NOT PEER REVIEWED
I read with interest the article "Global tobacco advertising, promotion, and sponsorship regulation: what’s old, what’s new, and where to next?[1]" published in Tobacco Control. As a psychiatrist specializing in addiction treatment at Taoyuan Psychiatric Center in Taiwan, I wish to share our institution's experience in implementing a successful smoke-free hospital program, which may serve as a model for other psychiatric centers.
Since 2014, Taoyuan Psychiatric Center has made significant progress in promoting a smoke-free environment through a comprehensive tobacco control program. Our program's objectives include creating a smoke-free hospital, increasing smoking cessation services for outpatients and inpatients, and improving patient smoking status documentation. Furthermore, we prioritize smoking cessation counseling for adolescents, pregnant women, and their families.
In psychiatric settings, smoking cessation is crucial as tobacco use can influence the blood concentration of psychotropic medications, potentially destabilizing psychiatric symptoms. Assisting patients in quitting smoking not only lowers the risk of tobacco-related diseases but also contributes to stabilizing their psychiatric conditions.
Our program encompasses various initiatives, including staff training, community tobacco harm prevention promotion, provision of second-generation smoking cessation treatments for outpatients and inpatien...
NOT PEER REVIEWED
I read with interest the article "Global tobacco advertising, promotion, and sponsorship regulation: what’s old, what’s new, and where to next?[1]" published in Tobacco Control. As a psychiatrist specializing in addiction treatment at Taoyuan Psychiatric Center in Taiwan, I wish to share our institution's experience in implementing a successful smoke-free hospital program, which may serve as a model for other psychiatric centers.
Since 2014, Taoyuan Psychiatric Center has made significant progress in promoting a smoke-free environment through a comprehensive tobacco control program. Our program's objectives include creating a smoke-free hospital, increasing smoking cessation services for outpatients and inpatients, and improving patient smoking status documentation. Furthermore, we prioritize smoking cessation counseling for adolescents, pregnant women, and their families.
In psychiatric settings, smoking cessation is crucial as tobacco use can influence the blood concentration of psychotropic medications, potentially destabilizing psychiatric symptoms. Assisting patients in quitting smoking not only lowers the risk of tobacco-related diseases but also contributes to stabilizing their psychiatric conditions.
Our program encompasses various initiatives, including staff training, community tobacco harm prevention promotion, provision of second-generation smoking cessation treatments for outpatients and inpatients with mental disorders, and organizing smoking cessation support groups and counseling. These efforts have led to a substantial increase in patients receiving smoking cessation services and a considerable decline in smoking rates among staff and patients.
In conclusion, Taoyuan Psychiatric Center's experience can serve as a valuable example for psychiatric institutions aiming to implement successful tobacco control programs. By addressing psychiatric patients' unique challenges, we can significantly impact their physical and mental well-being while contributing to global tobacco control efforts.
Sincerely,
Dr. LienChung Wei
Psychiatrist specializing in Addiction Treatment
Taoyuan Psychiatric Center, Taiwan
Reference:
[1] Freeman B, Watts C, Astuti PAS. Global tobacco advertising, promotion and sponsorship regulation: what’s old, what’s new and where to next? 2022;31(2):216-221.
NOT PEER REVIEWED
We acknowledge receipt of a private e-mail message from JLI regarding our paper (Yassine et al., 2022). Given the industry‘s long history of industry obfuscation, interference, and deception regarding research on tobacco products, we decided that the most transparent approach to the private e-mail that we received from an employee of a tobacco product manufacturer would be for us to report our results independently and respond to any public discussion of our work if and when it arose. Now that public discussion has arisen, we are pleased to respond to it.
We very recently analyzed the menthol and nicotine content of samples of liquid from six menthol flavor pods purchased in 2020. Three of these were liquids extracted from the pods in June 2021 for our paper and had been stored since in sealed amber glass containers at 5°C in the dark. The other three pods had been stored in their original sealed packages and were taken from the same batches as the pods analyzed in June 2021. These unopened packages were stored in the dark at room temperature over the intervening 18 months. The data from this small sample demonstrate a 24% reduction in menthol content over that period (12.01±0.46 vs 9.15±0.22 mg/ml), which helps to explain the results we reported (Yassine et al., 2022). We also found a 5% reduction in nicotine content (62.47±0.63 vs 59.52±0.49 mg/ml), as well as discoloration of the liquid in the pods that were stored at room temperatur...
NOT PEER REVIEWED
We acknowledge receipt of a private e-mail message from JLI regarding our paper (Yassine et al., 2022). Given the industry‘s long history of industry obfuscation, interference, and deception regarding research on tobacco products, we decided that the most transparent approach to the private e-mail that we received from an employee of a tobacco product manufacturer would be for us to report our results independently and respond to any public discussion of our work if and when it arose. Now that public discussion has arisen, we are pleased to respond to it.
We very recently analyzed the menthol and nicotine content of samples of liquid from six menthol flavor pods purchased in 2020. Three of these were liquids extracted from the pods in June 2021 for our paper and had been stored since in sealed amber glass containers at 5°C in the dark. The other three pods had been stored in their original sealed packages and were taken from the same batches as the pods analyzed in June 2021. These unopened packages were stored in the dark at room temperature over the intervening 18 months. The data from this small sample demonstrate a 24% reduction in menthol content over that period (12.01±0.46 vs 9.15±0.22 mg/ml), which helps to explain the results we reported (Yassine et al., 2022). We also found a 5% reduction in nicotine content (62.47±0.63 vs 59.52±0.49 mg/ml), as well as discoloration of the liquid in the pods that were stored at room temperature that suggests the possibility of other time-dependent changes in liquid constituents that we have not had an opportunity to evaluate comprehensively.
We acknowledge that the differences in menthol concentrations in JUUL products that were purchased across a three-year period, reported in Yassine et al., 2022, are consistent with changes in product composition that can occur during storage. A correction to the manuscript is now being published.
Our findings highlight that tobacco product manufacturers should be required to release to the public and the scientific community everything they know about their products, including product ingredients, abuse liability, potential adverse health consequences, and time- and temperature-dependent degradation of quality. For example, much of this information may be available in Premarket Tobacco Product Applications submitted to the Food and Drug Administration’s Center for Tobacco Products, and thus could be shared easily on each company’s website. This vital information should be available to all. In the meantime, our original article (Yassine et al., 2022), the industry response (Gillman, 2022), and this reply provide needed archival documentation for the scientific record.
