Clinical trial NCT06910202: Effects of Cigarette and E-cigarette Flavors on Substitutability in the ETM
Official title: Effects of Cigarette and E-cigarette Flavors on Substitutability in the Experimental Tobacco Marketplace (20-008)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cigarette Smoking Behavior
Keywords: Cigarettes
E-cigarettes
Experimental Tobacco Marketplace
Substitutability
Flavors
Lead sponsor: Virginia Polytechnic Institute and State University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Medical University of South Carolina
First posted: 2025-04-04
Enrollment: 28
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: In 2009, the FDA banned all flavored conventional cigarettes except menthol. While no such ban exists for e-cigarettes, proposals have emerged in several regions. Flavors are key targets for tobacco control policy, making it crucial to understand their role in substitution.The first wave of the PATH study found that 80% of youth, 73% of young adults, and 29% of older smokers used flavored products. Over 80% of young adults first used flavored tobacco, compared to about 50% of adults. Among ever-users, current tobacco use was 32% higher if their first product was flavored.One study reported that 75% of flavored product users would quit if flavors were removed. These findings highlight the importance of user type in shaping policy and raise the question of whether banning flavors would increase quitting or drive substitution.

The Experimental Tobacco Marketplace (ETM) is a novel method for estimating the effects of new tobacco policies and products on consumption and substitution. By experimentally controlling product mix, prices, and policies, ETM simulates "real-world" conditions to assess potential policy impacts.This methodology has been used to study various policies in adult smokers under this grant: nicotine dose variations (Study 1), tobacco taxes and subsidies (Study 2), and workplace restrictions (Study 3). Study 1 found that cigarette and e-cigarette substitutability increased with e-liquid nicotine strength, with 24mg/mL showing the highest substitution. Study 2 showed that cigarette taxes reduced cigarette purchases and increased e-liquid purchases, while e-liquid subsidies increased e-liquid purchases but did not affect cigarette consumption.

No study to date has experimentally examined the effects of flavored tobacco products availability on consumer behavior. The rationale for this specific proposal is to explore prospectively the possible consequences of a flavor ban on consumption and substitution with tobacco products. The results might inform tobacco control policies.

Detailed description: This study does not involve any smoking cessation interventions. This study does involve experimental manipulation of nicotine/tobacco product price and availability to understand consumers' behavior. Participants will be provided with a commercially available e-cigarette to use during the study, if they wish.

This study uses a within-between subject design. Participants will be assigned to four different groups according to their preferred cigarette flavor (tobacco/menthol) and product use (cigarettes only/cigarettes and e-cigarettes):

* tobacco cigarette smokers
* menthol cigarette smokers
* tobacco cigarette smokers and e-cigarette users (dual users)
* menthol cigarette smokers and e-cigarette users (dual users). Every participant will complete questionnaires on a computer, sample a range of tobacco products, and purchase tobacco products in an online store under four different scenarios: a) cigarette flavor restricted and e-cigarette flavor restricted, b) cigarette flavor unrestricted and e-cigarette flavor restricted, c) cigarette flavor restricted and e-cigarette flavor unrestricted, d) cigarette flavor unrestricted and e-cigarette flavor unrestricted.

Participants will complete a 1) consent and assessment session, and a product sampling phase, 2) an ETM session and a 3) follow-up session:

In the consent and initial assessment session, participants will go through standard consent procedures and then provide a breath sample to confirm recent levels of smoking. They may be asked to provide a urine sample for an analysis of cotinine content. Participants will complete a timeline follow back to assess previous month's recent smoking, e-cigarette use, and consumption of nicotine products, and to determine the ETM budget. A Qualtrics survey will administer demographics questions, smoking assessments (Questionnaire on Smoking Urges-Brief, Minnesota Nicotine Withdrawal Scale, Fagerstrom Test of Nicotine Dependence, Perceived Health Risk for cigarettes and e-cigarettes), and delay discounting tasks. At the end of the session, participants will experience a trial of the ETM that will be used in the next session.

For the 7-day sampling phase, they will be provided a list of available flavors and identify 5 that they would like to try. They will leave with a sample of each of the 5 flavors to try during the next few days. Participants will also be provided with a sample of any other tobacco product they wish to examine and try. They may sample any products in the smoking lab before they leave.

In the ETM session, participants will buy tobacco products to use throughout the next 7 days. Participants will complete a total of 40 purchasing trials each for 7 days' worth of products. They will be exposed to 4 conditions with all cigarettes increasing in price and repeat the same conditions with all e-liquids increasing in price across trials. A balanced Latin square design will be used to present the following conditions:

In the Cigarette Flavor Restricted, only conventional tobacco cigarettes will be available. In the Cigarette Flavor Unrestricted, tobacco and menthol cigarettes will be available. In the E-Cigarette Flavor Restricted, only tobacco flavor e-liquids will be available. In the E- Cigarette Flavor Unrestricted, tobacco flavor e-liquid and a variety of other flavors will be available from five broad categories: tobacco, fruit, dessert, menthol, and coffee. A range of other tobacco products will be available across conditions, such as snus, lozenge, gums, dip, and nicotine pouch.

