FDA Rejects Plea to Correct Smokeless Tobacco Warnings; A Closer Look at Flawed Interpretations

After two and a half years’ review, the FDA Center for Tobacco Products rejected Swedish Match’s request to eliminate or revise the 30-year-old, egregiously inaccurate warnings that are required to appear on snus products sold in the United States. 

In 2014, Swedish Match sought to:

·         Remove the warning, “This product can cause gum disease and tooth loss”;

·         Remove the warning, “This product can cause mouth cancer”; and,

·         Replace the warning, “This product is not a safe alternative to cigarettes” with this text: “No tobacco product is safe, but this product presents substantially lower risks to health than cigarettes.”

I explored this issue earlier (here).

The FDA justified its rejections in a six-page letter to the company (here) in a 115-page supporting document (here), and subsequently in an announcement proclaiming, “FDA Issues Science-Based Decisions on First MRTP Applications.” 

Science-based?  Following is my review of the FDA’s tortured interpretation of the scientific evidence in its decisions on the gum disease/tooth loss and mouth cancer warnings. 

Gum Disease/Tooth Loss Warning Decision

The agency interpreted removal of a warning as a marketing claim, obligating Swedish Match to prove that snus was entirely without risk – a virtually impossible task.  The FDA advised, for example, that “Omission of [the gum disease tooth loss warning] from a subset of smokeless tobacco products indicates that unlike other smokeless tobacco products, the eight General Snus products cannot cause gum disease or tooth loss.” (emphasis in original).

For this decision, the agency reviewed published studies of “dental conditions (e.g., plaque, caries, tooth wear or tooth loss), gingivitis, gingival recession and periodontal disease” that it claimed were related.  Here are the conclusions for each of these, with the FDA findings in bold:

·         Dental conditions: “Overall, the dental conditions data included no studies that evaluated tooth loss over time…The results on caries were mixed, and the only study to examine the association between Swedish snus and tooth wear found an association. No association was seen between Swedish snus and plaque…”

·         Gingivitis: “Overall the results of the studies on gingivitis were mixed.”

·         Gum recession: “Overall, the only adjusted study of gingival recession to include non-users found a significant positive association between Swedish snus and gingival recession, and several unadjusted studies found significant associations between Swedish snus and gingival recession, although the direction of the association was mixed.”

·         Periodontal disease: “Overall, nearly all of the studies which examine the association between Swedish snus and indicators of periodontal disease (plaque, pocket depth, attachment loss, bone loss) found no association…”

Note the repeated finding of “mixed,” suggesting that some studies showed a positive association while others showed no association or a negative one.  For periodontal, or gum, disease, there was no association. 

Despite these equivocal or nil findings, the FDA concluded: “Overall, the totality of the evidence demonstrates that the eight General snus products can cause gum disease and tooth loss, and, correspondingly, does not support the removal of the warning that these products can cause gum disease and tooth loss.”  The FDA's decision is entirely unsupported by the "totality of evidence."

Mouth Cancer Warning Decision

The FDA decision on mouth cancer is based on an improper analysis of six published studies.  Peter Lee in 2010 published a formal meta-analysis of these studies and one more (abstract here).  Here are his findings for mouth cancer:

“No overall association is seen for oropharyngeal cancer, the most studied cancer type.  For the whole population, an increase (RR 3.1, 95% CI 1.5–6.6) seen in the Uppsala county study (Roosaar et al., 2008), based on 11 cases, contrasts with six studies showing no increase, the overall estimate being 0.97 (0.68–1.37). The never smoker estimate, 1.01 (0.71–1.45), based on four studies, is also null. These results are supported by long-term follow-up of 1115 individuals with ‘‘snuff-dippers lesion’’ (Axéll et al., 1976), which observed no oral cancers at the sites of lesions seen initially (Roosaar et al., 2006).”

When Lee included Roosaar with the other studies in his analysis, there was no association of snus and mouth cancer.  The FDA basically agreed with Lee that Roosaar was the lone work that was positive for snus and mouth cancer, but it cited this study as the sole reason for maintaining the warning.  In fact, the FDA is saying it will ignore the broad consensus of scientific research (i.e. the "totality of evidence") if any one study reports a positive finding.

Having set this impossibly high bar for safer tobacco products, the FDA went further by focusing on tobacco-specific nitrosamines in snus.  Research documents that TSNAs exist in vanishingly small concentrations in snus – about two parts per million or lower (here), and there is no scientific evidence directly linking TSNAs to mouth cancer.  Still, the FDA cited “the presence of nitrosamines in the products that are the subject of these applications, the lack of a threshold dose for mouth cancer” as additional reasons to sustain the warning.  The FDA is effectively saying that TSNAs must be reduced to zero for the warning to be removed.

