Category: Science

Cigarette-Level Nicotine May Reduce Exposure

Photo: Auremar | Dreamstime.com
E-cigarettes that deliver a cigarette-like amount of nicotine are associated with reduced smoking and reduced exposure to a major cancer-causing chemical in tobacco, even with concurrent smoking, according to a new study led by researchers at Penn State College of Medicine and Virginia Commonwealth University (VCU).
“We found that e-cigarettes that delivered a similar amount of nicotine as traditional combustible cigarettes helped reduce smoking and exposure to a harmful carcinogen,” said Jonathan Foulds, a researcher at Penn State Cancer Institute and professor of public health sciences and psychiatry and behavioral health. “This study shows that when smokers interested in reduction are provided with an e-cigarette with cigarette-like nicotine delivery, they are more likely to achieve significant decreases in tobacco-related toxicants, such as lower exhaled carbon monoxide levels.”
The researchers conducted a randomized controlled trial of 520 participants who smoked more than nine cigarettes a day, were not currently using an e-cigarette device and were interested in reducing smoking but not quitting.

We found that e-cigarettes that delivered a similar amount of nicotine as traditional combustible cigarettes helped reduce smoking and exposure to a harmful carcinogen.
Jonathan Foulds, professor of public health sciences and psychiatry and behavioral health
According to Foulds, the findings represent an important addition to the scientific literature because they suggest that when e-cigarettes deliver nicotine effectively, smokers have greater success in reducing their smoking and tobacco-related toxicant exposure. Caroline Cobb, associate professor of psychology at VCU and lead author, said the study is important for two reasons.
“First, many e-cigarettes have poor nicotine-delivery profiles, and our results suggest that those products may be less effective in helping smokers change their behavior and associated toxicant exposure,” Cobb said.
“Second, previous randomized controlled trials examining if e-cigarettes help smokers change their smoking behavior and toxicant exposure have used e-cigarettes with low or unknown nicotine delivery profiles,” Cobb said. “Our study highlights the importance of characterizing the e-cigarette nicotine delivery profile before conducting a randomized controlled trial. This work also has other important strengths over previous studies, including the sample size, length of intervention, multiple toxicant exposure measures and control conditions.”
The study contributes to the ongoing question of what role e-cigarettes play in changing smoking behavior, and the findings support limited safety concerns for the use of the specific e-cigarette and liquid combinations over the short term, even in the context of concurrent cigarette smoking. However, Cobb added, very little is known about the effects of e-cigarettes over the course of years as opposed to the study’s 24-week period.
April 14, 2021
Broughton Launches Blue-Sky Thinking Hub

Photo: BNS
Broughton Nicotine Services (BNS) has launched its Blue-Sky Thinking Hub, an “open innovation community” for companies to collaborate and develop ideas within the electronic nicotine-delivery system (ENDS), pharmaceutical and cannabis markets.
BNS is a contract research organization with more than 10 years’ experience helping ENDS companies bring tobacco-free nicotine-delivery products to market.
The company has recently added services aligned with a number of new product categories, including modern oral nicotine products, cannabidiol (CBD) and cannabis-delivery devices and work with clients based in the U.S., China, U.K., Europe and the Middle East.

The Blue-Sky Thinking Hub seeks to engage companies with innovative ideas.
Nveed Chaudhary, chief regulatory officer, BNS
The Blue-Sky Thinking Hub encourages manufacturers and regulators to build strong relationships to overcome product development and regulatory challenges and work toward total harm reduction. An additional benefit is around considering solutions to potential regulatory concerns as part of the product development.
“Broughton Nicotine Services is dedicated to helping manufacturers meet regulatory requirements and delivering reduced-harm products to market,” said Nveed Chaudhary, chief regulatory officer at BNS.
“The Blue-Sky Thinking Hub seeks to engage companies with innovative ideas, which could be anything from new formulations to plastic-free or biodegradable products, technology to discourage and reduce youth access or even alternative charging for devices.
“Broughton helps these ideas to come to life by providing expert scientific and regulatory advice, contributing to the end goal of global total harm reduction.”

