Pharmacokinetics, Subjective Effects, and Abuse Liability of Nicotine Salt-Based Vaping Products With Tobacco or Unflavored E-liquids[SALTVAPE Study]
Phase: NA
Conditions: Nicotine Dependence
Sponsor: Roswell Park Cancer Institute

 
Pharmacokinetics, Subjective Effects, and Abuse Liability of Nicotine Salt-
Based Vaping Products With Tobacco or Unflavored E-liquids, SALTVAPE 
Study  
 
 
 
NCT number NCT04231539 
Document Date 04/28/2023 
 

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 1 of 78
PROTOCOL TITLE:
Pharmacokinetics, Subjective Effects, and Abuse Liability of Nicotine Salt-Based Vaping 
Products with Tobacco or Unflavored e-liquids [SALTVAPE Study]
PROTOCOL NUMBER:
I 475819 
PRINCIPAL INVESTIGATOR:
Amanda J Quisenberry PhD 
Roswell Park Comprehensive Cancer Center
Elm and Carlton Street
Buffalo, New York 14263
716-845-4918
Amanda.Quisenberry@RoswellPark.org
VERSION NUMBER: 
7
DATE: 
4/28/2023
SPONSOR:  Roswell Park Comprehensive Cancer Center
FUNDING:  NIH 
Confidentiality Statement
Any and all information presented in this document shall be treated as confidential and shall 
remain the exclusive property of the party (ies) mentioned above (Roswell Park Cancer Institute 
Corporation d/b/a Roswell Park Comprehensive Cancer Center). The use of such confidential 
information must be restricted to the recipient for the agreed purpose and must not be disclosed, 
published, or otherwise communicated to any unauthorized persons, for any reason, in any form 
whatsoever without the prior written consent of the party(ies) above.
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819 
4/28/2023
Page 2 of 78
Table of Contents
1
Objectives ................................................................................................................................3
2
Background..............................................................................................................................3
3
Inclusion and Exclusion Criteria .............................................................................................5
4
Local and Study-Wide Number of Subjects ............................................................................6
5
Local and Study-Wide Recruitment Methods .........................................................................6
6
Multi-Site Research .................................................................................................................7
7
Study Timelines.......................................................................................................................7
8
Study Endpoints.......................................................................................................................7
9
Design......................................................................................................................................7
10
INTERVENTION....................................................................................................................8
11
Procedures Involved ..............................................................................................................10
12
Withdrawal of Subjects..........................................................................................................12
13
Risks to Subjects....................................................................................................................13
14
Potential Benefits to Subjects ................................................................................................15
15
Data and Specimen Banking..................................................................................................15
16
Measurement of Effect ..........................................................................................................16
17
Safety Evaluation...................................................................................................................16
18
Data Management and Confidentiality..................................................................................17
19
Statistical Plan .......................................................................................................................18
20
Provisions to Monitor the Data to Ensure the Safety of Subjects..........................................20
21
Vulnerable Populations..........................................................................................................20
22
Community-Based Participatory Research............................................................................20
23
Sharing of Results with Subjects ...........................................................................................20
24
Setting....................................................................................................................................20
25
Provisions to Protect the Privacy Interests of Subjects .........................................................20
26
Resources Available ..............................................................................................................21
27
Prior Approvals......................................................................................................................21
28
Compensation for Research-Related Injury...........................................................................21
29
Economic Burden to Subjects................................................................................................21
30
Consent Process.....................................................................................................................21
31
Process to Document Consent in Writing..............................................................................22
32
Drugs or Devices ...................................................................................................................22
33
References..............................................................................................................................23
34
Appendices/ Supplements......................................................................................................24
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 3 of 78
1
OBJECTIVES

To determine the effect of nicotine salt (nicotine benzoate) and free-base nicotine in 
different flavored e-liquid solutions on puffing behaviors and systemic exposure to nicotine 
from ENDS by 1) Assessing short-term effects on nicotine cravings, withdrawal, and 
satisfaction from single use of ENDS refilled with flavored nicotine salt or flavored free-
base nicotine solutions with two different flavors (tobacco or unflavored) in current daily 
ENDS users following an overnight fast; and 2) Comparing users’ perceptions and 
preferences towards inhaling vapors containing nicotine salt (nicotine benzoate) or free-
base nicotine with two different  flavors (tobacco and unflavored) versus their regular 
brand. 

This project provides important information on whether the pharmacokinetics of nicotine 
delivery differ between salt and free-base forms of e-liquid of equivalent nominal 
concentration using the same device, and whether the previously observed effects of flavors 
on subjective effects differ between salt and free-base forms.  
1.1
Primary Objective(s)

 Determine whether Cmax or Tmax differ between free-base and salt-based versions of the 
same liquid, controlling for flavoring and nominal nicotine concentration [main effect of 
salt]

Determine whether the effect of flavoring on subjective effects (e.g., harshness, liking) 
differs between matched free-base and salt-based e-liquids [flavor X salt interaction]
1.2
Exploratory Objective(s)

Examine effects of salt and flavoring on abuse liability using the Experimental Tobacco 
Marketplace (ETM).  
2
BACKGROUND
Over the last 10 years electronic cigarettes also known as electronic nicotine delivery systems 
(ENDS) have gained considerable popularity especially among youth. Although definitive data are 
lacking, nicotine from ENDS is likely absorbed through the upper aero-digestive tract through 
mucosal surfaces or lung parenchyma that are in direct contact with ENDS aerosol. ENDS design 
has evolved over the past few years, from the small vaporizers that resembled conventional tobacco 
cigarettes (“cig-a-likes”) to larger tank systems (“mods”). “Pods,” the newest generation of ENDS, 
have soared in popularity in the past year, most notably, one brand, Juul. As of first quarter 2018, 
(per Nielson data) Juul had more than 50% of the ENDS market share, surpassing all of big 
tobacco’s e-cigarette products together. Use of Juul products (‘juuling’) among youth has raised 
significant concern. All pod devices have a simplistic compact design and features that make them 
lightweight, ultra-portable and easy to use inconspicuously, with many simply resembling a 
computer thumb drive.
Each pod holds nicotine salt solution. Although the exact physiological mechanisms of nicotine 
salts have not been studied in detail, these compounds are believed to increase the amount and rate 
of nicotine uptake in pod users, effectively increasing the dose of nicotine delivered to the 
circulation and central nervous system. Modification of physicochemical properties of tobacco 
products to increase its addictiveness and appeal to users is not a new approach: Tobacco 
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 4 of 78
companies have been known to add ammonia to tobacco to enhance nicotine’s bioavailability to 
smokers. In addition to their potentially increased bioavailability, nicotine salts appear to be easier 
to inhale, as users report less upper respiratory tract irritation when compared with other products 
containing high nicotine concentrations. While youth don’t identify nicotine as a reason for 
choosing ENDS products (indeed, youth often don’t know which products do and don’t contain 
nicotine), nicotine likely plays a determining role in the continued teen use of ENDS. Pods contain 
solutions with highly concentrated nicotine salts, primary nicotine benzoate. 
PILOT STUDIES: We measured total nicotine concentration in pod products, and found that all 
tested products contained high nicotine concentrations, varying from 22 to 59 mg/mL (1). These 
concentrations are much higher than reported in older ENDS products. We also measured total 
nicotine yields in aerosols generated from these products using a smoking machine and 
standardized laboratory puffing protocol. We estimated that users of prefilled pod systems (e.g. 
Juul) may inhale with 10 puffs from 0.77 to 0.85 mg of nicotine (1). This estimated nicotine dose 
is higher than previously reported in older generations of EC devices (0.02–0.51 mg/10 puffs) (2).
JUUL has emerged as the leading mass-marketed vaping product over the last year, and other 
manufacturers have commenced selling salt-based liquids.  There is emerging evidence suggesting 
that this form of nicotine delivery allows for higher nominal concentrations to be combined with 
lower heating temperatures for aerosol generation to provide less perceived harshness and fewer 
volatile organic compounds on a per-unit-nicotine basis.  However, the pharmacokinetics of 
nicotine delivery for salt-based liquids has not been fully elucidated, and it is unclear whether the 
salt per se affects absorption, subjective effects, or product choice under standardized conditions 
of use.  Similarly, while anecdotal evidence from users suggests that JUUL-like products are 
perceived as less harsh, there is little evidence from controlled studies.  There is also limited 
evidence from food research that sodium benzoate, the salt used in JUUL and other salt-based 
liquids, may enhance sweet tastes and suppress bitter tastes.  So, salts may have additional effects 
on flavor perceptions.  Understanding pharmacokinetics and subjective effects is crucial to 
understanding whether salt-based liquids differ from other e-liquids in terms of abuse liability.  
Behavioral economics provides additional insights into abuse liability, particularly with regard to 
appeal and substitution, which can be assessed with the Experimental Tobacco Marketplace (ETM) 
(3). The ETM, combined with PK and subjective effects data, can provide layers of insight into 
the abuse liability of salt-based flavored ENDS.  
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 5 of 78
3
INCLUSION AND EXCLUSION CRITERIA
Screening: Upon calling, potential participants will be given a brief explanation of the study and 
their eligibility to participate will be determined (Appendix D: Telephone Screening 
Questionnaire). All participants who meet the inclusion and exclusion criteria summarized in 
Section 3.1 and Section 3.2 will be treated on an outpatient basis. 
All four study visits will take place in the Department of Health Behavior - Human Exposure 
Lab at Roswell Park Comprehensive Cancer Center (Basic Science Bldg. Room 3920).  The 
laboratory is 10’10.5” x 11’8” space equipped with a sink, multiple infusion chairs, and an Axis 
Communications video camera. In addition, the laboratory also has a specialized mechanical 
exhaust system designed to keep the room under negative air pressure at all times. 
In order to minimize any carry-over effect, there will be a minimum 5-7-day wash-out period 
between each scheduled study visit and, the order of the e-liquid flavors will be randomly assigned. 
3.1
Inclusion Criteria

 Age ≥ 21 years and ≤ 55 years

Willingness to abstain from using ENDS product for 8-10 hours (overnight abstinence) 
prior to study visits

Current daily ENDS user as determined by
o
Has used ENDS product every day for the past 6 months (by history) 
o
Has used ENDS product or e-liquid containing nicotine (by history)

Participant must understand the investigational nature of this study and sign and 
Independent Ethics Committee/Institutional Review Board approved written informed 
consent form prior to receiving any study related procedure. 
Refer to Appendix A for the Investigator Study Eligibility Verification Form: Inclusion Criteria.
3.2
Exclusion Criteria

Smoked cigarettes in the past 7 days.

