Re-Analysis of Retracted Research on Heart Attacks Before Vaping

Dharma Bhatta and Stanton Glantz last year published a study claiming that e-cigarettes cause heart attacks. That assertion was based on 38 heart attack incidents, but the authors knowingly included people who had heart attacks years before first using e-cigarettes.

My economist colleague Nantaporn Plurphanswat and I described that fatal error in two letters to editors of the Journal of the American Heart Association.  I applied pressure for the next seven months, and the editors retracted the study on February 18 of this year.

Although the incident was reported by USA Today’s Jayne O’Donnell, Ivan Oransky at Retraction Watch, Alex Norcia of Vice and others, the tobacco research community showed little interest. Despite the obvious research flaw, some insisted that we show the effect of correctly classifying vapers who had heart attacks years before starting e-cigarette use.

Dr. Plurphanswat and I have met that challenge, and we now report our results in the professional journal Addiction.

From the public-use dataset we know that at least 11 of Bhatta-Glantz’s reported 38 heart attacks occurred prior to e-cigarette use.  But there are many more.  For our re-analysis we determined the exact number of prior heart attacks, but we cannot disclose that figure due to restrictions imposed by the Inter-university Consortium for Political and Social Research. Following are our results after correctly classifying all of the prior heart attacks.

 

Adjusted Odds Ratios For Heart Attack According to E-Cigarette Use
E-Cigarette Use	Bhatta-Glantz Original Results	Results After Correct Classification
Never	Referent	Referent
Non-Daily Current	1.99 (1.11 – 3.58)	0.18 (0.05 – 0.66)
Daily Current	2.25 (1.23 – 4.11)	0.69 (0.22 – 2.12)

 

Our work reveals that Bhatta and Glantz’s doubled odds ratios disappear after correctly classifying the time-warped e-cigarette heart attacks. 

Our article describes additional problems with the Bhatta-Glantz study, such as the fact that their definitions were internally inconsistent. They excluded current experimental e-cigarette users and smokers, but they included former experimental e-cigarette users and smokers, with no justification. Additionally, participants were not counted correctly. Bhatta-Glantz used all 32,320 survey participants in their analyses, but 7,183 of those had missing information on key variables; we don’t know what Bhatta and Glantz did with them, but they should not have been counted.

We note, “[Bhatta and Glantz] appeared to know about detailed information regarding when participants were first told about the heart attack and when they first used e-cigarettes. On page 9 of their [retracted] article, the authors said that they used those specific PATH survey questions to ‘address this problem’ of temporality with a secondary analysis ‘to select only those people who had their first MIs [myocardial infarctions] at or after 2007’ (n = 16, their Supporting Information, Table S6). Glantz also told a journalist that the secondary analysis reflected the timing of the heart attacks. However, despite this knowledge and claim, their secondary analysis did not address the temporality problem. We found that more than one-third of the current 16 e-cigarette users who had a heart attack after 2007 occurred before they first used e-cigarettes.” 

We conclude, “…[Bhatta and Glantz] did not account for heart attacks that occurred before first e-cigarette use, even after the temporality problem was raised in pre-publication peer review…The analysis presented here supports the decision by editors of the Journal of the American Heart Association to retract Bhatta & Glantz’s article on 18 February 2020. It raises questions as to what analyses the authors may have undertaken that were not reported and why they did not conduct the analyses reported here or requested during peer review of the original article.”

As I noted previously, the retracted study was supported by $13.6 million from American taxpayers.  Our new research warrants an investigation by federal officials to determine if those funds were misused. 

 

 

E-Cigarettes and Respiratory Disease: NO EVIDENCE

Drs. Dharma Bhatta and Stanton Glantz published a study in February’s American Journal of Preventive Medicine claiming that “Use of e-cigarettes is an independent risk factor for respiratory disease in addition to combustible tobacco smoking.” (here)  In a University of California San Francisco press release, Professor Glantz made additional claims: “We concluded that e-cigarettes are harmful on their own, and the effects are independent of smoking conventional tobacco…This study contributes to the growing case that e-cigarettes have long-term adverse effects on health and are making the tobacco epidemic worse.”

Now Cornell University researchers, led by economics professor Don Kenkel, have published a comprehensive re-analysis of that study (here), concluding:

“We find no evidence that current or former e-cigarette use is associated with respiratory disease.”

Kenkel and his co-authors explain why the Bhatta and Glantz claims are bogus: “The statistical associations that Bhatta and Glantz find between e-cigarette use and respiratory disease are driven by e-cigarette users who are also current or former smokers of combustible tobacco…almost all e-cigarette users were either current or former smokers of combustible tobacco. In the longitudinal analysis sample with 17,601 observations, there were only 12 current e-cigarette users who had never smoked combustible tobacco. None of the 12 respondents had incident (new) respiratory disease.”

In other words, while Bhatta and Glantz asserted that e-cigarettes were an “independent” risk factor for respiratory disease, only 12 vapers had never smoked and none of them developed the illness.

Last year, Bhatta and Glantz claimed in the Journal of the American Heart Association that e-cigarettes cause heart attacks.  Informed by my research group that many of the vapers’ heart attacks occurred years before they picked up their first e-cigarette, JAHA editors retracted that study in February.

