The passage of the Family Smoking Prevention and Tobacco Control Act in June 2009 empowers the Food and Drug Administration to regulate tobacco products. In the FSPTC, there is significant focus on tobacco products and its evaluation. One critical component of this product evaluation process is human clinical trials. These trials will inform the regulatory agency about the uptake of the product, how the product is used, the extent of toxicant exposure and possible health risk associated with this pattern of use. To date, no study has examined the best experimental methods to provide the information that is necessary to make a sound scientifically-based decision about a tobacco product (e.g., modified risk tobacco products) or any regulations imposed on tobacco products (e.g., performance standards) that assures no public harm will result based on this decision. The goals of this research project are to test a clinical trial method for assessing tobacco products and also address some methodological gaps so that guidance can be provided to the FDA and other international regulatory agencies on the best measures and methods for the evaluation of tobacco products. This trial is a between-subject, parallel-arm design in which subjects are randomized to one of the five experimental conditions, with different instructional sets, for a period of 12-weeks. The product chosen for testing is an oral tobacco product. Camel Snus. The instructional sets include: complete substitution vs. partial substitution for cigarettes by ad libitum use vs. specific instruction for snus use. A control group of continuing smokers will also be included in the design. The primary outcome measures include biomarkers of toxicant exposure and effect and subjective responses to the product. The overall goal for this P01 is to assimilate the results from this Project with the results from the other P01 Projects to determine consistency of findings across studies, predicitive validity of measures, and to determine if the proposed """"""""pre-market"""""""" studies can be used to determine risks and benefits of introducing a tobacco product into the market.

Public Health Relevance

With the new legislation that empowers the Food and Drug Administration to regulate tobacco products, clinical trials of tobacco products are going to be essential in making regulatory decisions. This research project examines a clinical trial method for testing a tobacco product and addresses some of the existing methodological gaps in this area.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-7)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Minnesota Twin Cities
United States
Zip Code
Bickel, Warren K; Mellis, Alexandra M; Snider, Sarah E et al. (2018) 21st century neurobehavioral theories of decision making in addiction: Review and evaluation. Pharmacol Biochem Behav 164:4-21
Harris, Andrew C; Muelken, Peter; Haave, Zach et al. (2018) Propylene glycol, a major electronic cigarette constituent, attenuates the adverse effects of high-dose nicotine as measured by intracranial self-stimulation in rats. Drug Alcohol Depend 193:162-168
Ho, Yen-Yi; Nhu Vo, Tien; Chu, Haitao et al. (2018) A Bayesian hierarchical model for demand curve analysis. Stat Methods Med Res 27:2038-2049
Stein, Jeffrey S; Heckman, Bryan W; Pope, Derek A et al. (2018) Delay discounting and e-cigarette use: An investigation in current, former, and never cigarette smokers. Drug Alcohol Depend 191:165-173
Bunney, Patricia E; Hansen, Mylissa; LeSage, Mark (2018) Effects of isolated tobacco alkaloids and tobacco products on deprivation-induced food intake and meal patterns in rats. Pharmacol Biochem Behav 165:45-55
LeSage, Mark G; Smethells, John R; Harris, Andrew C (2018) Status and Future Directions of Preclinical Behavioral Pharmacology in Tobacco Regulatory Science. Behav Anal (Wash D C) 18:252-274
Berman, Micah L; Hatsukami, Dorothy K (2018) Reducing tobacco-related harm: FDA's proposed product standard for smokeless tobacco. Tob Control 27:352-354
Stein, Jeffrey S; Koffarnus, Mikhail N; Stepanov, Irina et al. (2018) Cigarette and e-liquid demand and substitution in e-cigarette-naïve smokers. Exp Clin Psychopharmacol 26:233-243
Harris, Andrew C; Muelken, Peter; Smethells, John R et al. (2018) Effects of nicotine-containing and ""nicotine-free"" e-cigarette refill liquids on intracranial self-stimulation in rats. Drug Alcohol Depend 185:1-9
Smethells, John R; Harris, Andrew C; Burroughs, Danielle et al. (2018) Substitutability of nicotine alone and an electronic cigarette liquid using a concurrent choice assay in rats: A behavioral economic analysis. Drug Alcohol Depend 185:58-66

Showing the most recent 10 out of 58 publications