Currently smokes ≥ 5 cigarettes per month.

Unstable medical conditions (such as unstable heart disease, uncontrolled hypertension, 
thyroid disease, diabetes, renal or liver impairment, or glaucoma) or psychiatric condition 
(such as current major depression, history of schizophrenia or bipolar disorder) or current 
regular use of psychiatric medications (such as major tranquilizers and antidepressants).

History of serious side effects from nicotine or from any nicotine replacement therapies.

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, 
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or 
psychiatric illness/social situations that would limit compliance with study requirements.

Pregnant or nursing females.

Concurrent participation in another clinical trial
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 6 of 78

Unwilling or unable to follow protocol requirements.

Any condition which in the Investigator’s opinion deems the participant an unsuitable 
candidate. 
Refer to Appendix B for the Investigator Study Eligibility Verification Form: Inclusion Criteria.
3.3
Inclusion of Women and Minorities
Both men and women and members of all races and ethnic groups are eligible for this study.
3.4
Special Populations
The following special populations are excluded from this study:

Cognitively impaired adults/adults with impaired decision-making capacity

Individuals who are not yet adults (infants, children, teenagers)

Pregnant women

Prisoners
4
LOCAL AND STUDY-WIDE NUMBER OF SUBJECTS
This is a single center study to be conducted at Roswell Park. The target accrual is 20 evaluable 
participants (participants who have completed all 4 study visits), with an equal number of males 
and females. Accrual is expected to take up to 4 years. 
5
LOCAL AND STUDY-WIDE RECRUITMENT METHODS
Participants will be recruited from advertisements in local newspapers/magazines, posters, 
community centers, churches, and from several websites (Roswell websites, Craigslist.org, 
Facebook, and Instagram). An example of the participant recruitment material can be found in 
Appendix C.  Applicants will be invited to call a local number. On calling, applicants will be 
given a brief explanation of the study and their eligibility to participate will be assessed (Appendix 
D). Those who meet eligibility criteria will be included in the study and attend 4 weekly sessions. 
We anticipate that each session will take 120 minutes. After completion of each visit, participants 
will be asked to vape as usual over the next week, and the procedures will be repeated every week 
for the total of 4 visits.
Study participants will be compensated by cash for each study visit completed and will receive 
additional “bonus” cash if all study visits have been completed. Payments will be disbursed 
according to the following schedule (Table 1):
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 7 of 78
Table 1Study Payment Schedule
Study Visit
Payment Amount
1
$50.00
2
$60.00
3
$70.00
4
$80.00
All Visits Completed
$90.00 bonus
TOTAL
$350.00
6
MULTI-SITE RESEARCH

Not Applicable – This is a single-site study. 
7
STUDY TIMELINES

The anticipated duration of intervention is 4 weeks. Each participant will be scheduled for 
4 study visits.  Study visits may occur at a minimum of 5-7 days apart, but no more than 4 
weeks apart.
o
Each study session is expected to take approximately 2.0 to 2.5 hours. 
o
The duration anticipated to enroll all study participants is 4 years.
8
STUDY ENDPOINTS
8.1
Primary Endpoint(s)

 Maximum concentration of nicotine in plasma (Cmax), the area under the concentration – 
time curve from 0 to 120 min (AUC), and the time to maximum concentration (Tmax).
8.2
Secondary Endpoint(s)

 Perceived harshness, satisfaction, liking, and relief of nicotine withdrawal symptoms.
8.3
Exploratory Endpoint(s)

