514 e-Letters

  • Authors make broad-reaching conclusions that are not supported by the facts

    The objective of the systematic review by Braznell et al. was â€œđ˜”đ˜° đ˜€đ˜łđ˜Șđ˜”đ˜Șđ˜€đ˜ąđ˜­đ˜­đ˜ș 𝘱𝘮𝘮𝘩𝘮𝘮 đ˜”đ˜©đ˜Š đ˜źđ˜Šđ˜”đ˜©đ˜°đ˜„đ˜°đ˜­đ˜°đ˜šđ˜Șđ˜€đ˜ąđ˜­ đ˜€đ˜©đ˜ąđ˜łđ˜ąđ˜€đ˜”đ˜Šđ˜łđ˜Șđ˜Žđ˜”đ˜Șđ˜€đ˜Ž đ˜ąđ˜Żđ˜„ đ˜Čđ˜¶đ˜ąđ˜­đ˜Șđ˜”đ˜ș 𝘰𝘧 đ˜Șđ˜Żđ˜”đ˜Šđ˜łđ˜·đ˜Šđ˜Żđ˜”đ˜Ș𝘰𝘯𝘱𝘭 đ˜€đ˜­đ˜Ș𝘯đ˜Șđ˜€đ˜ąđ˜­ đ˜”đ˜łđ˜Ș𝘱𝘭𝘮 đ˜Șđ˜Żđ˜·đ˜Šđ˜Žđ˜”đ˜Șđ˜šđ˜ąđ˜”đ˜Ș𝘯𝘹 đ˜”đ˜©đ˜Š đ˜Šđ˜§đ˜§đ˜Šđ˜€đ˜”đ˜Ž 𝘰𝘧 đ˜©đ˜Šđ˜ąđ˜”đ˜Šđ˜„ đ˜”đ˜°đ˜Łđ˜ąđ˜€đ˜€đ˜° đ˜±đ˜łđ˜°đ˜„đ˜¶đ˜€đ˜”đ˜Ž (𝘏𝘛𝘗𝘮).” Âč The review was intended to examine the quality of HTP clinical trials “𝘣𝘩𝘧𝘰𝘳𝘩 đ˜€đ˜°đ˜Żđ˜Žđ˜¶đ˜źđ˜Šđ˜łđ˜Ž đ˜ąđ˜Żđ˜„ đ˜łđ˜Šđ˜šđ˜¶đ˜­đ˜ąđ˜”đ˜°đ˜łđ˜Ž 𝘼𝘱𝘬𝘩 đ˜Șđ˜źđ˜±đ˜°đ˜łđ˜”đ˜ąđ˜Żđ˜” đ˜„đ˜Šđ˜€đ˜Ș𝘮đ˜Ș𝘰𝘯𝘮 đ˜Łđ˜ąđ˜Žđ˜Šđ˜„ 𝘰𝘯 đ˜”đ˜©đ˜Š đ˜łđ˜Šđ˜Žđ˜¶đ˜­đ˜”đ˜Ž 𝘰𝘧 đ˜”đ˜©đ˜Šđ˜Žđ˜Š đ˜Žđ˜”đ˜¶đ˜„đ˜Ș𝘩𝘮.” We have three important observations in relation to Philip Morris International’s (PMI) clinical program, which impact the interpretation of the authors’ broad-reaching conclusions.

    (𝟭) đ—„đ—Č𝗮𝘂đ—čđ—źđ˜đ—Œđ—żđ˜† đ—±đ—Čđ—°đ—¶đ˜€đ—¶đ—Œđ—»đ˜€ đ—”đ—źđ˜ƒđ—Č 𝗯đ—Čđ—Čđ—» đ—șđ—źđ—±đ—Č 𝗯𝗼𝘀đ—Čđ—± đ—Œđ—» 𝗣𝗠𝗜’𝘀 𝗰đ—čđ—¶đ—»đ—¶đ—°đ—źđ—č đ˜€đ˜đ˜‚đ—±đ—¶đ—Č𝘀, đ˜„đ—”đ—¶đ—°đ—” 𝘄đ—Č𝗿đ—Č đ—·đ˜‚đ—±đ—Žđ—Čđ—± đ˜đ—Œ 𝗯đ—Č 𝗼𝘁 đ—čđ—Œđ˜„ đ—żđ—¶đ˜€đ—ž đ—Œđ—ł đ—Żđ—¶đ—źđ˜€
    Whilst we will only comment on the clinical studies performed by PMI, we were pleased to see the confirmation that the study designs in our clinical assessment program were not significantly associated with a risk of bias. The authors judged that all Tobacco Heating System (marketed as IQOS) clinical studies submitted to the United States Food and Drug Administration (FDA) and other regulators were at low risk of bias when the authors excluded “blinding of participants and personnel” to the product, due to the impracticality of concealing visually distinctive products. The authors also noted that the scoring was slightly improved when compared to a similar exercise performed as part of the recent Cochrane review. ÂČ

