Category: Cheryl Olson

  • The Dilemma of Diversification

    The Dilemma of Diversification

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    While lambasted by anti-smoking activists, the tobacco industry’s move into pharmaceuticals may well turn out to be a positive for public health.

    By Cheryl K. Olson

    “The pharmaceuticalization of the tobacco industry.” This awkward phrase comes from a 2017 Annuals of Internal Medicine article referring to industry moves into noncombustible nicotine products. But recently, it’s gaining some literal truth. Legacy tobacco companies are stepping up diversification into pharmaceutical ventures.

    Given that their current business direction is stalling, new adjacent opportunities that let tobacco companies use their specialized knowledge (say, of the tobacco plant genome or lung physiology or means of delivering substances) make sense. It may seem counterintuitive, or ethically iffy, for these companies to start offering solutions to problems they helped create. But they may frankly be well placed to do so because of their deep expertise. The criticisms of current industry moves into medical research and pharmaceuticals, such as Philip Morris International’s acquisition of Vectura and Fertin Pharma, seem more rooted in emotion than in practical concerns about effects on public health.

    A Tour of Recent Criticisms of Diversification

    Let’s review some recent criticisms and attempt to separate the moral from the practical. Take this September STAT+ article by Olivia Goldhill, titled “Tobacco Giant Philip Morris is Investing Billions in Health Care. Critics Say It’s Peddling Cures for Its Own Poison.”

    The tone of the article makes ordinary business behavior sound sinister. Vectura Fertin Pharma, a firm combining two companies previously acquired by PMI, was “quietly incorporated.” PMI has been “racking up patents and taking over healthcare companies, an unlikely pivot that has accelerated dramatically in the past year.” PMI has also been “poaching considerable regulatory and pharma expertise.” All this in the article’s first two paragraphs.

    The recent move by Matt Holman, who was director of the Office of Science at the Food and Drug Administration’s Center for Tobacco Products (Goldhill mislabels him as head of the CTP), to a position at PMI is described as a “move that shocked public health and tobacco researchers.” Why the surprise? Employees cycling from the FDA to the pharmaceutical companies they reviewed is commonplace; back in 2016, Time magazine called it “a revolving door.”

    When PMI purchased Vectura, best known for making asthma medicine inhalers, the Reuters headline read, “Philip Morris seals deal for U.K.’s Vectura despite health group concerns.” The chief executive of Asthma U.K. and the British Lung Foundation stated, “There’s now a very real risk that Vectura’s deal with big tobacco will lead to the cigarette industry wielding undue influence on U.K. health policy.”

    The U.S. reaction was similar. A joint statement by the presidents of the American Lung Association and American Thoracic Society called the acquisition a “reprehensible choice” by PMI. They were concerned that PMI might use Vectura’s inhalation technologies “to make their tobacco products more addictive.” They raised the prospect that PMI “could further profit from the disease their products have caused by now selling therapies to the same people who were sickened by smoking.”

    The idea of cigarette companies profiting from conditions such as asthma and lung disease was reportedly also raised by British government officials, with the U.K. business minister asking for information on PMI’s plans for Vectura.

    A deliberate company strategy to invest simultaneously in selling addictive poison and in peddling cures for that addiction would indeed be reprehensible. Is that what’s happening here? Or are tobacco companies making effortful attempts to find paths to replace the profits from cigarettes with profits from products that don’t harm and might improve public health?

    Time will tell. PMI’s website states, “We are focused on our mission to one day stop selling cigarettes.” The Guardian newspaper’s coverage noted that while the Vectura acquisition was part of PMI’s smoke-free vision, “the company still makes about three-quarters of its $28 billion in annual revenue from ‘combustible’ products that involve the burning of tobacco.” 

    Critics of the tobacco industry didn’t always take such a dim view of moves away from cigarettes. A quick search in Google Scholar for “tobacco industry diversification” brought up this 1985 piece by Alan Blum in the New York State Journal of Medicine. He stated, “Some health professionals believe that criticism of tobacco companies for promoting cigarette smoking should be tempered because they have become conglomerates that are diversifying into nontobacco products and services. By encouraging such diversification, it is reasoned, health professionals can help expedite the phasing out of smoking while tobacco companies can have an opportunity to replace the resultant lost revenue.”

    Blum’s concern was that this belief among “individuals working to eliminate smoking may be misguided.” This was not because those individuals saw industry diversification as a potentially positive step. Rather, he thought diversification wasn’t happening fast enough. Blum noted that tobacco companies were not decreasing investment in cigarette manufacturing and that “the percentage of total profit accounted for by tobacco sales is still the highest of all sources of revenue for tobacco companies.”

    “Those It Employs [or] Funds Are Therefore Banned”

    PMI’s announced acquisition of Vectura triggered efforts to exclude its employees and their research. The Drug Delivery to the Lungs conference terminated Vectura’s sponsorship. A Thorax editorial titled “Vectura and Philip Morris: The leopard has not changed its spots” stated that “The tobacco industry, those it employs and those it funds are therefore banned from membership of professional societies, including the British Thoracic Society (BTS).” The BTS would “exclude the tobacco industry as a legitimate partner in science and education,” including “publishing in respectable journals” and collaborations with universities. The editorial warns that “Vectura employees will need to consider their future.”

    The treatment Vectura’s employees received is far from unique. Ian Fearon, director of whatIF? Consulting, has conducted research in a variety of settings and helps manufacturers write up their scientific data for publication. “The barriers to publication for tobacco companies and independent ENDS [electronic nicotine-delivery system] manufacturers are high, with many journals flatly refusing to even accept a paper to undergo peer review,” he said. “One major irony is the ‘we need the industry to be transparent’ phrase, yet the reality is that the number of journals willing to publish manufacturers’ data, despite its potential importance in assessing public health impacts, is small and diminishing.”

    Fearon noted the criticism Juul received for “buying out” a 2021 special issue of the American Journal of Health Behavior to fully present their findings, which were a comprehensive examination of the potential impact of Juul on public health. Such publishing fees are common in academia; Juul even paid extra to make the articles free to all readers.

    Derek Yach, formerly with the World Health Organization and the Foundation for a Smoke-Free World, equates the opposition based on the tobacco industry’s past bad practices to the 1980s U.S. boycott of Nestle. “That pushed NGOs [nongovernmental organizations] and WHO to vilify them for decades despite changes in their marketing way back,” he said. “To this day, in many public health leadership settings, Nestle is a real villain, regardless of all they have done to change. I suspect that playbook will apply here too.”

    Yach sees the downside of diversification as less about ethics and public health and more about the practical difficulties. “It’s all about company focus and the inevitable clash of cultures—a pharma culture versus a tobacco company one, for example—and as a result, the ability to manage the transition.”

    David Sweanor

    Thinking About Diversification: A Conversation with David Sweanor

    David Sweanor of the Centre for Health Law, Policy and Ethics at the University of Ottawa has long monitored tobacco company behavior.

    Tobacco Reporter: Why are you interested in the issue of tobacco companies diversifying into things like pharmaceuticals?

    Sweanor: My main interest is public health policy: How do you end up with a healthier population? Is this doing anything that’s going to create poorer health—in which case, there’d be a need to oppose it or try to regulate it in some way? Is it going to be neutral in terms of public health? Then, who cares who owns these companies?

    If it’s something that could actually be good for public health, then we should be supporting it. And there’s reason to believe this could be the case. When companies have loads of resources to throw at something, and if this signals more of a move to transformation within the industry, it would be incredible for public health.

    If they are working on [inhalation] technologies for lower risk alternatives to cigarettes, we have the potential for enormous breakthroughs. If we can get any of the major companies to really switch to being all-in on risk reduction, it would completely change the environment. The impact globally would be remarkable and happen very quickly.

    If you want to get tobacco companies to switch to being in favor of transformation, the last thing you want to do is prevent them from doing things that would aid transformation. If you’re trying to get automobile companies to switch to electric cars, don’t prevent them from buying companies with battery technologies. You’re forcing them to continue to focus on internal combustion engines.

    What do you see as valid and invalid criticisms of this diversification?

    No valid ones immediately come to mind. If they were buying up technology that gave a far better alternative to cigarettes and then trying to kill that, then yeah.

    It’s easy to talk about the invalid criticisms. A really good example of that is in Canada, where Medicago, based in Quebec City, developed a vaccine for Covid-19. In developing countries, this vaccine would work well because it doesn’t need to be stored at cold temperatures. Philip Morris has an indirect holding of about 30 percent in Medicago. Anti-tobacco groups attacked the government for approving the vaccine, and WHO refused to approve it.

    What’s the thinking behind that? It’s saying: We don’t like this company because we think it’s done bad things in the past. To deal with this, we’ll prevent them from doing good things now. They created an epidemic of disease from smoking that became larger and lasted longer than it should have. So we’re going to prevent them from doing things that could reduce this epidemic of disease from Covid to make it last longer than it should.

    Are people following the principles of the Enlightenment or the Inquisition? So much now with mainstream anti-tobacco groups is the latter. We don’t care about the quality of your work; we won’t give you a platform to discuss or debate it. That some affiliation you have is more important than the knowledge you bring is pretty reprehensible. It’s like saying Roman Catholics are not allowed to express their views.

    What do you see as potential benefits to public health from this diversification? For example, Matt Holman’s new position as vice president of U.S. scientific engagement and regulatory strategy at PMI.

    Look at the counterfactual. If they don’t do that, the only people working in cigarette companies working on transformation spent their careers working on and understanding and benefiting from cigarettes. If General Motors says, “we’re hiring engineers who understand electric mobility rather than hydrocarbons,” isn’t that a good thing? How can you transform if all the people in senior positions have their expertise in internal combustion engines?

    We see this in high tech all the time; one company will buy another to get the expertise of their employees. You need them at the table when you make decisions on where to go with the next generation.–C.K.O

    Addendum

    In the main article above, I stated that the boycott of Nestle from the 1980s has had a lingering negative effect on WHO and many public health leaders’ views of the company many decades later. This despite Nestle being a global leader in addressing food insecurity, sustainable agriculture and the use of 21st nutrition science (see the company’s 2021 annual report).

    In the second half of October, Nestle’s past came back to haunt the company. The WHO Foundation, set up to build innovative private public partnerships, banned future Nestle contributions despite having originally accepted  a grant for their work on addressing Covid-19.

    The WHO Foundation already bans contributions from tobacco and arms manufacturers though it is unclear how “tobacco” is defined. Does it include governments with state monopolies? Does it include standalone e-cigarette, or nicotine pouch companies? Does it distinguish between companies where revenue from reduced risk products is increasing while combustible revenues are decreasing? Probably not.

    Labelling companies as good or bad is the far easier option. But that option that ignores serious transformation and the opportunity to nudge and support the good emerging faster.