 Demand indices including intensity and elasticity of demand for each device sampled and 
substitution levels of alternative tobacco products. 
9
DESIGN
This is a single center, randomized, double blind clinical trial pilot. Using a 2 (free-base vs salt) x 
2 (tobacco vs unflavored) factorial design, 20 current daily vapers will be asked to use one of four 
liquids across four 2.5-hour laboratory sessions.  The order of the tested conditions will be 
randomized and study personnel as well as participants will be blinded to the four liquids 
throughout the study. Participants will be aged 21-55, use a vaping product daily, have a preferred 
flavor of tobacco, and not currently smoke cigarettes (no cigarette use in the past seven days and 
no more than 5 cigarettes in last 30 days).  For each session, participants will arrive after overnight 
abstinence and be randomly assigned to one of the four liquids and puff according to a standardized 
protocol (10-minute bout, 20 puffs, 30 second inter-puff interval).  Venous blood samples (4 mL) 
to measure nicotine will be drawn by a either certified phlebotomist through a butterfly needle or 
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 8 of 78
through a catheter by a certified registered nurse before and at 2, 4, 5, 6, 8, 10, 13, 15, 20, 30, 45, 
60, 90, and 120 min after onset of use.  Samples will be processed within 2 hours and frozen at -
80°C until analysis.  Plasma samples will be analyzed for nicotine concentration using sensitive 
and validated UPLC-MS/MS method developed by TCORS analytical core located at Roswell 
Park. At the same time intervals, participants will complete standard subjective effects measures, 
including the Drug Effects scale, ENDS Nicotine Dependence Scale, Minnesota Nicotine 
Withdrawal Scale, Product Evaluation Scale, and the Duke Sensory questionnaire, Delay 
Discounting Task and the ETM with the product being tested available for the fixed price in the 
marketplace.  Participants will be compensated by cash for each study visit completed and will 
receive an additional $90.00 bonus if all study visits have been completed (Table 1).
10 INTERVENTION 
Active Substance and Source 
During each visit, following an overnight abstinence, participants will be asked to take 20 puffs 
over 10 minutes (one puff every 30 seconds) from an Innokin EQs Ultra-Compact 2 mL Refillable 
Pod Vaporizer equipped with a 800mAh battery. All devices and solutions will be purchased from 
a local vape shop called the House of Vapor located in Kenmore, NY. Study personnel will set the 
device to 11.5W for every study session. 
10.1 Dosing and Administration
The device will be filled with either (1) free-based nicotine e-liquid solution of unflavored (2) free-
based nicotine e-liquid solution of tobacco flavor (3) salt-based nicotine e-liquid solution of 
unflavored or (4) salt-based nicotine e-liquid solution of tobacco flavor. Both the study personnel 
and study participants will be blinded to the solution flavor and nicotine concentration. All e-
liquids will contain 0.148M nicotine (24 mg/mL free-base nicotine or 24 mg/mL nicotine 
benzoate). Participants are randomized to the order of the e-liquids by the study statistician using 
the Williams Design; a special case orthogonal latin squares design generated using SAS v9.3. 
Intervention will be administered on an outpatient basis. Reported adverse events (AEs) and 
potential risks are described in Section 13 and Section 17.
Nicotine (3-(1-methylpyrrolidin-2-yl)-pyridine) the primary alkaloid in tobacco products binds 
stereo-selectively to nicotinic-cholinergic receptors on autonomic ganglia, the adrenal medulla, 
neuromuscular junctions and in the brain. Nicotine exerts two effects, a stimulant effect exerted at 
the locus ceruleus and a reward effect in the limbic system. Intravenous administration of nicotine 
causes release of acetylcholine, norepinephrine, dopamine, serotonin, vasopressin, beta-endorphin 
and ACTH. Nicotine is a highly addictive substance. Nicotine also induces peripheral 
vasoconstriction, tachycardia and elevated blood pressure. Nicotine replacement therapies (like 
inhalers and patches) are used to treat smoking withdrawal syndrome. Nicotine is classified as a 
stimulant of autonomic ganglia.
Electronic nicotine delivery systems (ENDS) usually look similar to regular cigarettes, cigars, 
pipes, or pens, but do not contain tobacco. Instead, they are comprised of a battery-powered 
atomizer that produces vapor for inhalation from solutions that contain nicotine. Electronic 
cigarettes (e-cigarettes) are the most popular ENDS on the market. Different ENDS brands are 
engineered differently. The differences include the appearance, the nature of nicotine solution, the 
capacity of the cartridge containing the solution, the nature of the heating element, and size and 
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 9 of 78
type of battery. Propylene glycol or glycerin, are primary used as solvents for nicotine. Solutions 
may contain just one or both solvents mixed with water. Various additives and flavorings are 
commonly added to nicotine solution, including fruit and candy flavors, ethyl alcohol, non-nicotine 
pharmacologically active compounds and stabilizers. ENDS devices of newer generation often 
contain nicotine salt solution. Although the exact physiological mechanisms of nicotine salts have 
not been studied in detail, these compounds are believed to increase the amount and rate of nicotine 
uptake in pod users, effectively increasing the dose of nicotine delivered to the circulation and 
central nervous system. The heating elements are usually thin (filament) wire made with various 
metals (nickel, chromium, copper coated with silver). These engineering features affect the 
chemical composition of the ENDS vapor. The type of ENDS and e-liquid solution that will be 
provided to study participants includes: 
Table 2.                                        ENDS and E-liquid Solutions
Innokin EQs Ultra-Compact Refillable Pod 
Vaporizer 1 
Free-based nicotine solution Unflavored (24 
mg/mL)
Free-based nicotine solution Tobacco (24 
mg/mL)
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 10 of 78
Salt-based nicotine solution Unflavored (24 
mg/mL nicotine benzoate)
Salt-Based solution Tobacco (24 mg/mL 
nicotine benzoate)
1   ENDS used at all 4 study visits
11 PROCEDURES INVOLVED
A total of 20 ENDS users will be recruited for this study with equal numbers of men and women. 
All participants will be seen after an overnight abstinence of approximately 8 hours at Roswell 
Park Comprehensive Cancer Center (The Department of Health Behavior Human Exposure Lab) 
on 4 separate occasions, at least 5-7 days apart (with a maximum of 4 weeks between visits 
allowed before the participant is taken off study).  Each study visit is expected to last 
approximately 2.0 to 2.5 hours. The anticipated duration of intervention is 4 weeks.
After 8-10 hour overnight product abstinence (confirmed by self-report and expired CO less than 
8 ppm), participants will be admitted to The Department of Health Behavior Human Exposure 
Lab. This will be done so that effect of various e-liquid solutions on nicotine withdrawal symptoms 
might be assessed. (For analysis purposes, once the study is closed and the blood samples are 
analyzed, anyone with a nicotine concentration ≤ 2 mL in their blood for the T0 sample will be 
deemed as adhering to the overnight abstinence. Anyone with a nicotine concentration > 2 mL in 
their blood for the T0 sample will be marked as not adhering to the abstinence. Adjustments will 
be made for the analysis of this finding and controls set in place when running statistics on order 
to account for this finding. 
Participants will be asked to take 20 puffs over 10 minutes (one puff every 30 sec) from the 
assigned ENDS product (Innokin EQs Ultra-Compact 2mL Refillable Pod Vaporizer equipped 
with a 800mAh battery and wattage set to 11.5W), presumed equivalent in nicotine yield to a single 
cigarette (based on pilot studies 20 puffs generate aerosol with cumulative nicotine yields from 1.5 
mg to 1.7 mg). Participants will be video-recorded to analyze puffing behaviors (product operation, 
number of puffs, and time of puffing and exhaling vapors). Participants will also be asked to 
provide a urine sample before the 10 min puffing session as well as after the 10 min puffing 
session. Urine samples will be tested for cotinine, NNAL and VOC metabolites. 
Venous blood samples to measure nicotine will be taken either through butterfly needle by a 
certified phlebotomist or through a catheter by a certified registered nurse before and 2, 4, 5, 6, 8, 
10, 13, 15, 20, 30, 45, 60, 90, and 120 min after onset of use of ENDS product with tanks of each 
e-liquid solution. A total of 60 mL of blood may be collected using a 4mL green top heparinized 
vacutainer blood collection tube during each visit (15 collection time points, 4 mL at each time 
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 11 of 78
point, not all collection time points will be fulfilled at each visit). If the participant is experiencing 
excessive blood clotting, the butterfly needle will be removed and a new butterfly needle will be 
inserted to continue with blood collection (the number of new butterfly needle insertions will never 
exceed three per study session). The butterfly needle or catheter may be placed in upper extremity 
or the hand of the participant.  Nicotine in plasma will be measured by a high sensitivity GC-
MS/MS method (4). Vital signs will be taken and expired CO will be measured before and 3 
minutes after the use of each e-liquid solution (CO monitor, Bedfont, UK). Females of child-
bearing potential will be asked to test urine for pregnancy. 
At visit one only, participants will be asked to complete several questionnaires including: 
Demographics (Appendix E ), Smoking History (Appendix F ), Time-line Follow Back to assess 
past 30 day tobacco product use (5) (Appendix G ), Penn State E-cigarette Dependence Index 
(Appendix H), and Taste Preference (Appendix I ).  During each visit participants will be asked 
to report on the Minnesota Nicotine Withdrawal Scale (MNWS) and the strength of nicotine 
withdrawal symptoms (craving, irritability, difficulty in concentration, and restlessness) before 
and after product use (Appendix J). Participants will also rate their mood before and after product 
use (Appendix K). Satisfaction with and helpfulness of the product will be measured at the end of 
each session using an adapted questionnaire (Appendix L). Acute subjective responses to the 
effects of nicotine will also be measured using the Drug Effect Questionnaire (DEQ-5) after 
product use (Appendix M) as well as a questionnaire to assess a participant’s craving to smoke 
(Appendix N). Puffing topography will be assessed with an eTop monitor after all blood draws 
are complete. At this time, subjects will be asked to puff on the assigned ENDS product ad lib with 
the eTop monitor. Participants will also be asked to complete the product evaluation scale, which 
assesses subjective effects such as liking and satisfaction, at visit four after experiencing each e-
liquid solution (Appendix O). Additionally, participants will complete the Experimental Tobacco 
Marketplace product purchasing task (Appendix P). During the ETM, participants will purchase 
hypothetical tobacco products in an online store analog with an account balance determined by 
past 30 day-tobacco product use at Session 1. The product being sampled during the session will 
be available for purchase under four different price conditions. Other tobacco products will be 
simultaneously available at a constant price. Average time to completion using four price 
conditions is 8 minutes. Participants will also be asked to answer a series of questions regarding 
involving Sensory Measures (Appendix Q).             
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 12 of 78
Table 3. 
    Schedule of Procedures and Observations
Visit
#1
#2
#3
#4
Week
1
2
3
4
Nicotine Solution
E-liquid 
Solution 
#1
E-liquid 
Solution 
#2
E-liquid 
Solution 
#3
E-liquid 
Solution 
#4
Informed Consent1
X
Demographics and Smoking history (Appendix E) Timeline 
Follow-Back (Appendix G) Penn State E-Cigarette 
Dependence Index (Appendix H) Taste Preference (Appendix 
I), ENDS Dependence Scale (Appendix R)
X
Vital signs
X
X
X
X
Blood Draw for Analytical Testing2
X
X
X
X
Pregnancy Test (Urine)
X
X
X
X
Urine Sample (before and after 10min puffing session)
X
X
X
X
Puffing Topography
X
X
X
X
CO Pre and Post-Product Use3
X
X
X
X
 Minnesota Nicotine Withdrawal Scale (MNWS)(adapted)  
(Appendix J) Pre and Post Product Use
X
X
X
X
Positive Negative Affect Scale (PANAS) (Appendix K) Pre 
and Post Product Use
X
X
X
X
Satisfaction With and Helpfulness of the Products (Appendix 
L) Post Product Use  
X
X
X
X
Drug Effect Questionnaire (DEQ-5) (Appendix M) Post 
Product Use
X
X
X
X
Modified Questionnaire of Smoking Urges (QSU-brief) 
(Appendix N) Post Product Use
X
X
X
X
Adverse Events
X
X
X
X
Concomitant Medications
X
X
X
X
Product Satisfaction Scale (Appendix O) Post Product Use 
X
Experimental Tobacco Marketplace (ETM) (Appendix P)
X
X
X
X
Sensory Measures (Appendix Q) Post Product Use &
Delay Discounting Task 
X
X
X
X
1
Must be signed prior to any study related assessments or procedures.
2
See Section 15 for Data and Specimen Banking 
3
Expired CO will be measured before, and 3 minutes after the use of each product
12 WITHDRAWAL OF SUBJECTS
Participants will be given phone numbers for research associates and supervising physicians to call 
if there are adverse effects or other study-related problems. Participants will be advised that if they 
have any adverse effects and/ or wish to stop participating in the study for any reason, they are 
free to do so. Participants who are injured as a result of being in the study will have treatment 
available. The costs of such treatment may be covered by Roswell, depending on a number of 
factors. 
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 13 of 78
Any participant who discontinues due to an AE must be followed until the event resolves or 
stabilizes. Appropriate medical care should be provided until signs and symptoms have abated, 
stabilized, or until abnormal laboratory findings have returned to acceptable or pre-study limits. 
The final status of AE will be reported in the participant’s study records and to the study DSMB. 
Reasons for intervention discontinuation/withdrawal from the study should be classified as 
follows: 

Death.

Adverse side effects; related or unrelated to intervention.

The Investigator may discontinue a participant if, in his/her judgement, it is in the best 
interest of the participant to do so. 

Noncompliance (defined as missing scheduled visit by more than 2 weeks without contact).

Participant voluntary withdrawal. A participant may withdraw from the study at any time, 
for any reason.
13 RISKS TO SUBJECTS
The potential risks to participants in the clinical studies, and their likelihood and seriousness, are 
described below. Participants can choose, as an alternative, to not enroll in this study. Overall, 
there is minimal risk for serious adverse reactions as a consequence of enrolling in this study.

Nicotine overdose: Some people who use ENDS may experience symptoms of nicotine 
overdose such as nausea, sleep disturbance, headache, and vomiting; however, these 
symptoms are usually mild and temporary. Before ENDS are used in human participants, 
they have undergone laboratory testing to assess the yields of nicotine present in the 
products; this will also provide quality control information to select the safest product. 
o
The PK studies using ENDS in participants will be performed in a clinical setting 
accustomed to monitoring for adverse effects. The PI and Co-I’s have considerable 
experience with conducting outpatient studies on novel nicotine delivery devices 
and their effects on participants, and will be able to provide appropriate safety 
monitoring.
o
Participants will also be instructed that the investigational products are not to be 
ingested. If a product is ingested by mistake, the participant will be instructed to 
call the study physician (Dr. Mahoney). If they are experiencing serious symptoms 
of nicotine overdose, the participant should contact Poison Control or Emergency 
Medical Services.

Nicotine withdrawal: Many individuals who quit smoking exhibit a pattern of symptoms 
related to withdrawal from tobacco use. These symptoms include: sadness and anxiety, 
irritability, anger, difficulty concentrating, appetite change and weight gain, insomnia, and 
decreased heart rate. Because participants in the studies will be asked to refrain from 
smoking and or using their ENDS for portions of the study, it is likely that they will 
experience some of these symptoms. Consent forms will include sections describing the 
possibility of this occurrence. Study personnel will be trained to recognize these symptoms 
and educate the participants about them.

Respiratory irritation: Some people who use ENDS may experience irritation of the 
mucosal membranes of the upper respiratory tract, but as they are already regular ENDS 
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 14 of 78
users we do not think that this is likely. We will exclude participants or postpone 
procedures if they demonstrate chronic or acute respiratory problems.

Inconvenience: It is quite probable that participants will experience inconvenience due to 
the multiple study visits required.

Venipuncture is required for study participation and this could lead to local pain, swelling, 
bruising or infection. Significant complications (beyond typical local pain and mild 
bruising) are expected to be uncommon. The volume of blood to be withdrawn will never 
exceed 60 mL on any planned visit. This amount of blood is safe for the participants and 
will not produce any injury to a healthy individual.

Emotional distress: Participants may experience psychological discomfort during 
assessments when discussing feelings and attitudes about smoking and using ENDS, or 
from learning about the risks of smoking. However, all participants will be current ENDS 
users and we do not expect this type of reaction to be likely. Study personnel will be alerted 
to expect this from a small number of participants and will be trained to make referrals for 
mental health services as needed. Personnel will be trained to query for adverse emotional 
reactions during assessments and will be trained to deal with such reactions and to provide 
additional referrals if needed. In addition, if assessments indicate psychiatric concerns, 
referrals to appropriate psychological services will be provided.

