. Based on our experience with prior studies, we 
anticipate that 33% of participants don't complete the study.  
14.2 If this is a multi-site study, indicate the number of subjects to be enrolled 
at this site and the total to be enrolled from all sites: 
 
N/A 
 
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14.3 If applicable, indicate the number of potential subjects you expect to 
screen for enrollment, and the number of subjects you will need to 
complete the research procedures: 
 
As stated previously, we have developed and are currently using a separate pre-screening 
protocol, which occurs prior to enrolling participants into our research protocols. As 
described above, we anticipate enrolling 78 participants to complete a total of 52 
participants. 
 
14.4 If the study has more than one procedure, indicate the total number of 
subjects to undergo each procedure separately: 
 
All participants will undergo all three sessions unless they withdraw consent. 
 
15.0 Recruitment Methods 
15.1 Describe when, where, and how you will recruit potential subjects: 
Participants will be recruited from the community via flyers, word of mouth, and 
electronic advertisements (e.g., Craigslist, Facebook). Participants will be contacted if 
they have given prior permission (through previous informed consent form) or by 
completion of a confidential pre-screening questionnaire.  
 
15.2 Describe the source of subjects (for example, clinic patients with specific 
conditions, students in the library, community members at a gathering, or 
members of a local gym): 
 
Participants will usually be from the Blacksburg-Roanoke and surrounding areas. 
 
15.3 Describe the methods that you will use to identify potential subjects: 
 
Flyers and ads will generally describe the study and direct potential participants to either 
call our lab to screen over the phone or to complete our online pre-screener. Participants 
may also pre-screen in person.  
 
15.4 Describe materials that you will be use to recruit subjects. Attach copies 
of these documents with this protocol in Protocol Management and be 
sure to include the IRB protocol number on each document.  
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● For flyers, attach the final copy of printed flyers.  
● For Virginia Tech News, Facebook postings and ads, newspaper ads, 
websites, MTurk/SONA/online survey systems, etc., attach the final 
wording and graphics to be used.  
● For email recruitments, please include the subject line.  
● For advertisements meant for audio broadcast, please submit the 
wording of the advertisement prior to taping (to avoid having to re-
record with approved language) and submit the final recorded version 
for IRB review before use.  
● Describe any compensation to subjects. Separate compensation into 
appropriate categories, such as: reimbursement for expenses, time and 
effort, and additional incentives for study participation.  For each 
category, specify the amount (including any pro-rated amount), schedule, 
and method of payment. 
 
Flyers to be used in community and online posting are attached. 
 
Compensation for this study is for time and effort and an additional incentive for study 
completion.  
1) Time and effort: 
    Compensation is distributed according to individual progress through sessions. 
Participants may receive up to $150 for participating in this study, according to the 
following: 
   Session 1 (up to $25) 
$10 for completion of the consent  
$10 for completion of the assessment session 
$ 5 for the in-lab flavor assessment 
   Session 2 (up to $55) 
$25 for product sampling 
$30 for completion of the Experimental Tobacco Marketplace session 
   Session 3 (up to $70) 
$35 for the follow-up visit  
$35 bonus for completing the study 
 
Participants who are invited to provide supplementary breath and saliva samples will be 
additionally compensated up to $10 per session. 
 
2) Travel: 
    In addition to the above compensation for participation, participants may receive 
additional compensation for travel time, e.g. $11.00 per hour, consistent with Virginia 
minimum wage. Research personnel may also arrange and pay for cab or public 
transportation. 
 
To allow for payments that are both convenient and rapidly available, we will pay 
participants with reloadable prepaid cards through Greenphire ClinCard 
(www.greenphire.com), an FDIC-insured payment provider that specializes in clinical 
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trial stipend payments that comply with IRB privacy regulations and considerations. At 
the beginning of the study, the participant will receive a prepaid MasterCard debit card 
that can be used anywhere that accepts MasterCard. As payments are earned in the course 
of the study, additional funds will be added to the account for that participant. Funds are 
immediately available when added and participants can check their balance as desired.  
 
 
16.0 Withdrawal of Subjects 
16.1 Describe circumstances under which you anticipate subjects could be 
withdrawn from the research without their consent: 
 
Participants could be withdrawn from the study if they exhibit or report unstable medical 
illness, unmanaged psychiatric or neurological disorder, violation of research center 
policies or failure to attend scheduled sessions or to complete any of the study 
procedures. We will also stop participation if their answers or performance suggest that it 
is not safe and appropriate for them to continue in the study. 
 