    Derek Yach

    Cheryl K. Olson is a California-based public health researcher who specializes in behavioral health issues and consults on tobacco product behaviors via McKinney Regulatory Science Advisors. She spent 15 years on the faculty of Harvard Medical School.
  • Listening to Nicotine Users

    Listening to Nicotine Users

    Photo: G. Lombardo

    A GTNF panel puts “forgotten smokers” in the spotlight.

    Cheryl K. Olson

    Skip Murray used to be one of the forgotten smokers. “I think people that have a life like my background are invisible to the people who have more influence in the world,” she says. “I hate to use class terms, but lower class.” Heavy drinking and mental illness ran in her family. Her memories include events psychologists would call “adverse childhood experiences.” 

    When Murray started smoking at age 10, no one paid any mind. Today, in her sixties, she gets her nicotine from a vaping device. She and her son (who suffered a heart attack at age 29) both used vapor products to quit cigarettes.

    People who smoke find that their needs and views are routinely neglected by policymakers, physicians and other potential sources of support. Research shows that cigarette use is increasingly concentrated in what public health people describe as “vulnerable populations.” Some lack resources or homes, are challenged by physical or mental illnesses or are incarcerated. None want to be lectured to or labeled.

    On Sept. 28, the Global Tobacco and Nicotine Forum (GTNF) will literally put a spotlight on these issues in a plenary event on “forgotten smokers.” Panelists will share personal experiences and research on ways to raise empathy and visibility for people who smoke and ideas to spread the benefits of harm reduction more equitably. They include Alex Clark, CEO of the Consumer Advocates for Smoke-Free Alternatives Association (CASAA); Will Godfrey, founding editor-in-chief of the Filter news site and executive director of the Influence Foundation; Skip Murray, a Minnesota-based vaping advocate and former vape shop owner; and Brent Taylor, senior director of consumer and marketplace insights at Altria. I will moderate the panel.

    Who’s Still Smoking?

    In 1965, 42 percent of adult Americans smoked. According to the U.S. Centers for Disease Control and Prevention (CDC), as of 2020, just 12.5 percent, or 25 of every 200 adults, were smoking. Sounds great! But with population growth, the absolute number is still huge: Almost 31 million adults use combustible cigarettes. The plummet in smoking rates has slowed to a crawl because the easy wins are over.

    No job, or a poverty-level income. No high school diploma. Serious psychological distress. Disabilities that limit daily activities. Heavy alcohol use. Data from hundreds of thousands of people interviewed for the CDC’s National Health Interview Survey from 2008 to 2017 found that the more of those socioeconomic and health-related disadvantages you face, the more likely you are to start smoking and the less likely you are to quit. The majority of people who quit smoking during that period had zero or one disadvantage. 

    Sixteen million Americans live with a smoking-related disease, says the CDC. And the fallout is concentrated among those who can least afford it. Those who lack health insurance or use Medicaid are more than twice as likely as those with private insurance to smoke.

    Before Covid-19 shutdowns and media-driven fears about vaping safety shuttered her business, Murray and her adult son sold e-liquids and vaping equipment to low-income and disabled nicotine users. “If you make $60,000 a year, you can afford not to smoke if you don’t want to,” she says. “But when you’re surviving on 20 grand a year or less, on a Social Security or disability check—if we don’t keep vaping affordable, and cheaper than smoking, people will smoke.”

    The Case of People in Custody

    A good example of the link between compounded disadvantages and smoking is found in jails and prisons. People in custody smoke at roughly four times the rate of those “outside,” and most have a history of other substance use. Historically, cigarettes fill multiple important roles in these settings. According to a World Health Organization report, “Tobacco use is completely entangled in prison life where it helps to cope with boredom, deprivation or stress, relieve anxiety and tension and function as a source of pleasure or monetary value in an environment without currency.” 

    Researching the plight of those held in officially “smoke-free” prisons was eye-opening to me. One recently incarcerated person we interviewed described watching guards spit out chewing tobacco that was quickly scraped up by prisoners to re-chew or to save for later smoking. “That’s how desperate some of these guys are,” he said. “Tobacco in jail is basically air.”

    Another said, “People in jail crave tobacco. They want to relieve stress, and that’s a stress-reliever. I actually thought, when they took tobacco away, I thought there were going to be riots.” When cigarettes were banned in his facility, e-cigarettes were introduced. “Now, if they take this [vaping] away, there might be riots,” he said.

    Vaping has been introduced with great success as an alternative to smoking in Scotland’s prisons and in some U.S. facilities (with vapes specially designed for safety and trackability). My public health colleagues often think of e-cigarettes exclusively as a health risk to teenagers. I’ve found that talking about vaping in the context of the traumas and needs of people in custody reframes the issue. At the GTNF, Godfrey will say more about this vulnerable population as well as the links between harm reduction for tobacco and for other substances.

    Nicotine and Mental Health

    Murray has been open about her lifelong mental health struggles and how she perceived the effects of nicotine on her brain. “When I stole my grandpa’s cigarette and snuck it behind his barn, from day one, I liked smoking,” she says. “It wasn’t icky to me. I felt better.”

    When she finally sought professional help decades later, after attempts to quit nicotine led to suicidal thoughts, Murray received multiple diagnoses. After initially struggling with shame—“You hear stigmatizing things your whole life that you just accept as true”—she went public on social media with her story. “It was amazing how many people went, ‘Oh my God, me too,’” she says. “And amazing how many say they are self-medicating with nicotine.” 

    She finds relief from symptoms of attention-deficit/hyperactivity disorder through mindfulness practices and vaping nicotine. “And it helps me sleep. For most people, nicotine is a stimulant, but for people with ADHD, it has the opposite effect.” Many laboratory and real-world studies support the self-medication hypothesis for a range of mental health disorders, from depression to ADHD to schizophrenia.

    Understanding the Harm Reduction Journey

    New approaches are needed to help forgotten smokers who can’t or don’t want to quit nicotine find lower-risk options that work for them. An obvious next step is to stop blaming and start listening.

    “We need to make sure that we bring the voice of the adult tobacco consumer into the center of the discussion about tobacco harm reduction,” says Taylor. “We need to spend time getting to know the individuals, what this means to them and what it can mean if they are successful in their harm reduction journey.”

    At the GTNF, he’ll share insights from a recent deep dive into the daily lives of smokers trying to reduce their health risks, called the 21 Project. Named for the popular notion that it takes 21 days to change a habit, the Altria project recruited 21 smokers interested in making a change. Armed with information about the array of reduced-harm recreational nicotine products available, these individuals spent three weeks testing alternatives to cigarettes on their own. Researchers documented their stories of the day-by-day transition.

    “You can review numbers and bar charts, but what you never get from them is the heart and feelings of the adult tobacco consumer,” says Taylor. “How do you take the experience of moving from cigarettes to smoke-free alternatives and bring it to life so that everyone can feel and understand what that’s like?”

    Taylor is himself a former smoker who now uses alternative products. “Hearing the stories of people who smoked and switched to smoke-free alternatives was powerful and really emotional,” he says.

    He says the 21 Project taught invaluable lessons to his organization about how to support and empower people in making changes. “We learned a ton; to hear firsthand people’s challenges and successes and what would sustain them on their transition journey was critically important.”

    Adding to that perspective will be Clark of CASAA, which has long worked to highlight the issues facing nicotine consumers. Clark would like to do away with the victim narrative that casts people who smoke as dupes swayed by peer pressure and advertising.

    “Even with a growing awareness of the need to address issues of health, racial and economic equity, the legacy of stigma embedded in anti-smoking policies is leaving millions of people behind,” he says. “The overweighted focus on predatory marketing as the driver of youth tobacco use is ultimately dismissive of more powerful underlying factors contributing to any substance use.”

    Cheryl K. Olson is a California-based public health researcher who specializes in behavioral health issues and consults on tobacco product behaviors via McKinney Regulatory Science Associates. She spent 15 years on the faculty of Harvard Medical School.
  • Not “A Solved Problem”

    Not “A Solved Problem”

    Photo: nikodash

    Acknowledging reality at the E-Cigarette Summit

    By Cheryl K. Olson

    After weary years of disdainful comments and dismissive studies about nicotine, and especially vaping, from my public health colleagues, the recent 2022 E-Cigarette Summit in Washington, D.C., gave me cause for hope. It was energizing to see researchers, advocates and regulators sincerely attempt to share and discuss their varied findings and experiences rather than “preach to the choir” more evidence supporting preexisting beliefs.

    For example, Peter Hajek of Queen Mary University of London discussed nicotine’s effects on the developing brain. He threw cold water on assertions that nicotine can cut IQ by 10 or 15 points. These claims, he said, come primarily from chronic large doses, close to a lethal dose, in animal studies. It’s unclear whether this is relevant to voluntary dosing among humans. He went on to question the basis for accepted wisdom on age of smoking initiation and nicotine dependence. At last, nuance instead of diatribe!

    The U.S. Food and Drug Administration and public health researchers have always been concerned about tobacco product effects on vulnerable populations: people at greater risk of starting to use tobacco, suffering from tobacco-related diseases or having problems stopping use of tobacco products. But the scales were tilted toward stopping youth from initiating use and thus away from all those adults getting sick who can’t or won’t quit.

    At the E-Cigarette Summit, a rebalancing seemed to be underway. Along with the usual (and appropriate) concerns about youth and vaping, there were sessions with titles such as “Let’s not forget the smokers” and “‘Smoke-free’ means smoke-free not vape-free.” Could we be approaching a point where the famous appropriate for the protection of public health standard gives protection of smokers’ well-being the weight it deserves?

    This reframing of tobacco harm involves acknowledging some unpalatable facts. First, smokers still exist in persistently large numbers, many in marginalized pockets of society. As Nancy Rigotti of Massachusetts General Hospital/Harvard Medical School noted, “Disparities in tobacco use really drive health inequities in the U.S. And that’s another reason why we need to be addressing the adult smokers.”

    Second, medical best practice approaches to quitting are not working and have no hope of getting us to a smoke-free society. Third, although cessation of use is preferable, harm reduction is a valid goal, sometimes the only realistic one—and it requires actively promoting appealing alternatives to smoking.

    Dated and Overrated

    Various media campaigns have urged us to “make smoking history.” Sadly, that’s not the path we’re on. According to Vaughan Rees of the Harvard T.H. Chan School of Public Health, the commonly recommended “safe and effective” medications fail to help most smokers, especially those from marginalized populations. Calculating their overall impact at the population level, he said, “We see a less than 1 percent reduction in the prevalence of smoking using current first-line smoking cessation medications.”

    He concluded, “The best evidence-based interventions are dated, overrated and cannot meet the challenge of reducing tobacco-related harm in this century.”