Reproductive Risks: Women will be advised to notify the study staff if they become or 
intend to become pregnant during the study period. Because nicotine and e-cigarette vapor 
safety for an unborn baby is unknown, participants will be told that they should not become 
pregnant while on this study nor should they nurse a baby. If a woman is pregnant or breast 
feeding, she may not participate in this study, and if she becomes pregnant during the study, 
she will be removed from the study.
As general measures to minimize the likelihood of participants experiencing these side effects staff 
will have the study physician’s (Dr. Martin Mahoney) cell phone number and will contact Dr. 
Mahoney with all questions and concerns. We will also:
1. Employ a stringent list of exclusionary criteria to limit the chance of side effects listed 
above occurring. Potential participants will be screened for medical illnesses that would 
preclude the ENDS use and/or increase the risk of adverse events or side effects (e.g., 
respiratory diseases, cardiovascular conditions).
2. Administer the ENDS of the highest quality (based on the outcome of the pre-clinical 
studies).
3. Monitor self-reported side effects at each assessment time-point (i.e., each clinic visit). 
Participants will be informed about the potential for adverse events or side effects from 
ENDS use, including upper respiratory tract mucosa irritation, cough, phlegm, headache, 
nausea, and emotional distress from learning about the adverse health consequences of 
smoking. Participants will be told that they should proceed with caution until they are 
certain that ENDS do not affect their performance.
4. The study physician (Dr. Mahoney) will be alerted to any severe side effects or any reported 
adverse events. The study physician will review the information provided by the research 
staff and if applicable, will contact the study participant within 24 hours after being notified 
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 15 of 78
to gather more information and determine the appropriate course of action for the 
participant. Ultimately, the study physician will decide if the adverse event is related to 
study treatment and whether the participant should discontinue its use.
Participants will be told that they should proceed with caution when using ENDS and to report any 
adverse symptoms or side effects to study personnel immediately. 
14 POTENTIAL BENEFITS TO SUBJECTS
There is no direct benefit for those who decide to participate and enroll in this study. 
15 DATA AND SPECIMEN BANKING
Pharmacokinetic Blood Sample Collection
Whole blood samples for analytical testing of nicotine and cotinine levels will be collected via 
venipuncture using a butterfly needle or a venous catheter using 4 mL green-top heparinized 
collection tubes. The blood will be drawn by either a certified study phlebotomist using a 
butterfly needle, or a venous catheter placed by a registered nurse. Blood sample collection will 
be obtained at each study visit prior to and 2, 4, 5, 6, 8, 10, 13, 15, 20, 30, 45, 60, 90, and 120 
min after onset of use of each nicotine solution, approximately 4 mL will be taken at each time 
point (not all collection time points will be fulfilled at each study visit). If the participant is 
experiencing excessive blood clotting, the butterfly needle will be removed and a new butterfly 
needle will be inserted to continue with blood collection (the number of new butterfly needle 
insertions will never exceed three per study visit). The butterfly needle or venous catheter may 
be placed in the upper extremity or in the hand of the participant. 
For all participants, the amounts drawn will not exceed 240 mL for the entire study and 
collection will not occur more frequently than 2 times per week.
Urine Sample Collection
Urine samples will be taken before and after ENDS product use. Female urine samples will be 
tested for pregnancy.
All blood and urine samples will be immediately transported to the Health Behavior Department 
Laboratory (Roswell Park Comprehensive Cancer Center); the blood samples will be centrifuged 
to separate the plasma from whole blood. The plasma will be aliquoted into cryovials that are 
labeled with the participant’s initials, participant’s study number, clinical study number, protocol 
time point, product, and protocol day. Urine samples will be transferred to 15 mL Flacon tubes. 
The samples will immediately be frozen at -70ºC or below in Dr. Goniewicz’s Laboratory until 
analyzed. Plasma will be analyzed for cotinine and nicotine using UPLC-MS/MS method (6). 
Urine samples will be tested for cotinine, NNAL and VOC metabolites. Female urine samples will 
be tested for pregnancy. All blood and urine sample results are recorded in logs and kept in:
Dr. Goniewicz’s Laboratory
Gratwick Basic Science Building (GBSB)
Health Behavior Department Laboratory
Laboratory location: 4th Floor, Room 4942
Laboratory phone: 716-845-8603
Dr. Goniewicz’s office number: 716-845-8541
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 16 of 78
If there are remaining blood or urine samples after all analysis has been done and the participant 
checks yes on the consent document to having any extra samples stored for future studies, then the 
samples will be kept in a -70°C or below freezer in Dr. Maciej Goniewicz’s Laboratory listed 
above. If there are remaining samples and the participant checks no on the consent document to 
having any extra samples stored, then the extra samples of that participant will be immediately 
destroyed once they are taken off study or completed. 
Any future research on the remaining samples will only be done under IRB-approved protocols. 
Note: All investigator or analyzing research laboratories housing research samples need to 
maintain current Temperature Logs and study-specific Sample Tracking and Shipping Logs. The 
Principal Investigator/Laboratory Manager must ensure that the stated lab(s) have a process in 
place to document the receipt/processing/storage/shipping of study-related samples/specimens. 
This is required for both observational and interventional clinical studies collecting clinical 
samples.
16 MEASUREMENT OF EFFECT
Not Applicable
17 SAFETY EVALUATION
17.1 Safety Monitoring 
ENDS have been used before by us or by other researchers that we are aware of, and the risks 
appear to be minimal. Monitoring for safety will be carried out by review of all clinical 
complications and all of the data by the PI and Co-Investigators including Physicians. Reporting 
of adverse events will follow requirements mandated by the both IRBs (Committees on Human 
Research, CHRs). This will be followed by a detailed written report within ten (10) working 
days. In addition, any incidents or problems involving the conduct of the study or patient 
participation, including problems with the recruitment and/or consent processes will be reported 
within ten (10) working days. The Principal Investigator will provide a discussion of any 
problems noticed during each year in the course of the study to the both IRBs (CHRs) on an 
annual basis. The standard adverse event grading scale will be used to report any potential 
adverse events from phlebotomy, study device or other study procedures: 1) Mild AE – did not 
require treatment; 2) Moderate AE – resolved with treatment; 3) Severe AE – resulted in 
inability to carry on normal activities and required professional medical attention; 4) Life-
threatening or disabling AE; and 5) Fatal AE. The supervising study physician will be notified of 
all grades 2 through 5 AEs. Additionally, Dr. Quisenberry will be notified of all grades 4 and 5 
AEs. Grade 3 through 5 AEs will be reported to the IRBs (Grades 4 and 5 - within 24 hours; 
Grade 3 - within 10 days). Grade 2 will be included in the yearly progress report. Grade 1 will 
not be reported. Frequency of Safety Reviews: Subject safety data reporting is a formal part of 
weekly research group meetings at both collaboration centers and during teleconferences 
between PI and Co-I; safety reviews will be conducted through review of all clinical 
complications and data when it returns, including laboratory data. Safety data are collected on a 
daily basis. Safety reviews will be conducted annually in conjunction with the protocol renewal 
to IRBs.
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 17 of 78
17.2 Unanticipated Problems
An Unanticipated Problem (UP) is any incident, experience, or outcome that meets all of the 
following criteria:

Unexpected (in terms of nature, severity, or frequency) given:
o
The research procedures that are described in the study-related documents, 
including study deviations, as well as issues related to compromise of participant 
privacy or confidentiality of data.
o
The characteristics of the participant population being studied.

Related or possibly related to participation in the research (possibly related means there is 
a reasonable possibility that the incident, experience, or outcome may have been caused by 
the procedures involved in the research).

Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized and if in relation to an AE is also deemed Serious per Section 17.7.
17.2.1 Reporting Unanticipated Problems
The Reportable New Information (RNI) Form will be submitted to the CRS Quality Assurance 
(QA) Office within 1 business day of becoming aware of the Unanticipated Problem. After review, 
CRS QA Office will submit the RNI to the IRB.
When becoming aware of new information about an Unanticipated Problem, submit the updated 
information to CRS QA Office with an updated Reportable New Information Form. The site 
Investigator or designated research personnel will report all unanticipated problems to the IRB in 
accordance with their local institutional guidelines.
18 DATA MANAGEMENT AND CONFIDENTIALITY
To ensure data security and confidentiality, all assessments will be administered by trained 
research study staff, and blood draws will be performed by certified phlebotomists or registered 
nurses. 
Data management activities will be performed using REDCap (Research Electronic
Data Capture).  REDCap is a secure web-based application that supports data
capture and management for research studies. In the event of REDCap being inaccessible for a 
study visit, paper copies of the questionnaires will be administered to the participant at that point 
in time and data entry will be performed by the assigned Senior Research Associate after the 
study session is completed. Data can be entered and changed only by those with the rights to do 
so.  
All participant records and data will be held in the Health Behavior Department at Roswell Park 
Comprehensive Cancer Center. All personnel involved in the conduct of this study are Roswell 
Park staff. 

Access to the data by all necessary research personnel will be through a password-protected 
network computer. At no time will data be downloaded on a thumb drive or other portable 
media or laptop. Participant identity will not be disclosed in the event of publication or 
sharing of data.
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 18 of 78

Participant identity will not be disclosed in the event of publication or sharing of data.

Any paper files containing identifiers (if applicable to the research) will not be taken off 
Roswell Park premises; they will be kept in a locked filing cabinet in a secure building on 
the Roswell Park’s campus.

PHI will be not re-used or disclosed for purposes other than research use.

There are no outside entities to which PHI will be disclosed.