The FDA closed the door on the gum disease tooth loss warning, but it gave Swedish Match the option of submitting a revised application for the other warnings.  It appears that the agency’s revision/amendment pathway is designed to defeat all the but wealthiest and most determined applicants, leaving millions of smokers and future smokers with demonstrably false warnings against the use of safer smoke-free products.

Premarket Study Positive for Proposed Snus Warning Label Changes

The FDA is considering a request from Swedish Match to modify federally-mandated warnings on the company’s snus packages.  The company wants to remove the current mouth cancer and gum disease/tooth loss warnings; replace the not-safe-alternative warning with the more accurate “this product presents lower [or substantially lower] risks to health than cigarettes”; and retain the current addiction warning.

In support of its application, Swedish Match funded a premarket online survey to measure perceptions of current and proposed labels among 13,200 U.S. participants.  The company’s advisory board asked me and Nantaporn Plurphanswat, my University of Louisville colleague, to analyze the survey, together with University of Vermont psychiatrist John Hughes and Swedish tobacco/nicotine researcher Karl Fagerström.  Our results appear in Nicotine and Tobacco Research (abstract here).

We classified participants according to their tobacco use: smokers, former smokers, ST users, other [combustible] tobacco users and never users.  Participants viewed only one of the current or proposed warnings, after which they were asked if the warning was believable, if snus was harmful, and if they were likely to use snus or motivated to buy snus.  

Most participants, regardless of tobacco use status, found all the current ST warnings believable.  In contrast, they were not as likely to believe the more accurate proposed labels.  The vast majority of respondents also perceived that using snus is harmful.  The perceived odds of harm were mostly lower with the proposed labels, but these differences were not always statistically significant.

These results are not surprising. American health authorities have ignored the substantial body of evidence documenting that ST use is less harmful than smoking and have promoted the message that ST is not a safe alternative to cigarettes (Enter “misinformation” in the search box on this blog for numerous examples).  As a result, most of the population equates the risks of ST use with those of smoking.   

Compared with the current not-safe-alternative warning, smokers viewing the proposed labels were significantly more likely to use or buy snus; the same was true for ST users and other tobacco users viewing the substantially lower risk label. This indicates that the proposed labels could foster a transition from cigarettes and other combustible products to snus, a result that would represent a significant health advantage for individual smokers and public health generally.

Among former tobacco users, no increases in likelihood to use or motivation to buy were seen with the proposed labels. In never users, an increase in motivation to buy snus was noted for the substantially lower risk label; neither proposed label had higher odds for likelihood to use snus.

In summary, our analysis of this pre-marketing survey suggests that tobacco users viewing the proposed relative-risk labels are more likely to perceive snus as less harmful than cigarettes and may be more likely to use and buy snus.

FDA Must Correct Snus Warnings

An FDA advisory committee is meeting this week to discuss a landmark proposal to correct federal health warnings that have been misleading the public for almost 30 years.

 

Swedish Match, a manufacturer of the Scandinavian smokeless product called snus, petitioned the FDA to eliminate two package warning labels concerning mouth cancer, gum disease and tooth loss.  The company submitted numerous scientific studies documenting that these warnings, mandated in 1986, misrepresent the facts.

 

The mouth cancer warning was based on a flawed 1981 study of powdered dry snuff, an obscure product.  The reported cancer risk was far lower than from smoking, but it was incorrectly represented as high, and applicable to all American smokeless products (here and here).  In fact, numerous epidemiologic studies document that users of American moist snuff and chewing tobacco, and Swedish snus, do not have significantly elevated mouth cancer risk.

The gum disease/tooth loss warning is also unfounded.  There is no credible scientific evidence that smokeless tobacco is an independent risk factor for any dental problem.

Swedish Match has also urged the FDA to replace another 30-year old deceptive warning, “This product is not a safe alternative to cigarettes,” with this: “No tobacco product is safe, but this product presents substantially lower risks to health than cigarettes.”  The replacement warning is identical to a change requested by RJ Reynolds four years ago in a citizen petition filed with the FDA.  The agency ignored that petition.

   

The not-a-safe-alternative warning is particularly egregious, as I note in my book, “For Smokers Only” (here).  Accompanied by an incessant campaign for tobacco prohibition by government agencies and anti-tobacco extremists, the warning, appearing on packages and in advertising, has deceived millions of smokers.

