The Illogic of Condoning Vaping & Condemning Smokeless – Both Are Safer for Smokers

While many American tobacco researchers and policy experts have, of late, moved to endorse reasonable regulation of e-cigarettes and vaping, most persist in condemning smokeless tobacco products, which have been proven to be nearly harmless.  It is irrational to support one and prohibit the other, when both are legitimate harm reduction options for smokers.

The illogic of this dual position is displayed in the work of Dr. Dorothy Hatsukami, a prestigious tobacco researcher, author of 250 published articles (here) and recipient of tens of millions of dollars in NIH funding (available here, including $13 million to study reducing nicotine in cigarettes).  Dr. Hatsukami recently signed a letter to FDA Commissioner Scott Gottlieb (here) and published an article in Tobacco Control (here).

In the letter to the commissioner, Dr. Hatsukami applauded his “openness to the concept of tobacco harm reduction…There is already a considerable body of science and experience suggesting that a harm reduction approach…could yield substantial and highly cost-effective public health benefits…at this time we do not believe that the current regulatory framework for the low-risk nicotine products such as e-cigarettes and smokeless tobacco is appropriate or will deliver the substantial public health benefits we hope and expect FDA’s oversight will bring.”  The letter encouraged the FDA to regulate tobacco products according to risk and to “support informed choice through truthful communication of risk.”

However, in her Tobacco Control commentary, Dr. Hatsukami took a contrary view, fully endorsing the FDA’s proposed standard for NNN, which I have eviscerated here and here.  She wrote, “If [FDA] puts the proposed rule into effect, it would be a significant and important step towards minimising the harms from smokeless tobacco use.”  Surprisingly, she asserted that “the risk for oral cancer is considerably higher for smokeless tobacco users,” and cited a federal study documenting that American men who dip or chew tobacco have no mouth cancer risk (here).

Notably, other signatories to the Gottlieb letter are genuine tobacco harm reduction advocates who have endorsed the substitution of smoke-free tobacco by smokers.  They include Clive Bates of the UK and Canada’s David Sweanor, who filed a comment (here) labeling the NNN rule “reckless and pointless.”  American signatories who are on record about the relative safety of smokeless are Sally Satel (here and here), Kenneth Warner (here and here), David B. Abrams (here) and Raymond S. Niaura (here). 

Problems Multiply for Proposed FDA Smokeless Tobacco Rule

The FDA on January 23 published a proposed smokeless tobacco (ST) regulation that would require a radical reduction in levels of N-nitrosonornicotine (NNN), a tobacco-specific nitrosamine.  I documented (here) that the rule is based on erroneous calculations of ST risks; others have since raised additional concerns.

Scott Ballin, Health Policy Advisor to the University of Virginia’s Morven Dialogues, observes that the FDA ignored its statutory requirement, when setting product standards, to “invite appropriate participation though joint conferences, workshops, or other means, by informed persons representative of scientific, professional, industry, agricultural or consumer organizations who in the Secretary's judgment can make a significant contribution.”

Brian Fojtik, Senior Fellow at the Reason Foundation, notes (here) that the FDA invited participation from selected stakeholders: “Within hours of publication in the [Federal] Register, a comment was filed by a coalition of interest groups collaboratively (American Academy of Pediatrics, Cancer Action Network, American Heart Association, American Lung Association, Campaign for Tobacco Free Kids and Truth Initiative) . . . a reasonable person is left wondering how six large organizations could possibly have each reviewed a highly technical, 50-page rule, reached conclusions on the rule’s specific merits and crafted a collaborative response that all agreed to sign within hours of the rule’s publication in the Register.  Even in the most forgiving of lights, the appearance is unseemly and should necessitate the withdrawal of the proposed rule.”

Another major error in the FDA’s proposed rule-making process was identified by Altria in a March 3 comment submission.  The agency filed a regulatory impact analysis (here) for the rule, estimating that 30% of moist snuff products currently meet the 1 ppm dry-weight limit (Table 3, panel A).  However, FDA miscalculated the wet-weight to dry-weight conversion, invalidating the estimate. 

Moist snuff is about 50% water; when it is dried, the level of any agent in the remaining tobacco will double.  The FDA did the reverse, calculating that a product with 2 ppm NNN wet-weight would have 1 ppm dry weight.  The correct conversion is 0.5 ppm wet-weight to 1.0 ppm dry weight.  Almost no moist snuff products on the U.S. market are at 0.5 ppm wet weight.

Altria urged the FDA to withdraw the proposed rule because it “would fail to provide a scientifically valid formula for manufacturers to measure and maintain records of NNN levels on a dry weight basis in order to demonstrate compliance with the product standard.”

