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DR. KIRI STAUCH, Applied Research and Analysis Company (ARAC)
Received B.A. in Anthropology and Psychology from Illinois Wesleyan University. Later Stauch received a M.S. in Primate Behavioral and Ecology from Central Washington University followed by a M.S. in Psychology and a Ph.D. in Experimental Psychology (specializing in Comparative Neurobiological Psychology) with a quantitative methods concentration and a graduate certificate in Neuroscience) from Oklahoma State University. With an impressive academic background and a wealth of experience in research and teaching, Dr. Stauch has been an excellent addition to Applied Research and Analysis Company (ARAC) as a valued Behavioral Scientist. Learn more > ARACscience.com
About Applied Research and Analysis Company (ARAC): Social and behavioral sciences research firm that designs, executes, and presents scientific-based, customizable MODULE 6 studies to support manufacturers, regulatory agencies, and industry consultants. Fully staffed contract research organization with in-house psychologists, behavioral scientists, statisticians, medical monitoring team, and a survey methodologist. ARAC’s data-driven approach ensures rigorous, evidence-based insights to support innovation and regulatory compliance in the nicotine industry.
Introduction
One of the goals of tobacco harm reduction research is to evaluate whether the use of pouches, ENDS, and other alternative nicotine products reduce the use of combustible cigarettes. Internationally, these products can have varying amounts of nicotine ranging from no nicotine to higher concentrations, such as 50mg all the way up to 250mg or more. Within the US market, products with these higher concentration levels are not typically seen due to the increased rigor of the US marketing authorization process, differences in consumer expectations and use behavior, and perhaps because of the ethical considerations for marketing such products. While the use of and potential benefits of using noncombustible nicotine products versus combustible tobacco products (e.g., combustible cigarettes) are being researched in many Pre-Market Tobacco Product Application (PMTA) Module 6 studies, the addictive nature of nicotine makes it crucial that researchers do their due diligence to ensure ethical study conduct and safety of participants in studies where nicotine and tobacco study products are being provided to participants.
The Module 6 studies center on the use, health impact, and perceptions and intentions of the candidate nicotine/tobacco products. The results from these studies provide critical information on smoking and candidate product use by smokers, the types of candidate products and strengths preferred, and how the candidate product may help them reduce or stop smoking combustible cigarettes. The data from these studies include qualitative and quantitative data allowing researchers to capture information on the public’s attitudes toward the product and the likelihood that the product will fulfill the Appropriate for the Protection of Public Health (APPH) standards assessed by the Food and Drug Administration (FDA).
As psychologists and researchers, there are several factors to consider conducting PMTA Module 6 studies. The internal ARAC team has three Ph.D. level psychologists who are ethically obligated to consider the impact of product testing in human subjects. Some variables that are important to consider in designing and conducting experiments are nicotine levels, the addition of adverse event protocols and ensuring additional checks in place to ensure participants who should be excluded do not participate. We will discuss these facets more in-depth as they apply to the different types of studies discussed below.
Human factors studies
When designing and implementing a human factors study, researchers center their questions around the potential for misuse of the candidate products by consumers to ensure the protection of the consumer. This type of research allows researchers to determine whether or not the candidate product’s instructions and labeling are being accurately interpreted and the candidate product would be used correctly by consumers. Combined, these variables provide researchers with insight into how the packaging and instructions contribute to the consumers’ understanding of how to use the candidate product and identify potential changes to incorporate to help prevent product misuse.
Ethically, researchers need to consider several factors when conducting human factors studies. Aligned with the FDA PMTA guidance, ARAC recognizes the importance of ensuring that the study demographics accurately reflect the target audience, current consumer population, as well as those who should not use the product (non-users). To do this, researchers need to ensure they are recruiting both individuals who are users and non-users. By including non-users, it allows researchers to determine the potential risks to a naive consumer (e.g., understanding who the target audience of the product is, that the product contains nicotine). Throughout the study there need to be risk controls in place to protect the participants from harm due to misuse should the product be authorized for marketing. Risk controls can include having a detailed screener, plan for adverse events, qualified and experienced interviewer prompting discussion, and proper debriefing.
When assessing comprehension of candidate product packaging and labeling, an important factor to consider is the appeal of the product to the youth population (21 years and under). While researchers need to ensure that individuals under the legal age are screened out of the study and do not view the products, they also need to test “young adults” as a proxy to youth. By including “young adults” in study samples, researchers are able to qualitatively assess the impact that packaging (e.g., bright colors, youth-appealing flavor names and graphics, font styles) may have on individuals who are under the legal age to purchase and consume nicotine. The consideration of these factors helps the FDA determine whether a product is APPH.