We invite industry professionals to discuss, debate and develop their ideas for new products aligned with regulatory requirements and to hopefully help influence and shape new policies.
Paul Moran, chief executive, BNS
“We are delighted to be launching the Blue-Sky Thinking Hub, which is the first of its kind in the industry,” said Paul Moran, chief executive at BNS.
“We invite industry professionals to discuss, debate and develop their ideas for new products aligned with regulatory requirements and to hopefully help influence and shape new policies.
“Together we can achieve total harm reduction and a smoke-free future.”
April 1, 2021
Fourth-Generation Atomizers Not Harmless

Photo: Tobacco Reporter archive
Fourth-generation electronic cigarette pod atomizers are similar in design to those of previous generations and contain elements that may adversely affect health and accumulate in the environment, according to a new study by the University of California (UC), Riverside.
According to the researchers, chronic exposure to the elements/metals in atomizers could adversely affect human health. Further, e-cigarette pod products, which eventually enter the environment, could contribute to chemical pollution in water and soil.
“The more these devices aesthetically evolve, the more the atomizer components and elemental composition stay the same,” said Esther Omaiye, a graduate student in the Department of Molecular, Cell and Systems Biology at UC Riverside and the first author of the research paper that appeared in PLOS ONE, in a statement.
“While major components such as filaments, thick wires, filament-wire joints, air tubes and wicks have been preserved across generations, we see newer components in fourth-generation pod products, such as connector pins, connector-wire joints, ceramic wicks and chambers that house these wicks.”
The more these devices aesthetically evolve, the more the atomizer components and elemental composition stay the same.
Esther Omaiye, UC Riverside
“We set out to characterize the design features of pod-style atomizers and analyze the elemental composition of the atomizers,” said Prue Talbot, a professor of cell biology at UC Riverside, who led the research team. “These elements may, upon heating, enter the aerosol and be inhaled by users.”
The external appearance, design, battery power, atomizers and nicotine delivery of e-cigarettes have evolved over the last decade. Fourth-generation pods have low-powered batteries, an e-liquid reservoir and an atomizer/mouthpiece. According to the researchers, they contain high concentrations of nicotine and acid.
Scientists have only limited understanding of what exactly makes up pod atomizers, which are required components for aerosol production in e-cigarettes.
“Since elements in the atomizers can leach into the e-fluids or transfer to the aerosols when the e-fluids are heated, it is important to know what these elements are that users can get exposed to,” said Omaiye, who works in Talbot’s lab.
The researchers examined 11 fourth-generation pods from six brands/manufacturers. Of 23 elements they identified in the pod atomizers, 11—nickel, chromium, iron, gold, copper, zinc, tin, oxygen, silicon, carbon and sodium—were present in relatively high abundance. Some of these elements have been linked to human illnesses, including cardiovascular diseases, immune system suppression, lung injury, cancer, renal damage, neurotoxicity and silicosis. Nickel, chromium, iron and gold were found to be the most abundant elements in fourth-generation atomizers.
“We now know what elements users may be inhaling by using fourth-generation products,” Omaiye said. “Our work reinforces the idea that e-cigarettes are not without harm. Our next line of research is evaluating fluids and aerosols generated from fourth-generation products to get a clearer picture of how their elements may be directly affecting e-cigarette users’ health.”
March 26, 2021
Juul: Dual Use Often a Transition to Switching