    One problem is that people who could encourage smokers to quit have become complacent. As Rigotti described in her talk, “Let’s Not Forget the Smokers: A Clinician’s Perspective,” “These days, for some of our clinicians, it’s really tobacco use is a solved problem.”

    Rigotti quoted a cardiologist colleague who told her, “Gee, most of my smokers have quit now.” This doctor’s patients are well-off, with good health insurance. “If instead she were working in a safety net hospital,” Rigotti noted, “she would know that there are lots of smokers but that their smoking behavior was very intractable.”

    Even before Covid-19, tobacco treatment struggled to gain physician mindshare. “We’re not very exciting because we haven’t had a new tobacco product on the market for more than 10 years,” said Rigotti. That is, physicians lack new pharmaceuticals to treat nicotine addiction.

    What might change clinicians’ attitudes and practices? The comfortable route, Rigotti said, would be e-cigarette products designated as medical devices, similar to the U.K. approach. But that is likely years away. In the meantime, promoting the fact that the FDA has authorized the marketing of some e-cigarettes “is an opportunity FDA could take advantage of to say the public health benefits outweigh the risks for some members of this class of products,” she noted.

    Her final recommendation was increasing doctors’ comfort with the idea and practice of harm reduction: helping patients who can’t or won’t quit. “Everyone’s comfortable with long-term NRT [nicotine-replacement therapy] now; you’re doing it [harm reduction] already,” she said to her fellow physicians. “And maybe you should be doing more of it.”

    In the last decade, recreational nicotine products have proliferated like wildflowers: pouches, gums, heat-not-burn and many more. I would add: Why not do more to educate physicians about those? Especially given the new recognition that alternatives to smoking should be (gasp) appealing.

    Push and Pull

    Treat nicotine addiction with a medicine: That’s the traditional approach to smoking. Another welcome development at the E-Cigarette Summit was hearing multiple speakers advocate for new options, even flavored ones.

    Dorothy Hatsukami of the University of Minnesota focused on factors that might push people away from smoking and pull those who won’t quit toward alternatives. Given that (as her slides noted) “nicotine maintains addiction, but other constituents kill people,” her recommended “push” was policies to reduce the nicotine in cigarettes.

    However, she noted, for those smokers who are unable or unwilling to quit, a “pull” is also needed toward alternative nicotine-delivery systems. Hatsukami described a colleague’s study supporting that “in the context of very low-nicotine cigarettes, you still need to have [alternative] products that are appealing. That have a range of flavors as well as higher nicotine doses.”

    “New technologies clearly are needed to fulfill the promise of tobacco harm reduction,” Rees asserted in his talk. “We need reduced exposure products that meet the needs of smokers.” Such products, he said, along with regulatory standards that reduce or eliminate known toxicants, are the way to prevent a pandemic of 1 billion deaths from smoking in this century.

    Rees showed a refreshing willingness to consider what works, whatever the source, including a 1991 paper from the Philip Morris archives. “One size does certainly not fit all. I learned that from seeing what were previously secret tobacco industry internal documents,” he said. “They designed cigarettes to meet the needs of specific subgroups of smokers. And were successful at creating demand for their products.”

    Along with a focus on rapid delivery of nicotine to the brain, “they also worked very hard to ensure that tobacco products are attractive, that they are convenient, that they are easy to use. That the chemo-sensory qualities of smoking are appealing enough to promote continued use,” said Rees.

    Several speakers made it clear, citing randomized trials and real-world evidence, that boosting continued use is key to reducing harm through e-cigarettes. This included Andrew Hyland of Roswell Park Comprehensive Cancer Center and the FDA-funded Population Assessment of Tobacco and Health (PATH) study. He talked about PATH data on the one in six U.S. daily smokers with no plans to ever quit and who don’t vape. About 2 percent of this group tried and stuck with e-cigarettes, becoming accidental quitters.

    These never-quitting smokers deserve more attention, said Hyland; they are “at much higher risk for a bad cigarette-caused health outcome because they are much older, heavier smokers and at the low end of the socioeconomics distribution.” Electronic nicotine-delivery system products have the potential to expand the pool of smokers engaged in cessation, thus raising overall quit rates.

    How can we get the level of switching success seen in randomized trials of e-cigarettes to happen for more smokers in the real world? David Ashley of Georgia State University, former director of the Office of Science at the FDA’s Center for Tobacco Products, focused much of his opening keynote, “Thinking Outside the Box on E-Cigarettes,” on that question. He stressed that smokers need the opportunity to try various products to find the right one for them as well as coaching on how to use the product.

    “Purchasing a poor device from a gas station or grocery store shelf, trying it out by yourself with no instructions, does not maximize the likelihood of successful quitting,” Ashley said. He contrasted this with a vape shop that takes a “hands-on interactive approach … working with smokers to find the best product for them.”

    Living with Uncertainty

    Jamie Hartmann-Boyce of the Centre for Evidence-Based Medicine at the University of Oxford, summarizing the latest Cochrane Review of electronic cigarettes for smoking cessation, made a plea in her talk’s title for “Living with and Addressing Uncertainty.” There is now moderate-certainty evidence from randomized trials, for example, that quit rates are higher with nicotine e-cigarettes than with NRT. As more results pour in, the Cochrane Review is now updated monthly.

    In closing, Hartmann-Boyce noted that this field “since its inception has been hampered by false dichotomies: Are [e-cigarettes] safe? Are they not safe? Do we protect children? Do we help adults? And now it’s ‘Is the evidence certain or is it uncertain?’”

    She pointed out that just as risk exists on a continuum, so does uncertainty, and that science is working as it should to move us toward firmer ground on e-cigarette effects. “We are getting more certain,” she said. “But what always remains certain is how harmful cigarettes are. And we should not let unnuanced discussions about the uncertainties of e-cigarettes get in the way of communicating that evidence as well.”

    Cheryl K. Olson is a California-based public health researcher who specializes in behavioral health issues and consults on tobacco product behaviors via McKinney Regulatory Science Associates. She spent 15 years on the faculty of Harvard Medical School.
  • Not a Bot

    Not a Bot

    Photo: UVA

    Consumer advocates are for real.

    By Cheryl K. Olson

    “My initial reaction is that I’m surprised. That’s not a sentiment I’ve heard from industry before,” said Danielle Jones, president of the board of the Consumer Advocates for Smoke-Free Alternatives Association (CASAA). I was passing on what I’d been told by industry sources: that consumer advocates should take the lead in correcting widespread public perceptions about nicotine harm reduction.

    “From a personal standpoint, it’s a little disheartening,” she added. “Because that’s a lot of responsibility to put on underfunded nonprofit advocacy groups.” However, unlike industry, “we can’t get in trouble for saying whatever we want.”

    Who are these harm reduction consumer advocates­: Are they grassroots voices or artificial turf? What are they doing to change the narrative and to help individual smokers? What else could they be doing—and what is fair or reasonable to ask of them?

    Not a ‘Smokers’ Rights’ Repeat

    My first exposure to the CASAA was an email from its member coordinator, Kristin Noll-Marsh, in response to a Tobacco Reporter column. She asked me to join a “live YouTube advocacy show” as a guest that weekend. I was wary of lending my credibility to a consumer advocacy group that might turn out to be a corporate public relations facade. Although faux “astroturf” organizations are not unique to the tobacco industry, public health people remember well Big Tobacco’s late 20th century global strategy of founding “smokers’ rights” groups to fight the spread of smoke-free policies.  

    Happily, the CASAA turned out to be the real thing: a 501(c)(4) nonprofit advocacy organization dedicated (as its website says) to ensuring “the availability of a variety of effective, affordable, reduced-harm alternatives to smoking.” Founded in 2009, it sprang from an online forum for vaping enthusiasts stunned by attacks from anti-tobacco organizations on a product that had (by plan and by accident) turned them into nonsmokers. They were advocating for vaping as harm reduction years ahead of the legacy tobacco companies.

    After our invigorating podcast conversation, I reviewed the CASAA’s impressive collection of online resources and got to know Danielle Jones, who helms the CASAA’s all-volunteer board of directors. (She’s a graphic designer by profession.) I’ve often said that most people in public health and politics don’t know smokers; it’s easy to treat them as abstractions instead of fellow humans. The CASAA puts faces on those smokers, collects their stories and seeks to amplify their voices. I’m embarrassed it took me so long to notice. 

    “Our approach, which is limited by funding,” Jones said, “is all about organically bringing people into the tobacco harm reduction conversation.” The CASAA works largely through social media (Facebook, Twitter and Instagram), including scheduled podcasts recapping news and events. The group also works to raise the profile of research and opinions from other sources.  

    The CASAA sells apparel, noted Jones, “so advocates can wear messages that provoke conversations out in the wild.” Projects in its pipeline include creating information pages about vaping geared toward the needs of physicians and researchers.

    I asked Jones what the CASAA doesn’t do. It doesn’t endorse vaping products or companies. It also avoids engaging with youth, she said, “even to correct misinformation or help with school projects—we get a lot of those requests—as we would almost instantly be accused of trying to market or promote vaping to kids.”

    ‘I Want a Good Face for Vaping’

    Alongside consumer groups such as the CASAA, there is an ecosystem of individuals influencing nicotine product opinions and behavior via social media. Jones referred me to Nicholas “Grimm” Green, a YouTuber and harm reduction advocate.

    Back in 2009, Green was looking for something to cut back on but not to quit smoking. He enjoyed “the ritual of it, inhaling, exhaling, the smoke, everything about it.” 

    He stumbled across an online review by “this charming old bald man who had discovered vaping.” Soon, with the right device and flavor (root beer), “it was almost effortless to switch completely,” Green said. “And I knew I just had to tell other smokers about it.”

    His mission to change the public perception of vaping involves a portfolio of activities. He reviews products on multiple social media channels, trying to “cater toward smokers” to help them find the approach that works for them, whether they become vapor hobbyists or want something more cigarette-like. He does a weekly YouTube livestream covering vaping news and opportunities to advocate (such as phoning politicians about particular legislation), often coordinating with the CASAA.

    Green strives to respond effectively to misinformation on Twitter and Facebook, “engaging people as often as possible” through polite sharing of stories and research studies. “When you see [anti-vaping organizations] tweeting stuff about vaping causing brain damage, there’s a gut reaction to want to just yell at that person and call them names and tell them how wrong they are,” Green admitted. “But that’s not something that changes minds.”

    He also works to amplify voices that others are likely to heed. “You retweet the more credible voices,” he said. “It means more if there’s a pro-vaping article or stance coming from the University of Michigan or any of these professors than a guy on YouTube with a throat tattoo.” Green is a fan of body art.

    “I know what I look like,” he said. “So I try not to put myself out there so much. I want a good face for vaping in the United States of America.”

