Fake Science Denying the Relative Safety of Smokeless Tobacco Cost Millions of Lives; Don’t Repeat that Error with New Smoke-Free Products

 

Dr. Jay Bhattacharya, recently confirmed as director of the National Institutes of Health, tweeted on November 23, 2024, “If the NIH were serious about the replication crisis, it would devote a significant chunk of its budget to funding replication studies by independent researchers and require NIH funded researchers to make research materials available to replicators.”

I welcomed that statement because, over the past decade, my colleague Nantaporn Plurphanswat and I have challenged distorted and blatantly false studies concerning safer tobacco products (examples here, here, here and the list below).  Those efforts followed my earlier work with other authors on similar flawed research articles, but together they addressed only a fraction of defective FDA/NIH-sponsored tobacco research.  Because replication is time-consuming, it detracts from the performance of original research; additionally, findings are rarely published, and they often draw derision from the original authors and the research establishment. 

One might ask, why bother to address bad studies?  I answer that question in a new Sensible Medicine article titled, “Defining the Risk of Oral Tobacco Products,” in which I focus on the false narrative of a 1981 New England Journal of Medicine study that fatally undercut the fact that smokeless tobacco is vastly safer than cigarettes.  As a result of the 1981 publication, millions of smokers were denied information that could have extended their lives. 

Repeating that deadly error with vapor products, heat-not-burn tobacco and nicotine pouches will cost millions more lives.

 

 

List

Plurphanswat N, Rodu B.  Is the smoking population in the United States really softening?  Addiction, 2016 Jul;111(7):1299-303. doi: 10.1111/add.13340. Epub 2016 May 13. http://www.ncbi.nlm.nih.gov/pubmed/27177450

Farsalinos K, Rodu B.  Metal emissions from e-cigarettes: a risk assessment analysis of a recently-published study.  Inhalation Toxicology 2018. https://pubmed.ncbi.nlm.nih.gov/30384783/ 

Rodu B, Plurphanswat N.  A re‐analysis of e‐cigarette use and heart attacks in PATH wave 1 data. Addiction, First published 13 August 2020.  https://pubmed.ncbi.nlm.nih.gov/32794213/

Rodu B, Plurphanswat N. Heterogeneity and other problems in a pooled analysis of snus use and mortality. F1000Research 2021, 10:388 (https://doi.org/10.12688/f1000research.52127.1 )

Rodu B, Plurphanswat N.  Cross-sectional e-cigarette studies are unreliable without timing of exposure and disease diagnosis. Internal and Emergency Medicine 18(1):319-323, 2023. Epub 2022 Nov 25. https://link.springer.com/article/10.1007/s11739-022-03141-3

Plurphanswat N, Selya A, Rodu B. Questionable effects of electronic cigarette use on cardiovascular diseases from the National Health Interview Survey (NHIS, 2014-2021). Cureus 2024. DOI:10.7759/cureus.57119. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055619/

Rodu B, Cole P.  Excess Mortality in Smokeless Tobacco Users Not Meaningful (Letter).  American Journal of Public Health 85:118, 1995. https://pubmed.ncbi.nlm.nih.gov/7832248/

Rodu B, Cole P. A deficient study of smokeless tobacco use and cancer (letter).  International Journal of Cancer 118: 1585, 2006.  https://pubmed.ncbi.nlm.nih.gov/16206262/

Rodu B. Snus and the risk of cancer of the mouth, lung, and pancreas.  Lancet 370: 1207, 2007.  https://pubmed.ncbi.nlm.nih.gov/17920914/

Rodu B, Heavner KK.  Errors and omissions in the study of snuff use and hypertension (letter).  Journal of Internal Medicine 265: 507-8, 2009. https://pubmed.ncbi.nlm.nih.gov/19019185/

Rodu B, Heavner KK, Phillips CV.  Snuff use and stroke (letter).  Epidemiology 20: 468-9, 2009.  https://pubmed.ncbi.nlm.nih.gov/19363361/

Rodu B, Plurphanswat N, Phillips CV.  Discrepant results for smoking and cessation among electronic cigarette users (letter).  Cancer 2015 Mar 4. doi: 10.1002/cncr.29307. https://pubmed.ncbi.nlm.nih.gov/25740231/

Rodu B, Phillips CV.  Regarding “Discontinuation of Smokeless Tobacco and Mortality Risk after Myocardial Infarction” (letter).  Circulation 2015 Apr 28;131(17):e422. doi: 10.1161/CIRCULATIONAHA.114.012038.  https://pubmed.ncbi.nlm.nih.gov/25918044/

Rodu B.  Re: Smokeless tobacco use and the risk of head and neck cancer: pooled analysis of US studies in the INHANCE consortium.  American Journal of Epidemiology 2017.  https://pubmed.ncbi.nlm.nih.gov/28911014/

Rodu B, Plurphanswat N.  Response to Bhatta and Glantz.  Addiction First published: 13 August 2020. https://pubmed.ncbi.nlm.nih.gov/32794301/ 