Photo: Juul Labs
Juul Labs announced findings from its science and research program at the 2021 Annual Meeting of the Society for Research on Nicotine & Tobacco (SRNT), which was held virtually. The studies presented covered a wide range of topics that contribute to the growing body of scientific evidence on ENDS products, including information about their harm reduction potential as well as rates of complete switching to ENDS among adult smokers.
To better understand patterns of tobacco product use among adult smokers, Juul Labs has developed an extensive behavioral research program that includes measurements of complete switching from combustible cigarettes to the Juul System among adult smokers. Among the data presented at SRNT are the results of a longitudinal study, which found that more than 50 percent of adult smokers who purchased the Juul system reported complete switching at a 12-month follow-up assessment. Complete switching was defined as no cigarette smoking in the past 30 days.
Another new study presented this week examined trends in dual use of the Juul system and cigarettes among adult smokers who recently purchased Juul products as well as any changes in cigarette consumption among these dual-users. While dual use of Juul products and cigarettes was initially high, it declined over time, and most adult smokers who began by dual-using ultimately switched completely away from cigarettes 12 months after initial purchase. Additionally, over 60 percent of dual users at 12 months substantially reduced their average daily cigarette consumption. Researchers concluded that dual use is often a transitional stage characterized by reductions in cigarette consumption followed by complete switching away from cigarettes.
February 25, 2021
Perception and Intention Studies
Photo: Darya Petrenko | Dreamstime.com
The most confusing part of an FDA application explained
By Cheryl K. Olson
In October 2020, the U.S. Food and Drug Administration’s (FDA) Center for Tobacco Products issued draft guidance sharing “current thinking” about “principles for designing and conducting tobacco product perception and intention studies.” As a researcher, I raise a glass in celebration. Unlike toxicology, behavioral science is fuzzy and subject to interpretation. We need signposts to follow.
The guidance applies to premarket tobacco product applications (PMTA), modified-risk tobacco product (MRTP) applications and substantial equivalence reports. If you understand why and how to do tobacco product perception and intention (TPPI) research, your application is more likely to be approved. Let’s stroll through the guidance, highlighting key points and noting ways to put the FDA’s suggestions into action.
Why TPPI?
Behavioral research is one type of evidence the FDA uses to decide if a new tobacco product is “appropriate for the protection of public health.” As the guidance notes, perceptions refers to “beliefs, attitudes, judgments and expectancies” about a tobacco product. In other words, how do you—a tobacco user or nonuser—understand what the label says, what the risks are or who this product is meant for?
Why do we ask about intentions? As the guidance says, “intentions to use tobacco products may help predict future tobacco use behavior,” especially near-future actions. The FDA wants to know whether smokers will switch to your smokeless, electronic nicotine-delivery system (ENDS) or heat-not-burn product (a good thing) and whether nonsmokers or former smokers will take it up (a bad thing). But it’s seldom practical or affordable to follow people around to watch what they do or to survey them repeatedly.
So, we fall back on measuring behavioral intentions as the next best thing. We compare smokers intending to quit—now or within the next six months—to smokers with no plans to quit. We measure whether smokers’ quit intentions change after reading about your product and seeing pictures of your packaging or advertising.

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TPPI study aims: your essential roadmap
“[The] FDA recommends that you develop TPPI study aims (the overall goals of the study) prior to conducting the study.” This step is not a nice-to-have; it’s essential. Defining the aims of your study and turning them into answerable research questions creates a roadmap for everything you do. Just as important, study aims tell you what not to pay attention to. If you skip this step, you’ll end up wading through confusing piles of data, perhaps shoveling it all into your application and hoping the FDA can make sense of it.
As you write your survey questions, figure out your sample quotas and review your data tables, you will periodically get lost in the details and need a touchpoint. Referring to your study aims will reorient you and keep you moving in the right direction.
Here’s another way to look at study aims. What product story do you want to tell the FDA? There are some research questions all PMTAs need to address, such as perceptions of risk (more on that later). Others will be specific to your product and your story.
Perhaps your smokeless product appeals more to a particular group, such as female or lower income smokers, than competing products do; your story includes addressing the needs of that underserved group of smokers. Or your high-nicotine vape product is “appropriate for the protection of public health” in part because it attracts heavily nicotine-dependent smokers who, to use FDA-speak, perceive it as an acceptable substitute for cigarettes. If your less-toxic tobacco product appeals to smokers not intending to quit—who are discouraged or unmotivated—that’s a further public health win. If your product and its various flavors do not appeal disproportionately to youth or you have a solid method of restricting youth access, say so.
From market research or conversations with customers, you might have a good idea of your story. But to tell that story to the FDA, you must design research questions and collect data to support it.