16.2 If applicable, describe any procedures for orderly termination (e.g., 
discontinuation of a study drug or debriefing after a behavioral 
intervention): 
 
If a participant is withdrawn from the study, they will be informed the reasons for 
terminating their participation. If a participant is withdrawn or voluntarily discontinues, 
their compensation for the study will be pro-rated accordingly. 
 
16.3 Describe procedures that you will follow when subjects withdraw from the 
research, including partial withdrawal from procedures with continued 
data collection (e.g., participant declines to continue with regular blood 
draws, but continues with periodic behavioral questionnaires): 
 
If a participant is discontinued, they will be withdrawn from the entire study. 
 
17.0 Risks to Subjects 
17.1 List the reasonably foreseeable risks, discomforts, hazards, or 
inconveniences to the subjects related the subjects’ participation in the 
research. Include for the IRB’s consideration a description of the 
probability, magnitude, duration, and reversibility of the risks. Consider 
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physical, psychological, social, legal, privacy, and economic risks. Do not 
indicate “No risk” or “N/A.” Instead, for studies with very low risk (e.g., 
anonymous online questionnaire on a mundane topic) indicate “The 
investigators are not aware of any risks from participation in this study.” 
or “No more than risks than are found in everyday life.” The example 
consent form presents a tabular method for risk information, which you 
can also use here. Common risk types include: 
● Physical (e.g., potential for pain, discomfort, infection) 
● Psychological (e.g., potential for stress, discomfort, and/or 
embarrassment) 
● Social (e.g., potential for discrimination or stigmatization and 
disruption of personal and family relationships) 
● Legal (e.g., potential for disclosure of illegal activity, negligence) 
● Privacy (e.g., potential for personal information being accessed, used, 
or disclosed without the subjects’ knowledge or consent, breach of 
confidentiality/security) 
● Economic (e.g., potential for individuals to lose access to economic 
services, employment, insurability) 
 
There will be no direct costs for participation, although there are risks.  
 
1. Possible embarrassment: This may result from answering questions that participant 
considers sensitive. Some of our questions will ask for information about medical and 
psychiatric conditions and/or drug use.  
 
2. Possible discomfort: There is also the possibility that participant may become bored or 
frustrated during the research sessions. 
 
3. Loss of confidentiality: The research team will employ every effort to maintain 
participant confidentiality, however the loss of confidentiality is a potential risk. 
 
4. Adverse effects associated with nicotine use: Because the present experiment allows 
and sometimes involves self-administering nicotine products, participants might 
experience adverse effects associated with the use of such products (e.g., nausea, 
vomiting, dizziness, diarrhea, weakness, rapid heartbeat, minor increase in throat or sinus 
irritation).  
 
5. Adverse effects associated with nicotine withdrawal: participants might experience 
adverse effects associated with withdrawal from nicotine (e.g., dizziness, headache, 
irritability, sleepiness, decreased alertness, difficulty concentrating, impatience, 
sleeplessness, and increased eating).  
 
6. NVP/HTP/NPP exposure: Participants may not enjoy sampling the study products. 
 
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Due to the investigative nature of this study, there may be other risks that are currently 
unknown. 
 
17.2  Indicate the measures you will use to minimize risks and monitor subjects 
for safety. (e.g., asking a subject at regular intervals to rate how they are 
feeling from 1 to 10, or to slowly crouch in order to check their balance.) 
 
Informed Consent. All consenting methods will be conducted using standard operating 
procedures, and all staff (including recruitment staff) will be provided with human 
subjects protection training. All participants will enroll on a voluntary basis and sign an 
IRB-approved consent form prior to study participation. 
Protections against risk. Participants will be screened, using medical history and 
structured interviews for a history of medical contraindications (e.g., pregnancy, recent 
myocardial infarction) and current unstable medical illnesses. Participants will be free to 
withdraw from the study at any time. In addition, if participants develop medical 
problems or experience adverse events during the course of the study, assessments to 
determine whether participants should continue in the study and/or continue to use study 
products will be conducted and necessary referrals will be provided. Participants will also 
be told that they can stop using the study products at any time.  
 
The risks enumerated above will be addressed by the following: 
1. Possible embarrassment: Participants are free to refuse to answer questions and 
withdraw from the study at any time. 
 