    We agree that regulatory decisio...

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  • Health effects of heated tobacco products remain unknown.

    We appreciate the interest of the world’s largest transnational tobacco company, PMI,1 in our recent systematic review and would like to follow up on the points raised in Dr Baker’s rapid response.

    Our review did not seek to assess the harms or benefits of HTPs. As public health researchers we are most interested in the quality of studies according to whether they give reliable evidence of the health outcomes and public health impact of HTPs. We sought to critically appraise the quality of clinical trials on HTPs and lay out for Tobacco Control readers all aspects of their design which may have implications for interpretation, especially in regard to the potential impacts of HTPs.

    We decided to explore overall risk of bias when excluding the blinding of participants and personnel domain because we wanted to differentiate between studies. This is a really important domain. We excluded it because so few studies were judged to be at low risk of bias in this domain. Performance bias (which blinding if done well can guard against) remains an important source of bias that can influence study results, and one which was present in all of PMI's studies submitted to the U.S. Food and Drug Administration (FDA).1 As we explain in our risk of bias assessments, the consequences of this bias could have been minimised had the control intervention been active. Likewise, PMI’s withdrawal of its carbon-heated tobacco product from the market, which o...

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  • No uncertainty exists around the failure of novel products as harm reduction strategies in Italy

    We welcome discussion of our research even when it comes from those whose view on accepting tobacco industry funding is very different from ours. Tomaselli and Caponnetto, from the Center of Excellence for the acceleration of HArm Reduction (CoEHAR),[1] a group funded by the Foundation for a Smoke-Free World (FSFW), an organisation established by Philip Morris International (PMI) with funding of US$1 billion that promotes electronic cigarettes (e-cigarette) and heated tobacco products (HTP),[2] take issue with our finding [3] that these products increase smoking initiation and relapse and reduce quitting. [4]
    First, we are puzzled by their main criticism. Of course we agree that smokers who have failed to quit, ex-smokers prone to relapse, and never smokers prone to engage in addictive behaviours could be overrepresented among the baseline e-cigarette or HTP users in our study.[4] But this does not undermine our main conclusions. Even if we were to assume that either none or all novel product users in our cohort were more prone to addiction, our results would still be incompatible with the argument, which underpins the work of FSFW, that these products can reduce smoking conventional cigarettes when used as consumer products.
    Second, we hope that they agree with us that we should consider the totality of evidence on a topic as it is rare for a single study to provide a definitive answer, and especially given the record of the tobacco ind...

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  • Response to critiques on Asfar et al. in Tobacco Control: “Risk and safety profile of electronic nicotine delivery systems (ENDS): an umbrella review to inform ENDS health communication strategies.”

    We thank Cummings and colleagues for their interest in and comments on our umbrella review published recently in Tobacco Control.[1] The authors criticize us for not including the latest studies. Yet, for an umbrella review, those studies need to be in a published review to be included, as we indicated in our methods and limitations. Generally, given the lengthy review and publication processes, any review will not be inclusive of all studies in a field that has as high a publication breadth and intensity as tobacco regulatory science. In addition, the authors mentioned that our meta-analysis was not available in PROSPERO pre-registration. This is because the review registration was completed in the very early stages of the review. We have updated this information in PROSPERO now to include the meta-analysis. The issue of overlap was addressed in our limitations, as we had to screen over 3,000 studies included in our selected reviews. However, given the importance of this issue for the meta-analysis, we performed a new meta-analysis that included the individual studies in each domain instead of using the odds ratio reported by the review to eliminate the effect of including the same study more than one time on our results. We confirm that the results of the new meta-analysis, which includes each study only once, are similar to the original meta-analysis (Supplement A: https://www.publichealth.me...