References
Yassine A, El Hage R, El-Hellani A, Salman R, Talih S, Eissenberg T, Shihadeh A, Saliba N. Did JUUL alter the content of menthol pods in response to US FDA flavour enforcement policy? Tob Control. 2022 Nov;31(Suppl 3):s234-s237. doi: 10.1136/tc-2022-057506. PMID: 36328458; PMCID: PMC9641543.
NOT PEER REVIEWED
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,...
NOT PEER REVIEWED
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, and therefore flavor levels may decrease over time.” [4][5][6][7]
I never received a reply to this email from the publication’s authors and the manuscript does not recognize the issues that were raised, nor does it provide sufficient information to address the most likely flaw in the authors’ interpretation: that likely the loss of menthol during product storage played a vital and determinative role in the lower menthol amount observed in the aged JUULpods purchased in 2017 and 2018.
We request that Tobacco Control require the authors to provide detailed information regarding the timing of their analyses and ideally responses to all of the issues raised in our email to them. We would furthermore appreciate the opportunity to share with Tobacco Control the documentation I referenced in my initial email to study authors - including batch records and certificates of analysis - that demonstrate that we made no changes to our products’ formulations.
Assuming this further engagement demonstrates to the editors that the authors’ assertions that Juul Labs altered its products are unfounded, we ask that this article be retracted.
Dr. Gene Gillman
Vice President, Regulatory Chemistry
Juul Labs
NOT PEER REVIEWED
I would like to make three comments by way of a brief post-publication review.
1. The impacts of vaping tax on smoking have been completely overlooked
For a study of e-cigarette taxation to have any public health relevance, it must consider the impact of e-cigarette prices on *cigarette* demand. Cigarettes and e-cigarettes are economic substitutes. The demand for one responds to changes in the price of the other, an idea well understood in economics and quantified through the concept of cross-elasticity. The paper appears to pay no regard to the impact of vaping taxes on cigarette demand, Yet such effects might easily overwhelm any benefits from reduced e-cigarette use - in fact, impact on demand for other tobacco products and the development of informal markets are by far the most important impacts of a vaping tax. By way of example, a 2020 paper by Pesko et al. [1] concluded:
"Our results suggest that a proposed national e-cigarette tax of $1.65 per milliliter of vaping liquid would raise the proportion of adults who smoke cigarettes daily by approximately 1 percentage point, translating to 2.5 million extra adult daily smokers compared to the counterfactual of not having the tax."
2. The case for reducing adult vaping by taxation has not been made
The authors have based their paper on an unexamined assumption that it is a justifiable goal of policy to lower rates of adult e-cigarette use. Why should...
NOT PEER REVIEWED
I would like to make three comments by way of a brief post-publication review.
1. The impacts of vaping tax on smoking have been completely overlooked
For a study of e-cigarette taxation to have any public health relevance, it must consider the impact of e-cigarette prices on *cigarette* demand. Cigarettes and e-cigarettes are economic substitutes. The demand for one responds to changes in the price of the other, an idea well understood in economics and quantified through the concept of cross-elasticity. The paper appears to pay no regard to the impact of vaping taxes on cigarette demand, Yet such effects might easily overwhelm any benefits from reduced e-cigarette use - in fact, impact on demand for other tobacco products and the development of informal markets are by far the most important impacts of a vaping tax. By way of example, a 2020 paper by Pesko et al. [1] concluded:
"Our results suggest that a proposed national e-cigarette tax of $1.65 per milliliter of vaping liquid would raise the proportion of adults who smoke cigarettes daily by approximately 1 percentage point, translating to 2.5 million extra adult daily smokers compared to the counterfactual of not having the tax."
2. The case for reducing adult vaping by taxation has not been made
The authors have based their paper on an unexamined assumption that it is a justifiable goal of policy to lower rates of adult e-cigarette use. Why should this be a policy goal any more than reducing caffeine use or moderate alcohol use? The goal of public health policy is to address significant harms or self-destructive patterns of use, not to modify behaviours that the authors find distasteful. What are the harms that justify state intervention to reduce adult vaping with a tax? Further, they appear indifferent to welfare costs and the distributional impact of imposing a regressive tax burden on people who use vaping products. Tobacco control advocates should become more familiar with the idea that punitive policies impose harm on users, even though these users are supposed to be the intended beneficiaries. For example, a vaping tax harms families by drawing on the household budget of those who continue to vape.
3. The analysis to support the policy recommendations is wholly inadequate
The authors make over-confident policy recommendations without considering the full range of impacts of the measures they are proposing.
"Our findings suggest that adopting a vaping product excise tax policy may help reduce ENDS use and suppress the increase of ENDS use prevalence among young adults. Considering that there are still a number of US states that have not implemented vaping product excise tax policy, wider adoption of such policy across the nation would likely help mitigate ENDS use prevalence."
Without considering all the possible responses to the tax they support, they may easily be proposing tobacco control policies that do more harm than good. In fact, the most important public health impact of this policy is entirely excluded from the analysis. That is the effect of a vaping tax on smoking or other tobacco use. Given the two orders of magnitude difference in risk between smoking and vaping, only a tiny uptick in smoking would be needed to completely offset the benefits, if any, arising from reduced vaping
NOT PEER REVIEWED
I have a number of concerns with the paper as currently written.
1) The authors write: “Besides, none of the previous studies except Pesko et al (15) that examined the associations between vaping product excise tax adoption and ENDS use has accounted for the clustering of respondents within the same localities…” This is not accurate, as citation 19 also clusters standard errors at the locality level in all specifications.
2) The authors write: "A working paper reported reduced ENDS sales, but not ENDS use prevalence or behaviours, after implementation of a vaping product excise tax policy. (19)” This is not accurate, as the cited study uses the magnitude of e-cigarette tax values, rather than an indicator variable for tax implementation. States have adopted e-cigarette taxes of different magnitudes and a number of them (such as California) have changed the magnitudes of these taxes after adoption. All of this variation is used in citation 19, contrary to the current study’s description. It's also unclear from the sentence whether citation 19 studied use and found imprecise estimates, or did not study use. It's the latter and this should be clarified. It's also unclear why the authors did not use magnitude of e-cigarette taxes themselves in the current paper, as has been commonly done in the referenced literature.