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Study types (qualitative or quantitative) and methods
Are you telling your story with words or numbers? When you don’t know a lot about perceptions and intentions (say, a new product or target population), start with focus groups or individual interviews. But qualitative doesn’t equal free-form; a structured set of questions, an unbiased interviewer and an analysis plan are a must if the FDA is going to take you seriously.
Some research questions might be answered with experimental studies. For example, you could test effects of new labeling by seeing how subjects randomly assigned to view that labeling answer questions about product perceptions differently than a control group. Another option is an observational study: for example, watching a subject follow directions to operate or charge a new vaping device without prompting from researchers.
Often, your behavioral research aims can be met entirely through cross-sectional quantitative studies: one-time surveys of people who’ve used your product and people who haven’t.
You can get some of the benefits of a qualitative study by adding open-ended questions to your multiple-choice survey. Let’s say you’re surveying users of Vape A. You ask, “Why did you choose to try Vape A? (Select all that apply).” You then invite those who clicked on “To help me quit smoking cigarettes” to “Please tell us more about your experience using Vape A to cut down or quit.” This offers two benefits: It helps you better understand how people use Vape A. And, when paired with solid numbers, user quotes help make your case to FDA reviewers that Vape A deserves a spot on that continuum of risk.
Study measures
Your best bet is to adapt questions from research published in academic journals, especially studies by authors who work for the FDA or other government health agencies. Next best are validated measures from the industry—for example, Philip Morris International has tested questions on addiction and health risk perceptions. Note that your questions need to “be written or adapted in a manner that specifically refers to the product (by name) that is the subject of the study.”
Perception questions should include risks to health and risk of addiction asked in several ways: the absolute risk of using your product; the relative risk as compared to other products in the category as well as cigarettes, nicotine-replacement therapies and no tobacco use; and the effects of dual use (health risks of sticking with smoking, partly substituting your product or switching completely). A good question will be direct, specific and unambiguous: Ask about perceived personal risk of specific types of serious illnesses or earlier death from using Vape A not generically about harm to health.
Behavior intention questions include intent to buy, try, use or stop use of your product. Detailed questions, such as intent to partially or completely replace cigarettes with Vape A, are best left to surveys of Vape A users; it’s too much guesswork for people new to the product. (The guidance doesn’t cover “actual use” studies, but don’t forget to ask your customers about monthly and daily use, reasons for use and use situations.)

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Participant sampling and recruitment
Now that you know what to ask … who do you ask, and where do you find them?
For the who part, you need a sampling plan and eligibility criteria. You want to show that Vape A appeals to intended users (smokers or users of other tobacco products) and not to unintended users (nontobacco users and former users, especially youth). Your sampling plan might call for equal numbers of smokers intending to quit, smokers not intending to quit, never-smokers and former smokers—making sure to include a disproportionate number of young adults and a minimum number of people with vaping experience.
Eligibility criteria can be tricky; check the published research. For example, a “never-smoker” is often defined as someone who has smoked fewer than 100 cigarettes in their lifetime!
As to the where … the FDA is open to a variety of modes of data collection (e.g., online, phone, in person) and subject recruitment methods (such as online panels and random-digit dialing). All methods will introduce some bias; online panels may have fewer low-literacy participants, for example. Have a scientific justification for the approach you choose. And phrase your screening questions carefully, so online panel members who just want the dollars can’t guess the “right” answers to join.
Common TPPI mistakes