    I mentioned that 2018 AP file photo, shown repeatedly next to news and opinion articles about vaping: a blond teen with acne and peeling black nail polish, sucking on a vape device. “That’s how they want to portray vaping,” said Green. “They don’t want to show you the 65-year-old grandmother who smoked her entire life who now loves strawberry cheesecake e-liquid.”

    ‘Not a Bot’

    A 2021 academic paper, “#FlavorsSaveLives: An Analysis of Twitter Posts Opposing Flavored E-cigarette Bans,” illustrates the divide between academics and advocates. The authors tracked patterns of tweets pertaining to vaping, including flavor bans and safety fears, in 2019 to 2020. They noted that the state of California and the U.S. Congress “have investigated the role that social bots play in driving online discussions about e-cigarettes.” The spike in posts containing “not a bot,” they said, were “most likely to note that the backlash against e-cigarette regulation is not coming from automated accounts but instead real-life people who can vote.” Although the paper is not anti-vaping, its tone suggests that the authors never met any of those real-life folks whose tweets they analyzed.

    Green was one of them. He recalled that, largely in response to e-cigarette or vaping use-associated lung injury misinformation, “we more or less mobilized a pretty large army of vapers to get on Twitter and make their voices heard. And when they saw this enormous spike in actual people getting on Twitter, those news reports came out that we weren’t real people. We got called bots.”

    “That stings,” he said. “All we were doing was trying to defend our choice to not smoke cigarettes. So all these vapers started changing their Twitter handles to their real name plus ‘not a bot.’”

    This throws some cold water on the idea that consumer advocates have inherent credibility. The emotions and history associated with nicotine complicate changing minds. Although organizations like the CASAA will accept funding from anyone, industry ties and control are often assumed. “People commenting online get called bots, paid shills, all the time,” affirmed Jones. “Our opinions as users of the products are constantly dismissed and trampled on as having some tie to Big Tobacco.”

    “Vapers are so desperate for any recognition or public mouthpiece that we get susceptible to astroturfing,” said Green. “I don’t want to name names, but organizations have come in that have been associated with other, not-so-great organizations and tried to get vapers to do things or sign things or text things.” (The World Vapers’ Alliance and The 95 Percent were most recently outed as astroturf.) However, Green is optimistic that a steady drip of genuine engagement will pay off. “There is no magic bullet that will suddenly change the course of history for vaping. It has to be a slow, grassroots, honest consumer-based initiative.”

    The Consumer Perspective

    I asked Danielle Jones what the CASAA might do if it had more funding. Her wish list included “PR campaigns in print, digital and television, hold events and potentially hir[ing] a lobbying firm to help educate legislators.” They could expand their paid staff beyond one-and-a-half employees. Funding of research studies, by others and by the CASAA, are also on her list. She noted that researchers have recruited subjects through the CASAA’s lists but did not seek to involve the CASAA in their work.

    The consumer perspective is newly prominent in health research. For example, the Patient-Centered Outcomes Research Institute (PCORI) has received millions of dollars from the U.S. Congress for effectiveness studies that give weight to patient circumstances and preferences. The nicotine user’s perspective surely deserves the same courtesy.

    Cheryl K. Olson is a California-based public health researcher who specializes in behavioral health issues and consults on tobacco product behaviors via McKinney Regulatory Science Associates. She spent 15 years on the faculty of Harvard Medical School.
  • White Coats, Fuzzy Facts?

    White Coats, Fuzzy Facts?

    Photo: Lisa F. Young

    Educating physicians on nicotine and the risk continuum.

    By Cheryl K. Olson

    In an earlier edition of Tobacco Reporter, I described the globally widespread, misplaced fears about the health risks of nicotine—and the critical need for credible messengers to counter those fears (see “Watch Your Mouth,” Tobacco Reporter, March 2022). People generally trust their doctors for health information. Smokers do too.1 The limited data available suggest smokers trust their doctors over other sources of information on e-cigarettes2 and that most patients using e-cigarettes would appreciate at least a brief discussion or handout.3

    Are physicians positioned to take advantage of that trust? Can they effectively guide patients who can’t or won’t quit nicotine toward lifesaving alternatives to smoking? Getting patients to stop smoking is top priority. Cigarettes are still the leading preventable cause of illness and death in the U.S. and many other nations. Smoking rates are stagnant among vulnerable populations, including those who are older, low-income or struggling with chronic physical or mental illness.4 Thanks in part to media-driven fears of vaping lung injuries and to e-cigarette flavor bans, cigarette sales are actually on the rise.5, 6

    Before doctors can help, they must be armed with accurate information and believe that taking action is necessary.

    Physicians are Confused About Nicotine

    One huge obstacle is a widespread physician perception that nicotine is dangerous. The first sentence in a 2021 survey report from the Journal of General Internal Medicine states, “Nicotine is responsible for the highly addictive nature of tobacco products, but most tobacco-caused disease is not directly caused by nicotine but rather by other chemicals present in tobacco or tobacco smoke.”7 Stunningly, four of five physicians in this U.S. survey strongly agreed (incorrectly!) that nicotine causes cancer, cardiovascular disease and chronic obstructive pulmonary disease. There were only minor variations across medical specialties. Recent surveys across countries have similar findings.

    What effects might these beliefs have on physician willingness to recommend nicotine-replacement therapies to patients who smoke? And what about recreational nicotine products?

    Physicians Don’t Understand the Continuum of Risk

    Another barrier is ignorance about or fear of reduced-harm products that aren’t pharmaceuticals. I couldn’t locate any studies on what, if anything, doctors know about the full range of novel recreational nicotine products. However, a 2020 review from the University of Queensland8 found 45 qualitative and quantitative studies internationally that looked at what physicians believe and do regarding electronic nicotine-delivery systems (ENDS). Doctors were aware of ENDS but far from experts in their health effects and use for smoking cessation. Most of what they knew came from media stories or patients. “This lack of knowledge and feeling of being ‘uninformed’ was reported consistently by [healthcare professionals] across and within studies.”

    The latest and largest U.S. study of what doctors say to patients about vaping appeared in the April 2022 issue of JAMA Network Open.9 The Rutgers University authors surveyed a national cross-section of 2,058 board-certified physicians. The conclusion? “More than half of the physicians believed that all tobacco products are equally harmful, and this belief was associated with lower rates of recommending e-cigarettes.” The authors argue that “it is critical to address physician nicotine misperceptions and to correct misperceptions regarding the relative harm of various tobacco products,” as the “FDA authorization process” introduces more modified-risk products.

    What Might Start to Open Minds?

    I asked a young physician friend (a third-year resident at Virginia Commonwealth University) what he and his fellow doctors would want to know about reduced-harm nicotine products that their patients might be using. He immediately mentioned wanting to see results from randomized controlled trials (RCTs) on “products that will help patients quit harmful tobacco products but also data regarding health outcomes. For example, what are the rates of lung cancer in a patient who smokes cigarettes for 10 years versus someone who vapes for 10 years?”

    This is the sort of response we expect and was consistent with the JAMA Network Open survey findings. But can data alone change beliefs?

    An earlier study from the Rutgers researchers involving structured interviews with doctors gives reason for doubt.10 Most doctors they talked to were at least neutral about attempts to switch to e-cigarettes for patients who had failed with traditional smoking cessation methods. But five of the 35 doctors were adamantly opposed; they would not recommend vaping to patients even if future RCTs found e-cigarettes to be equal or superior to other quit methods. One oncologist said, “Based on what I’ve heard and read about them, I don’t think so. It seems like they’re actually, like I said, kind of dangerous.”

    A careful read suggests that physicians who believed e-cigarettes could be effective switching tools—about half of those interviewed—were so persuaded by a combination of stories and data. Patients, friends or family members had cut down or quit cigarettes through vaping. And, perhaps sensitized to the issue by these stories, the doctors recalled seeing one or more studies that backed up their personal observations. Interestingly, 11 of the doctors who doubted e-cigarette effectiveness cited the hand-to-mouth behavior similarities to smoking as a negative rather than a positive for switching. This suggests they don’t know smokers.

    Physician Harm Reduction

    Sudhanshu Patwardhan

    During his postdoctoral training as a primary care physician, Sudhanshu Patwardhan grew increasingly concerned about the ineffectiveness of the advice and treatments given to patients who smoked combustible cigarettes. Since then, he’s focused his clinical and research career on harm reduction for addicted smokers. He’s currently based in Great Britain, where he’s the director of the Centre for Health Research and Education.

    Patwardhan has researched physicians and nicotine in the U.K., Sweden, Greece and India. For the past year, he and I have been talking about the clinical and public policy challenges that come with shifting toward a harm reduction approach to smoking cessation.

    “Consistently, between 65 [percent and] 80 percent of surveyed physicians across all these countries harbor misperceptions about nicotine,” he said. “It’s no wonder that, universally, ‘Why replace one addiction with another?’ is one of the commonest attitudes [among physicians] for nicotine-replacement therapy for tobacco cessation using a harm reduction approach.

    “Doctors forget that in addition to its long-term effects, inhaling the smoke from burning tobacco induces the breakdown of many drugs, thus making those treatments ineffective. Many psychiatrists I interact with admit to simply increasing the dose of the administered medications to compensate for the loss of effectiveness due to smoke-induced breakdown but don’t offer cessation support simultaneously. This, of course, leads to higher side effects and poorer patient outcomes—all because physicians are not sensitized to and empowered about tobacco cessation and harm reduction.

    “Most freshly minted doctors would know how to recognize the most esoteric heart murmur but have no practical experience in the basics of behavioral intervention or the role of medications for tobacco cessations. Pharmacology and clinical medicine barely touch on nicotine-replacement therapy and give no clues to trainee doctors on what to prescribe, for how long and how to manage cravings and withdrawal symptoms effectively. Most noncommunicable diseases have tobacco use as a risk factor. Yet doctors simply do not address it along with the presenting complaint.

    “Our center’s strategy focuses on the root of the issue: We’re developing and conducting peer-based education of healthcare providers in a safe and nonjudgmental environment. Our approach and materials are country specific. For example, in the U.K., e-cigarettes are a part of the suite of potential harm reduction tools offered by the National Health Service. In India, however, e-cigarettes are currently banned and not licensed for smoking cessation. There, we focus on approved approaches, such as nicotine-replacement therapy, bupropion and varenicline.”

    “We need to start overhauling the medical education curriculum in this area. We’re conducting pilot programs at some medical schools with exciting results and will publish those data. Practicing physicians also need training to increase their effectiveness. Finally, scaling up of nicotine education for healthcare providers can be a significant challenge, especially for countries as wide as the U.S. or as populated as India. Digital tech tools, such as cessation apps, short media presentations, including online videos and smart print campaigns designed for social media, can all help.”–C.K.O.