Rodu B, Plurphanswat N.  Gaiha et al. disregarded conventional publishing standards (letter).  Journal of Adolescent Health 68;215, January 1, 2021. https://www.jahonline.org/article/S1054-139X(20)30566-8/fulltext 

Plurphanswat N, Rodu B.  “Association between electronic cigarette use and fragility fractures among US adults” contains significant errors.  American Journal of Medicine Open 8: December 2022, https://doi.org/10.1016/j.ajmo.2022.100017 

Rodu B.  Methods questions.  Tobacco Control June 12, 2023. https://tobaccocontrol.bmj.com/content/early/2023/03/20/tc-2022-057717.responses 

 

Rodu B.  The many dangers of e-cigarette misinformation. Oral Surgery Oral Medicine Oral Pathology 2024.  https://www.oooojournal.net/article/S2212-4403(24)00893-9/fulltext  

 

 

Misrepresentation of Snus Use in Karolinska Institute Studies

As I documented in a previous blog entry, Karolinska Institute (KI) studies on the health effects of snus use have profoundly influenced regulatory action worldwide, but those studies are compromised by important, troubling and unresolved discrepancies. Following is evidence that KI investigators misrepresented snus use among the revolving-door cohort in multiple journal articles.

From 1971 to 1974, 135,000 Swedish construction workers were enrolled in a health program that served as the basis for epidemiologic follow-up studies investigating associations between many risk factors and diseases. The first report, claiming that snus use had risks for cardiovascular diseases, was published by Gunilla Bolinder (abstract here); subsequent studies variously included and excluded this group, prompting me to label it the “Bolinder Revolving-Door” cohort (here).

There are many other problems with the KI studies that are technical in nature, but one deserves special mention because it is so basic and egregious. It involves the definition of snus use.

When conducting epidemiologic research, it is critically important to classify subjects according to current or former exposure to a risk factor; there are often large differences in risk in these groups. For example, current smokers have higher risks for heart attacks than former smokers. Sometimes, researchers don’t collect information on current and former use, in which case they designate subjects as “ever-users” and “never-users.” The ever-never classification is not nearly as informative as current-former-never classification.

In her 1994 publication, Dr. Bolinder clearly stated that she investigated cardiovascular diseases among “present” (i.e., current) snuff users. Keep in mind that Bolinder’s cohort probably had “former” users of snus, but she didn’t mention them.

Now, fast-forward to 2007, when Maria-Pia Hergens published a study of snus use and heart attack among construction workers (abstract here). As I mentioned previously, Hergens excluded the Bolinder cohort, and this was her reason: “During the period 1971–1974 exposure information on snuff use was limited to ever or never use.” (emphasis added)

Thus, Bolinder claimed that she studied “present” (i.e., current) snus users in her cohort, but in 2007 Hergens said the only information available in the Bolinder cohort was ever or never use. To make matters more interesting, Gunilla Bolinder was a co-author on Hergens’ publication.

Did the Bolinder Revolving-Door Cohort have current snus users or ever snus users? The Bolinder and Hergens-Bolinder descriptions of snus use are not only conflicting but irreconcilable; one of them is a gross misrepresentation.

Last year, I described a 30-year misinformation campaign in the United States, almost entirely based on Dr. Deborah Winn’s misrepresentation of dry powdered snuff in her influential 1981 New England Journal of Medicine report (my entry here). Winn exaggerated and conflated the risks of a rarely used smokeless product (dry powdered snuff), and attached those risks to popular chewing tobacco and moist snuff products, which have virtually no risks (evidence here).

The credibility of the KI studies is contingent on the resolution of their many significant discrepancies. It would be a public health travesty if the KI misrepresentation persisted as the basis for a Winn-style misinformation campaign in Sweden and throughout the world.

Winn’s Legacy: The Fifty Fabrication

In a previous post I explained how Deborah Winn, an epidemiologist at the National Cancer Institute, misinformed the American public and America’s doctors about the oral cancer risks of smokeless tobacco use.
Winn is also responsible for the widespread statement that smokeless tobacco users are 50 times more likely to develop oral cancer. That statement is a complete fabrication.

Winn’s 1981 study in the New England Journal of Medicine is the source for this completely erroneous information. As I discussed previously, Winn reported that the relative risk for oral cancer among powdered dry snuff users was 4. The puzzle is how a relative risk of 4 has been transformed into 50. Here are the keys to the puzzle’s solution.

First, oral cancer is a very rare disease, but smokers and heavy drinkers have considerably elevated risks. The most common sites for oral cancer are the sides of the tongue and underneath the tongue; other surfaces of the mouth are hardly ever affected. There are rare exceptions: oral cancer infrequently occurs among dry snuff users in the location where they place the product -- the gum and cheek. Winn’s 50 number applies only to the gum and cheek, not to the entire oral cavity (for which the number is still only 4). Even a few cases of cancer in the gum and cheek, which are virtually never otherwise involved, can raise the risk calculation.