3) Authors write they use a “nationally representative sample of US young adults.” I do not beli...
NOT PEER REVIEWED
I have a number of concerns with the paper as currently written.
1) The authors write: “Besides, none of the previous studies except Pesko et al (15) that examined the associations between vaping product excise tax adoption and ENDS use has accounted for the clustering of respondents within the same localities…” This is not accurate, as citation 19 also clusters standard errors at the locality level in all specifications.
2) The authors write: "A working paper reported reduced ENDS sales, but not ENDS use prevalence or behaviours, after implementation of a vaping product excise tax policy. (19)” This is not accurate, as the cited study uses the magnitude of e-cigarette tax values, rather than an indicator variable for tax implementation. States have adopted e-cigarette taxes of different magnitudes and a number of them (such as California) have changed the magnitudes of these taxes after adoption. All of this variation is used in citation 19, contrary to the current study’s description. It's also unclear from the sentence whether citation 19 studied use and found imprecise estimates, or did not study use. It's the latter and this should be clarified. It's also unclear why the authors did not use magnitude of e-cigarette taxes themselves in the current paper, as has been commonly done in the referenced literature.
3) Authors write they use a “nationally representative sample of US young adults.” I do not believe this is not accurate. The TUS-CPS sample itself may be nationally representative, but this representativeness may be lost when subgroups are explored.
4) The “vaping product excise tax policy” variable in Table 3 appears to be re-defined mid-table. Based on the discussion of the results, in column 1 it appears that this variable is an indicator equal to 1 only at the time when a state has an e-cigarette tax in place. In column 2 though, this indicator equals 1 when a state ever has an e-cigarette tax in place (even prior to it being in place). The use of the same row for a variable that changes across columns is unusual and can easily lead to the wrong interpretation.
We appreciate the comments from Bates and the opportunity for us to respond and clarify.
First, Bates' argument heavily relies on the assumption that e-cigarettes and combustible cigarettes are substitutes, which is theoretically possible as some consider vaping as a harm reduction alternative to combustible cigarettes. Empirically, however, there have been mixed findings about whether e-cigarettes and combustible cigarettes are substitutes (or complements). Bates cited Pesko et al. (2020) that concludes e-cigarettes and combustible cigarettes are substitutes, whereas other studies have shown that they are complements. For example, Cotti et al. (2018) found that higher cigarette excise taxes, in fact, decrease sales of both e-cigarettes and combustible cigarettes, suggesting that they are complements. Such mixed results abate Bates' argument that taxing ENDS could lead to more use of combustible cigarettes.
Second, Bates might have ignored that our study focused on young adults aged 18-24 years rather than general adults when examining the effect of vaping product tax on e-cigarette use. Although Pesko et al. (2020) suggests that e-cigarettes and combustible cigarettes are substitutes, the findings are based on the general adult population (average age: 55 years) which may not be generalizable to the young adult population. In fact, one study conducted by Abouk and Adams (2017) indicates that e-cigarettes and combustible ci...
We appreciate the comments from Bates and the opportunity for us to respond and clarify.
First, Bates' argument heavily relies on the assumption that e-cigarettes and combustible cigarettes are substitutes, which is theoretically possible as some consider vaping as a harm reduction alternative to combustible cigarettes. Empirically, however, there have been mixed findings about whether e-cigarettes and combustible cigarettes are substitutes (or complements). Bates cited Pesko et al. (2020) that concludes e-cigarettes and combustible cigarettes are substitutes, whereas other studies have shown that they are complements. For example, Cotti et al. (2018) found that higher cigarette excise taxes, in fact, decrease sales of both e-cigarettes and combustible cigarettes, suggesting that they are complements. Such mixed results abate Bates' argument that taxing ENDS could lead to more use of combustible cigarettes.
Second, Bates might have ignored that our study focused on young adults aged 18-24 years rather than general adults when examining the effect of vaping product tax on e-cigarette use. Although Pesko et al. (2020) suggests that e-cigarettes and combustible cigarettes are substitutes, the findings are based on the general adult population (average age: 55 years) which may not be generalizable to the young adult population. In fact, one study conducted by Abouk and Adams (2017) indicates that e-cigarettes and combustible cigarettes are not substitutes for young people. Established cigarette smokers may use e-cigarettes as a cessation tool but it is less common in young adults. In addition, even if e-cigarettes and combustible cigarettes are substitutes to some degree, the direction of substitution as well as co-use versus subsequent use should not be overlooked. Studies have shown that e-cigarettes may serve as a gateway to future combustible cigarette smoking among young people. For example, a study conducted by Hair et al. (2021) shows that youth and young adults who reported ever e-cigarette use had significantly higher odds of ever cigarette use one year later. Therefore, e-cigarette use versus combustible cigarette smoking is not simply an issue of substitution in particular among young people.
Disclosure: We did not receive any funding from the tobacco industry.
References:
1. Abouk, R., & Adams, S. (2017). Bans on electronic cigarette sales to minors and smoking among high school students. Journal of Health Economics, 54, 17-24.
2. Cotti, C., Nesson, E., & Tefft, N. (2018). The relationship between cigarettes and electronic cigarettes: Evidence from household panel data. Journal of Health Economics, 61, 205-219.
3. Hair, E. C., Barton, A. A., Perks, S. N., Kreslake, J., Xiao, H., Pitzer, L., ... & Vallone, D. M. (2021). Association between e-cigarette use and future combustible cigarette use: Evidence from a prospective cohort of youth and young adults, 2017–2019. Addictive Behaviors, 112, 106593.
4. Pesko, M. F., Courtemanche, C. J., & Maclean, J. C. (2020). The effects of traditional cigarette and e-cigarette tax rates on adult tobacco product use. Journal of Risk and Uncertainty, 60(3), 229-258.
NOT PEER REVIEWED
We thank Pesko for his comments and the opportunity for us to respond and clarify.
First, we appreciate Pesko’s clarification that Cotti et al. (2020) clustered standard errors to account for clustering. In the present study, we used multilevel analysis not only to account for clustering of respondents (i.e., design effects) but also to incorporate different error terms for different levels of the data hierarchy which yields more accurate Type I error rates than nonhierarchical methods where all unmodeled contextual information ends up pooled into a single error term of the model.