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  • Inappropriate study design cannot predict smoking initiation and relapse with e-cigarette and heated tobacco product use

    The study by Gallus et al. [1] sought to establish whether electronic cigarettes (ECs) and heated
    tobacco products (HTPs) reduce or increase the probability of smoking in a cohort of Italian
    participants and concluded that both EC and HTP use predict smoking initiation and relapse
    among respondents. We would like to raise some concerns about the interpretation of the study
    findings. The study suffers from a potentially crucial bias of the outcome being present at baseline, as
    compared non-users with people who were already using products at baseline. Specifically,
    smokers who were using ECs or HTPs at baseline may already represent failed attempts to quit at
    baseline. Additionally, ex-smokers using these products may have already been in a trajectory to
    relapse to smoking at, or even long before, baseline, and may in fact have initiated such product
    use in order to avoid relapse. Still, this group may represent ex-smokers who were at higher risk
    for relapsing at baseline compared to ex-smokers who did not use these products. Similarly,
    never smokers who use novel nicotine products may represent individuals prone to the
    engagement of an inhalational habit. Therefore, they would be more likely to initiate smoking.
    The situation is very similar to assessing if people who drink beer at baseline are more likely to
    drink whiskey at follow up compared to non-drinkers of bee...

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  • Implications made about JUUL products in this study are contradicted by our own contemporaneous and detailed product and manufacturing records, and are more readily explained by a methodological artifact that the authors have not fully reported

    Authors previewed this study on March 16, 2022, at the Annual Meeting of the Society for Research on Nicotine and Tobacco[1]. Prompted by this presentation, on April 5, 2022, I emailed Drs. Talih, Eissenberg, and Shihadeh with product-specific information and questions that raised substantial doubt in the authors’ claims about JUUL products, specifically the purported modification of Menthol JUULpods.

    Due to word limits here, we have posted a full copy of my email to the authors on PubPeer[2]. This email predated by almost a month the authors’ submission to the journal. Below please find an excerpt from this correspondence:

    “In your presentation, you conclude that Juul Labs has in some way altered or otherwise modified its e-liquid formulations, but these claims are incorrect. Juul Labs has not altered or modified these e-liquid formulations since they were introduced into the market before August 2016 (i.e., FDA’s deeming date). We have supporting documentation, including batch records and certificates of analysis to confirm this.

    “Setting aside any issues with methodologies or environmental conditions in the study, there are a number of possible explanations for the variations you found. For example, one potential explanation for the differences in tested products is the loss of menthol over time. It is well-documented in scientific literature[3] that menthol may migrate from areas of high concentration to low concentration,...

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  • Comments on paper by Asfar et al. “Risk and safety profile of electronic nicotine delivery systems (ENDS): an umbrella review to inform ENDS health communication strategies”

    The paper by Asfar et al (1) had a noble objective, which was to inform ENDS health risk communications by updating the 2018 evidence review by the US. National Academies of Sciences, Engineering and Medicine (NASEM) (2). The need for improved risk communications about ENDS is reinforced by a recent study which found that only 17.4% of US smokers believe that nicotine vaping is safer than smoking (3). While ENDS use is not safe, the evidence from toxicant exposure studies does show that ENDS use is far safer than smoking cigarettes and may benefit public health by assisting those who smoke to quit smoking (4, 5).
    An important limitation of the umbrella review method utilized by the authors is that it does not directly attempt to systematically characterize new research. This is a concern because the marketplace of ENDS products used by consumers has evolved since the 2018 NASEM report (4, 5). Furthermore, the authors have included some meta-analyses of selected reviews for some domains, but these meta-analyses were not in the Prospero pre-registration (6), nor explained in the paper. It’s thus unclear how or why certain reviews were selected for meta-analysis, and also whether the comparators are the same for these reviews. More importantly, these meta-analyses risk single studies contributing multiple times to the same pooled estimate. The authors noted this as a limitation commenting inaccurately that ‘it was impossible to identify articles that were included in...