Essential documents will be retained per Roswell Park’s policy for 6 years from the study 
termination date. These documents could be retained for a longer period, however, if 
required by the applicable local regulatory requirements or by an agreement with Roswell 
Park. 
19 STATISTICAL PLAN
19.1 Sample Size Determination
The sample size calculations are based on the primary analysis of the area under plasma nicotine 
concentration-time curve (AUC nicotine), which is compared between salt and free-base forms of 
e-liquid. A simplified calculation is based on the two-sided two-sample t-test, where a sample size 
of n=18 provides 80% power (at a significance level of 0.05) to detect a true difference of at least 
700 ng/mL × min. This is based on the assumption that the within-patient standard deviation of 
the response variable is 500 ng/mL × min.
The reduction in AUC of 700 ng/mL x min corresponds to 4-fold reduction in nicotine content in 
tobacco cigarettes. This effect was observed among smokers who switched from cigarettes with 
high nicotine content (12 mg) to low nicotine content cigarettes (4 mg) 
To account for potential drop-out, a maximum of 20 participants will be enrolled. Accrual for this 
study is expected to take 4 years.
19.2 Randomization
This study is a randomized within-subject cross-over study, where the order of four types of 
nicotine solutions that the participant receives will be randomized. Participants will be provided 
with cartridges of maximum available amounts of nicotine (labeled as high: approx. 24 mg). All 
participants and study personnel will be blinded to the flavor names and nicotine content in 
cartridges. Participants will be provided with cartridges of different nicotine solutions at each visit, 
instructed on how to use the product, and partake in the controlled 10-minute puffing session (1 
puff every 30 seconds, 20 puffs total).
Note: In order to minimize any carry-over effect, there will be a minimum 5-7-day wash-out period 
between each scheduled study visit and, the order of the nicotine solutions will be randomly 
assigned (with a different randomization order for each participant). In addition, we will consider 
linear mixed models that will incorporate a carry-over effect. This will provide a more conclusive 
analysis, but also potentially validate the effectiveness of the wash-out period, which could help 
in the design of future studies.
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 19 of 78
19.3 Demographics and Baseline Characteristics
Descriptive statistics (as appropriate: n, percent, mean, median, min and max) will be used to 
summarize demographic and baseline characteristics.
19.4 Primary Analysis
The primary objective is to evaluate whether AUC nicotine, Cmax or Tmax differ between free-base 
and salt-based versions of the same liquid, controlling for flavoring and nominal nicotine 
concentration.
Each outcome will be modeled as a function of base (free-base versus salt-based), flavor (tobacco 
versus unflavored), their interaction, prior combination indicator (for carry-over effect), and a 
random subject effect using a linear mixed model. All model assumptions will be verified 
graphically and transformations will be applied as appropriate. The effect of “base” on the AUC 
nicotine, Cmax and Tmax measures will be evaluated using tests about the least square means of 
“base”. Additionally, 95% confidence intervals about the mean differences will be obtained.
19.5 Secondary Analysis
The secondary objective is to evaluate the effect of flavoring on subjective effects (i.e. perceived 
harshness, satisfaction, liking, and relief of nicotine withdrawal symptoms) differences between 
matched free-base and salt-based e-liquids.
Each outcome will be modeled as a function of base, flavor, their interaction, prior combination, 
and a random subject effect using a linear mixed model. All model assumptions will be verified 
graphically and transformations will be applied as appropriate. An F-test about the interaction-
term of base and flavor will be used to determine whether the impact of flavor on these subject 
measures differs between bases.
19.6 Exploratory Analysis
Exploratory analysis/analysis of exploratory aim: First, to quantify the relationship between 
purchasing and the price of e-cigarettes, the data will be fit to a modification of a model proposed 
by Hursh and Silberberg (2008):
Q Q0 10k(eQ0C1),
where Q is amount of the commodity purchased, C is the price, Q0 is the derived initial 
consumption without cost constraints (i.e., demand intensity and a secondary measure of abuse 
liability), k is the logarithmic range of the function, and α is the demand elasticity (i.e., sensitivity 
to price and the primary measure of abuse liability). Q and C are determined by the data and k is a 
set constant, leaving only Q0 and α as free parameters to be fit. Second, the fit parameters, Q0 and 
α will be compared with a 2 (nicotine type: salt- or free-based) X 2 (flavor: tobacco or unflavored) 
ANOVA to determine the abuse liability level of nicotine type, flavor, and the interaction between 
the two. Then, to analyze the level of substitution of alternative tobacco products, we will fit linear 
regressions for each product type. Slopes that differ from zero will be considered substitutes within 
each product availability condition. To compare the level of substitutability in the different product 
availability conditions, slopes will be compared using a 2 X 2 ANOVA.
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 20 of 78
20 PROVISIONS TO MONITOR THE DATA TO ENSURE THE SAFETY OF 
SUBJECTS
Subjects will be given phone numbers for research associates and supervising physicians to call 
if there are adverse effects or other study-related problems. Subjects will be advised that if they 
have any adverse effects and/ or wish to stop participating in the study for any reason, they are 
free to do so. The data collected from this study will be organized by a unique identification 
number assigned to the participant so that their identity will be available only to project staff and 
will remain completely confidential. The clinical study coordinator and staff and PI of the study 
will have access to the data records. All study records will be kept electronically in Roswell Park 
Comprehensive Cancer Center maintained and secured equipment. Any data, specimens, forms, 
reports, and other records that leave the site will be identified only by a participant identification 
number (Participant ID, PID) to maintain confidentiality. All records will be kept in a limited 
access environment. All computer entry and networking programs will be done using PIDs only. 
Information will not be released without written authorization of the participant. 
21 VULNERABLE POPULATIONS
Not Applicable. 
22 COMMUNITY-BASED PARTICIPATORY RESEARCH
Not Applicable.
23 SHARING OF RESULTS WITH SUBJECTS
No results will be shared with study participants or with parties outside of the research team. 
24 SETTING
All study sessions will take place in The Health Behavior Human Exposure Lab located at Roswell 
Park Comprehensive Cancer Center. The research team will identify and recruit potential 
participants from the Western New York region. 
25 PROVISIONS TO PROTECT THE PRIVACY INTERESTS OF SUBJECTS
Participants will be given phone numbers for research associates and supervising physicians to 
call if there are adverse effects or other study-related problems. Participants will be advised that 
if they have any adverse effects and/ or wish to stop participating in the study for any reason, 
they are free to do so.
The data collected from this study will be organized by a unique identification number assigned 
to the participant so that their identity will be available only to project staff and will remain 
completely confidential. The clinical study coordinator and staff and PI of the study will have 
access to the data records. All study records will be kept electronically in Roswell Park 
Comprehensive Cancer Center maintained and secured equipment.
Any data, specimens, forms, reports, and other records that leave the site will be identified only 
by a participant identification number (Participant ID, PID) to maintain confidentiality. All 
records will be kept in a limited access environment. All computer entry and networking 
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 21 of 78
programs will be done using PIDs only. Information will not be released without written 
authorization of the participant.
26 RESOURCES AVAILABLE
All data and specimen collection will be done by trained registered nurses, clinical research 
coordinators, research associates, or certified phlebotomists working on this study.
All study procedures will be performed in the:
Health Behavior Human Exposure Lab
Gratwick Basic Science Building (GBSB)
Laboratory location: 3rd Floor, Room 3920
Laboratory phone: 716-845-3312
The laboratory is 10’10.5” x 11’8” space equipped with a sink, multiple infusion chairs, and an 
Axis Communications video camera. In addition, the laboratory also has specialized mechanical 
exhausts and ducts designed to keep the room under negative air pressure at all times. 
In addition, our University at Buffalo collaborator, Nicholas Felicione, will be involved in 
design, data analysis, and manuscript preparation. 
27 PRIOR APPROVALS
No prior approvals. 
28 COMPENSATION FOR RESEARCH-RELATED INJURY
If the participant believes they have been injured as a direct result of their participation in this 
research study, they will be advised to notify the Roswell Park Patient Advocate at (716) 845-1365 
or the Study Doctor at (716) 845-3597.
Medical diagnosis and treatment for the injury will be offered, and a determination will be made 
regarding appropriate billing for the diagnosis and treatment of the injury. A financial counselor 
(716-845-3161) will be able to provide an explanation of coverage and to answer questions the 
participant may have regarding study related billing.
The participant is not prevented from seeking to collect compensation for injury related to 
malpractice, fault, or blame on the part of those involved in the research.
29 ECONOMIC BURDEN TO SUBJECTS
Participants will be responsible for transportation to and from the research site and any costs that 
might entail. The remainder of the study will be conducted at no financial cost or obligation to the 
participant. 
30 CONSENT PROCESS
The Investigator (or IRB approved designee) is responsible for obtaining written consent from 
each participant in accordance with ICH-GCP guidelines using the approved informed consent 
form, before any study specific procedures (including screening procedures) are performed. The 
informed consent form acknowledges all information that must be given to the participant 
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 22 of 78
according to ICH-GCP, including the purpose and nature of the study, the expected efficacy and 
possible side effects of the treatment(s), and specifying that refusal to participate will not influence 
further options for therapy. Any additional information that is applicable to the study must also be 
included. Additional national or institutionally mandated requirements for informed consent must 
also be adhered to. The participant should also be made aware that by signing the consent form, 
processing of sensitive clinical trial data and transfer to other countries for further processing is 
allowed.
The Investigator shall provide a copy of the signed consent form to the participant and the signed 
original shall be given to the CRS Regulatory Research Associate for the Regulatory Binder.  A 
copy of the signed consent form must be filed in the participant file. At any stage, the participant 
may withdraw from the study and such a decision will not affect any further treatment options.
The consenting process will take place at the first visit for every participant. The consent MUST 
be signed by every participant before any study procedure is performed. 
The Roswell Park SOP: Informed Consent Process for Research (HRP-090) will be followed.
31 PROCESS TO DOCUMENT CONSENT IN WRITING
The Roswell Park “SOP: Written Documentation of Consent (HRP-091)” will be followed.
32 DRUGS OR DEVICES
During each visit, participants will be asked to take 20 puffs over 10 minutes (one puff every 30 
seconds) from an Innokin EQs Ultra-Compact 2 mL Refillable Pod Vaporizer equipped with a 
800mAh battery (Table 2). Study personnel will set the device to 11.5W at every study session. 
The device will be filled with either (1) free-based nicotine e-liquid solution of unflavored (2) free-
based nicotine e-liquid solution of tobacco flavor (3) salt-based nicotine e-liquid solution of 
unflavored or (4) salt-based nicotine e-liquid solution of tobacco flavor. Both the study personnel 
and study participants will be blinded to the solution flavor and nicotine concentration. 
All e-liquids will contain 0.148M nicotine (24 mg/mL free-base nicotine or 42 mg/mL nicotine 
benzoate).
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819 
4/28/2023
Page 23 of 78
33 REFERENCES
1. Goniewicz ML, Boykan R, Messina CR, Eliscu A, Tolentino J. High exposure to nicotine 
among adolescents who use Juul and other vape pod systems (‘pods’) Tobacco Control. 
2018 September 7; doi: 10.1136/tobaccocontrol-2018-054565. PMID: PMC6453732
2. Goniewicz ML, Hajek P, McRobbie H. Nicotine content of electronic cigarettes, its 
release in vapour and its consistency across batches: regulatory implications. Addiction. 
2014 Mar; 109(3):500-7. PMID: 24345184
3. Bickel WK, Moody LN, Snider SS, Mellis AM, Stein JS, Quisenberry AJ. 2017. The 
behavioral economics of tobacco products: Innovations in laboratory methods to inform 
regulatory science, in: Hanoch Y, Barnes A, Rice T, (Eds.), Behavioral economics and 
healthy behaviors: Key concepts and current research. Routledge, London. 
4. Xu AS, Peng LL, Havel JA, Petersen ME, Fiene JA, Hulse JD. Determination of nicotine 
and cotinine in human plasma by liquid chromatography-tandem mass spectrometry with 
atmospheric-pressure chemical ionization interface. J Chromatogr B Biomed Appl. 1996 
Jul 12;682(2):249-57. PMID: 8844417
5. Sobell LC, Sobell MB. 1992. Timeline Follow-back: A technique for assessing self-
consumption., in: Allen J, Litten RZ, (Eds.), Measuring Alcohol Consumption: 
Psychosocial and Biological Methods. Humana Press, Totowa, NJ, pp. 41-72. 
6. Jacob P 3rd, Yu L, Duan M, Ramos L, Yturralde O, Benowitz NL. Determination of the 
nicotine metabolites cotinine and trans-3'-hydroxycotinine in biologic fluids of smokers 
and non-smokers using liquid chromatography-tandem mass spectrometry: biomarkers 
for tobacco smoke exposure and for phenotyping cytochrome P450 2A6 activity. J 
Chromatogr B Analyt Technol Biomed Life Sci. 2011 Feb 1;879(3-4):267-76. PMID: 
21208832
7. Hursh SR, Silberberg A. Economic demand and essential value. Psychol Rev. 2008 Jan; 
115(1): 186-98. PMID: 18211190
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 24 of 78
34 APPENDICES/ SUPPLEMENTS
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 25 of 78
Appendix A
INVESTIGATOR STUDY ELIGIBILITY VERIFICATION FORM
INCLUSION CRITERIA
Participant Name:  ___________________________
Participant ID:  _____________________________
Title: Pharmacokinetics, Subjective Effects, and Abuse Liability of Nicotine Salt-Based Vaping 
Products with Tobacco or Unflavored e-liquids [SALTVAPE Study]
INCLUSION CRITERIA
Yes
No
N/A
All answers must be “Yes” or “N/A” for participant enrollment.
Date
1.
Age ≥ 21 years and ≤ 55 years
2.
Current daily ENDS user as determined by:
a)
Has used ENDS product everyday regularly for the past 6 
months (by history); and 
b)
has used ENDS product or e-liquid containing nicotine (by 
history). 
3.
Willingness to abstain from using ENDS and any other nicotine-
containing products (incl. tobacco cigarettes) for 8-10 hours (overnight 
abstinence) prior to study visits.
4.
Participant must understand the investigational nature of this study and 
sign an Independent Ethics Committee/Institutional Review Board 
approved written informed consent form prior to receiving any study 
related procedure.
Investigator Signature: ___________________________________
Date: ___________
Printed Name of Investigator: __________________________________________________
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 26 of 78
Appendix B
INVESTIGATOR STUDY ELIGIBILITY VERIFICATION FORM
EXCLUSION CRITERIA
Participant Name:  ___________________________
Participant ID: _____________________________
Title: Pharmacokinetics, Subjective Effects, and Abuse Liability of Nicotine Salt-Based Vaping 
Products with Tobacco or Unflavored e-liquids [SALTVAPE Study]
EXCLUSION CRITERIA
Yes
No
N/A
All answers must be “No” or “N/A” for participant enrollment.
Date
1.
Smoked cigarettes in the past 7 days 
2.
Currently smokes ≥ 5   cigarettes per month.  
3.
Unstable medical conditions (such as unstable heart disease, 
uncontrolled hypertension, thyroid disease, diabetes, renal or liver 
impairment,,  or glaucoma) or psychiatric condition (such as current 
major depression, history of schizophrenia or bipolar disorder) or 
current regular use of psychiatric medications ( such as major 
tranquilizers and antidepressants).
4.
History of serious side effects from nicotine or from any nicotine 
replacement therapies.
5.
Uncontrolled intercurrent illness including, but not limited to, ongoing 
or active infection, symptomatic congestive heart failure, unstable 
angina pectoris, cardiac arrhythmia, or psychiatric illness/social 
situations that would limit compliance with study requirements.
6.
Pregnant or nursing female participants.
7.
Concurrent participation in another clinical trial
8.
Unwilling or unable to follow protocol requirements.
9.
Any condition which in the Investigator’s opinion deems the participant 
an unsuitable candidate. 
Participant meets all entry criteria:
  Yes
  No
If “NO”, do not enroll participant in study.
Investigator Signature: ___________________________________
Date: __________
Printed Name of Investigator: ______________________________________________
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 27 of 78
Appendix C Recruitment Flyer
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819 
4/28/2023
Page 28 of 78
Appendix D Telephone Screening Questionnaire 
Date
/
/
2
0
Participant number
What is your date of birth? (age ≥ 21 years  ≤ 55 years) 
______/______/_________
Do you currently use ENDS (Electronic Nicotine Delivery System or E-
Cigarette)? (must be yes)
Yes □
No □
Have you used ENDS for at least 6 months? (must be yes)
Yes □
No  □
Does your ENDS contain nicotine? (must be yes)
Yes □
No  □
What flavour do you prefer?
□
 “Are you currently….” Or “Have you….”
YES
NO
Smoked cigarettes in the past 7 days? 
□
□
Smoke more than 5 cigarettes in a month? 
□
□
Pregnant/breastfeeding (females only)
□
□
Being treated for any medical conditions (such as unstable heart disease, 
uncontrolled hypertension, thyroid disease, diabetes, renal or liver 
impairment, or glaucoma) 
□
□
Being treated for any psychiatric conditions (such as current major 
depression, history of schizophrenia or bipolar disorder) or current 
regular use of psychiatric medications (such as major tranquilizers and 
antidepressants).
□
□
Being treated for any illness including, but not limited to, ongoing or 
active infection, symptomatic congestive heart failure, unstable angina 
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that 
would limit compliance with study requirements.
□
□
Ever had any history of serious side effects from nicotine or from any 
nicotine replacement therapies.
□
□
NEED TO ANSWER ‘NO’ TO ALL CRITERIA. IF ANSWERED ‘YES’ TO ANY OF ABOVE: INELIGIBLE 
How did you hear about our study?   ____________________________________________________________
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 29 of 78
If Eligible:
Great— it looks like you’re eligible to participate in the study.  Can I have your name and number 
in case we get disconnected?
Thank you. Now I’d like to give you some more information before asking whether you’d like to 
make an appointment to come in for your first study session. The purpose of this study is to 
determine the levels of nicotine effectively delivered by various types of e-liquid solutions to the 
bloodstream and to compare users’ preferences and perceptions of the various e-liquid solutions. 
If eligible this study requires 4 visits where we ask that you test out different e-liquid solutions, 
complete surveys and give blood samples. Is this something you think you are interested in doing?
If Answer No:
Thank you for your time. If you have any friends or family that may be interested in this study, 
feel free to pass along our number. Again, thank you for your time. Goodbye.
If Answer Yes:
Great! We would like to set up an appointment to have you come here to Roswell for your first 
study session? I would also like to mention that this research has received ethics clearance from 
the Roswell Park Institute Institutional Review Board and all the information you provide will be 
kept strictly confidential. Only the investigators directly associated with the study will have access 
to this information and it will be destroyed once the study is completed.   This study is funded by 
the National Institute of Health (NIH) and the investigators have no affiliations with any tobacco 
company or maker of nicotine products.
I realize I’ve given you a lot of information- do you have any questions about the study?
Would you like to make an appointment to come in for your fist session?
If no:
Thank you and goodbye.
If yes:
Great.
We need to book you for an appointment here at Roswell.  These are scheduled for [time to be 
determined] on [day of week to be determined]
DATE: ________________________________                          
Time: _______________________
Participant Name
Phone Number
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 30 of 78
Directions
You may park in the ramp which is located on the corner of Carlton and Michigan Streets; we will 
reimburse your parking. After parking, walk across the street and enter through the main entrance 
of Roswell. Once you walk in someone will be waiting for you by the gift shop and ATM which 
will be right on your left. We would like to give you a confirmation phone call the day before your 
visit. Is this a good number to reach you at on that day?
If not: What would be a good number to reach you at? ____________________________________________
If Ineligible:
Unfortunately, we won’t be able to conduct the study with you.  However, we have studies running 
all the time so would you mind leaving us your name and number to contact you about other 
studies?
Name
Phone Number
We thank you for your interest and if you have any friends or family that may be interested in the 
study, feel free to pass along our number.  Again, we are sorry that it is not going to work.  
Goodbye.
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 31 of 78
Appendix E
Demographics
1. What is your birthdate?
MM/DD/YYYY _______________
[] Don’t know 
[] Refused 
2. [Follow-up question if participant selects “don’t know”] – ONLY IF THEY SELECT 
DON’T KNOW TO QUESTION #1
About how old are you?
AGE______
[] Don’t know 
[] Refused 
3. On your original birth certificate, was your sex assigned as male or female? 
[] Male
[] Female
[] Don’t know 
[] Refused 
4. To which gender identity do you most identify?
[] Male
[] Female
[] Transgender female  
[] Transgender male 
[] Gender variant/ Non-Conforming  
[] Other  __if selected let them write in response_________
5. What race or races do you consider yourself to be? Please select one or more. 
CHECK ALL THAT APPLY
[] American Indian or Alaska Native
[] Asian
[] Black or African American 
[] Native Hawaiian or Pacific Islander
[] White
[] Other 
[] Don’t know
[] Refused
6. Do you consider yourself to be Hispanic, Latino, or of Spanish origin?
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 32 of 78
[] Yes
[] No
[] Refused
[] Don’t know
7. Where do your ancestors come from?  ONLY IF THEY SELECT YES TO QUESTION 
#6
[] Puerto Rican 
[] Cuban/Cuban America
[] Dominican Republic
[] Mexican/Mexican American 
[] Central/South American 
[] Other Latin American
[] Other Hispanic or Latino
8. What is your best estimate of the total income of all family members from all sources, 
before taxes, in the last calendar year?
[] Less than $10,000
[] $10,000 to $14,999
[] $15,000 to $19,999
[] $20,000 to $24,999
[] $25,000 to $29,999
[] $30,000 to $34,999
[] $35,000 to $39,999
[] $40,000 to $49,999
[] $50,000 to $74,999
[] $75,000 to $99,999
[] $100,000 to $149,999
[] $150,000 to $199,999
[] $200,000 or more
[] Prefer not to say
9. What is the highest grade or level of school you have completed or the highest degree 
you have received?
[] 8th grade
[] 12th grade, no diploma
[] High school graduate 
[] GED or equivalent
[] Some college, no degree
[] Associate degree
[] Bachelor’s degree (ex.: BA, AB, BS, BBA)
[] Master’s degree or higher 
[] Refused
[] Don’t know
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 33 of 78
10. We would like to know about what you do—are you working now, looking for work, 
retired, keeping house, a student, or what?
[] Working now
[] Only temporarily laid off, sick leave or maternity
[] Looking for work
[] Retired
[] Disabled, permanently or temporarily
[] Keeping house
[] Student 
[] Other (Specify) __if selected let them write in response_________
11. Are you pregnant now? 
[] Yes
[] No
[] NA
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 34 of 78
Appendix F
Smoking History 
1.) Have you ever smoked a cigarette, even one or two puffs?
              ☐ Yes
              ☐ No (Skip to question #6) 
2.) For about how long did you smoke? 
☐ I still use them (skip to question #5)
☐ Just tried one or two cigarettes 
☐ A few days
☐ A couple of weeks
☐ A few months
☐ About 1 year
☐ More than 2 years 
3.) Why did you stop smoking 
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
__________________
4.) When you did smoke, how many cigarettes, on average, did you smoke per day? 
________________ per day
5.) When was the last time you smoked a cigarette? 
☐ Today
☐ This past week
☐ About a month ago
☐ A few months ago
☐ More than a year ago
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 35 of 78
6.) What type(s) of e-cigarettes have you used before? (even once, check all that apply)
☐ Disposable
☐ Rechargeable with replacement cartridges
☐ eGO model with refillable tank
☐ Vaporizer with refillable tank
☐ Pods devices like Juul or similar
☐ e-Cigar
☐ e-Pipe
☐ Other (please describe)__________________________________________________
7.) Have you ever used an e-cigarette similar to any of the devices pictured below? 
YES
□
NO
□
YES
□
NO
□
YES
□
NO
□
YES
□
NO
□
YES
□
NO
□
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 36 of 78
YES
□
NO
□
YES
□
NO
□
8.) Do you currently vape e-liquid containing nicotine? 
☐ Yes
☐ No
9.) Do you currently vape e-liquid containing nicotine salt? 
☐ Yes
☐ No
☐ Don’t know
10.)
What level of nicotine do you most commonly use?
☐ 0-2 mg
☐ 3-5 mg
☐ 6-11 mg
☐ 12-17mg
☐ 18-23 mg
☐ 24-36 mg
☐ 37-42 mg
☐ 43-50 mg
☐ 51 or more mg
☐ Other  
Please Specify:________________ if checked participant prompted to write in details
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 37 of 78
11.)
What flavor(s) of e-cigarettes have you tried before? (list all)
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
__________________
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 38 of 78
Appendix G
Time-Line Follow-Back