Second, we understand that Cotti et al. (2020) evaluated the magnitude of e-cigarette tax values, which does not contradict to our statement because our study focused on the effects of e-cigarette excise tax policies on individual e-cigarette use and prevalence rather than aggregated sales at state or county levels. We also clearly described the reason why we examined the e-cigarette excise tax policy implementation indicator rather than its magnitude in our paper’s discussion section.
Third, our study used a nationally representative sample of young adults (rather than a nationally representative sample of general adult population). While we understand Pesko’s concern that a sample’s representativeness might be lost when subgroups are explored, we believe our use of sampling weights in analysis has reduced such a concern.
NOT PEER REVIEWED
We thank Pesko for his comments and the opportunity for us to respond and clarify.
First, we appreciate Pesko’s clarification that Cotti et al. (2020) clustered standard errors to account for clustering. In the present study, we used multilevel analysis not only to account for clustering of respondents (i.e., design effects) but also to incorporate different error terms for different levels of the data hierarchy which yields more accurate Type I error rates than nonhierarchical methods where all unmodeled contextual information ends up pooled into a single error term of the model.
Second, we understand that Cotti et al. (2020) evaluated the magnitude of e-cigarette tax values, which does not contradict to our statement because our study focused on the effects of e-cigarette excise tax policies on individual e-cigarette use and prevalence rather than aggregated sales at state or county levels. We also clearly described the reason why we examined the e-cigarette excise tax policy implementation indicator rather than its magnitude in our paper’s discussion section.
Third, our study used a nationally representative sample of young adults (rather than a nationally representative sample of general adult population). While we understand Pesko’s concern that a sample’s representativeness might be lost when subgroups are explored, we believe our use of sampling weights in analysis has reduced such a concern.
Fourth, in Table 3, please note that vaping product excise tax policy indicator is a time-variant variable in Model 1. However, to present results of a standard difference-in-differences model with a binary indicator, the policy implementation status was operationalized as a time-invariant variable in Model 2, which is not unusual.
Disclosure: We did not receive any funding from the tobacco industry.
References
1. Cotti, C. D., Courtemanche, C. J., Maclean, J. C., Nesson, E. T., Pesko, M. F., & Tefft, N. (2020). The effects of e-cigarette taxes on e-cigarette prices and tobacco product sales: evidence from retail panel data. National Bureau of Economic Research. NBER Working Paper No. w26724.
NOT PEER REVIEWED
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...
NOT PEER REVIEWED
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 occurred after our first literature searches, does not excuse the substandard aspects of these trials, including selective reporting of study results.
We are perplexed by Dr Baker's argument that PMI’s clinical studies were designed to meet specific FDA requirements and “are not designed to assess the overall impact of HTPs on public health”. In its assessment the FDA aims to "evaluat[e] the benefit to health of individuals and of the population as a whole" (pg 8)2. As Dr Baker explains, PMI included its clinical studies as evidence on the relative risks of IQOS in its application to the FDA. While we concur no one study could wholly assess the impact of HTPs on public health, each clinical study indirectly or directly assesses this to some extent, whether it be assessing the impact of HTPs on exposure to harmful chemicals or on health outcomes. In the words of PMI's Chief Life Sciences Officer, PMI conducts "biomarker, clinical outcome and real-world evidence studies to demonstrate individual clinical and public health benefit of our smoke-free products."3
On the one hand, PMI suggests its clinical studies are appropriate evidence in establishing whether HTPs are beneficial to public health. Yet, Dr Baker's response contradictorily indicates PMI's studies were never designed to address this question and, in fact, agrees with our conclusion that they are therefore inadequate in assessing whether HTPs are beneficial to public health.
Our review found the existing HTP clinical trials provide evidence on exposure to toxicants compared to cigarettes, but fall short of what is needed to determine whether HTPs reduce the risks of tobacco-related diseases and whether they are beneficial to public health in real-world settings. This is in line with the FDA’s conclusions that PMI "has not demonstrated that, as actually used by consumers, the products sold or distributed with the proposed modified risk information will significantly reduce harm and the risk of tobacco‐related disease to individual tobacco users and benefit the health of the population as a whole, taking into account both users of tobacco products and persons who do not currently use tobacco products" (pg8, emphasis in original)1. We agree with the FDA, as quoted by Dr Baker, that subsequent studies are needed to establish the public health impact of HTPs.
Our review focused on clinical trials as giving the best evidence of a causal effect, but we read the two longer term observational studies Dr Baker points us to with interest. We do note that neither study is able to separate the population health effects of different cigarette alternatives or cessation interventions. We agree longer clinical and epidemiological studies are required to determine the harms or benefits of HTPs. We are pleased such studies are emerging in the literature and we look forward to reading the results of PMI's ongoing studies referenced by Dr Baker. We hope that despite the FDA’s MRTP authorisation for IQOS, PMI will remain incentivised to publish these new longer-term studies with clinical outcomes, as well as the observational study it has already completed.4
We are glad our review provided useful insight to PMI for areas of improvement. Improving future clinical research was fundamental in our desire to conduct this review. PMI's application to the FDA was a valuable source of data which have not been published in traditional academic literature. For future reviewers, the full-length reports provide a greater depth and breadth of clinical data, including data on outcomes yet to be reported in journal articles. The full reports included in the FDA application have been uploaded to PMI's data sharing website, INTERVALS.5 Unfortunately, PMI has not yet made full reports available for all its clinical studies. We encourage PMI to not only publish its study results in a timelier manner, but also to publish the full clinical study reports, which provide far greater detail and results than its journal publications.
With regards to our own funding and conflicts of interest, we accurately declared these as per Tobacco Control's policies. We note, once again, that no funders had any role or input in the design, conduct or reporting of our study.
References
1. Tobacco Tactics. Philip Morris International. 2022. Available: https://tobaccotactics.org/wiki/philip-morris-international/ [accessed 9th December 2022].
2. US Food & Drug Administration. Scientific Review of Modified Risk Tobacco Product Application (MRTPA) Under Section 911(d) of the FD&C Act -Technical Project Lead 2020. Available: https://www.fda.gov/media/139796/download [accessed 9th December 2022].
3. Insuasty, J. A letter from our Chief Life Sciences Officer. PMI Science. Available: https://www.pmiscience.com/en/about/welcome-to-pmi-science/ [accessed 9th December 2022].