    References

    1 Nelms E et al. Trust in physicians among rural Medicaid-enrolled smokers. Journal of Rural Health, 2014: 30(2), 214–220. doi:10.1111/jrh.12046.

    2 Wackowski OA et al. Smokers’ sources of e-cigarette awareness and risk information. Preventive Medicine Reports, 2015: 906–910, http://dx.doi.org/10.1016/j.pmedr.2015.10.006.

    3 Doescher MP et al. Patient perspectives on discussions of electronic cigarettes in primary care. Journal of the American Board of Family Medicine, 2018, doi: 10.3122/jabfm.2018.01.170206.

    4 Zhu S-H et al. Smoking prevalence in Medicaid has been declining at a negligible rate. PLoS One, 2017, https://doi.org/10.1371/journal.pone.0178279.

    5 Xu Y et al. The impact of banning electronic nicotine-delivery systems on combustible cigarette sales: Evidence from U.S. state-level policies. Value in Health, 2022, doi: 10.1016/j.jval.2021.12.006.

    6 Federal Trade Commission. FTC report finds annual cigarette sales increased for the first time in 20 years. October 2021. www.ftc.gov/news-events/news/press-releases/2021/10/ftc-report-finds-annual-cigarette-sales-increased-first-time-20-years.

    7 Steinberg MB et al. Nicotine risk perceptions among U.S. physicians. Journal of General Internal Medicine, 2020, doi: 10.1007/s11606-020-06172-8.

    8 Erku DA et al. Beliefs and self-reported practices of healthcare professionals regarding electronic nicotine-delivery systems (ENDS): a mixed-methods systematic review and synthesis. Nicotine & Tobacco Research, 2020 https://doi.org/10.1093/ntr/ntz046.

    9 Delnevo CD et al. Communication between U.S. physicians and patients regarding electronic cigarette use. JAMA Network Open, 2022, doi:10.1001/jamanetworkopen.2022.6692.

    10 Singh B et al. Knowledge, recommendation and beliefs of e-cigarettes among physicians involved in tobacco cessation: A qualitative study. Preventive Medicine Reports, 2017 http://dx.doi.org/10.1016/j.pmedr.2017.07.012.

    Cheryl K. Olson is a California-based public health researcher who specializes in behavioral health issues and consults on tobacco product behaviors via McKinney Regulatory Science Associates. She spent 15 years on the faculty of Harvard Medical School.
  • Unlikely Bedfellows

    Unlikely Bedfellows

    Photo: Dmitry

    How free-flowing data streams can help advance public health goals for nicotine products.

    By Cheryl K. Olson

    How might new technologies engage public health in transforming the tobacco sector? Let’s take a look at three unlikely scientific bedfellows: sewage, Covid-19 and smoking harm reduction.

    Of the many innovations born from the Covid-19 pandemic, my favorite is the U.S. Centers for Disease Control and Prevention’s National Wastewater Surveillance System (NWSS). Since September 2020, the NWSS has tapped into underused data streams flowing through our communities to get early warnings of local disease spread. It’s not perfect; you can’t predict how many people are sick, and it misses people not hooked up to municipal collection systems. But the information is there for the taking. It doesn’t depend on persuading people to show up and get tested. 

    The smoking harm reduction parallel? Technology innovations can also help advance public health goals for nicotine products using the less malodorous but equally free-flowing data streams of search engines and social media. This is information people have already provided, with no need to persuade them to fill out surveys or file a report. We can systematically search those streams to look for evidence of product adverse experiences or youth misuse of tobacco products or to hunt for and counteract nicotine misinformation.

    I found a guide to some of these new methods in sociologist Navin Kumar, a postdoctoral associate at the Yale School of Medicine. He uses techniques like social computing, machine learning and natural language analysis to promote health, including tobacco harm reduction.

    Countering Misinformation

    Kumar’s research group has done several studies looking at how new technologies can identify and potentially counter health misinformation. As an example of how to study web-based narratives in tobacco control, the researchers tackled two controversial areas at once by mapping how misinformation spread about vaping (especially CBD from cannabis) to help treat Covid-19. This included collecting vaping-related text fragments from a wide range of web sources, including health provider forums, news articles and blogs as well as social media. They also generated word clouds (a fun and intuitive way to depict the most-used words) to see how the use of key terms changed before and after Covid-19 was reported to the World Health Organization. The results showed a shift from words related to vaping bans to positive mentions of CBD and CBD oil.

    There are many challenges in applying these techniques to counter nicotine misinformation. For a start, we need to understand how people talk about nicotine products in online conversations as opposed to formal news reports. A study by Kumar and colleagues analyzed the framing of vaping in social media and how words used to describe vaping and their meanings shifted over time. In earlier years, “happy” and “wonderful” were among the most frequent words associated with vaping. From 2017 on, these gave way to words like “ban,” “lung” and “teen.” The study vividly illustrates (with those wonderful word clouds) the social media shift from seeing vaping as an alternative to cigarettes to viewing vaping as about harm and regulation like the news media did.

    Another problem: It turns out it’s easier to get people to buy into twaddle than to stop them from doing so. Said Kumar, “People tend to believe new misinformation; it’s harder to remove misinformation such as ‘vaccines have microchips.’” One of Kumar’s recent studies was a randomized controlled trial to try to counter tobacco product misinformation. Results were promising, but the challenge is huge. How can a metaphorical cupful of accurate information received in a study counter the buckets of misinformation people get on a daily basis?

    That’s why researchers such as Kumar are working on automated ways to detect misinformation on social media using machine learning. If responsible parties can detect the latest mutation in tobacco product misinformation as it emerges, “They could respond before it has a chance to take hold. And go to Facebook and other outlets to counteract it,” said Kumar.

    New technologies, such as social computing, machine learning and natural language analysis, may help counter online misinformation about nicotine products. (Photo: Jo Panuwat D)

    Adverse Experiences 

    The goals of reporting are to identify safety risks, to share lessons learned so our mistakes are new instead of repeats of the past and to raise the cost to potential bad actors of disregarding customer safety. The U.S. Food and Drug Administration’s Center for Tobacco Products takes voluntary reports from anyone—including product users, researchers and health professionals—about “adverse experiences.” You can report a tobacco product concern through the FDA’s central safety reporting portal at www.safetyreporting.hhs.gov, which also takes reports about marketed human and animal drugs and biologics, foods and dietary supplements.

    Traditional ways of reporting adverse experiences to the FDA leave a lot to be desired. Since the system is primarily voluntary, a busy human must find the time and motivation to report the problem. Under-reporting is assumed, but no one knows by how much or how reporting may differ by product, user or symptom type. Important details may be left out of the report, making it hard to spot patterns (or creating misleading patterns as in the case of e-cigarette or vaping use-associated lung injury (EVALI)). Reporting can also be biased by things like news reports and litigation. The blossoming variety of reduced-harm nicotine products further complicates finding and addressing safety issues when market shares are small and issues are infrequent.

    If your company’s tobacco product gets a premarket tobacco product application (PMTA) marketing granted order from the FDA, postmarket reporting of adverse experiences is required as part of the deal. “Serious and unexpected” adverse experiences that companies are told about or discover must be reported through that FDA portal within 15 days. The FDA may also require other postmarket reporting to stay comfortable with keeping a new tobacco product on the market. It’s in your interest to avoid surprises.

    This approach is still untested for tobacco products, but publications are proliferating using these methods. I ran across articles that used machine learning and natural language processing to monitor for adverse effects of Covid-19 vaccines on Twitter and for health risks from the mood-altering plant kratom on Reddit and Twitter.

    As with our example of using wastewater to predict Covid-19 spread, Kumar notes that multiple data sources better predict outcomes. “So you can use reports on Twitter combined with YouTube and [the] news to predict adverse experiences,” he said. Look to computer science publications for the latest publications on nicotine products; they aren’t caught up in the tobacco harm reduction battles now raging in many public health journals.

    How do These Tech Innovations Look to Public Health Authorities?

    Are these promising innovations likely to percolate through into accepted practice? Will regulators look upon creative high-tech approaches with favor or scorn? To look for clues, I searched the abstracts (summaries) of studies accepted for the March 2022 meeting of the Society for Research on Nicotine and Tobacco (SRNT). (SRNT is not, at present, an industry-friendly organization and, therefore, is a useful gauge of sentiment among academics and regulators.) Over two dozen studies involved using social media data for research, most simply to gather information and look for patterns. Some involved lifting data from Reddit, Twitter or Instagram about descriptions or perceptions of particular tobacco products then using conventional qualitative methods (coding by human readers) to explore topics and feelings. Others used social network analysis to understand how information about products or policies spread. 

    Two studies supported the possibility of collecting adverse experiences through social media. One coded mentions of positive and negative health outcomes from vaping found on Twitter and Reddit. Another studied videos posted to the TikTok app (with hashtag #nicsick).

    One study combined old and new methods by using an age detection algorithm with Reddit metadata to sort posted comments on vaping and then hand-reviewing the most popular posts by each age group. A nicotine product company could potentially use an age detection algorithm to show regulators that their social media accounts don’t attract youth.

    Wearable sensors were used to detect smoking behavior as part of a smartphone-delivered smoking cessation program. Behavior studies documenting the transition from smoking to vaping might benefit from including wearable technologies. We might find, for example, that people who’ve completely transitioned to vaping have better sleep quality.

    New technologies bring new potential but also novel problems. For example, social media has been hailed as a new cost-effective, efficient way to recruit subjects for research, especially hard-to-find subgroups. My research team did have some success recently using social media platforms, such as Facebook, to locate a particular “vulnerable population” for PMTA behavioral studies. However, it also attracted responses from scammers, automated survey bots and professional survey takers, which took a lot of time and creativity to block or identify and remove.

     

    Cheryl K. Olson is a California-based public health researcher who specializes in behavioral health issues and consults on tobacco product behaviors via McKinney Regulatory Science Associates. She spent 15 years on the faculty of Harvard Medical School.

    Forewarned is Forearmed

    Derek Yach

    One example of using these advanced techniques to find early signals of both misinformation and potential health concerns is an e-cigarette or vaping use-associated lung injury (EVALI) monitoring and alerting platform developed by Skai (formerly Signals Analytics) for the Foundation for a Smoke-Free World.

    As a proof of concept, the platform retrospectively analyzed and compared vaping-related content from social media and news sources. In social media comments about specific symptoms and vape ingredients, Skai’s platform spotted signals of the direct link between seizures and vaping synthetic CBD nearly a year before official reports appeared. This kind of early information, while not definitive, would allow public health authorities and the industry to respond quickly to prevent harm and provide corrective facts in appropriate language.