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  • Revisiting the Research on Flavor Bans and Youth Smoking: A Response to Liu et al (2022)

    On March 17th, 2021, Tobacco Control published a paper online revealing that the 2019 wave of the Youth Risk Behavior Surveillance System (YRBSS) in San Francisco was fielded in the fall of 2018, as opposed to spring of 2019 as is typical for that survey. [1] On March 21st 2022, I received confirmation from San Francisco’s YRBSS site coordinator that the 2019 wave was fielded from November 5th, 2018 to December 14th, 2018. I appreciate Liu and colleagues bringing this to light. However, their claim that this information invalidates the findings from my 2021 JAMA Pediatrics paper [2] —linking San Francisco’s ban on sales of flavored tobacco and nicotine products to increases in youth cigarette smoking—is both methodologically and historically inaccurate: it overlooks both the assumptions required for difference-in-differences research designs and the full timeline of San Francisco’s flavor ban implementation.

    In its simplest form, a difference-in-difference (DD) analysis of a particular policy compares outcomes in jurisdictions that did vs. did not adopt the policy, before vs. after that policy officially went into effect (See Figure at https://figshare.com/articles/figure/Figure_1_BasicDDExplanation_pdf/203...). If time-trends in the adopting and non-adopting jurisdictions’ outcomes were parallel in the pre-policy period, the non-adopters’ trends are c...

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  • In reply: Youth tobacco use before and after flavoured tobacco sales restrictions in Oakland, California and San Francisco, California

    These arguments by Pesko and Friedman cannot undo the central flaw in the Friedman paper. We are surprised that Pesko and Friedman continue to argue that Friedman’s analysis of the YRBSS fall data as “after” data is valid despite the Friedman paper defining the exposure variable as follows: “A binary exposure variable captured whether a complete ban on flavoured tobacco product sales was in effect in the respondent’s district on January 1 of the survey year.”[1] If Friedman had intended to treat the period immediately after July 21 2018 as the “after” period, why had she not selected July 21 of each year as the cut-off date for indicating exposure to the policy effects? It seems apparent that Friedman chose the January 1, 2019 as the cut-off for “after” data because she knew this was the enforcement date and she assumed wrongly that the YRBSS data were collected after January 1, 2019. This is evident in her own response[2] to a critique[3] of her paper as we already noted in our previous response.[4]
    Friedman states that “the official/legislated effective date are used to ensure that resulting estimates capture unconfounded responses to the policy change.” Again, if this approach made sense in the specific San Francisco case, why did Friedman use January 1, 2019 in her paper? Perhaps because it simply doesn’t make sense to attribute a policy’s effects before the policy is actually implemented. Similarly, the use of enforcement date rather than...

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  • Friedman's Use of a Pre-Post Study Design was Appropriate

    After seeing the response from the authors of “Youth tobacco use before and after flavored tobacco sales restrictions in Oakland, California and San Francisco, California” to the Rapid Response, “Scientific Concerns,” I was dismayed by the reply of the authors that dismissed the efforts of fellow scientists to rigorously discern the effects of flavored tobacco sales restrictions. The central point of their critique of Friedman’s paper is that it only contains pre-flavored tobacco product sales ban datapoints. Hence, a pre-post difference-in-differences design is inappropriate. Friedman most certainly had post-data in her sample. Despite the criticisms from Liu et al, they have not unseated her primary contribution; after a policy change, youth tobacco use behavior in San Francisco changed. Liu et al. provide no rigorous counter-analysis on this point. The author’s argument that no behavior had changed in San Francisco during YBRSS data collection in late 2018 falls apart at close inspection.
    First, Liu et al. claim the flavored tobacco sales ban was not yet affecting retailer behavior in late 2018. This question is binary; it can either be answered yes or no. As of July 21, 2018, it was not legal to sell flavored tobacco products in San Francisco. No grace period was in place. Sales of all prohibited flavored products plummeted in the months after the policy became effective (Gammon et al., 2021 ; Table S1). However, sales did not reach zero,...

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