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  • The Need for Nuance

    The Need for Nuance

    Photo: Andrey Popov

    It’s time for regulators to stop lumping all tobacco products together as being equally risky.

    By George Gay

    “It’s still difficult for me to understand how the European Commission can claim on the one hand that they want to do everything in their power to fight cancer, including revising tobacco policy, yet on the other hand completely reject the idea of liberalizing regulations for one of the very few products that has shown it can displace cigarettes.”

    The above is a quote attributed to the Swedish member of the European Parliament, Sara Skyttedal, as part of a Snusforumet story published on Nov. 19. Skyttedal is clearly frustrated and angry with the commission, and, according to my interpretation of the story, her frustration comes down in part to the fact that while the commission says it wants to reduce the incidence of smoking throughout the EU to the low level at which it stands in Sweden, it is not willing to remove the ban on snus, the product that has largely displaced cigarettes in Sweden but that, for inexplicable reasons, is banned in the EU with the exception of Sweden.

    I feel certain Skyttedal is merely making a point: She doesn’t really believe there is a logical conflict in the commission’s position. The apparent conflict is easily resolved by pointing out that while the commission might say it wants to do everything in its power to fight cancer, that is not the case. In fact, this becomes clear later in the story when, talking about the connection between Sweden’s low level of tobacco-related cancers relative to those in the rest of the EU and the fact that Sweden is the only country in the EU where snus is legally available, Skyttedal says the commission sees the connection but is not willing to act on it.

    I hate to state the obvious, but I would guess that one of the commission’s hang-ups has to do with tobacco. It can tolerate the idea that nicotine in the form of nicotine-replacement therapy products or even vaping products should be allowed to replace tobacco products, but it cannot bear the idea that tobacco products might be allowed to substitute tobacco products. Tobacco has pariah status; nicotine is somewhere lower on the continuum of the unacceptable.

    Let me provide an example. In November, my newspaper ran a story about how, because of the goods transport chaos afflicting the U.K. post-Brexit, there might be a shortage of alcohol this Christmas. This was seen as a negative because, apparently, we cannot celebrate this Christian festival without being off our heads, and despite the fact that such a shortage would probably result in fewer family fights, stomach-pumping hospital visits, drunk driving and all that entails, assaults on hospital accident and emergency staff and even deaths, since alcohol kills.

    Imagine, however, if the story had been about a shortage of tobacco at Christmas. This would have been presented as a positive, though it would have caused a number of negative outcomes and almost no positive results, with the exception that a few people might have discovered they were able to quit their habit.

    Language Matters

    But I digress. Let me return to Skyttedal’s original complaint about the commission’s failure to follow through on its aim to do everything in its power. There are certain categories of phrases that immediately flash warning signs to the effect that what is being said should be taken with a pinch of salt, and one such category comprises those with superlatives. Just think of the phrases “nobody wants to see …” and “everyone agrees that ….” You hear and see such phrases used all the time, but it doesn’t take more than a second’s thought to realize they cannot be correct. It is almost impossible to imagine an instance when nobody or everybody was in favor of something. So when somebody tells you they are doing “everything in their power” to bring about a certain result, you know it’s time to look somewhere else for help.

    Language matters, and, to my way of thinking, one of the problems that people who champion tobacco harm reduction have helped to create is down to the fact that they have been too willing to accept and parrot some of the extreme language and figures used by those people also involved in tobacco control but who are opposed to harm reduction. For instance, there has been a willingness to go along with claims of nicotine addictiveness that are clearly unsupportable, even though some health professionals keep this pot simmering by telling smokers they cannot give up nicotine without the support of … yup, there’s a surprise, health professionals.

    Probably the ultimate superlative is “smoking kills,” which has become so ingrained that you are mocked if you say you don’t agree with it, but the truth of the matter is that a certain percentage of smokers die of smoking-related diseases, mostly after a long and possibly enjoyable history of smoking. The other smokers die of something else—perhaps of injuries caused by a drunk driver. And, I hate to be downbeat, nonsmokers die too, perhaps of “tobacco-related diseases,” though ones caused by pollution. If they didn’t die, the world would become full up, and the gene pool would lose its vigor.

    OK, some will argue the smoking problem is not only about death but about the physical and economic costs of smokers living with medical conditions linked to their habit. But we are all prisoners of the choices we make. I doubt there are many people who reach the age of 50 without carrying some physical ailment linked to something they did when they were young. Some footballers die at relatively young ages having suffered from dementia attributable to their playing football, but few would claim playing football kills. Rather, we try to change the rules of the game and the equipment used to prevent brain damage—we employ harm reduction techniques.

    Perhaps it’s time to reconsider what we mean by “smokeless.” After all, some tobaccos are cured using artificial heat—in some cases by burning wood fuel and contributing to deforestation. (Photo: phanasitti)

    Distortion is a Problem

    On the question of parroting figures, take the annual death toll attributed to tobacco-related diseases. Over the years, it has been increased a number of times, usually in lots of one million, so it now stands at the nicely rounded figure of 8 million. At the same time, the World Health Organization, which has ownership of this figure, has been claiming success in its efforts to prevent the deaths attributed to tobacco. But even given the world’s population has been increasing, it cannot be the case that the figure for tobacco-related deaths keeps leapfrogging this supposed success.

    Why is this important? Because by exaggerating the problems caused by tobacco, some sections of tobacco control have been allowed to distort the picture to such an extent that it becomes difficult to sell the idea of tobacco harm reduction. When tobacco is depicted as being “deadly”—a superlative you often see applied to this product—and that depiction is not challenged, it becomes too counterintuitive even for the uncommitted to imagine that the problem caused by tobacco can be significantly reduced by another tobacco product such as snus. Additionally, because too many people have, for a quiet life, gone along with the U.S. Food and Drug Administration’s airy-fairy idea that e-cigarettes can be “deemed” “tobacco” products, the use of even vaping products as tobacco harm reduction agents can be challenged easily by those who wish to do so.

    What we need is honesty. For instance, we need to stop lumping all combustibles together as if the consumption of cigarettes, cigars or pipe tobacco is equally risky. This cannot be the case, especially at a population level. And we have to do the same in respect of smokeless products. For instance, what do we mean by “smokeless”? Are we talking only of the consumption of the final product? Perhaps it’s time we checked out whether some of the tobaccos used in some “smokeless” products are cured using artificial heat—in some cases by burning wood fuel and contributing to deforestation.

    It has become fashionable to talk of both individual and population risk, so, in this context, is it OK to reduce the harm caused to individuals by tobacco consumption if the production of the less risky items involves damaging the environment and, by extension, threatening the health of tobacco and nontobacco users alike?

    This is a massively complex question, the answer to which would mean a descent into not altogether helpful relativities. One thing seems clear to me, however. If you drew up a continuum of environmental risk caused by tobacco and nicotine products, you would wind up with a picture somewhat different to the continuum of individual consumer risk caused by tobacco and nicotine products, which we are more used to seeing. But one thing would remain pretty much the same. Smokeless products, such as nicotine pouches, snus and chewing tobacco, would be the stand-out products when it comes to reduced environmental risks. What would change, I think, is that the divisions between combustibles in respect of environmental risks would widen appreciably, and vaping products, which are smokeless, while scoring well on the individual consumer risk continuum might well end up in free fall on the environmental risk continuum, something that needs to be addressed.

    I’ve seen it said that there should be one set of rules for combustible products and another set of rules for noncombustible products. I think the rules need to be more nuanced than that.

  • 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?