2. Possible discomfort: Participants will able to selected a date and time of their choice to 
start the study. They will also be given breaks during sessions, if desired. To increase 
data validity and reliability, breaks will be incorporated within the ETM session. 
 
3. Loss of confidentiality: The use of ID numbers for participants, and keeping all data in 
a locked cabinet in locked offices, will protect confidentiality. Password protected 
computer databases will have coded identifiers. Master databases linking subject names 
to study ID numbers will be kept separate from the data. These screening, monitoring, 
and confidentiality procedures have been in effect for decades and for thousands of 
participants across the various protocols employed by our group across various 
institutions. 
 
4. Adverse effects associated with nicotine use: Participants will be informed of the 
potential adverse effects prior to sampling nicotine products.   
 
5. Adverse effects associated with nicotine withdrawal: Participants will be informed of 
the potential adverse effects of stopping use of nicotine products.    
 
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6. NVP/HTP/NPP: Participants are only required to try, but not to keep using the NVPs, 
HTPs and NPPs throughout the study, if they don't want to. Participants will be asked 
about any health changes throughout the study. 
 
17.3 If applicable, indicate which procedures might have risks to the subjects 
that are currently unforeseeable. This will be rare, and usually applicable 
when testing a new drug or device or a new use of an existing drug or 
device: 
 
The use of study product may have risks to participants that are currently unforeseeable. 
However, see section 17.2 for details on how these risks will be monitored and mitigated. 
 
17.4 If applicable, indicate which procedures might have risks to an embryo or 
fetus should the subject be or become pregnant: 
 
Nicotine/tobacco use can be a risk to an embryo or fetus. However, during the consent 
session, female participants will be tested for current pregnancy. Currently pregnant 
females will be discontinued from participation.  
 
17.5 If applicable, describe risks to others who are not subjects (e.g., collection 
of sensitive health data that might affect sexual partners if disclosed, 
mandatory reporting of abuse, DNA testing that might affect family 
members or relationships): 
 
N/A 
 
18.0 Potential Benefits to Subjects 
18.1 Describe the potential benefits that individual subjects might experience 
from participating in the research. Include the probability, magnitude, and 
duration of the potential benefits, as this will be useful to the IRB’s 
risk:benefit analysis. Do not include benefits to society or others. Do not 
list monetary or non-monetary compensation for participation, as this is 
not a benefit These should be included in section 2 or 3 of this document: 
 
Participants will not directly benefit from participating in this study. However, the current 
study may help identify effective methods of assessing the use of tobacco products as 
well as policy changes, which may help the health of people in the future.   
 
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18.2 If applicable, specify that there are no anticipated direct benefits for 
participants:  
 
There are no anticipated direct benefits for participation in this study. 
 
19.0 Data Management and Confidentiality 
19.1 Describe procedures that you will use for quality control to ensure validity 
of collected data: 
 
The PI will oversee monitoring of the data collection procedures. These procedures will 
be reviewed regularly in a number of settings. For instance, issues pertaining to data 
validity and integrity will be addressed formally during regularly scheduled study 
personnel meetings in which all study personnel, including the PI, will be in attendance. 
Issues pertaining to participant safety also will be addressed at these meetings.  
 
19.2 Describe any existing data or biospecimens you will obtain as part of this 
study. Include:  
● 
Variables or samples to be obtained  
● 
Source of the data or specimens 
● 
Your authorization to access or receive the data or biospecimens 
● 
Whether the data or biospecimens are publicly available 
● 
Whether the data or specimens you receive will contain identifiers  
 
We may collect urine samples to test for pregnancy, breath samples for carbon monoxide 
and saliva to assess recent levels of smoking. All tests will be used to obtain the desired 
measurement and then appropriately discarded, i.e., the tests/samples will not be retained. 
 
19.3 Describe the steps that you will take to handle and secure study data 
during data collection, storage, use, and transmission.  Include 
information about training of study staff, authorization of access, 
password protection, encryption, physical controls, certificates of 
confidentiality, separation of identifiers and data, etc.: 
 
N/A 
 
 
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19.4 For multi-site studies, describe how data or specimens will be handled 
and secured for each site (e.g., central or disseminated data storage, data 
coordinating center): 
 
N/A 
 
19.5 Describe the plan for data disposition following the conclusion of the 
study (e.g., long term maintenance of data, data destruction methods).  
● 
What information will be included in the long term storage of data 
or specimens? 
● 
How long will the data or specimens be stored? 
● 
Where and how data or specimens will be stored? 
● 
Who will have access to the data or specimens during long term 
storage? 
● 
Who is responsible for receipt or transmission of the data or 
specimens? 
● 
How will data or specimens be shared or transported? 
● 
When and how will personal identifiers be destroyed? 
 