4. Sponsiello-Wang Z, Langer P, Prieto L, et al. Household Surveys in the General Population and Web-Based Surveys in IQOS Users Registered at the Philip Morris International IQOS User Database: Protocols on the Use of Tobacco- and Nicotine-Containing Products in Germany, Italy, and the United Kingdom (Greater London), 2018-2020. JMIR Res Protoc. 2019; 8(5):e12061. doi: 10.2196/12061. PMID: 31094340; PMCID: PMC6532333.
5. INTERVALS. 2022. Available: https://intervals.science/homepage [accessed 9th December 2022].
NOT PEER REVIEWED
The objective of the systematic review by Braznell et al. was “𝘵𝘰 𝘤𝘳𝘪𝘵𝘪𝘤𝘢𝘭𝘭𝘺 𝘢𝘴𝘴𝘦𝘴𝘴 𝘵𝘩𝘦 𝘮𝘦𝘵𝘩𝘰𝘥𝘰𝘭𝘰𝘨𝘪𝘤𝘢𝘭 𝘤𝘩𝘢𝘳𝘢𝘤𝘵𝘦𝘳𝘪𝘴𝘵𝘪𝘤𝘴 𝘢𝘯𝘥 𝘲𝘶𝘢𝘭𝘪𝘵𝘺 𝘰𝘧 𝘪𝘯𝘵𝘦𝘳𝘷𝘦𝘯𝘵𝘪𝘰𝘯𝘢𝘭 𝘤𝘭𝘪𝘯𝘪𝘤𝘢𝘭 𝘵𝘳𝘪𝘢𝘭𝘴 𝘪𝘯𝘷𝘦𝘴𝘵𝘪𝘨𝘢𝘵𝘪𝘯𝘨 𝘵𝘩𝘦 𝘦𝘧𝘧𝘦𝘤𝘵𝘴 𝘰𝘧 𝘩𝘦𝘢𝘵𝘦𝘥 𝘵𝘰𝘣𝘢𝘤𝘤𝘰 𝘱𝘳𝘰𝘥𝘶𝘤𝘵𝘴 (𝘏𝘛𝘗𝘴).” ¹ The review was intended to examine the quality of HTP clinical trials “𝘣𝘦𝘧𝘰𝘳𝘦 𝘤𝘰𝘯𝘴𝘶𝘮𝘦𝘳𝘴 𝘢𝘯𝘥 𝘳𝘦𝘨𝘶𝘭𝘢𝘵𝘰𝘳𝘴 𝘮𝘢𝘬𝘦 𝘪𝘮𝘱𝘰𝘳𝘵𝘢𝘯𝘵 𝘥𝘦𝘤𝘪𝘴𝘪𝘰𝘯𝘴 𝘣𝘢𝘴𝘦𝘥 𝘰𝘯 𝘵𝘩𝘦 𝘳𝘦𝘴𝘶𝘭𝘵𝘴 𝘰𝘧 𝘵𝘩𝘦𝘴𝘦 𝘴𝘵𝘶𝘥𝘪𝘦𝘴.” 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) 𝗥𝗲𝗴𝘂𝗹𝗮𝘁𝗼𝗿𝘆 𝗱𝗲𝗰𝗶𝘀𝗶𝗼𝗻𝘀 𝗵𝗮𝘃𝗲 𝗯𝗲𝗲𝗻 𝗺𝗮𝗱𝗲 𝗯𝗮𝘀𝗲𝗱 𝗼𝗻 𝗣𝗠𝗜’𝘀 𝗰𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝘀𝘁𝘂𝗱𝗶𝗲𝘀, 𝘄𝗵𝗶𝗰𝗵 𝘄𝗲𝗿𝗲 𝗷𝘂𝗱𝗴𝗲𝗱 𝘁𝗼 𝗯𝗲 𝗮𝘁 𝗹𝗼𝘄 𝗿𝗶𝘀𝗸 𝗼𝗳 𝗯𝗶𝗮𝘀
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. ²
NOT PEER REVIEWED
The objective of the systematic review by Braznell et al. was “𝘵𝘰 𝘤𝘳𝘪𝘵𝘪𝘤𝘢𝘭𝘭𝘺 𝘢𝘴𝘴𝘦𝘴𝘴 𝘵𝘩𝘦 𝘮𝘦𝘵𝘩𝘰𝘥𝘰𝘭𝘰𝘨𝘪𝘤𝘢𝘭 𝘤𝘩𝘢𝘳𝘢𝘤𝘵𝘦𝘳𝘪𝘴𝘵𝘪𝘤𝘴 𝘢𝘯𝘥 𝘲𝘶𝘢𝘭𝘪𝘵𝘺 𝘰𝘧 𝘪𝘯𝘵𝘦𝘳𝘷𝘦𝘯𝘵𝘪𝘰𝘯𝘢𝘭 𝘤𝘭𝘪𝘯𝘪𝘤𝘢𝘭 𝘵𝘳𝘪𝘢𝘭𝘴 𝘪𝘯𝘷𝘦𝘴𝘵𝘪𝘨𝘢𝘵𝘪𝘯𝘨 𝘵𝘩𝘦 𝘦𝘧𝘧𝘦𝘤𝘵𝘴 𝘰𝘧 𝘩𝘦𝘢𝘵𝘦𝘥 𝘵𝘰𝘣𝘢𝘤𝘤𝘰 𝘱𝘳𝘰𝘥𝘶𝘤𝘵𝘴 (𝘏𝘛𝘗𝘴).” ¹ The review was intended to examine the quality of HTP clinical trials “𝘣𝘦𝘧𝘰𝘳𝘦 𝘤𝘰𝘯𝘴𝘶𝘮𝘦𝘳𝘴 𝘢𝘯𝘥 𝘳𝘦𝘨𝘶𝘭𝘢𝘵𝘰𝘳𝘴 𝘮𝘢𝘬𝘦 𝘪𝘮𝘱𝘰𝘳𝘵𝘢𝘯𝘵 𝘥𝘦𝘤𝘪𝘴𝘪𝘰𝘯𝘴 𝘣𝘢𝘴𝘦𝘥 𝘰𝘯 𝘵𝘩𝘦 𝘳𝘦𝘴𝘶𝘭𝘵𝘴 𝘰𝘧 𝘵𝘩𝘦𝘴𝘦 𝘴𝘵𝘶𝘥𝘪𝘦𝘴.” 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) 𝗥𝗲𝗴𝘂𝗹𝗮𝘁𝗼𝗿𝘆 𝗱𝗲𝗰𝗶𝘀𝗶𝗼𝗻𝘀 𝗵𝗮𝘃𝗲 𝗯𝗲𝗲𝗻 𝗺𝗮𝗱𝗲 𝗯𝗮𝘀𝗲𝗱 𝗼𝗻 𝗣𝗠𝗜’𝘀 𝗰𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝘀𝘁𝘂𝗱𝗶𝗲𝘀, 𝘄𝗵𝗶𝗰𝗵 𝘄𝗲𝗿𝗲 𝗷𝘂𝗱𝗴𝗲𝗱 𝘁𝗼 𝗯𝗲 𝗮𝘁 𝗹𝗼𝘄 𝗿𝗶𝘀𝗸 𝗼𝗳 𝗯𝗶𝗮𝘀
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. ²
We agree that regulatory decisions should be based on a critical scientific review of the evidence available, taking into consideration the quality and source of the data. The U.S. FDA performed a rigorous multi-year review of the totality of evidence for IQOS which resulted in the granting of Modified Risk Tobacco Product orders with exposure modification claims for the product. They