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 39 of 78
Appendix H
Penn State E-cigarette Dependence Index
1. How many times per day do you usually use your electronic cigarette (assume that one 
“time” consists of around 15 puffs or lasts around 10 minutes)?
0-4 times/day
5-9 times/day
10-14 times/day
15-19 times/day
20-29 times/day
30+ times/day
2. On the days that you can use you electronic cigarette freely, how soon after you wake up 
do you use your electronic cigarette?
0-5 min
6-15 min
16-30 min
31-60 min
61-120 min
121+ min
3. Do you sometimes awaken at night to use your electronic cigarette?
Yes
No
4. If yes, how many nights per week do you typically awaken to use your electronic 
cigarette?
0–1 nights
2–3 nights
4+ nights 
5. Do you use an electronic cigarette now because it is really hard to quit?
Yes
No
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 40 of 78
6. Do you ever have strong cravings to use an electronic cigarette?
Yes
No
7. Over the past week, how strong have the urges to use an electronic cigarette been?
None/Slight
Moderate/Strong
Very Strong/Extremely Strong
8. Is it hard to keep using an electronic cigarette in places where you are not supposed to?
Yes
No
9. Did you feel more irritable because you couldn’t use an electronic cigarette?
Yes
No
10. Did you feel nervous, restless, or anxious because you couldn’t use an electronic 
cigarette?
Yes
No
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 41 of 78
Appendix I
Taste Preference
(Meier et al JPSP 2012)
For each of the foods shown below, please check the box that corresponds to how much you like 
or dislike that food. If you never tried a food, please check that box.
1.) Sweet items: 
1a.)  Candy
    