Federal Studies: ZERO Mouth Cancer Deaths Among Men Who Dip or Chew Tobacco

The U.S. Food & Drug Administration (FDA) on January 23, 2017 published a proposed smokeless tobacco (ST) regulation (here) that is based on erroneous calculations of ST risks.

The agency would require a radical reduction in N-nitrosonornicotine (NNN), a tobacco-specific nitrosamine, in smokeless tobacco (ST) products.  Most American ST products today have very low NNN levels: about 2-10 millionths of a gram per gram of product – that is, 2-10 parts per million (ppm), while a limited number of products contain 10-15 ppm (here).  The FDA proposes to limit the NNN level in ST products to one ppm or lower. 

As is typical with FDA action on ST (here and here), this proposal is based on obscure calculations and flawed assumptions and interpretation.  Here is a summary of the FDA logic:

• Compared with never users, ST users have an excess risk of mouth and throat cancer (Relative risk, RR = 2.16). 


• ST use causes 276 deaths from mouth and throat cancer in the U.S. each year (this number was rounded to 300 in the proposed rule) – 268 men and 8 women. 


• ST products contain NNN, a human carcinogen that causes mouth and throat cancer. 


• Reducing NNN levels to no more than 1 ppm will reduce the number of deaths by about 115 per year.

While the latter two statements are by no means scientific certainties, in this post I will focus on the demonstrably inaccurate first assertion, which is the flawed basis for the FDA’s calculation of “300” deaths due to ST use.

The FDA’s use of an RR of 2.16 is in error. The figure, based on a 2008 report (abstract here), combines radically different RRs for men and women.  In 2002, I documented (here) that men, who generally use moist snuff (also called dip) or chew, do not have significantly elevated risk for mouth and throat cancer (RR ~ 1).  In contrast, women, who primarily use powdered dry snuff, have significantly elevated risk (RR ~ 4-6). 

My research is in general agreement with risk estimates published last year by the National Institute of Environmental Health Sciences’ Annah Wyss and colleagues at the National Cancer Institute and over a dozen universities and health centers in the U.S. and beyond (abstract here).  They determined odds ratios (ORs, interpreted the same as RRs) among snuff and chew users for head and neck cancer – which includes voicebox cancer in addition to mouth and throat, but the risk estimates are applicable.  The combined OR among snuff users, men and women combined, was 1.71, which is similar to the FDA estimate.  However, the OR among men was 0.86, while the OR among women was 8.89.  The ORs for chewing tobacco were not significantly elevated for men or women. 

I will use the Wyss ORs to show how the application of risks specific to men and women change the FDA estimates.  First, the following table (adapted from Table 5 in the FDA’s proposed rule) summarizes the data the FDA used (ST prevalence, RRs and total numbers of deaths from mouth-throat cancer in the U.S.) and the agency’s estimates for deaths attributable to ST (last column).  The FDA erred in applying a single RR (2.16) for men and women when, in fact the RR is 0.86 for men and 8.89 for women.

Table 1. FDA Estimate of Annual Deaths from Mouth and Throat Cancer Attributable to Smokeless Tobacco (ST), Men and Women in the U.S.
	Prevalence of ST Use (%)	Relative Risk	All Mouth/Throat Cancer Deaths	Percentage Attributable to ST	Number Attributable to ST
Men
Age 35-64 years	4.6	2.16	2,770	5.1	140
Age 65+ years	3.9	2.16	2,997	4.3	128
Women
Age 35-64 years	0.2	2.16	832	0.3	2
Age 65+ years	0.3	2.16	1,699	0.3	6
All			8,298		276

In the next table I illustrate how the death estimates change if the specific ORs for men (0.86) and women (8.89) from the Wyss study are used. 

Table 2. Revised Estimate of Annual Deaths from Mouth and Throat Cancer Attributable to Snuff Use, Men and Women in the U.S.
	Prevalence of ST Use (%)	Relative Risk	All Mouth/Throat Cancer Deaths	Percentage Attributable to ST	Number Attributable to ST
Men
Age 35-64 years	4.6	0.86	2,770	0	0
Age 65+ years	3.9	0.86	2,997	0	0
Women
Age 35-64 years	0.2	8.89	832	1.56	13
Age 65+ years	0.3	8.89	1,699	2.31	39
All			8,298		52

As noted earlier, my revised estimates are specific to snuff use – powdered dry snuff for women and moist snuff for men.  However, the risks for chewing tobacco in the Wyss study are not significantly elevated for men or women, so that product would add zero deaths. 

In summary, the FDA failed to use RRs specific to men and women, resulting in overestimation of cancer deaths in the former and underestimation in the latter.  Using the same FDA formula and assigning the proper risks, I estimate that 52 women using powdered dry snuff die each year from mouth-throat cancer, but the number of deaths among men who use dip or chew is zero.  The proposed regulation is therefore unjustified for dip and chew products.