concluded “𝘵𝘩𝘢𝘵 𝘢 𝘮𝘦𝘢𝘴𝘶𝘳𝘢𝘣𝘭𝘦 𝘢𝘯𝘥 𝘴𝘶𝘣𝘴𝘵𝘢𝘯𝘵𝘪𝘢𝘭 𝘳𝘦𝘥𝘶𝘤𝘵𝘪𝘰𝘯 𝘪𝘯 𝘮𝘰𝘳𝘣𝘪𝘥𝘪𝘵𝘺 𝘰𝘳 𝘮𝘰𝘳𝘵𝘢𝘭𝘪𝘵𝘺 𝘢𝘮𝘰𝘯𝘨 𝘪𝘯𝘥𝘪𝘷𝘪𝘥𝘶𝘢𝘭 𝘵𝘰𝘣𝘢𝘤𝘤𝘰 𝘶𝘴𝘦𝘳𝘴 𝘪𝘴 𝘳𝘦𝘢𝘴𝘰𝘯𝘢𝘣𝘭𝘺 𝘭𝘪𝘬𝘦𝘭𝘺 𝘪𝘯 𝘴𝘶𝘣𝘴𝘦𝘲𝘶𝘦𝘯𝘵 𝘴𝘵𝘶𝘥𝘪𝘦𝘴, 𝘢𝘯𝘥 𝘪𝘴𝘴𝘶𝘢𝘯𝘤𝘦 𝘰𝘧 𝘢𝘯 𝘰𝘳𝘥𝘦𝘳 𝘪𝘴 𝘦𝘹𝘱𝘦𝘤𝘵𝘦𝘥 𝘵𝘰 𝘣𝘦𝘯𝘦𝘧𝘪𝘵 𝘵𝘩𝘦 𝘩𝘦𝘢𝘭𝘵𝘩 𝘰𝘧 𝘵𝘩𝘦 𝘱𝘰𝘱𝘶𝘭𝘢𝘵𝘪𝘰𝘯 𝘢𝘴 𝘢 𝘸𝘩𝘰𝘭𝘦, 𝘵𝘢𝘬𝘪𝘯𝘨 𝘪𝘯𝘵𝘰 𝘢𝘤𝘤𝘰𝘶𝘯𝘵 𝘣𝘰𝘵𝘩 𝘶𝘴𝘦𝘳𝘴 𝘰𝘧 𝘵𝘰𝘣𝘢𝘤𝘤𝘰 𝘱𝘳𝘰𝘥𝘶𝘤𝘵𝘴 𝘢𝘯𝘥 𝘱𝘦𝘳𝘴𝘰𝘯𝘴 𝘸𝘩𝘰 𝘥𝘰 𝘯𝘰𝘵 𝘤𝘶𝘳𝘳𝘦𝘯𝘵𝘭𝘺 𝘶𝘴𝘦 𝘵𝘰𝘣𝘢𝘤𝘤𝘰 𝘱𝘳𝘰𝘥𝘶𝘤𝘵𝘴.” ³
(𝟮) 𝗖𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝘀𝘁𝘂𝗱𝗶𝗲𝘀 𝗶𝗻 𝗴𝗲𝗻𝗲𝗿𝗮𝗹, 𝗯𝘂𝘁 𝘀𝗽𝗲𝗰𝗶𝗳𝗶𝗰𝗮𝗹𝗹𝘆 𝗣𝗠𝗜’𝘀 𝗰𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝘀𝘁𝘂𝗱𝗶𝗲𝘀, 𝘀𝗵𝗼𝘂𝗹𝗱 𝗻𝗼𝘁 𝗯𝗲 𝗲𝘃𝗮𝗹𝘂𝗮𝘁𝗲𝗱 𝗮𝗴𝗮𝗶𝗻𝘀𝘁 𝗽𝗼𝘀𝘁 𝗵𝗼𝗰 𝗼𝗯𝗷𝗲𝗰𝘁𝗶𝘃𝗲𝘀
Braznell et al. fail to acknowledge that almost all of PMI’s clinical studies were specifically designed to deliver the pre-market scientific evidence that regulatory agencies need to authorize modified risk tobacco products (see FDA’s “Modified Risk Tobacco Product Applications. Guidance for Industry” ). ⁴
This means that the study duration, study populations, study endpoints, and analyses are selected to answer very specific research questions and are not designed to assess the overall impact of HTPs on public health by themselves. Some studies were of short duration (e.g., pharmacokinetic/ pharmacodynamic studies); some were performed in confinement because they were designed to provide evidence on the impacts of confirmed complete switching, and some with ambulatory study phases to better evaluate the impacts with a closer representation of real-world use. The ultimate real-world use studies are being conducted in the post-market setting.
It is inappropriate to assess the quality of a diverse set of studies—studies that were specifically designed to answer a range of different scientific questions—against a broad post hoc scientific objective that none of the studies were intended or designed to address by themselves. It is, therefore, misguided for Braznell et al. to conclude that “many characteristics of the reported clinical trials, such as short duration, confined settings, and choice of comparator and participants, are not representative of real-world use and fail to adequately investigate whether HTPs reduce harm and are beneficial to public health.” What the authors describe as “inadequacies” are, in fact, crucial elements of the individual study design.