Not documenting your research methods (e.g., survey response rates, how you recruited)
Biased recruiting; for example, if you offer product coupons as an incentive to fill out your survey, people who don’t like your product won’t respond, and your study sample won’t be representative of the larger population. Use neutral incentives (like a choice of retailer gift cards).
Not enough people in your study—this might be a too-small total sample size or not enough members of important subgroups to detect between-group differences (e.g., women versus men).
Unclear questions or incomplete response options: Prevent confusion by pre-testing your survey with individuals from your target groups (including less-educated folks).
Generic questions—the FDA doesn’t want general perceptions of vapes or snus. They need to draw conclusions about your product, including any flavor or strength options.
Not protecting privacy of research subjects—document your “adequate procedures for human subjects protection;” that is, their “rights, safety and welfare.”
Treating TPPI studies like market research—the FDA asks that companies “select appropriate study personnel for TPPI studies … who have sufficient formal education, training and experience in conducting social or behavioral science research to ensure the study is designed or conducted appropriately.” Translation: We want to hear from academics like us who speak our lingo.
Cheryl K. Olson is a California-based public health researcher and consultant who specializes in behavioral health issues. She spent 15 years on the faculty of Harvard Medical School.
February 1, 2021
Higher-Nicotine Juuls May Facilitate Switching

Photo: Juul Labs
The nicotine delivery of Juul products available in the United States and Canada (59 mg/mL or 5 percent nicotine by weight) more closely resembles the nicotine delivery and experience of cigarette smoking than Juul products available in the European Union, which contain 18 mg/mL and/or 9 mg/mL of nicotine, according to a new study from Juul Labs published in Nicotine & Tobacco Research.
Researchers posited that heavier and more dependent smokers in particular may require the greater nicotine delivery of the higher nicotine concentration Juul pods (59 mg/mL) in order to successfully transition away from cigarettes.
The new study, which consisted of 24 adult smokers, assessed the nicotine delivery and subjective effects of combustible cigarettes compared to the Juul system with three nicotine concentrations: 59 mg/mL (U.S. and Canada), 18 mg/mL (U.K. and Canada) and 9 mg/mL (U.K.).
At each of five study visits, participants used one of four Juul products or smoked their usual brand of cigarette during controlled (10 puffs) and ad libitum use (5 minutes) sessions. Blood samples were collected, and levels of nicotine in the bloodstream were measured for each study product. Subjective effects, including relief of craving for cigarettes and withdrawal symptoms, were assessed 30 minutes after participants used each product.

The higher concentration (59 mg/mL) Juul product delivered significantly greater levels of nicotine and significantly reduced craving and withdrawal compared to the Juul with 18 mg/mL and 9 mg/mL nicotine concentrations. Researchers concluded that the lower nicotine delivery and craving relief from the 18 mg/mL and 9 mg/mL Juul pods available in the EU may limit the product’s ability to provide a satisfying alternative to cigarette smoking—particularly for more dependent adult smokers living in that region.
“When considering laws and regulations governing nicotine concentration in ENDS, policymakers should bear in mind that the availability of a variety of alternative nicotine products may facilitate even more smokers transitioning away from cigarettes,” said Mark Rubinstein, vice president of global scientific affairs at Juul Labs.
January 26, 2021
Study: Vaping Clouds Thinking

Photo: Kevinsphotos from Pixabay
Vaping can have a negative effect on memory, thinking skills and the ability to focus, particularly for young people, according to a recent study by researchers at the University of Rochester (New York) Medical Center.
“Our studies add to growing evidence that vaping should not be considered a safe alternative to tobacco smoking,” said Head researcher Dongmei Li.
The study is based on data analyzed from the over 886,000 participants involved in the Behavioral Risk Factor Surveillance System Survey and the more than 18,000 responses from the National Youth Tobacco Survey.
The researchers concluded that those who vaped or smoked cigarettes were more likely to struggle with cognitive function than those who had never smoked in any capacity. Also, the researchers noted that age played a large role in the participants’ cognitive abilities as they found that when participants were younger than 14 when they started vaping or smoking, they were even more likely to have cognitive struggles as adults.
“With the recent rise in teen vaping, this is very concerning and suggests that we need to intervene even earlier. Prevention programs that start in middle or high school might actually be too late,” Li added.
January 2, 2021
FDA Orders Spectrum Research Cigarettes