    Disinformation on social media, from naive misunderstandings to deliberate manipulations, will be a fact of life for years to come. Taking advantage of these analytical techniques allows the industry to demonstrate socially responsible leadership in advancing public health. Why be blindsided by EVALI’s inevitable successor when there are tools to detect and respond to it? –Derek Yach

    *https://skai.io/reports-and-whitepapers/early-detection-of-pandemics-and-outbreaks/?msclkid=4ac806b7a95011ecb5d22adb0bd2b48e

  • Watch Your Mouth

    Watch Your Mouth

    Image: martialred

    What the industry can’t (and could) say about harm reduction

    By Cheryl K. Olson

    Surveys show that the public perceives nicotine as the devil behind most of the cancer and heart disease caused by smoking. E-cigarettes and nicotine-replacement therapies alike are misperceived as relatively risky by many smokers. Even physicians are likely to believe nicotine is dangerous. The now entrenched view of nicotine as public health villain is the predictable result of years of emotion-based anti-vaping campaigns from government and advocacy groups and a steady drip of media reports on the latest perceived danger or deception from the nicotine industry. This includes coverage of the e-cigarette or vaping use-associated lung injury crisis that wrongly linked deaths from THC vaping to nicotine vapes.

    The hundreds of thousands of deaths from smoking take place out of sight; they’re old news, not worth mentioning. When I was a public health graduate student in the 1990s, there was much conversation about how to make those deaths newsworthy. Advocacy groups looked for vivid imagery and metaphors to make their case: Hey, deaths from smoking are like a jumbo jet crashing in flames every day! Those deaths are still happening; the campaigns are not.

    The Real Cost media campaign, run by the U.S. Food and Drug Administration since 2014, now targets vaping instead of smoking. Creativity in advertising is now focused on fanciful brain worms and similarly unsupported high-fear imagery.

    Over drinks at the 2021 London GTNF meeting, I heard conversations bemoaning the passing of those government antismoking efforts and wondering how the FDA or Centers for Disease Control (CDC) could be persuaded to target nicotine misperceptions. In the “before times” (pre-FDA regulation and pre-Tobacco Control Act of 2009), as an academic who consulted to the industry, I headed a multi-year stop-smoking campaign funded by Philip Morris USA. QuitAssist was created to expand upon and encourage the use of existing smoking cessation materials from government and nonprofit organizations. This naturally made me wonder whether, even in this changed regulatory environment, the industry could find a way to pick up the dropped baton and lead a new communications effort.

    What stops nicotine product companies from pushing back against this tide of misinformation and misperceptions? You’d think there would be a strong incentive for companies to educate the public. After all, if everyone believes that the health danger in cigarettes comes from the nicotine instead of the byproducts of combustion, why would smokers who can’t or won’t quit even consider switching to vastly less dangerous alternative nicotine products?

    Since the GTNF meeting, I’ve talked with people from legacy and upstart nicotine product companies working with these issues from various corporate communications, regulatory and legal angles to try to understand the “carrots and sticks” that shape how the industry responds.

    Companies reflexively blame the FDA regulations for their inaction. This has merit. To prevent new outbreaks of old Big Tobacco deceptive practices, the wording of the law can block companies from speaking obvious truths. But there are also surprising hidden disincentives to educate the public about nicotine. Will it upset shareholders? Will it upset regulators? Is it worth the money? Will it create litigation risk?

    What makes nicotine product makers watch their mouths when it comes to public education? It’s complicated. If we envision the forces blocking industry communication as an iceberg, let’s start with the visible tip: what the law says that you can’t say.

    The Rules

    The most commonly cited roadblock to correcting misperceptions about nicotine harm reduction is Section 911 of the Family Smoking Prevention and Tobacco Control Act of 2009.

    Without a specific modified-risk claim pre-authorized by the FDA, a product’s label or advertising can’t state or imply it carries lower risk of disease or harm than another commercially marketed tobacco product. That’s pretty straightforward. But what’s next is not: you can’t even say the product “or its smoke contains a reduced level of a substance or presents a reduced exposure of a substance” or that the product “does not contain or is free of a substance” even when those statements are empirically true.

    Based on this language, a company could not repeat facts from published research. It could not share the grudging admission from the CDC’s website that “E-cigarette aerosol generally contains fewer toxic chemicals than the deadly mix of 7,000 chemicals in smoke from regular cigarettes.”

    This seemingly outrageous restriction on factual speech should be understood in historical context. The Act initially only covered cigarettes, cigarette tobacco, roll-your-own tobacco and traditional smokeless tobacco. With the language about advertising and communications, its authors were thinking about “light” cigarettes and similarly implied health claims that were misleading or taken out of context—not novel nicotine products that might be truly and even massively less risky. The FDA was empowered to issue regulations deeming other tobacco products to be covered by the Act, adding e-cigarettes in 2016.

    The Risk/Benefit Calculation

    Now, let’s look at the larger underwater part of that iceberg: the less visible factors that block companies from taking action.

    Shareholders. Legacy tobacco companies like to focus publicly on their novel nicotine products and the transition away from combustibles. But there’s no denying that traditional tobacco products, especially cigarettes, are where the money is. Shareholders expect companies to act conservatively when it comes to their primary source of income. And some of the profits from combustibles support the massive R&D costs of transitioning to less dangerous products. However desirable the transition to the future world of reduced consumer harm and reduced litigation risk … as one person told me, it’s a good ESG (environmental, social and governance) story, but the incentives aren’t there.

    Litigation risk. Despite the 1998 Master Settlement Agreement and FDA regulation, multinational tobacco companies remain in near-constant litigation on the cigarette front. Today’s tobacco industry is stuck with the legacy of decades of bad behavior; every action is scrutinized for intent to addict and harm fresh generations of users. So, an attempt to partner with a physician for public education conjures up images of 1930s Lucky Strike ads with smiling white-coated pitchmen. And as one insider explained, it becomes a cost to the business if it gets interpreted in court as evidence of further bad acting.

    Cost. Section 911 of the Tobacco Control Act does allow the option of seeking authorization through the modified-risk tobacco product (MRTP) pathway to make a modified-risk claim. In 2019, Swedish Match was first to earn this status, allowing claims of lower risk of mouth cancer and five other ills if used instead of cigarettes to appear on eight General Snus products.

    Unlike Europe, which takes a category approach to regulation, the U.S. regulates products one by one, even for very similar products with low youth use, such as vaping liquids. One person estimated that the cost of research to support an MRTP claim would be equivalent to what their company spent to support that product’s PMTA for marketing authorization: millions of dollars for claims that may not even be relevant or understandable to the average smoker.

    Regulator pushback. Especially in the current regulatory environment of low trust, confusing guidance, pending legal cases and thousands of products in regulatory limbo, few companies want to risk further antagonizing the FDA. When I raised hypotheticals of education efforts that could be undertaken by nicotine product makers, I heard stories of wonderful might-have-been campaigns nixed by lawyers. A collaboration between the industry and respected researchers and their university, based on extensive focus group testing with smokers? Add a catchy slogan and creative messaging plus incentives and prizes to encourage smokers to try reduced-risk products and to stay off cigarettes? The FDA is lukewarm on the plan. Big Tobacco dollars that could have supported a huge smoking cessation effort go unspent.

    The Right Audience and the Best Messenger

    A final concern among industry insiders is a frank understanding of their own lack of credibility. Does it make sense to spend money on messages that won’t be believed? They point to research showing that government agencies and health professionals are the most trusted sources of information.

    It’s noteworthy that recent research suggests that government agencies are less trusted by groups that disproportionately suffer from smoking, such as racial/ethnic minorities and lower income persons. And the FDA’s actions speak loudly: When smokers see their favorite vaping products removed from websites or store shelves while very low-nicotine cigarettes are authorized, what message does that send to consumers?

    The industry’s best hope for correcting nicotine misperceptions likely comes from indirect public education, through health professionals and consumer advocacy organizations. But industry folks might also consider how to educate regulators, who may not know many or even any smokers, about the realities of their lives and needs.

    Cheryl K. Olson is a California-based public health researcher who specializes in behavioral health issues and consults on tobacco product behaviors via McKinney Regulatory Science Associates. She spent 15 years on the faculty of Harvard Medical School.
  • Appropriate for the Protection of Health?

    Appropriate for the Protection of Health?

    Photo: 22nd Century Group

    The FDA’s focus on nicotine is coming at the expense of true harm reduction.

    Cheryl K. Olson

    I was gobsmacked last December when the U.S. Food and Drug Administration issued modified-risk tobacco product (MRTP) authorizations for two reduced-nicotine combustible cigarettes, 22nd Century Group’s VLN King and VLN Menthol King. Both contain non-GMO tobacco that’s very low in nicotine (VLN). If 22nd Century Group can reduce the disastrous health effects of smoking by offering low-nicotine combustible cigarettes, that’s great. What took me aback was the implicit message from the FDA on its priorities.

    VLN products such as these were supposed to be part of a smoking harm reduction landscape—one that includes approaches proven to reduce the risks of illness and death among cigarette smokers, such as vaping, heat-not-burn and smokeless tobacco. But this ideal, data-driven society in which addicted smokers bob gently down the famous continuum of risk via the path they prefer (perhaps starting with VLN cigarettes, perhaps with another product and ultimately landing at their low-risk nicotine maintenance or tobacco-free destiny) isn’t where we’re living.

    Such a Candide-like world would feature a rainbow of reduced-risk products that match the needs of individual smokers and smokers and people who influence them (such as doctors) fully aware of these products and of how and why they’re lower risk. They’d also know that traditional approaches to quitting (hello, “cold turkey” and nicotine-replacement therapy) have proved depressingly ineffective, especially among heavily addicted, low-income, longtime smokers: the folks who need our help the most.

    The FDA claimed to envision such an environment when Scott Gottlieb, then the agency’s commissioner, stated in 2017 that “Nicotine lives at the core of both the problem and, ultimately, the solution to the question of addiction and the harm caused by combustible forms of tobacco. … So, how can we take a new and comprehensive approach to nicotine?”

    Gottlieb continued, “Armed with the recognition of the risk continuum, and the reality that all roads lead back to cigarettes as the primary cause of the current problem, we need to envision a world where cigarettes lose their addictive potential through reduced nicotine levels. And a world where less harmful alternative forms, efficiently delivering satisfying levels of nicotine, are available for those adults who need or want them.”

    Instead, the FDA prioritized very low-nicotine cigarettes and dropped the ball on that last, essential part: the “less harmful alternative forms.” Those products, despite considerable and growing scientific evidence of their real-world effectiveness, have been left in limbo.

    A Passing Grade on the Wrong Test

    What exactly happened? An MRTP is simply a request to the FDA that a tobacco-related company be allowed to make some specified changes in how it describes a product or set of products to the general public through its packaging, marketing, advertising and other forms of promotion and communication.