As a follow-up to these pre-market studies, in 2022, PMI initiated three new clinical studies on IQOS—a 3-year chronic obstructive pulmonary disease (COPD) study (NCT05569005) ⁵, a 1-year cardiovascular disease study (NCT05566678) ⁶, and a cross-sectional study to assess reduced exposure, inflammation, and oxidative stress two years after switching compared to continued smoking (NCT05385055) ⁷—which will examine longer-term switching and clinically relevant health changes in adult smokers who have switched to IQOS. These studies should be reassuring for those who have expressed concern that the assessment of HTPs relies on short-term studies in the absence of long-term epidemiological studies. The authors may perhaps be unaware of more recent epidemiological studies in the published literature (by both PMI and independent researchers), which have assessed the potential impact of HTPs and other smoke-free alternatives in the real world. Choi et al., 2021 ⁸ looked 5.16 million South Korean adult men and concluded that smokers switching to smoke-free products were associated with a lower cardiovascular disease risk than those continuing to smoke cigarettes, although higher than cessation (no smoke-free product use). Van der Plas et al., 2022 ⁹ observed a significant reduction in the number of hospitalizations for COPD and a non-significant reduction in hospitalizations for COPD plus lower respiratory tract infections as well as ischemic heart disease following the introduction of HTPs in a time-trend analysis of the Japanese Medical Data Center (JMDC) database.
(𝟯) 𝗔𝗿𝗲𝗮𝘀 𝗳𝗼𝗿 𝗶𝗺𝗽𝗿𝗼𝘃𝗲𝗺𝗲𝗻𝘁 𝗲𝘅𝗶𝘀𝘁 𝗳𝗼𝗿 𝗮𝗹𝗹 𝗽𝗮𝗿𝘁𝗶𝗲𝘀
We recognize that our reporting on clinicaltrials.gov may not meet the expectations of today; however, at the time the clinical program was initiated, publishing smoking cessation studies was common; however, publishing tobacco and tobacco harm reduction studies in this database was not common; in fact, we were among the first to report these types of studies there and did so to increase our scientific transparency. The authors accurately reflect incomplete reporting on a small number of our clinical studies, including studies on a carbon-heated tobacco product. However, in 2021, we took a decision not to proceed with commercialization ¹⁰, meaning that, according to the authors’ exclusion criteria, this study should not have been part of their analysis. Additionally, we have two studies that have been completed. Although the data for the endpoints have been posted on clinicaltrials.gov and therefore are in the public domain, the study publications with additional secondary and exploratory endpoints have just been or are in the process of being published. Whilst we are actively working on publishing these studies, we acknowledge that this delay in publication is not ideal and must be improved in the future. We recognize the importance of publishing the results of our studies in peer-reviewed journals but also note that we often face significant challenges in achieving timely publication because a number of journals (including Tobacco Control) refuse to accept or even review such publications based purely on affiliation and not the quality of the research.
Constructive criticism of our research is always welcome, but we reject the suggestion that PMI’s clinical studies “ 𝘸𝘦𝘳𝘦 𝘴𝘶𝘣𝘴𝘵𝘢𝘯𝘥𝘢𝘳𝘥 𝘪𝘯 𝘮𝘢𝘯𝘺 𝘳𝘦𝘴𝘱𝘦𝘤𝘵𝘴.” As mentioned above, the FDA conducted a substantive review of our studies, including inspection visits at our facilities and at some of our clinical research partners. FDA noted that their inspections of two U.S. clinical sites “𝘳𝘦𝘷𝘦𝘢𝘭𝘦𝘥 𝘯𝘰 𝘮𝘢𝘫𝘰𝘳 𝘉𝘐𝘔𝘖 [𝘉𝘪𝘰𝘳𝘦𝘴𝘦𝘢𝘳𝘤𝘩 𝘔𝘰𝘯𝘪𝘵𝘰𝘳𝘪𝘯𝘨] 𝘪𝘴𝘴𝘶𝘦𝘴 𝘰𝘳 𝘤𝘭𝘪𝘯𝘪𝘤𝘢𝘭𝘭𝘺-𝘴𝘪𝘨𝘯𝘪𝘧𝘪𝘤𝘢𝘯𝘵 𝘱𝘳𝘰𝘵𝘰𝘤𝘰𝘭 𝘥𝘦𝘷𝘪𝘢𝘵𝘪𝘰𝘯𝘴 𝘵𝘩𝘢𝘵 𝘸𝘰𝘶𝘭𝘥 𝘤𝘰𝘮𝘱𝘳𝘰𝘮𝘪𝘴𝘦 𝘥𝘢𝘵𝘢 𝘷𝘢𝘭𝘪𝘥𝘪𝘵𝘺 𝘢𝘯𝘥 𝘪𝘯𝘵𝘦𝘨𝘳𝘪𝘵𝘺.” In addition, the results of the authors’ own review confirm the appropriate design and conduct of our studies (i.e., low risk of bias). Therefore, the authors’ non-scientific statement that their failure to find significant differences in the risks of bias between the trials from different affiliations should only be interpreted as “𝘢𝘣𝘴𝘦𝘯𝘤𝘦 𝘰𝘧 𝘦𝘷𝘪𝘥𝘦𝘯𝘤𝘦, 𝘯𝘰𝘵 𝘦𝘷𝘪𝘥𝘦𝘯𝘤𝘦 𝘰𝘧 𝘢𝘣𝘴𝘦𝘯𝘤𝘦” is pure speculation and has no basis in fact in regard to PMI’s studies.