3) In the follow-up session, participants will be able to return the e-cigarette if they wish. They will answer Perceived Health Risk assessments, complete hypothetical purchase tasks for cigarettes and e-cigarettes, rank order the products they sampled, and complete a liking scale for every tobacco product.

The analysis of each group will assess whether substitutability occurs as a function of different flavor conditions. The relationship between consumption and condition will be modeled according to:

y_ij=μ+α_i+τ_j+ε_ij,

where y_ij represents the average log consumption for the ith flavor restriction and the jth subject, α_i is the effect of the ith condition on log consumption, τ_j is the effect of the jth subject, ε_ij is the error term, i=1, 2, 3, 4 and j=1,...,n.

Additionally, all the groups will be compared to assess whether substitutability occurs as a function of different flavor conditions. The relationship between consumption and condition will be modeled according to:

y_ijk=μ+α_i\*b_j+τ_k+ε_ijk,

where y_ijk represents the average log consumption by condition for the ith flavor restriction, in the jth smoking status and the kth subject, α_i is the effect of the ith condition on log consumption, b_k is the effect of the jth group on log consumption τ_k is the effect of the kth subject, ε_ijk is the error term, i=1, 2, 3, 4, j=1, 2, 3, 4 and k=1,...,n.

Additional analyses might be conducted.

Eligibility criteria: Inclusion Criteria:

* Be between 21 and 65 years of age
* Cigarette smokers

  * Smoke cigarettes daily (≥ 5 cigarettes/day)
  * Do not use e-cigarettes regularly (no more than 9 times in the last month)
  * Be willing to try e-cigarettes
* Dual-users

  * Smoke cigarettes daily (≥ 5 cigarettes/day)
  * Have used e-cigarettes 10 or more days in the past month

Exclusion Criteria:

* Pregnant or lactating women
* Plans to move out of the area
* Use of prescription medication that might affect smoking or nicotine metabolism
* Unmanaged medical or psychiatric conditions
* Plans to quit smoking within the next 30 days
* This study will focus on cigarette smokers and dual users. We will not include individuals under the age of 21 in compliance with Virginia state law. Minors, pregnant women, prisoners, and adults not capable to consent on their own behalf will be excluded from this study.

  1. Minors, as defined by state law where the study is performed (infants, children, teenagers)
  2. Pregnant women (can be included in minimal risk studies by mentioning in section 13.1)
  3. Prisoners (including all incarcerated individuals)
  4. Adults not capable to consent on their own behalf

Primary outcomes:
measure: Nicotine/tobacco products substitution
timeFrame: During the intervention, session 2 (1 day per participant)
Secondary outcomes:
Other outcomes:
Locations:
city: Roanoke
country: United States
facility: Fralin Biomedical Research Institute at VTC
state: Virginia
Study officials:
affiliation: Fralin Biomedical Research Institute at VTC
name: Roberta Freitas Lemos, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pope DA, Poe L, Stein JS, Kaplan BA, DeHart WB, Mellis AM, Heckman BW, Epstein LH, Chaloupka FJ, Bickel WK. The Experimental Tobacco Marketplace: Demand and Substitutability as a Function of Cigarette Taxes and e-Liquid Subsidies. Nicotine Tob Res. 2020 Apr 21;22(5):782-790. doi: 10.1093/ntr/ntz116.
citation: Pope DA, Poe L, Stein JS, Kaplan BA, Heckman BW, Epstein LH, Bickel WK. Experimental tobacco marketplace: substitutability of e-cigarette liquid for cigarettes as a function of nicotine strength. Tob Control. 2019 Mar;28(2):206-211. doi: 10.1136/tobaccocontrol-2017-054024. Epub 2018 Apr 18.
citation: Bickel WK, Pope DA, Kaplan BA, DeHart WB, Koffarnus MN, Stein JS. Electronic cigarette substitution in the experimental tobacco marketplace: A review. Prev Med. 2018 Dec;117:98-106. doi: 10.1016/j.ypmed.2018.04.026. Epub 2018 Apr 24.
citation: Harrell MB, Loukas A, Jackson CD, Marti CN, Perry CL. Flavored Tobacco Product Use among Youth and Young Adults: What if Flavors Didn't Exist? Tob Regul Sci. 2017 Apr;3(2):168-173. doi: 10.18001/TRS.3.2.4.
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citation: Providenceri.com. Providence Tobacco Laws Go Into Effect January 3. Healthy Communities 2013. https://www.providenceri.com/healthy-communities/providence-tobacco-laws-go-into-effect-january-3.
citation: FOX32News. Illinois attorney general: ban e-cigarette flavors. 2014. http://www.myfoxchicago.com/story/26238470/illinois-attorney-general-ban-e-cigarette-flavors. Accessed 11-3-14.
citation: Durkin E. Bill would ban sale of flavored e-cigarettes. Celeste Katz Daily Politics. New York: New York Daily News; 2014.