NEJM Evidence has published two letters to the editor that raised questions about our meta-analysis, Population-Based Disease Odds for E-Cigarettes and Dual Use versus Cigarettes that concluded that for cardiovascular disease, stroke and metabolic disorder e-cigarette risks are similar to cigarettes and for respiratory and oral disease, while lower risk than cigarettes, the risks are still substantial and that dual use (using e-cigarettes and cigarettes at the same time) is riskier than smoking alone for all outcomes.
The journal also published our response.
The first letter, by Michael Cummings, Nancy Rigotti, Neal Benowitz, and Dorothy Hatsukami, raised questions about whether enough time had passed for the risks of e-cigarettes to be fully manifest, the questions used to determine of e-cigarette and cigarette use, the possibility that our findings were and artifact of current or former smoking, and the fact that many biomarkers of cigarette use were lower in e-cigarette users. The second letter, by Jamie Hartmann-Boyce, Steven Cook, and Jonathan Livingstone-Banks raised questions about our assessment of possible bias in the studies included in the meta-analysis and how we assessed the overall confidence we had in our conclusions.
In our published response in the journal, we note that none of these issues go to the heart of our paper. In particular, it is important to note what they did not criticize:
- how we formulated and conducted our literature search
- our inclusion and exclusion criteria
- our data extraction
- how comparisons of e-cigarette and dual use risks to cigarette risks were estimated
- adjustments for multiple studies using the same dataset
- the random effects meta-analysis calculations
- our sensitivity analyses and their interpretation
- our assessment of possible publication bias
These are the key elements supporting our conclusions.
I urge everyone to read the criticisms and our response; they are available open access here.
Other useful links:
- The meta-analysis paper (open access)
- One page plain language summary and Q&A
- Johns Hopkins podcast interview with Stan Glantz about the paper
- Stan Glantz video presentation (Passcode: ?FCk!$3&) on the paper to Clean Air Coalition of British Columbia
Stanton Glantz blog 
Thanks for posting the comments on your 2024 NEJM Evidence paper and the two responses to this paper by readers..
I thought your response letter was lucid, cogent, and appropriately on target and will not say anything further about it.
In contrast, I thought that for the two reader responses, the points they tried to make were not well supported. I have a few comments in addition to the ones the Glantz et al. authors posted.
The authors of the Cummings et al. letter start by claiming that because e-cigarettes are a relatively new product it is “premature” to examine for significant relations with disease outcomes. I had trouble seeing this as a cogent response. There is a simple logical test here: If it is really too soon to assess relations with disease, then there shouldn’t be any significant odds ratios in the meta-analyses. But there were significant odds ratios, all over the place. So right out of the gate this response fails a simple logical test.
The authors then try to buttress their argument with a citation to a paper in Cureus by Brad Rodu and associates. They fail to note that this is a controversial journal with a minuscule impact factor; also they fail to note that the authors have extensive tobacco industry connections. Dr. Rodu in fact holds an endowed chair supported by the tobacco industry; and if you want further information about their tobacco-industry connections, see the Disclosures section of that article. Reviews have shown that industry-supported research arrives at systematically different–sometimes drastically different– conclusions than studies by independent investigators (e.g., Pisinger et al., Preventive Medicine 2019). Hence the attempt at refutation by an independent investigation falls on its face.
And it goes on from there. The authors suggest that unlike short-term biomarker measurements there is supposedly something not objective with the studies included in the Glantz et al. meta-analysis because they used self-reported disease outcomes. But what could be more meaningful than a self-reported diagnosis by a health professional of a long-term health condition, the outcome in typical studies of cardiovascular and respiratory disease, and these are supported by validation against direct clinical measures.
They assert that there is “uncertainty regarding the relation between e-cigarette exposure and disease outcomes.” Really? Maybe you missed the 30-odd epidemiological studies, both cross-sectional and prospective, showing significant associations of e-cigarette use with disease outcomes in large representative samples. Or the large body of controlled laboratory research showing effects of e-cigarette exposure for biological measures such as oxidative stress and inflammation, which have been decisively linked to a range of disease outcomes (for starters see European Respiratory Journal 2021; Annual Review of Pharmacology and Toxicology 2021).
For the Hartmann-Boyce letter, I’m not an expert in meta-analysis but on the face of it, I thought they quibbled with details about assessing study quality but didn’t raise any fundamental questions about the meta-analysis.
I could go on and address the bunch of tangential arguments but I’ll just stop here.
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