 
All behavioral data collected in this study (including participants' characteristics, tobacco 
related assessments and tobacco purchasing) will be retained and destroyed in accordance 
with the center's policy that requires a 3-year retention period following final publication 
of the data. To secure study data computer databases will have coded identifiers, only ID 
numbers will be used, data will be kept in secure locations and/or in locked offices. 
Access to study data will be limited to study personnel who have completed the IRB 
Human Subjects Training and who have been delegated the responsibility of data 
collection, management, or analyses by the PI. Currently, there are not plans for data to 
be sent/transmitted outside the research group. In the event that someone requests the 
data, only de-identified data will be shared by the lead and principal investigator though a 
secure virtual server. Personnel identifiers may be kept long term if participants express 
interest in being considered for future research. 
 
 
 
20.0 Provisions to Protect the Privacy Interests of Subjects 
20.1 Describe the steps that you will take to protect subjects’ privacy interests. 
“Privacy interest” refers to a person’s desire to place limits on with whom 
they interact or to whom they provide personal information (e.g., 
collecting the minimal amount of private information required to complete 
the study, protecting the data once it is obtained):  
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The amount of private information collected in this study is minimal. The information 
collected is necessary to assure subject safety, completion of the study and proper 
compensation. Procedures to keep the information safe are described in section 9.4. 
 
20.2 Describe steps that you will take to make subjects feel at ease with the 
research situation in terms of the questions being asked and the 
procedures being performed. “At ease” does not refer to physical 
discomfort, but the sense of intrusiveness a subject might experience in 
response to questions, examinations, and procedures (e.g., use of a same 
gender investigator to place sensors on the torso, a private changing area 
if clothing must be changed, sensitivity when discussing  pregnancy testing 
with subjects, making it clear on surveys that participants can discontinue 
at any time, not asking questions about private or sensitive issues unless 
necessary for the research): 
 
The locations where this study will be conducted have private offices, individualized 
computer testing and interview rooms. In cases in which private information is collected, 
the participant is in a private interview room with a trained research staff member. The 
lab is equipped with white-noise machines to reduce excess noise and maintain 
confidentiality. All participants are informed that their information is confidential. 
 
20.3 Describe how you plan to access existing sources of information about the 
subjects (e.g., medical records, grades) and how you will protect 
participant privacy through the data security plan: 
 
Participants who have previously given consent to be contacted for future studies will be 
searchable in the REDCap database. Eligibility criteria, based on demographics and 
current nicotine/tobacco use, may be reviewed to contact potentially eligible participants 
for this study.  
 
20.4 Describe any required reporting that might occur as a result of your 
research questions, study populations, and data collection methods. 
Examples for Virginia and Virginia Tech include: 
• Any suspicions (e.g., circumstantial, disclosed) of child abuse (physical, 
emotional, sexual) and neglect  
• Sexual discrimination and/or sexual violence that involves a student 
• Disclosure or signs of intention to harm oneself (i.e., suicidal ideation 
and/or plan) 
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• Disclosure or signs of desire to harm others (i.e., homicidal ideation 
and/or plan) 
• Suspected abuse, neglect or exploitation of vulnerable adults (e.g., 
individuals with a disability, elderly persons) 
 
 
We do not expect any required reporting to occur as a result of our research questions and 
data collection methods. However, as a safeguard, we include in our consent form that 
any instances of child or elderly abuse or intent to harm self or others will be reported.  
Any cases of disclosure or signs of sexual discrimination and/or sexual violence will be 
reported according to Title IX report procedures.   
 