○  Never tried
 1b.) Caramel
○ Never tried
 1c.) Chocolate cake
○ Never tried 
1d.) Honey
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 42 of 78
○ Never tried
1e.) Ice cream
○ Never tried
1f.) Maple syrup
○ Never tried
1g.) Pears
○ 
Never tried
 1h.) Raisins
○ Never tried
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 43 of 78
 1i.) Strawberries
○ 
Never tried
 
1j.) Sugar
○ Never tried
2.) Sour items:  
2a.) Granny Smith apples
○ Never tried
2b.) Lemons
○ Never tried
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 44 of 78
2c.) Lemon drops
    
○ Never 
tried
2d.) Limes
○ Never tried
2e.) Lime sherbet
○ Never tried
2f.) Plain yogurt
○ Never tried
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 45 of 78
2g.) Sauerkraut
○ Never tried
2h.) Sour cream
○ Never tried
2i.) Vinegar
○ Never tried
3.) Bitter items:
3a.) Beer
○ Never tried
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 46 of 78
3b.) Celery
○ Never tried
3c.) Coffee
○ Never tried
3d.) Cottage cheese
○ Never tried
3e.) Ginger ale
○ Never tried
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 47 of 78
3f.) Grapefruit
○ Never tried
3g.) Radishes
○ Never tried
3h.) Rye bread
○ Never tried
 3i.) Tea
○ Never tried
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 48 of 78
3j.) Tonic water 
○ 
Never tried
4.) Salty items: 
4a.) Bacon
○ Never tried
4b.) Beef jerky
○ Never tried
4c.) Caviar
○ Never tried
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 49 of 78
4d.) Dill pickles
○ Never tried
4e.) Green olives
○ Never tried
4f.) Pretzels
○ Never tried
4g.) Salt 
○ Never tried
4h.) Saltine crackers
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 50 of 78
○ Never tried
 4i.) Salty peanuts
○ Never tried
4j.) Soy sauce
○ Never tried
5.) Spicy items:
 5a.) Cajun foods
○ Never tried
 5b.) Cayenne pepper
○ Never tried
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 51 of 78
5c.) Chilies
○ 
Never tried
 5d.) Curry
○ Never tried
5e.) Horseradish
○ Never tried
5f.) Hot salsa
○ Never tried
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 52 of 78
5g.) Jalapeno peppers 
○ Never tried
5h.) Spicy sausage
○ Never tried
5i.) Peppers
○ Never tried
5j.) Tabasco sauce
○ Never tried
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 53 of 78
Appendix J
Minnesota Tobacco Withdrawal Scale
How are you feeling at this very moment?                                      
Please mark an (X) in ONE box for each condition 
Not at all
Slightly
Somewhat
Very
Extremely
Depressed
☐
☐
☐
☐
☐
Irritable
☐
☐
☐
☐
☐
Anxious, 
nervous
☐
☐
☐
☐
☐
Restless
☐
☐
☐
☐
☐
Dizziness
☐
☐
☐
☐
☐
Hungry
☐
☐
☐
☐
☐
Nausea
☐
☐
☐
☐
☐
Poor 
concentration
☐
☐
☐
☐
☐
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 54 of 78
Appendix K
The Positive Negative Affect Scale (PANAS)
This scale consists of a number of words that describe different feelings and emotions. Read each item and then 
mark the appropriate answer in the space next to that word. Indicate to what extent you feel this way right now, 
that is, at the present moment. Remember, there is no right or wrong answer so please give us your honest 
opinion. 
1
2
3
4
5
very slightly or 
not at all
a little
moderately
quite a bit
extremely
__________
interested 
__________
Irritable
__________
Distressed
__________
Alert
__________
Excited
__________
Ashamed
__________
Upset
__________
Inspired
__________
Strong
__________
Nervous
__________
Guilty
__________
Determined
__________
Scared
__________
Attentive
__________
Hostile
__________
Jittery
__________
Enthusiastic
__________
Active
__________
Proud
__________
Afraid
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 55 of 78
Appendix L
Product Evaluation Form: Satisfaction With and Helpfulness of the Product
Please answer the following questions about the Nicotine Solution you just used.   
Please mark an (X) in ONE box for each question
Much less 
than my 
regular 
device & e-
liquid
A little less 
than my 
regular 
device & e-
liquid
The same as 
my regular 
device & e-
liquid
A little more 
than my 
regular 
device & e-
liquid
Much more 
than my 
regular 
device & e-
liquid
1. How good did 
it taste?
☐
☐
☐
☐
☐
2. How pleasant 
was it?
☐
☐
☐
☐
☐
3. How much did 
it relieve your 
urge to vape
☐
☐
☐
☐
☐
4. How was the effect of the e-Cig vapor on your:
Tongue?
☐
☐
☐
☐
☐
Nose?
☐
☐
☐
☐
☐
Back of mouth 
and throat?
☐
☐
☐
☐
☐
Windpipe?
☐
☐
☐
☐
☐
Chest?
☐
☐
☐
☐
☐
5. How harsh 
was it?
☐
☐
☐
☐
☐
6. How much e-
cigarette taste 
☐
☐
☐
☐
☐
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 56 of 78
versus ‘just air’ 
did you get?
Much less 
than my 
regular 
device & e-
liquid
A little less 
than my 
regular 
device & e-
liquid
The same as 
my regular 
device & e-
liquid
A little more 
than my 
regular 
device & e-
liquid
Much more 
than my 
regular 
device & e-
liquid
7. Was it 
embarrassing to 
use in front of 
others?
☐
☐
☐
☐
☐
8. How hard was 
it to draw vapor 
from?
☐
☐
☐
☐
☐
9. How fast did it 
relieve your urge 
to vape?
It did not 
relieve my 
urge to 
smoke
☐
Within a 
few puffs
☐
Within 5 
minutes
☐
Within 10 
minutes       
☐
Within 15 
minutes
☐
10.) How satisfying did you find the ENDS product and solution compared to your normal 
device and solution? (please mark an (X) on ONE of the boxes)
1
2
3
4
5
6
7
8
9
10
Not enjoyable at 
all
As enjoyable as 
normal 
cigarettes
11.) How enjoyable did you find the ENDS product and solution compared to your 
regular device and solution? (please mark an (X) on ONE of the boxes)
1
2
3
4
5
6
7
8
9
10
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 57 of 78
Not enjoyable at 
all
As enjoyable as 
normal 
cigarettes
12.) How dangerous to your health did you find the ENDS product and solution compared 
to your regular device and solution? (please mark an (X) on ONE of the boxes)
1
2
3
4
5
6
7
8
9
10
 Less dangerous 
than normal 
cigarettes 
More  
dangerous than 
normal 
cigarettes 
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 58 of 78
Appendix M –Drug Effect Questionnaire 
This questionnaire asks about how you are feeling after using the provided nicotine product. Please draw a mark 
on the line to show how strongly you are feeling each of the following effects right now.  You can mark anywhere 
on the line, but please draw a vertical line (one that goes straight up and down). 
1.
Do you FEEL a nicotine effect right now? 
2.
Are you HIGH right now? 
3.
Do you DISLIKE any of the effects you are feeling right now?
4.
Do you LIKE any of the effects you are feeling right now?
5.
Would you like MORE nicotine right now? 
NOT AT ALL                                                                                        EXTREMELY
NOT AT ALL                                                                                         EXTREMELY
NOT AT ALL                                                                                         EXTREMELY
NOT AT ALL                                                                                         EXTREMELY
NOT AT ALL                                                                                         EXTREMELY
APPROVED RPCI IRB
6/5/2023