Photo: Simone van den Berg | Dreamstime
The U.S. Food and Drug Administration (FDA) in coordination with the National Institute on Drug Abuse and other organizations, has ordered 3.6 million Spectrum-brand variable nicotine research cigarettes from 22nd Century Group.
The research cigarettes will be used for independent, scientific studies to validate the public health benefits identified by the FDA and others of implementing a national standard requiring all cigarettes to contain minimally or non-addictive levels of nicotine.
“We are proud to partner with public health researchers and look forward to the next step in the FDA’s plan to reduce the nicotine content of all cigarettes sold in the U.S. to minimally or non-addictive levels,” said James A. Mish, chief executive officer of 22nd Century Group, in a statement.
“22nd Century remains the leader in reduced nicotine content tobacco products. We believe when the FDA mandate ultimately goes into effect, we will be well-positioned to capitalize on this tremendous opportunity, and we are committed to licensing our technology to make it possible for every cigarette manufacturer in the U.S. to comply with the standard.”
According to 22^nd Century Group, the selection of Spectrum cigarettes is not connected to 22nd Century’s modified risk tobacco application for the company’s reduced nicotine content VLN cigarettes, which feature 95 percent les nicotine than conventional brands.
22nd Century believes that authorization of the company’s MRTP application is imminent, and it plans to launch VLN cigarettes within 90 days of authorization.
December 8, 2020
Inaccuracies in EU E-Cigarette Review
Photo: BAT
British American Tobacco (BAT) has called on a European Commission scientific committee to enhance the quality of its ongoing review into e-cigarettes.
As part of the European Commission’s forthcoming review of the Tobacco Products Directive, the Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) Committee was tasked with producing a scientific review of the health effects of e-cigarettes. On Sept. 23, SHEER adopted its preliminary opinion. The public consultation on the preliminary opinion closed on Oct. 26.
In its response, BAT pointed out “major flaws with the methodology and conclusions.” The report, says BAT:
Fails to contextualize the risks of e-cigarettes relative to those associated with continued smoking.
Makes inaccurate claims regarding e-cigarettes many of which have been widely debunked by the scientific and public health communities.
Contains false assumptions that e-cigarette aerosol is the same as tobacco smoke.
Neglects landmark independent studies showing that many smokers view e-cigarettes as an acceptable alternative to smoking.
Relies on data from non-EU markets and studies on products pre-dating the current Tobacco Products Directive that are not relevant to the current EU context.
“If future regulations on vaping were to be based on the review as it stands now, they would be based on flawed evidence,” said Eric Sensi-Minautier, Vice President EU Affairs at BAT, in a statement. “We call on the SCHEER Committee to address the serious gaps in the review and reflect the weight of evidence supporting the harm reduction potential of e-cigarettes relative to continued smoking.”
November 2, 2020
PMI to Present During General Assembly

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Andre Calantzopoulos
Philip Morris International (PMI) CEO Andre Calantzopoulos and Chief Operating Officer Jacek Olczak will discuss the role of science in driving innovation, progress and policy in a series of events over the course of the United Nations General Assembly this week.
Jacek Olczak
Events will take place between Sept. 21 and Oct. 1 and can be found on the PMI’s website.
The speeches and panel participation follow the launch of PMI’s latest white paper, “In Support of the Primacy of Science,” presenting findings from an independent survey, conducted by Povaddo for PMI, of more than 19,000 adults across 19 countries and territories.
The results show that citizens around the world want governments, public authorities and private businesses to prioritize science and facts when tackling critical global issues.
September 21, 2020