 
 
21.0 Provisions to Monitor the Data to Ensure the Safety of Subjects 
Safety monitoring is required when research involves greater than minimal risk 
and is sometimes appropriate for other studies. 
21.1 Describe: 
● 
The plan to periodically evaluate the data collected regarding both 
harms and benefits to determine whether subjects remain safe  (e.g., 
periodic reporting to the IRB, establishing a data monitoring 
committee, reporting data monitoring committee findings to the IRB 
and the sponsor). 
● 
What data you will review, including safety data, unexpected events, 
and data that show the ability to produce the intended results. 
● 
How the safety information will be collected (e.g., with case report 
forms, at study visits, by telephone calls with subjects). 
● 
The frequency of data collection, including when safety data 
collection starts. 
● 
Who will review the safety data and with what frequency. 
● 
The statistical tests for analyzing the safety data to determine 
whether harm is occurring. 
● 
Any conditions that will trigger an immediate suspension of the 
research (e.g., a serious adverse event). 
 
 
The study leader and PI will review any reported health changes or adverse events and 
report as necessary. 
 
 
22.0 Compensation for Research Related Injury 
22.1 If the research involves more than minimal risk to subjects, describe the 
available compensation in the event of research-related injury, if any: 
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N/A 
 
22.2 Provide a copy of contract language, if any, relevant to compensation for 
research-related injury. At Virginia Tech, this is most common for 
sponsored research: 
 
N/A 
 
23.0 Economic Burden to Subjects 
23.1 Describe any costs that subjects might be responsible for because of 
participation in the research, including any uncompensated costs for items 
such as transportation, missed work, and childcare: 
 
There are no costs to participate in this study. To the extent possible, we will attempt to 
minimize obstacles to participation. For example, travel barriers may be addressed by 
providing transportation or compensation through additional time.  
 
24.0 Consent Process 
24.1 Indicate the process by which you will obtain consent for study 
participation. Please upload all consent, parental permission, and assent 
forms, documents, and scripts referenced in this section to Protocol 
Management. 
Describe the following: 
● 
Where the consent process will take place (e.g., clinic waiting area, 
classroom, online) 
● 
The time interval between sharing the consent information with the 
prospective subject and obtaining consent. For lab, interview, and 
focus group studies, the Virginia Tech IRB prefers that subjects have 
at least 24 hours to review the consent form and study information 
before the appointment where consent will be obtained. For simple 
online survey studies, you can typically present the consent 
information immediately before subjects begin participation. 
● 
If applicable, processes to ensure ongoing consent or assent (e.g., 
for multiple sessions; for research in which a minor will turn 18 
during the study; for longitudinal research with minors who will 
later be asked to provide or affirm their assent). 
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● 
Please review “SOP: Informed Consent Process for Research (HRP-
090)” for recommended procedure. Describe your process, being 
sure to include: 
o 
The name and role of all study personnel who will be trained 
and certified by the PI to conduct the consent process 
o 
The time that will be devoted to the consent discussion 
o 
Steps that you will take to minimize the possibility of coercion 
or undue influence 
o 
Steps that you will take to gauge or ensure the subjects’ 
understanding 
 
Participants will be provided with a copy of the consent form following phone or online 
screening by email or mail when possible. To accommodate "walk-in" study screens 
and/or participants unable to receive email or physical mail (e.g., without physical 
address, email address, or access to a computer), we will provide a hard copy of the 
consent form to review. In all cases, participants will be given as much time as possible 
to review the consent and ask any questions. Participants will also be informed that they 
may choose to take the consent with them and return at a later date to enroll into the 
study. During the consent process, participants will be given adequate time in a quiet 
room to read (or further review) the written consent form. 
 
Research staff will review each element of the written consent form with the potential 
participant. The potential participant will be given the opportunity to ask questions and 
will have as much time as they need to decide whether they would like to participate in 
the study. Staff will reiterate that the potential participant can choose to decline 
participation in the study at that time or at any time thereafter without consequence. The 
potential participant and person obtaining consent will sign the consent form after the 
potential participant verbally states that they understand the conditions of the study, have 
no more questions, and chooses to participate. Participants unable to provide informed 
consent for themselves will not be eligible. 
 
Non-English Speaking Subjects 
● 
Indicate what language(s) other than English are understood by 
prospective subjects or representatives. 
● 
If non-English speakers will be recruited, describe the process you 
will use to ensure that the oral and/or written consent information 
provided will be in a language that they understand.  
● 
If you translate consent forms and study materials, please provide a 
certified translation of the form as well as the certification 
document. 
● 
Indicate the spoken language that study personnel obtaining consent 
will use. Describe how you will assess fluency of personnel obtaining 
consent to ensure that the translation is accurate. 
 