    In this case, 22nd Century Group wanted to state that each of its products contains “95 percent less nicotine,” “helps reduce your nicotine consumption” and “VLN smells, burns and tastes like a conventional cigarette but greatly reduces your nicotine consumption.” They provided the scientific evidence to back up those claims.

    Among the hurdles for a successful MRTP authorization is that the manufacturer demonstrates that the product is “appropriate for the protection of the public health,” or APPH. In other words, that the requested modifications do or have the potential to do more good than harm if approved. That’s a core question that needs to be addressed in any tobacco-related application or authorization request to the FDA.

    The Tobacco Control Act of 2009 begins with the words, “To protect the public health ….” That shows the clear focus and intent of the legislation. While the phrase “appropriate for the protection of the public health” appears several times in the act, it’s frustratingly vague and subject to interpretation.

    What’s clear, however, is that the FDA should prioritize those aspects of smoking that are the most harmful to individual and public health. While reducing nicotine intake is appropriate for the protection of the public health, it should be nowhere near the top of the list.

    It’s Not the Nicotine That Kills

    Morbidity and mortality among smokers, including cancers and heart disease, are caused by the “tars” and other byproducts of combustion—what researchers often call harmful and potentially harmful constituents (HPHC). Because it’s addictive, nicotine is also considered an HPHC. As Michael Russell famously put it, “People smoke for the nicotine, but they die from the tar.”1

    In its February 2020 presentation on its products to an FDA Tobacco Products Scientific Advisory Committee panel, 22nd Century Group clearly states, “VLN cigarettes yield essentially the same HPHCs as conventional cigarettes. The benefits of VLN accrue from reduced cigarettes per day and reduced abuse liability.” That’s consistent with their authorization request since they’re only claiming a reduction in the amount of nicotine.

    Think about that for a moment. The premise that reduced nicotine in combustible cigarettes will reduce harm is based on an assumption that the number of cigarettes smoked will decrease. That’s because the other HPHCs—the substances that lead to illness and death—are the same in the very low-nicotine and the regular cigarettes. Will they?

    Compensatory Smoking

    Maybe. Maybe not. It’s an empirical question that requires research with these specific products. Researchers studying smokers who switched to earlier generations of low tar and low nicotine cigarettes, known as low-yield cigarettes, found that many engaged in what’s known as compensatory smoking.

    According to the Centers for Disease Control, “Most people who smoke are addicted to nicotine. They may compensate when smoking low-yield cigarettes in order to take in more nicotine.”5

    A historical review of tobacco industry approaches to marketing low-yield cigarettes concluded, “Unfortunately for the industry, smokers did not care much for the taste of reduced tar cigarettes and, as expected, the lower nicotine levels became a problem as well. Smokers were not receiving the same nicotine ‘satisfaction’ and therefore began to compensate for the reduction in nicotine by smoking more cigarettes, thus increasing their health risk.”2

    These earlier studies were conducted on combustible cigarettes with significantly higher levels of nicotine than the VLN products. Some well-respected smoking harm reduction experts such as Clive Bates theorize that the nicotine levels in this generation of cigarettes is so low that compensatory smoking will not be a problem. But how, then, is this different from the low success cold turkey approach? Also, what about dual use? There is nothing to prevent a smoker from using both types of products.

    What’s the Real Harm?

    But this distracts from the fundamental problem. The FDA’s focus is on the wrong chemical: nicotine. It’s often the first or only chemical most people can name when describing tobacco. That’s one of the reasons why the addictive quality of nicotine is so often conflated with combustible tobacco’s relationship with heart disease and cancer.

    Several studies of physicians’ knowledge about the clinical effects of nicotine find misperceptions are frustratingly common. Roughly four out of five doctors surveyed incorrectly linked nicotine to cardiovascular disease (83.2 percent), chronic obstructive pulmonary disease (80.9 percent) and cancer (80.5 percent).9 They should know better.

    This distortion of the role of nicotine among smokers, and some of the people who counsel them when they try to quit or at least reduce their medical risk, can interfere with their motivation to use some of the proven pathways away from combusted tobacco.

    This focus on nicotine reduction and the misunderstanding of its risks may be precluding addicted smokers from switching to products that significantly reduce harm. According to Public Health England, “One assessment of the published data on emissions from cigarettes and e-cigarettes calculated the lifetime cancer risks. It concluded that the cancer potencies of e-cigarettes were largely under 0.5 percent of the risk of smoking. Comparative risks of cardiovascular disease and lung disease have not been quantified but are likely to be also substantially below the risks of smoking. Among e-cigarette users, two studies of biomarker data for acrolein, a potent respiratory irritant, found levels consistent with nonsmoking levels.”

    My frustration is that the FDA, through its priorities and recent actions, is inadvertently reinforcing misinformation that interferes with the goal of protecting the public health by focusing on nicotine reduction at the expense of true harm reduction.

    Last year, I interviewed former industry scientist Justine Shaw Jackson for another Tobacco Reporter column; she spoke of the need to give people nicotine “without all the nasties in the smoke.” That phrase stuck in my head, creating a mashup of her words and Russell’s insight: “It’s not the nicotine that kills—it’s the nasties in the smoke.” Let’s embroider that phrase on pillows and send one to every doctor and nurse in the world.                

    Cheryl K. Olson is a California-based public health researcher who specializes in behavioral health issues and consults on tobacco product behaviors. She spent 15 years on the faculty of Harvard Medical School.
  • Who D’Ya Think You Are?

    Who D’Ya Think You Are?

    Photo: EwaStudio

    Your business from the regulators’ perspectives

    Willie McKinney and Cheryl K. Olson

    Let’s do a thought experiment. Imagine—some of this may sound familiar—that you’re one of two brilliant young graduate students attending a university in the middle of Silicon Valley. You come up with a jewel of an idea for a product that could help cigarette smokers reduce their mortality and morbidity by delivering nicotine with far fewer health-destroying byproducts of combustion than traditional cigarettes.

    The business environment around you is laced with artificial intelligence, self-driving cars and apps that brashly take on entire industries. The ethos of your fellow entrepreneurs is to challenge everything, smash things when they get in your way and loudly proclaim that you’re changing the world for the better. You can always correct your mistakes later.

    What business are you in? To your eyes, you’re in the smoking cessation business. That is, after all, your stated goal and the purpose of the device you’ve designed. It’s a noble cause that could save millions of lives while making your investors and you a fortune. You’ve hit that ideal of doing good while doing well. What could possibly go wrong?

    A lot, it turns out. Predicting those potential disasters requires that you know whether you perceive the fundamentals of your business the way that others—especially government regulators—perceive it. In our not-really-hypothetical example, the protagonists saw themselves as fighting Big Tobacco. They approached marketing their product as if it were a kind of ride share or housing share offering, industries in which regulations are both few and local. They were making consumer goods, so they mostly hired executives from packaged goods industries little acquainted with addictive ingredients or tobacco industry history. 

    The U.S. Food and Drug Administration viewed your imagined company through a different lens. To the government (and soon the press and the general public), you were simply an extension of Big Tobacco. Your Silicon Valley brashness backfired, triggering memories of industry lies about the addictiveness of nicotine and cynical attempts at youth smoking prevention by tobacco companies. A hero’s journey became a cautionary tale.

    Can this still happen today? Can the lens through which you view your company be dramatically different from the perspective taken by government regulators? Unfortunately, we see it all the time.

    A Tale of Two Companies

    Josh Israel started Hale Therapeutics with a co-founder who lost a family member to smoking combustible cigarettes. His device is programmed to deliver and taper off heated, aerosolized nicotine as a way of ending the addiction.

    “It minimizes the discomfort of nicotine withdrawal while you learn to live a smoke-free life,” said Israel.

    Hale approached the FDA’s Center for Drug Evaluation and Research (CDER) to open discussions toward approval of what Israel viewed as an innovative pharmaceutical delivery system for a much-studied drug. That may sound like a strange approach to take. Why not pursue a marketing authorization from the FDA’s Center for Tobacco Products (CTP)? That would be faster and likely to succeed. CTP had already authorized VUSE, calling that ENDS device’s aerosol “significantly less toxic than combusted cigarettes.”

    “We’re not a tobacco product. So we don’t want to be licensed as a tobacco product, and we don’t want to be looked at as a tobacco product,” Israel continued. “It’s a smoking cessation product. Why would we be classified as anything else?”

    The FDA saw things differently. New CDER guidance on testing “inhaled nicotine-containing drug products” focuses on the word “heated,” and the “novel chemicals” that heat might generate. CDER may have viewed Hale’s device as akin to an e-cigarette because it heats. This difference in perceptions led CDER to point Hale toward spending a substantial chunk of time and money on animal studies that would not have been required had Hale gone down the CTP path for permission to market the same device. (And run counter to FDA pledges and initiatives to reduce use of animals in research.)

    Meanwhile, Brian Quigley, the COO of Respira Technologies, was preparing to meet with CDER about his product, a nebulizer for use as a nicotine-replacement therapy. It creates and controls an unheated nicotine aerosol.

    “It’s kind of shocking to think that in 2021, the number one way that smokers try to quit is cold turkey,” said Quigley.

    Unlike Hale’s experience, CDER apparently viewed Respira’s product much as the company did. The fact that the nicotine was unheated worked to Respira’s advantage. CDER was more comfortable allowing the data to guide what preclinical studies Respira’s product will need. Quigley expects to submit an Investigational New Drug application to CDER in 2022.

    Hale Therapeutics, however, faced a potentially costly choice. It could fight CDER. It could devote time and capital to research that it contends is unnecessary. It could switch paths, reluctantly accept the perception that it was making a tobacco product, and apply to CTP. After much deliberation, Josh Israel decided to … do something different. Hale would keep talking with the FDA about reducing the testing burden but would take action to forward its mission elsewhere.

    Hale went to the U.K. and applied for a license from its Medicines and Healthcare products Regulatory Agency (MHRA) as a smoking cessation device.

    “The goal for any public health agency should be to get people off combustible cigarettes, full stop,” said Israel. “We were embraced by the MHRA. And it’s unfortunate that the FDA is not taking the same approach.”

    What is that approach? The MHRA is developing a licensing process by which e-cigarettes could be prescribed by the National Health Service in England as a medical product for smokers who wish to quit smoking. It would be the first country in the world to do so.

    There are about 6.1 million smokers in England, with rates of smoking roughly inversely correlated with socioeconomic status. That means that smokers generally are at greater risk for a variety of other health and social problems, making smoking cessation especially impactful. For several years, e-cigarettes have been promoted by the governmental to combustible cigarette smokers as an effective way of both reducing immediate harm and putting those smokers on a path to quitting nicotine completely.