It is important to note that Bhatta and Glantz used the same federal grants, totaling $13.6 million, to fund both the retracted JAHA heart attack study and the bogus AJPM respiratory disease study.  As I said in February, massive amounts of taxpayer dollars flowing to U.S. researchers who are anti-tobacco, anti-harm-reduction, in service of the government’s stated objective “to create a world free of tobacco use.”  Still, it is intolerable for public funds to be used in the production of scientifically unsound research.

The re-analysis by Kenkel and colleagues should prompt the American Journal of Preventive Medicine’s editors to revisit their decision to publish Bhatta and Glantz’s latest study.

Federal Funds Misspent on Anti-Vaping Research

The Journal of the American Heart Association on February 18 retracted an article by Dharma Bhatta and Stanton Glantz.  As I documented earlier, Bhatta and Glantz published demonstrably false findings.  Details of the retraction were reported by USA Today’s Jayne O’Donnell, Ivan Oransky at Retraction Watch and Alex Norcia of Vice, among others.

The Bhatta-Glantz article states that “This work was supported by grants R01DA043950 from the National Institute on Drug Abuse, P50CA180890 from the National Cancer Institute and the Food and Drug Administration Center for Tobacco Products, U54HL147127 from the National Heart, Lung, and Blood Institute and the Food and Drug Administration Center for Tobacco Products.”  Those grants, itemized below (Source, NIH RePORTER), probably funded additional research beyond the flawed vape heart attack study.

Federal Support of Retracted JAHA Article By Dharma Bhatta and Stanton Glantz
Federal Grant Number	2017	2018	2019	All Years
R01DA043950	$511,397	$526,209	$541,346	$1,578,952
P50CA180890	$3,829,020	$155,362	---	$3,984,382
U54HL147127	---	$4,000,000	$4,000,000	$8,000,000
All	$4,340,417	$4,681,571	$4,541,346	$13,563,334

The $13.6 million are termed “direct costs,” the amount of money Dr. Glantz was awarded to conduct his research.  Each university negotiates an additional payment from NIH for facility and administrative (F&A) costs.  The rate for UCSF during the period was about 59%.  That means the federal government paid UCSF as much as $8 million more, a significant sum.

Still, that $13.6 million was only a fraction of the $51 million funneled from the National Institutes of Health to Glantz since 2005.  That funding supported 292 Glantz articles recorded in PubMed.

The next chart, courtesy of Clive Bates, illustrates Glantz's annual NIH funding since 1985.  Note the significant increase in 2013, which reflects the start of massive transfers from FDA to NIH of hundreds of millions in tobacco company user fees.

This body of taxpayer-supported work, universally anti-tobacco, anti-harm-reduction, is in keeping with the government’s stated objective “to create a world free of tobacco use.”  This prohibitionist mission supports thousands of NIH-funded researchers, and cows countless more into silence when they could be producing life-saving harm reduction data and analyses.

A true public health agenda would include federal support for honest research aimed at prolonging healthy lives, regardless of lifestyle.

UC San Francisco Authors Inadvertently Validate Our Call for Retraction

In the previous post I described fatal flaws in a study by University of California San Francisco’s Benjamin W. Chaffee, Shannon Lea Watkins and Stanton A. Glantz in the journal Pediatrics (here).  Their published response (here) validates my criticism.

Chaffee et al. correctly observed that I have frequently challenged flawed research, and they kindly provided three examples of my published letters to editors of scientific and medical journals.  My professional blog is replete with fact checks of published claims by federal officials (here, here, here, here, here, here) and government-funded researchers (here, here, here, here, here, here here, here) that e-cigarettes are a gateway to teen smoking.  My criticism has extended to research published by UCSF faculty (here, here, and here)

The recent Pediatrics analysis by Chaffee et al. showed that teen e-cigarette users in the Wave 1 FDA Population Assessment of Tobacco and Health (PATH) survey had higher odds of consuming 100+ cigarettes or past 30-day smoking one year later at follow-up.  I noted that the authors ignored important information about lifetime cigarette consumption (LCC), from as little as “1 puff but never a whole cigarette” all the way to having smoked 99 cigarettes.  When my research team applied LCC data to Dr. Chaffee’s analysis, his positive results for an e-cigarette “gateway” essentially disappeared. 

In response, Chaffee et al. called our addition of the LCC information a “statistical trick.”  By using that term, it appears that they believe, incorrectly, that the LCC variable is an outcome rather than a confounding factor.  Inexplicably, they described our analysis as “akin to suggesting that a study of hypertension should adjust for confounding by systolic blood pressure.” 

In this, Chaffee et al. prove our case. 

Let’s say we are studying the effect of dietary salt consumption on development of hypertension (systolic blood pressure, bp >140 mm) after one year of follow-up among participants who were not hypertensive at baseline (that is, they had a systolic bp = 90 to 139 mm).  If someone has a baseline bp of 139 mm, it is much more likely that they will have a bp of >140 mm after one year, compared to a person who had a baseline bp of 90.  It would be negligent to blame salt for causing hypertension while completely ignoring baseline systolic bp values in this example. 

The same principle applies to Dr. Chaffee’s e-cigarette study. 

The chart below clearly illustrates the large differences in LCC that Chaffee et al. ignored between never e-cigarette users and past 30 day users or triers.

It is negligent to ignore cigarette consumption at baseline while placing all the blame for smoking one year later on e-cigarette use. 

The Chafee article must be retracted.