The second key doesn’t involve Winn’s main findings, but a secondary analysis she performed on the duration of dry snuff use. Winn found that the highest risk for cancer of the gum and cheek was among women who had used dry snuff for over 50 years. That risk number was 47.5, and it was based on only 15 cases (the small number of cases determined that the 95% confidence interval – the range within which the estimate lies – was very wide, from 9 to 250!). Winn rounded up her estimate to “50-fold” in the abstract.

It is important to point out that the 50 and the 4 refer to the same number of oral cancer cases. Here is an example of how these numbers relate to each other. Let’s say that you have $100 in a savings account, and the average savings account in that bank has $25. This means that you have 4 times as much money as the average customer at that bank. But you decide to move your account to another bank, where the average savings account only has $2. Now you can correctly boast that you have 50 times more than the average account holder, even though you still only have $100.

So, Winn’s “50” number (actually 48) is appropriately used only in the following specific description: Women who used powdered dry snuff for over 50 years were 48 times more likely than nonusers to develop a cancer of the gum or cheek where the snuff was placed.

That is not how anti-tobacco extremists use the “50” number. They are eager to portray smokeless tobacco use as life-threatening, so they say that users of any type of smokeless tobacco for any duration have a fifty-fold elevated risk of oral cancer. This is a total canard.

The “50” fabrication continues to be peddled by organizations and government agencies that know better. Here are some examples:

The American Cancer Society (here)

The Centers for Disease Control and Prevention (here)

The University of Iowa (here) and Brown University (here)

State agencies in Kentucky (here), Rhode Island (here) and Wyoming (here).

It appears that Winn’s “50” legacy will persist until Americans demand that organizations and government agencies provide accurate information about the risks of tobacco.

Three Decades of Smokeless Tobacco Misinformation

On Wednesday April 14, the U.S. House Subcommittee on Health had a “kangaroo-court” hearing on smokeless tobacco. Announced only a week earlier, it was clearly a reaction by anti-tobacco extremists to an April 4th “60 Minutes” story about Sweden’s successful tobacco harm reduction efforts (watch it here).

The hearing was a diatribe against smokeless tobacco. Organizers invited only strident anti-tobacco crusaders to testify. One notable witness was Deborah Winn, a National Cancer Institute epidemiologist who fueled the misinformation campaign against smokeless tobacco almost 30 years ago.

Winn was the first author of an epidemiologic study concluding that “exceptionally high mortality from [oral cancer] among white women in the South is primarily related to chronic use of snuff. The relative risk associated with snuff dipping among white nonsmokers was 4.2.” The study, published in the New England Journal of Medicine in 1981 (abstract here), irresponsibly led the public and the medical establishment to falsely believe that smokeless tobacco was responsible for an American oral cancer epidemic.

First, Winn exaggerated her own findings. She claimed that smokeless tobacco produced an “exceptionally high mortality from [oral cancer],” even though her risk estimate only resulted in approximately 12 deaths per year among 100,000 long-term smokeless tobacco users. That mortality rate is not trivial, but it is not “exceptionally high.” It is comparable to the annual death rate of 12 to 15 per 100,000 users of automobiles – a figure that does not deter American drivers.

Exaggeration is unacceptable, but Winn’s study has a special place in the annals of American smokeless tobacco misinformation. It focused solely on a niche tobacco product -- powdered dry snuff -- used by a tiny number of women in the southern U.S. But this passage in Winn’s article transferred dry snuff’s risk to all smokeless products: “The carcinogenic hazard of oral snuff is of special concern in view of the recent upswing in consumption of smokeless tobacco in the United States.” This misleading statement appeared in the Associated Press wire story carried by the nation’s media.

Winn’s results should never have applied to chewing tobacco and moist snuff, popular American smokeless products that have been used widely with significantly fewer medical consequences than powdered dry snuff. Long after her widely cited article was published, Winn acknowledged in two obscure scientific forums that her results were specific to powdered dry snuff. In 1986, Winn was asked whether the patients in her study had used “dry snuff or [moist] snuff.” She replied, “Almost exclusively dry snuff,” and then admitted that “Dry snuff is now [in 1986] a minor portion of the U.S. market.” Her late acknowledgment in a sparsely attended scientific meeting did nothing to deter tobacco prohibitionists from misapplying her mortality claims to all smokeless products.

Epidemiologist Philip Cole and I first demonstrated the significance of Winn’s omission in our meta-analysis of smokeless tobacco and oral cancer, published in 2002 (abstract here). Our conclusion was unequivocal: “The use of moist snuff and chewing tobacco imposes minimal risks for cancers of the oral cavity and other upper respiratory sites, with relative risks ranging from 0.6 to 1.7. The use of dry snuff imposes higher risks, ranging from 4 to 13.”

The impact of Winn’s sloppy epidemiology and obfuscation is hard to overestimate. It is as if the federal official investigating the Toyota Prius accelerator problem stated that all automobiles are at risk for the defect. Winn’s 1981 report effectively projected the risk from a small subset of smokeless products to the entire smokeless category.

After nearly 30 years, Winn’s misinformation should no longer be used to keep millions of American smokers from switching to vastly safer smokeless tobacco products.