 

The current warnings have been shown to discourage smokers from switching (here).  The proposed label would set the facts straight.  Numerous studies (reviewed here) document that the health risks of smokeless tobacco use are so low as to be barely measurable, even for mouth cancer.  (The European Union removed warning labels for that disease from Swedish snus packages in 2001.)  Statistically, smokeless users have about the same risk of dying from their habit as automobile users have of dying in a car accident.

 

Swedes have a history of embracing harm reduction. They invented the modern seat belt, and they’ve eagerly substituted relatively safe snus for cigarettes.  Snus use is directly associated with low smoking rates in Sweden, where men have smoked less and used more smokeless tobacco than in any other developed country.  The result: Swedish men have the lowest rates of lung cancer -- indeed, of all smoking-related deaths -- in the developed world.  If men in the rest of the EU smoked at the rate of Swedish men, there would be over one-quarter-million fewer dead smokers in the EU each year. (here).  Inexplicably, the EU has banned snus in every country except Sweden, denying smokers this life-saving option.

The good news is that snus is now widely available in the U.S. (as are e-cigarettes, another safer-than-cigarettes option).  A 2006 study funded by the National Cancer Institute (here) estimated that four million American smokers would switch to snus if they were informed about the vastly lower health risks of that product.  Research shows that smokeless tobacco (here) has already helped many smokers quit deadly cigarettes.

With no good science behind them, anti-tobacco extremists have resorted to scaremongering.  Dr. Michael Steinberg, director of the Tobacco Dependence Program at Rutgers, recently told NPR this convoluted story:

“If you imagine a young person who sees on a label that this is a less harmful tobacco product, they may interpret that as, ‘Oh, this is not harmful at all. I might as well try it and see what it's all about.’  And that person can still become addicted to the nicotine effects, which could either lead to them becoming a long-term smokeless tobacco user, or could escalate to them starting to smoke cigarettes.”

The FDA cannot take action based on fantasy scenarios.  Swedish Match’s request is scientifically sound.  Revised labels will tell the truth about snus, giving U.S. smokers life-saving information.

How Dangerous Is Snus? Don’t Ask New York Times Editors

The New York Times has added more fuel to the anti-tobacco-harm-reduction fire with a December 4 editorial (here) rehashing the somewhat slanted reporting that appeared in the paper’s news pages on November 30.  In two stories that day, the Times explored issues surrounding Swedish Match’s FDA application to change the warnings on its snus products.  As I noted (here), “The Times and their quoted experts did a major disservice to their audience; they failed to report the simple truth, that mouth cancer risk for Swedish snus is next to nil.”

The original warning labels that Congress ordered for tobacco product packages in 1986 were factually wrong and fatally misleading to smokers, chewers and dippers.  Congress didn’t make the warnings more accurate when  it ordered the FDA to regulate tobacco in 2009, it just made them cover more of the package – an action it didn’t take with cigarettes. 

The Times editorial acknowledged that snus is “is less harmful than smoking tobacco,” but it painted Swedish Match’s application as a marketing ploy.  That ignores the critical need to terminate government’s lie about products’ health risks.

The editors echoed tobacco prohibitionists in denying that snus played a role in the Swedish experience.  Said the Times, “reduced smoking rates and lower rates of tobacco-related diseases such as lung and oral cancer” in Sweden since the 1970s “is debatable,” attributing the successes to “various bans, restrictions and public health campaigns.”  The editors failed to consider that the reductions are exclusively seen in men – who use snus and have the lowest lung cancer rate in Europe – not in women, who rank fifth in Europe for lung cancer.

The Times acknowledged that their reporters had “cited independent experts who found that snus is not nearly as lethal as cigarettes,” but it added the qualifier “[snus] is not risk-free either, especially for users who also smoke.”  It is patently obvious that smoking is risky for anyone, including snus users.  It should also be obvious that a smokeless tobacco can labeled “this product is not a safe alternative to cigarettes” encourages smokers to stick with their habit.

The Times editors revisit the discredited gateway theory (“the danger is that snus might lead some nonsmokers and former smokers to…progress on to cigarette smoking”), but they ignore substantial evidence that this has not happened in Sweden (here) or in the U.S. (here).

Summing up, the Times observes: “abstention would be the safest approach.”  That might work in Neverland, but in the U.S., abstention was impossible for the 8 million smokers who died in the 20 years since I first described our government’s warnings as bogus.  That is no one’s definition of safe.