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Non-English speakers will not be recruited. 
Waiver or Alteration of Consent Process (consent will not be obtained, 
required information will not be disclosed, or the research involves 
deception) 
● 
Review the “CHECKLIST: Waiver or Alteration of Consent Process 
(HRP-410)” to ensure you have provided sufficient information for 
the IRB to make these determinations (i.e., that it meets the criteria 
for a waiver or alteration of the consent process). 
 
N/A 
 
Subjects who are not yet adults (minors: infants, children, teenagers) 
● 
Describe the criteria that you will use to determine  legal age for 
consent to treatments or procedures involved in the research under 
the applicable law of the jurisdiction in which the research will be 
conducted (e.g., in Virginia, individuals under the age of 18 years). 
o 
For research conducted in Virginia, review “SOP: Legally 
Authorized Representatives, Minors, and Guardians (HRP-
013)” to determine which individuals in the state meet the 
definition of “minor.” 
o 
For research conducted outside of the state, please describe 
the legal requirements for the definition of “minor.”  
● 
Describe the process for obtaining parental permission.  
o 
Permission from one parent is acceptable for studies that 
involve no greater than minimal risk OR involve greater than 
minimal risk but present the prospect of direct benefit to the 
minor subject. 
o 
Permission from both parents is required in all other 
cases (unless one parent is deceased, unknown, 
incompetent, or not reasonably available, or when only 
one parent has legal responsibility for the care and 
custody of the minor). 
● 
Describe whether you will obtain permission from individuals other 
than parents or Legally Authorized Representatives, and if so, who 
will be allowed to provide permission. Describe the process you will 
use to determine these individuals’ authority to consent to the 
minor’s general medical care. 
● 
Indicate whether you will obtain assent from all, some, or none of 
the minors. If you will obtain assent from some minors, indicate 
which minors will be required to assent. Consider chronological age 
and intellectual capacity when determining who will be required to 
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provide assent (e.g., infants are unable to assent. However, 
teenagers are likely able to read and sign an assent form). 
● 
When assent of minors is obtained, describe whether and how you 
will document it.  Will minors sign an assent form or give verbal 
assent? 
● 
Attach parental permission and minor assent forms or scripts in 
Protocol Management.  
 
 
N/A 
 
 
Adults Unable to Consent  
● 
Describe the process you will use to determine whether an individual 
adult is capable of consent. 
● 
List the individuals from whom you will obtain permission in order 
of priority (e.g., durable power of attorney for health care, court 
appointed guardian for health care decisions, spouse, and non-
minor child). 
o 
For research conducted in the Virginia, review “SOP: Legally 
Authorized Representatives, Minors, and Guardians (HRP-
013)” to determine which individuals in the state meet the 
definition of “legally authorized representative.” 
o 
For research conducted outside of Virginia, please describe 
the legal requirements for obtaining permission from a legally 
authorized representative in the state where the research will 
occur. 
● 
Describe the process for assent of the subjects. 
o 
Indicate whether you will require assent from all, some, or 
none of the subjects. If some, indicate which subjects will be 
required to assent and which will not. 
o 
If you will not obtain assent from some or all subjects, please 
provide justification for not obtaining assent. 
o 
Describe whether and how you will document assent.  
 
N/A 
 
25.0 Process to Document Consent in Writing 
25.1 Consult “SOP: Written Documentation of Consent (HRP-091)” for 
recommended procedures, and describe whether and how consent of the 
subject will be documented in writing: 
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Written consent will include participants' printed name, signature, and date from each of 
the person obtaining consent (e.g., research coordinator/study staff member), and the 
research participant on the last page. In addition, a copy of the consent form (paper or 
electronic) will be offered to the study participant. 
 
25.2 If the research presents no more than minimal risk of harm to subjects and 
involves no procedures for which written documentation of consent is 
normally required outside of the research context, you can request that the 
IRB waive the requirement to obtain written documentation of consent 
(e.g., consent to participate is indicated by pressing a button for an online 
questionnaire – after the consent information is presented and before the 
questionnaire begins): 
 
N/A 
 
25.3 If you will document consent in writing, attach a consent document with 
places for signatures. If you will obtain consent, but not document consent 
in writing, please attach the consent script or text. Review “CHECKLIST: 
Waiver of Written Documentation of Consent (HRP-411)” to ensure that 
you have provided sufficient information. You should use “TEMPLATE 
CONSENT DOCUMENT (HRP-502)”to create the consent document or 
script: 
 
Written informed consent and consent statement are attached. 
 
