E-cigarette makers face an existential threat. By May, they must submit applications to the U.S. Food and Drug Administration proving that their products provide a net benefit to public health. If a company fails to make its case, the FDA has the power to order its products off the market.

The agency will judge that benefit with a two-part test: Are e-cigarettes effective in getting smokers to quit? And, if so, does that benefit outweigh the health damage to new e-cigarette users — including teenagers — who never smoked in the first place?

That’s a particularly high hurdle for the largest e-cigarette maker, Juul Labs Inc, according to a Reuters analysis of the latest available data on trends in cigarette and e-cigarette use from the U.S. Centers for Disease Control and Prevention.

The data show that e-cigarettes are having little impact in reducing U.S. cigarette smoking, while growth in vaping since 2015 has come entirely from users under 25 years old, including teenagers. Those trends present a special problem for Juul because of its dominance of the U.S. market and its enormous popularity among teenagers, according to more than a half dozen tobacco researchers and medical experts who assessed the data at Reuters' request.

"I don't see it as a surmountable hurdle," Suzanne Colby, a tobacco researcher at Brown University, said of the FDA standard for public health benefits. "The data look like their product differentially attracts youth instead of adults, in such great numbers."

Between 2017 and 2018 — the period when Juul rapidly grew to become the U.S. market leader — e-cigarette use among U.S. adults grew from 2.8 percent of the population to 3.2 percent, according to the CDC. But rates of cigarette smoking among adults barely budged, dropping from 14 percent to 13.7 percent — not enough to be statistically significant, according to the CDC. (For a graphic showing vaping trends for various age groups, see: here.)

Use of e-cigarettes by high-school students, by contrast, shot up by 78 percent over the same period – from 11.7 percent to 20.8 percent of students, data from the CDC and the FDA show. Juul is by far the most popular e-cigarette among teens, with more than half of high school and middle school students naming it as their favorite brand in surveys by the CDC and the FDA.

Moreover, the biggest growth in adult e-cigarette use came among the youngest age cohort of adults, people aged 18 to 24. E-cigarette use among young adults is nearly four times more common than among those aged 45 to 64, the CDC numbers show.

Another dynamic that undermines the public-health case for e-cigarettes is the large proportion of "dual users." The most recent federal data show that 41 percent of adult e-cigarette users continue to also smoke cigarettes.

Some studies show dual use could be more harmful than smoking alone. A study last December found people who used both products tested higher than cigarette smokers for a range of volatile organic compounds and other toxins associated with tobacco-related disease. A separate study last year of heart disease risk among e-cigarette users found that dual use was "more dangerous than using either product alone."

For the industry as a whole, the usage data cast serious doubts on whether e-cigarettes are providing a clear benefit among adult smokers, said Brian King, a deputy director at the CDC's Office on Smoking and Health.

"When it comes to net public health impact, you have to consider both ends of the scale," King said. "Right now it does appear the youth initiation is outweighing the adult use."

Juul declined a request for an interview with executives including CEO K.C. Crosthwaite, a veteran of Marlboro maker Altria Group Inc who took the helm in September, on how it plans to pass the FDA's regulatory test. As pressure on the company has mounted, Crosthwaite has made the FDA application process a central goal, laying off 650 employees, including many in marketing, last month in an effort to restructure the company to focus on regulatory approval.

In written responses to questions from Reuters, Juul said it believes its products "already are playing a critical role in transitioning adult smokers from combustible cigarettes and have the potential to convert tens of millions of smokers in the U.S." The company cited studies it has commissioned showing that between 30 percent to 50 percent of adult smokers who use Juul "switch completely from smoking cigarettes within six months."

Juul has said its customers are “the world’s 1 billion smokers,” but the company did not directly address questions about the disparity in youth and adult uptake in the United States. Juul acknowledged it must address any potential impact on nonsmokers who start using e-cigarettes. It said it is "committed to working cooperatively with regulators, public health officials and other stakeholders to combat underage use and convert adult smokers."

In October, Crosthwaite brought on another Altria executive, Joe Murillo, who helped navigate a successful FDA application for IQOS, a Phillip Morris International Inc product that heats up but doesn't burn packages of ground-up tobacco. Altria has an agreement with Philip Morris to market IQOS in the United States. The IQOS device is one of only two tobacco products that have successfully made it through the FDA process.

Juul’s competitors in the U.S. market face the same regulatory challenge. One rival, Japan Tobacco International, says it is confident in the FDA application it filed in August for its Logic products because it contains company data showing the brand — unlike Juul — is used overwhelmingly by older adults.