Tobacco product perception and intention (TPPI) studies
The TPPI study design allows researchers to collect data from users’ and nonusers’, providing a comparison of their viewpoints on the candidate product. It is crucial to collect data from product-naïve individuals when determining the risk of a candidate product. A user may have a basis of knowledge that a non-user does not have when it comes to viewing the potential risks associated with nicotine and tobacco. FDA also wants assurance that non-users are not tempted to try the candidate product or develop an intention to try or initiate use of the product after viewing the product stimuli. If non-users indicate, they want to try/use the product then that risk needs to be accounted for when considering whether a candidate product should be allowed on the market.
While it is necessary take all possible measures to prevent those who do not meet eligibility criteria from entering into a study (in this case, those who are under the legal of purchase), a question is raised for TPPI research – why aren’t researchers assessing youth views? There are many ethical concerns when attempting most research with the youth population, especially around nicotine and tobacco products, however they are currently the population considered of most concern for nicotine and tobacco product initiation and use. An alternative, and perhaps controversial, approach could be that TPPI research includes those who are underage the legal age of purchase (i.e., individuals in the youth population) within a controlled and supervised research environment. While researchers use “young adults” as a proxy for youth, it could be more advantageous for the larger youth population if “youth” appeal and behavioral intention data was captured among an appropriate subgroup of youth after viewing product and product packaging. By having FDA and researchers working together to address the concerns and develop robust safeguards for youth TPPI data collection, researchers could potentially provide more relevant results reflective of the actual population and thus more concrete evidence of whether products/product packaging are appropriate or not for market.
The surveys used for these studies can often be long and tedious, presenting participants with an unnecessary burden. Researchers can streamline their surveys, allowing them to maintain the rigor of the study while also reducing the burden on the participant. Through focusing on one subject at a time and only asking questions associated with that subject aids in the survey flow, making it easier for participants to answer questions. For example, if the participants are asked about a specific candidate product label, then all of the questions about the label should follow. Additionally, only survey questions which are considered absolutely relevant should be included in the assessments to reduce participant burden and survey fatigue.
Longitudinal randomized experimental switching studies (LRESS)
The main goal of LRESS studies is to determine whether a candidate product could switch participants from combustible cigarettes at a higher rate than a control group (e.g., no candidate product) or a reference group (e.g., a regular tobacco flavor). The ideal timeframe for these studies is 1-2 years to assess sustained switching that may be most beneficial to individual health; however, a 3-to-6-month study has also been found to be appropriate in assessing switching behaviors.
An important ethical consideration for this type of study is what nicotine strengths to offer participants. Researchers need to consider the ethical basis for initially offering participants candidate study products at higher levels of nicotine, particularly when testing products that are novel to the smoker. With the goal of reducing consumer combustible cigarette use we need to weigh whether offering products with these unreasonably high levels of nicotine can be harmful. When conducting studies where participants are using candidate products, having a plan of how to prevent and handle adverse events (AE) is critical to protecting participant health. The inclusion of detailed information on how to use the product is key to ensuring participants know how to properly use the candidate product.
Highlighting key factors and frequently asked questions about proper candidate product refilling, charging, disposal, and consumption helps to minimize potential misuse. One option for handling adverse event reporting is to have a medical monitoring team that is available through 24-hour phone number which participants are instructed to reach out to at any time. Proper documentation and reporting of these events is critical to understanding potential risks of the candidate product.
The goal of the US regulatory pathway is to develop and market candidate products that benefit public health by changing the smoking patterns of current adult combustible cigarette smokers. Ideally, current smokers would reduce their smoking until they ceased smoking by replacing their cigarettes with the candidate product.
Conclusion
Module 6 studies are conducted with the goal of ensuring that consumers are protected by weighing the risks and benefits of candidate products. As researchers it is our duty to protect participants by designing studies that minimize the risks associated with participation. Through accordance to the guidelines and standards for these studies set forth by FDA, researchers are developing rigorous research that account for product use patterns and intentions related to smoking and the role that candidate products may play in changing smokers’ behavioral patterns Through keeping ethical considerations at the forefront of Module 6 study designs and implementation, researchers can conduct robust research while minimizing participant harm.