 
 
26.0 Resources Available 
26.1 Describe the resources available to conduct the research. For example, as 
appropriate: 
● 
Describe the PI’s availability to supervise the research. 
● 
Justify the feasibility of recruiting the required number of suitable 
subjects within the agreed recruitment period. For example, how 
many potential subjects do you have access to? What percentage of 
those potential subjects do you need to recruit? 
● 
Describe the time that you will devote to conducting and completing 
the research. 
● 
Describe your facilities. 
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● 
Describe the availability of medical or psychological resources that 
subjects might need as a result of an anticipated or unanticipated 
consequence of participation in the research. 
● 
Describe your process to ensure that all persons assisting with the 
research are adequately informed about the protocol, the research 
procedures, and their duties and functions (e.g., training plans, 
detailed study notebooks). 
 
The organizational structure of the study team involves overall leadership by Dr. Warren 
Bickel, who will assume full responsibility for all aspects of the project, including design 
and participant eligibility. Dr. Bickel will oversee recruitment and retention of 
participants. He will also oversee and delegate to the Co-Investigators and other study 
team members the responsibility of training study personnel, consenting of participants, 
and data collection. The Research Coordinator(s) and Research Assistant(s) will be 
trained and supervised as appropriate for any delegated study procedures. Behavioral data 
analysis will be overseen by Dr. Bickel and conducted by the Co-Is and the Statistician.  
All staff involved in the conduct and/or monitoring of this study will have completed the 
IRB Human Subject Protection Training and Good Clinical Practice Training. 
Documentation of training will be maintained. The PI will be responsible for continuous 
data and safety monitoring of all participants enrolled in this study. In terms of standard 
operating procedures, trained research staff members will administer all assessments.  
 
Participants will be recruited from the community via flyers, word of mouth referrals, and 
electronic advertisements (e.g., Craigslist, Facebook). To the extent possible, we will 
attempt to minimize obstacles to participation. For example, travel barriers will be 
addressed by providing transportation to participants, and scheduling barriers will be 
minimized by offering a flexible session schedule. All methods and measures will be 
conducted using standard operating procedures, and all staff (including recruitment staff) 
will be provided with human subjects' research training. We have a history of successful 
recruitment of smokers and drug users. All participants will enroll on a voluntary basis 
and sign an IRB-approved consent form prior to study participation. Note that we have 
been successfully recruiting cigarette smokers and e-cigarette users in our community for 
the past 10 years and the demographics of participants have been stable.  
 
As far as facilities, the Addiction Recovery Research Center (ARRC; Director, Bickel) is 
part of the FBRI, located in Roanoke, Virginia. Multidisciplinary research projects 
include examining the effects of behavioral, pharmacological, and transcranial magnetic 
stimulation (TMS) interventions as potential therapies for alcohol, cocaine, and nicotine 
dependence as well as other health behaviors such as obesity. ARRC also develops 
potential computerized therapies, applies principles from behavioral and neuro-
economics to the understanding of addiction, and assesses nicotine product abuse 
liability. 
ARRC resides on the 3rd floor of the FBRI and consists of several laboratories for 
clinical research. ARRC has private offices, individualized computer testing and 
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interview rooms.  The lab has a ventilated, negative air pressure smoking laboratory that 
is equipped with computers and five additional behavioral booths, a dedicated TMS suite, 
and a conference room. The research space also includes an adjacent male and female 
restroom with one-way observation windows and connecting stainless steel specimen 
pass-through cabinets. Office space for PI Bickel, Co-Investigators, Project Coordinators, 
Postdoctoral Associates, and Research Coordinators/Assistants is provided in the FBRI. 
The ARRC office suite has a copy machine, fax machine, network printer, scanner, and 
storage space for participant files and supplies as well as comfortable waiting rooms with 
entertainment (e.g., magazines, television, etc.) for research participants. 
  
VTCRC has a conference room, private offices, individualized computer testing and 
interview rooms plus a network printer and access to secured shared servers.  
 
27.0 Multi-Site Research 
Contact the HRPP for multi-site research (involving multiple institutions) and 
the details required for this section will be provided. Otherwise, indicate N/A. 
 
N/A 
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