Anthony Hemsley, an executive for Japan Tobacco International's U.S. division, acknowledged the population-wide trends in e-cigarette and cigarette use. But he pointed out that the FDA's decision on net public health benefit will be made on a product-by-product basis — not across the entire industry. He added that Juul has "a significant challenge ahead of them, in overcoming the concerns that exist out there."

The FDA declined requests for an interview with Mitch Zeller, who heads tobacco regulation at the agency, about its oversight of e-cigarettes. In written answers to questions, the agency did not directly address the population-level data on smoking and vaping trends but said it is “tasked with threading a public health needle” in crafting regulations on e-cigarette firms.

A Reuters investigation in November detailed how Juul's developers used tobacco industry research and patents to formulate its smooth but potent "nicotine salts" blend of liquid nicotine, a key factor in its popularity among teenagers. The report showed company leaders were aware of the product's popularity among teenagers soon after its 2015 launch, contradicting statements that Juul was caught off guard by teenage use last year.

Former FDA Commissioner Scott Gottlieb told Reuters that he agreed with public health advocates and tobacco researchers that whatever benefits Juul may be having for cigarette smokers are offset by attracting children who otherwise wouldn't have tried other tobacco products. Before Gottlieb left the department in April, he and his staff explored the option of halting sales of Juul and similar high-nicotine devices if their popularity continued rising among teens.

"We could take these products off the market tomorrow,” he said. “We don't need the applications."

(For a graphic tracking the rise of vaping amid regulatory delays, see: here.)

Juul and the FDA did not respond to questions on Gottlieb’s assertion that the agency should immediately remove Juul and similar products from the market.

Mounting pressure on the FDA

E-cigarettes have been available in the United States since at least 2007, but the FDA did not formally get authority over the industry until nine years later, in 2016.

The agency initially tried to regulate e-cigarettes as a drug, which would have carried more stringent requirements for e-cigarette firms, such as extensive clinical trials or animal testing. E-cigarette makers sued the FDA and won, leaving the agency to regulate the devices as tobacco products.

FDA officials started crafting a rule to regulate e-cigarettes in 2011, but the industry pushed back and successfully delayed the rule until May 2016, in the final months of the administration of President Barack Obama. During that time, Juul and dozens of competitors introduced products that were grandfathered into the market because they were already being sold before the regulation took effect.

The rule extended certain cigarette restrictions to e-cigarettes, like requiring health warning labels, setting a minimum sales age of 18 and prohibitions on free samples.

A key part of the new rule also required e-cigarette makers to submit applications to the agency by August 2018 — demonstrating why their products provide a net benefit to public health — along with studies and data on potential toxins in the products.

When Gottlieb was appointed by President Donald Trump to lead the agency in 2017, one of his first moves was to delay that deadline by four years, a decision public health advocates criticized. Just months later, school administrators, parents and politicians raised alarms about the rapid rise of vaping among high schoolers, who were particularly transfixed with the Juul device.

Some public health advocates feared the new administration’s commitment to the Obama-era regulations after an initial three-month delay, as the FDA faced litigation from the industry. Gottlieb declined to comment on whether the some in the administration wanted to kill the regulations but said his effort to push them forward was “not an easy process.” He said he delayed the deadline because the previous administration had not drafted guidelines that companies could follow for the application process, leaving the agency open to a legal challenge from the regulated industries.

"They would have sued me, and I would have lost," he said.

But today’s FDA could — and should — pull Juul and other products from the market, Gottlieb said.

"I thought that's where the agency would land," he said.

In March, just before he left the agency, Gottlieb said publicly that the FDA was considering prohibiting sales of cartridge-based e-cigarettes like Juul from the market if teen usage rates went up for a second year in a row. Federal youth tobacco survey data first released in September showed that teenage usage did in fact keep rising, with the percentage of teenagers reporting they used e-cigarettes in the last 30 days growing from nearly 21 percent to more than 27 percent.

In a statement, the FDA said it has sent more than 1,100 warning letters to retailers selling to minors; issued warning letters to companies marketing teen-friendly e-cigarette products, such as those with sweet flavors; and launched advertising campaigns aimed at e-cigarette prevention in schools.

"Taken together, all of these efforts have had a wide-ranging impact on the manufacturing, marketing and selling" of e-cigarettes, the agency said. "FDA's work is constant in its effort to keep these products out of the hands of kids."

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