    “The MHRA evaluation program for e-cigarettes is focused on nicotine delivery—not cessation per se—as a measure of efficacy, and with as few harmful and potentially harmful constituents as possible,” said Ian Fearon, a U.K.-based clinical research scientist who consults on nicotine and tobacco product studies. “It appears easier to obtain a medical license with MHRA than a market authorization from the Center for Tobacco Products, given the volumes of data required to support a PMTA.”

    A Difference in Politics and Philosophies

    One reason why there may be such a difference is that regulators reflect and illuminate the values and experiences of the countries they regulate. When CDER issued its guidance for inhaled nicotine-containing drugs in October 2020, the public perception of vaping in the U.S. had hit new lows.

    San Francisco had recently banned the sale of all e-cigarettes within the city limits, ironically using a supposedly pro-health agenda to push an unknown number of former smokers who were using vaping to quit back to using combustible cigarettes. E-cigarette or vaping use-associated lung injury, which had been falsely associated with commercial vaping products, was still in the headlines.

    Not surprisingly, the CDER guidance focuses on what could go wrong. It recommends hunting for potentially toxic “novel chemicals” through years of rodent inhalation studies before testing heated nicotine products in humans.

    The U.K. has never experienced an American-style moral panic over e-cigarettes and youth. This takes a political thumb off the scale in their pragmatic weighing of the science.

    It’s also not surprising that the two FDA centers that regulate nicotine products can be fractious. CDER has been part of the FDA since the 1980s. Its pathways to approval are well entrenched and clearly marked. Its mission is “making sure that safe and effective drugs are available to improve the health of the people of the United States.”

    By contrast, the FDA’s Center for Tobacco Products is a newbie, born from the Tobacco Control Act of 2009. It’s about balancing health risks among different segments of the public. CTP plays by different rules, proclaiming on its website that the “FDA’s traditional ‘safe and effective’ standard for evaluating medical products does not apply to tobacco.” It doesn’t approve products; it permits them to be marketed. Because of its youth, CTP procedures are still forming and solidifying. 

    So, let’s go back to our mind experiment for a moment. Now how do you view the business your company is in?

    Willie McKinney is the founder of McKinney Regulatory Science Advisors. He’s held senior regulatory roles at major tobacco product companies and served for three years as the industry representative on the FDA’s Tobacco Products Scientific Advisory Committee.
    Cheryl K. Olson is a California-based public health researcher who specializes in behavioral health issues and consults on tobacco product behaviors. She spent 15 years on the faculty of Harvard Medical School.
  • Acting Unnaturally

    Acting Unnaturally

    Photo: artefacti

    Synthetic versus tobacco-derived nicotine

    Cheryl K. Olson and Willie McKinney

    Every year, the National Youth Tobacco Survey gathers data from U.S. middle school and high school students about all sorts of nicotine products and how they’re used. In 2021, for the first time the most popular brand of e-cigarette among underage users was a synthetic nicotine vape. Puff Bar was named “usual brand” by 26.1 percent of underage vapers, equaling the sum of the next three most popular brands: Vuse (10.8 percent), Smok (9.6 percent) and Juul (5.7 percent). While the summary of these latest findings in Morbidity and Mortality Weekly Report didn’t mention the word “synthetic,” the U.S. Food and Drug Administration certainly took note.

    One reason the FDA pricked up its ears is that synthetic nicotine, also known as nontobacco nicotine, lives in a legal gray area. The Family Smoking Prevention and Tobacco Control Act of 2009 expanded the FDA’s authority to regulate products “made or derived from tobacco” and created its Center for Tobacco Products.

    This begs the question of whether the FDA has regulatory authority over synthetic nicotine. Predictably, manufacturers who use it in ENDS products claim that the FDA does not have that authority. If that’s true, those manufacturers can bypass the lengthy and expensive premarket tobacco product application process and go directly to market. But there are others, including attorneys who’ve studied this law, who believe that even if synthetic nicotine is technically not covered by the 2009 Tobacco Control Act, it meets the definition of a drug and is therefore subject to FDA regulation.

    The substitution of synthetic nicotine for tobacco-derived nicotine has profound implications both for manufacturers and distributors of reduced-harm nicotine products. Is it a smart workaround, a temporary shelter or a costly dead end? Here are some of the key issues as well as ways to limit your risk as a company.

    The Options

    Over the past few months, many makers of flavored e-cigarette products have received marketing denial orders (MDOs) or fear receiving one. An MDO gives that manufacturer a limited number of choices: reapply for approval, get out of the business or sue the FDA for redress—or search for what it hopes is a legal loophole to the FDA’s regulatory authority. Hence, the move to synthetic nicotine as a too clever by half solution that carries with it underlying scientific, economic, legal and ethical issues.

    Let’s start with an economic issue, which may trump all the others. Synthetic nicotine is expensive. In fact, it’s up to 10 times the cost of tobacco-derived nicotine, according to Kevin Burd, CEO of North America Nicotine. One reason is that tobacco-derived nicotine is made from leftover scraps from processing tobacco leaves—often literally the stuff left on the factory floor. Synthetic nicotine, most of which is manufactured in China, is created through a variety of proprietary chemical processes.

    “As volumes increase, I can’t see the price of chemicals used in synthetic coming down to the price of waste tobacco, including dust,” said Burd. “It’s highly unlikely ever to be competitive.”

    Both synthetic nicotine and tobacco-derived nicotine occur in two structural forms (enantiomers) known as R-nicotine and S-nicotine. More than 99 percent of the nicotine in tobacco is S-nicotine. In synthetic nicotine, that balance can be 50-50.

    “Little is known about the pharmacological and metabolic effects of R-nicotine in humans,” says a 2021 article on the rise of synthetic nicotine  in Tobacco Control (Jordt SE. Synthetic nicotine has arrived. Tobacco Control 2021. doi: 10.1136/tobaccocontrol-2021-056626). In other words, synthetic product users could be unwitting research subjects. There are inexpensive tests for distinguishing between R- and S- forms of the chemical and ways of separating the R-isomer from the S-isomer. By comparison, telling the difference between synthetic S-nicotine and tobacco-derived S-nicotine can be quite costly.

    This leads to an interesting paradox. We don’t know how much of the supposed synthetic nicotine is actually tobacco-derived nicotine. There’s a financial incentive for a manufacturer simply to replace the more expensive version with the cheaper chemical and mislabel it. In fact, on its website, Next Generation Labs warns prospective customers, “There are several companies from China claiming to have synthetic nicotine. NGL has tested several of these products and discovered they are made or derived from tobacco.”

    Burd adds, “Quite likely, many [products that claim to be synthetic] are not really synthetic.”

    Some companies are weighing the cost of regulatory compliance versus the higher manufacturing cost of using synthetic nicotine. That’s a false choice, for it underestimates the costs of unknown safety risks, product testing and emerging regulations. Simply marketing a new synthetic nicotine product without providing the necessary scientific and behavioral research data to the FDA will, at the very least, generate a warning letter.

    Remember that the key reason for generating research data on a new product is to explore whether it will harm people. The FDA uses the term APPH (appropriate for the protection of public health). Not doing so puts your business at risk not only from regulatory actions but from civil litigation if someone gets hurt.

    A regulatory update by FDA Center for Tobacco Products Director Mitch Zeller at an Oct. 27 Food and Drug Law Institute conference addressed the challenge posed by synthetic nicotine. Zeller’s slide deck makes clear his belief that e-liquids that do not contain tobacco-derived substances “may still be components or parts of tobacco products and, therefore, subject to FDA’s tobacco control authorities.” It also states that the FDA is “in discussions with Congress about a potential legislative fix.”

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    The Wild West

    Burd expressed concern that synthetic nicotine, and the regulatory uncertainty driving its use, have put the vaping industry “back to the Wild West.” Even the pure S synthetic may contain residues from the unknown solvents that some new manufacturers use. Burd recommends that manufacturers who use synthetic nicotine “test their incoming material (emphasizing impurities and solvents), audit the supplier, do a toxicology review for product safety and be sure to use S-nicotine only.”

    That type of analysis is impractical for end users, of course.

    Finally, there’s the issue of whether a company is a “bad actor” that focuses on short-term financial profits at the expense of both public health and the lives of their customers. The FDA runs the risk of encouraging such unethical behaviors if it broadly bans products from those companies making sincere efforts to reduce the harm done to smokers of combustible cigarettes while ignoring companies that look for legal loopholes.

    A Marketing Throwback?

    The issue of synthetic nicotine regulation is likely to be resolved fairly soon. One reason is that the attractiveness of e-cigarettes to youth is rightfully a major concern of the FDA. Marketing materials for synthetic nicotine products have the tone of advertising done by an earlier iteration of Big Tobacco when it claimed that paper filters, toasting and other irrelevant variables reduced cigarettes’ negative health effects.

    • American Tobacco Company (1930): “20,679 physicians say Luckies are less irritating. Toasting removes dangerous irritants.”
    • Liggett & Myers (1931): “Chesterfield Cigarettes are just as pure as the water you drink.”
    • Brown and Williamson (1949): “Viceroys filter the smoke. As your dentist, I’d recommend Viceroys.”
    • Puff Bar (2021): “Our nicotine products are crafted from a patented manufacturing process, not from tobacco. The result? A virtually tasteless, odorless nicotine without the residual impurities of tobacco-derived nicotine.”
    • Next Generation Labs (2021): “TFN Nicotine is not derived from tobacco leaf, stem, reconstituted sheet, expanded or postproduction waste dust. The nicotine is made using a patented manufacturing process that begins with a natural starter material and progressively builds around the molecules of that material to create a pure synthetic nicotine.”

    These claims (from company websites) about differences between synthetic and tobacco-derived nicotine misleadingly hint at safety without providing real data. They skirt the important scientific issues and focus on emotionally resonant phrases like “begins with a natural starter material,” “without the residual impurities” and “create a pure synthetic nicotine.”

    Adolescents in particular may make the false inferential leap that synthetic nicotine somehow carries less risk or is less addictive than tobacco-derived nicotine, according to new research from Rutgers University and the National Institutes of Health. This, in turn, may lead nonsmoking, nonvaping teens to use the products often enough to become addicted. The risk of any new product to children is a tried-and-true political plank, so it’s likely to gain the attention of members of Congress, who could pass a law declaring all forms of nicotine to be under the purview of the FDA. —WMK and CKO

    Willie McKinney is the founder of McKinney Regulatory Science Advisors. He’s held senior regulatory roles at major tobacco product companies and served for three years as the industry representative on the FDA’s Tobacco Products Scientific Advisory Committee.
    Cheryl K. Olson is a California-based public health researcher who specializes in behavioral health issues and consults on tobacco product behaviors. She spent 15 years on the faculty of Harvard Medical School.