Roswell Park Protocol No.:  I 475819 
4/28/2023
Page 59 of 78
Appendix N
 
Modified Questionnaire of Smoking Urges (QSU-breif)
Please answer each statement below on a scale from 0 (Strongly Disagree) to 100 (Strongly Agree)
1.
I have a desire for my regular device and e-liquid right now. 
                                                          _______
2.
Nothing would be better than using my regular device and e-liquid right now.                                  _______
3.
If it were possible, I would probably use my regular device and e-liquid right now.                         _______
4.
I could control things better right now if I could use my regular device and e-liquid right now.        _______
5.
All I want right now is my regular device and e-liquid right now.                           
_______
6.
I have an urge for my regular device and e-liquid right now.                         
              _______
7.
My regular device and e-liquid would taste good right now.             
   
              _______
8.
I would do almost anything for my regular device and e-liquid right now.          
              _______
9.
Using my regular device and e-liquid would make me less depressed.                                               _______
10. I am going to use my regular device and e-liquid as soon as possible.        
_______

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 60 of 78
Appendix O
Nicotine Solution Rating Scale
1.) Please order the following nicotine solutions you tested from 1- 4 based on how satisfied you were with the 
solutions. 
(4= Most satisfying and 1= Least satisfying)
Product
Rating 
Solution A
________
Solution B
________
Solution C
________
Solution D
________

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 61 of 78
Appendix P
Experimental Tobacco Marketplace

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 62 of 78
Appendix Q
Sensory Measures
Based on the e-liquid you just tried, please rate the taste on the following characteristics:
1. ) Pleasantness
2.) Irritation
3.) Relaxing
-100
-80
-60
-40
-20
0
20
40
60
80
100
Least intense 
ever intense 
experience 
Most intense 
ever experience 
Neutral 
-100
-80
-60
-40
-20
0
20
40
60
80
100
Least intense 
ever intense 
experience 
Most intense 
ever experience 
Neutral 
-100
-80
-60
-40
-20
0
20
40
60
80
100
Least intense 
ever intense 
experience 
Most intense 
ever experience 
Neutral 

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 63 of 78
4.) Satisfying
5.) Sweet
6.) Sour
-100
-80
-60
-40
-20
0
20
40
60
80
100
Least intense 
ever intense 
experience 
Most intense 
ever experience 
Neutral 
-100
-80
-60
-40
-20
0
20
40
60
80
100
Least intense 
ever intense 
experience 
Most intense 
ever experience 
Neutral 
-100
-80
-60
-40
-20
0
20
40
60
80
100
Least intense 
ever intense 
experience 
Most intense 
ever experience 
Neutral 

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 64 of 78
7.) Bitter
8.) Cool/cooling
9.) Sharp/biting/astringent/pungent
-100
-80
-60
-40
-20
0
20
40
60
80
100
Least intense 
ever intense 
experience 
Most intense 
ever experience 
Neutral 
-100
-80
-60
-40
-20
0
20
40
60
80
100
Least intense 
ever intense 
experience 
Most intense 
ever experience 
Neutral 
-100
-80
-60
-40
-20
0
20
40
60
80
100
Least intense 
ever intense 
experience 
Most intense 
ever experience 
Neutral 

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 65 of 78
Sensory 
E-cigarette 
Experience Scale
1
Strongly 
Agree
2
3
4
5
6
7
Strongly 
Disagree
1. I like the smell of the vapor.
2. I like the taste of vaping.
3. I like the feeling of creating 
vapor clouds.
4. I like how creating vapor 
clouds looks visually appealing 
/ cool. 
5. I like the flavor of vapor.
6. I like how vaping makes me 
feel good physically. 
7. I like the feeling of 
satisfaction that I get from 
vaping.
8. I like the feeling of pleasure 
that I get from vaping. 
9. I like doing vape tricks (eg. 
Blowing vapor clouds or shapes 
like rings). 

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 66 of 78
PROMIS-E
0
Never
1
2
3
4
Almost 
Always
1. I find myself reaching for 
my e-cigarette without 
thinking about it. 
2. I drop everything to go out 
and buy e-cigarettes or e-juice.
3. I vape more before going 
into a situation where vaping 
is not allowed.
4. When I haven’t been able to 
vape for a few hours, the 
craving gets intolerable. 

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 67 of 78
SHERI-E
Vaping/using an e-cigarette/JUULing is something……….
1
Agree
2
3
4
5
6
7
Disagree
1. I do automatically.
2. I do without having to 
consciously remember.
3. I do without thinking.
4. I start doing before I 
realize I’m doing it. 
5. I would find hard not 
to do. 
6. That is typically 
“me”. 

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 68 of 78
Duke Sensory Evaluation 
Please rate the puffs you just took.
1
Not at all
2
Very little
3
A little
4
Moderately
5
A lot
6
Quite a lot
7
Extremely
1. How much did you 
like the puffs you just 
took?
2. How satisfying 
were the puffs you 
just took?
3. How high in 
nicotine do you think 
the puffs were?
4. How similar to 
your own brand were 
the puffs? 
Rate how strong the puffs were in the following places. 
5. Strength of puffs on 
tongue?
6. Strength of puffs in 
nose?

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 69 of 78
7. Strength of puffs in 
back of mouth and 
throat?
8. Strength of puffs in 
windpipe?
9. Strength of puffs in 
chest?
HEDONIC ATTRIBUTE PROFILE
For each item, please indicate how you would describe the ECIG you just used by placing a mark on the vertical numbered line. 
1.) Draw
2.) Mouthful of vapor

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 70 of 78
3.) Visible vapor
4.) Smell

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 71 of 78
5.) Impact 
6.) Irritation 
7.) Strength 

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 72 of 78
8.) Smoothness
9.) Taste
10.) Aftertaste

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 73 of 78
11.) Throat hit
12.) Dryness

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 74 of 78
13.) Tingling
14.) Burning
15.) Similarity to usual brand
16.) How would you describe the overall flavor sensation of the ECIG you just used?

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 75 of 78
17.) How would you describe the overall harshness/irritancy of the ECIG you just   used?
18.) How would you describe the throat hit of the ECIG you just used?

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 76 of 78

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 77 of 78
Appendix R
ENDS Nicotine Dependence Scale
1. If you currently or did you previously smoke cigarettes regularly, how many cigarettes a day do/did you smoke?

I never smoked cigarettes regularly <0>

1 – 10
< 1 >

11 – 20
< 2 >

21 – 30
< 3 >

31+
< 4 >
2. Do you use other forms of tobacco such as cigars, cigarillos, hookah, or smokeless tobacco? 
o
No
< 0 >
o
Yes
< 1 >
3. Do you vape more frequently during the first few hours after awakening than during the rest of the day?
o
Yes
< 1 >
o
No
< 0 >
4. How soon after you wake up do you vape?
o
0 – 5 m
< 3 >
o
6 – 30 m
< 2 >
o
31 – 60 m
< 1 >
o
61+ m
< 0 >
5. Of all the times that you vape, which time would you hate most to give up?
o
1st of Day
< 1 >
o
All Others
< 0 >
6. Do you find it difficult to refrain from vaping in places where it is forbidden?
o
Yes
< 1 >
o
No
< 0 >

Roswell Park Protocol No.:  I 475819
4/28/2023
Page 78 of 78
7. How many pods, cartridges, or refills do you typically use each week?
o
Less than 1 per week
< 0 >
o
1 – 4 per week
< 1 >
o
5 or more per week
< 2 >
8. How often do you vape?
o
1 day or less each week
< 0 >
o
2 – 3 days each week
< 1 >
o
4 – 6 days each week
< 2 >
o
7 days each week
< 3 >