In the spirit of constructive criticism, we note that whilst the authors were investigating the possibility of bias in PMI’s studies, it is possible that their own bias may be affecting their interpretation of results. When disclosing their competing interests, they fail to note that their own affiliation with, and funding from, Bloomberg Philanthropies’ “𝘚𝘛𝘖𝘗: 𝘚𝘵𝘰𝘱𝘱𝘪𝘯𝘨 𝘛𝘰𝘣𝘢𝘤𝘤𝘰 𝘖𝘳𝘨𝘢𝘯𝘪𝘻𝘢𝘵𝘪𝘰𝘯𝘴 𝘢𝘯𝘥 𝘗𝘳𝘰𝘥𝘶𝘤𝘵𝘴” could create a risk of bias. In fact, that potential for bias is plain since the lead author has previously written that “𝘵𝘩𝘦𝘳𝘦 𝘪𝘴 𝘭𝘪𝘵𝘵𝘭𝘦 𝘳𝘰𝘭𝘦 𝘧𝘰𝘳 𝘩𝘦𝘢𝘵𝘦𝘥 𝘵𝘰𝘣𝘢𝘤𝘤𝘰 𝘱𝘳𝘰𝘥𝘶𝘤𝘵𝘴 𝘢𝘵 𝘦𝘪𝘵𝘩𝘦𝘳 𝘪𝘯𝘥𝘪𝘷𝘪𝘥𝘶𝘢𝘭 𝘰𝘳 𝘱𝘰𝘱𝘶𝘭𝘢𝘵𝘪𝘰𝘯 𝘭𝘦𝘷𝘦𝘭” and that “𝘩𝘦𝘢𝘵𝘦𝘥 𝘵𝘰𝘣𝘢𝘤𝘤𝘰 𝘱𝘳𝘰𝘥𝘶𝘤𝘵𝘴 𝘩𝘢𝘷𝘦 𝘯𝘰 𝘱𝘶𝘣𝘭𝘪𝘤 𝘩𝘦𝘢𝘭𝘵𝘩 𝘳𝘰𝘭𝘦.” ¹¹ This potential conflict was not made clear to readers. The reference by Bero ¹² used by the authors in their introduction states that “𝘤𝘰𝘯𝘴𝘪𝘥𝘦𝘳𝘢𝘵𝘪𝘰𝘯 𝘴𝘩𝘰𝘶𝘭𝘥 𝘣𝘦 𝘨𝘪𝘷𝘦𝘯 𝘵𝘰 𝘢𝘧𝘧𝘪𝘭𝘪𝘢𝘵𝘪𝘰𝘯 𝘰𝘳 𝘪𝘯𝘵𝘦𝘳𝘦𝘴𝘵 𝘨𝘳𝘰𝘶𝘱 𝘣𝘪𝘢𝘴.” Bero notes that “[𝘢]𝘯 𝘪𝘯𝘵𝘦𝘳𝘦𝘴𝘵 𝘨𝘳𝘰𝘶𝘱 𝘪𝘴 𝘢𝘯 𝘰𝘳𝘨𝘢𝘯𝘪𝘻𝘦𝘥 𝘨𝘳𝘰𝘶𝘱 𝘸𝘪𝘵𝘩 𝘢 𝘯𝘢𝘳𝘳𝘰𝘸𝘭𝘺 𝘥𝘦𝘧𝘪𝘯𝘦𝘥 𝘷𝘪𝘦𝘸𝘱𝘰𝘪𝘯𝘵, 𝘸𝘩𝘪𝘤𝘩 𝘱𝘳𝘰𝘵𝘦𝘤𝘵𝘴 𝘪𝘵𝘴 𝘱𝘰𝘴𝘪𝘵𝘪𝘰𝘯 𝘰𝘳 𝘱𝘳𝘰𝘧𝘪𝘵𝘴. 𝘛𝘩𝘦𝘴𝘦 𝘨𝘳𝘰𝘶𝘱𝘴 𝘢𝘳𝘦 𝘯𝘰𝘵 𝘦𝘹𝘤𝘭𝘶𝘴𝘪𝘷𝘦𝘭𝘺 𝘣𝘶𝘴𝘪𝘯𝘦𝘴𝘴 𝘨𝘳𝘰𝘶𝘱𝘴 𝘣𝘶𝘵 𝘤𝘢𝘯 𝘪𝘯𝘤𝘭𝘶𝘥𝘦 𝘢𝘭𝘭 𝘬𝘪𝘯𝘥𝘴 𝘰𝘧 𝘰𝘳𝘨𝘢𝘯𝘪𝘻𝘢𝘵𝘪𝘰𝘯𝘴 𝘵𝘩𝘢𝘵 𝘮𝘢𝘺 𝘢𝘵𝘵𝘦𝘮𝘱𝘵 𝘵𝘰 𝘪𝘯𝘧𝘭𝘶𝘦𝘯𝘤𝘦 𝘨𝘰𝘷𝘦𝘳𝘯𝘮𝘦𝘯𝘵𝘴. 𝘐𝘯𝘵𝘦𝘳𝘦𝘴𝘵 𝘨𝘳𝘰𝘶𝘱𝘴 𝘤𝘢𝘯 𝘣𝘦 𝘦𝘹𝘱𝘦𝘤𝘵𝘦𝘥 𝘵𝘰 𝘤𝘰𝘯𝘴𝘵𝘳𝘶𝘤𝘵 𝘵𝘩𝘦 𝘦𝘷𝘪𝘥𝘦𝘯𝘤𝘦 𝘢𝘣𝘰𝘶𝘵 𝘢 𝘩𝘦𝘢𝘭𝘵𝘩 𝘳𝘪𝘴𝘬 𝘵𝘰 𝘴𝘶𝘱𝘱𝘰𝘳𝘵 𝘵𝘩𝘦𝘪𝘳 𝘱𝘳𝘦𝘥𝘦𝘧𝘪𝘯𝘦𝘥 𝘱𝘰𝘭𝘪𝘤𝘺 𝘱𝘰𝘴𝘪𝘵𝘪𝘰𝘯.” We encourage the authors to transparently disclose that their own funding from, and affiliation with, “𝘚𝘛𝘖𝘗: 𝘚𝘵𝘰𝘱𝘱𝘪𝘯𝘨 𝘛𝘰𝘣𝘢𝘤𝘤𝘰 𝘖𝘳𝘨𝘢𝘯𝘪𝘻𝘢𝘵𝘪𝘰𝘯𝘴 𝘢𝘯𝘥 𝘗𝘳𝘰𝘥𝘶𝘤𝘵𝘴”—an interest group that actively campaigns against HTPs, the tobacco industry, and PMI—presents a potential conflict of interest.
(𝟰) 𝗖𝗼𝗻𝗰𝗹𝘂𝘀𝗶𝗼𝗻
There are legitimate concerns about bringing any new nicotine or tobacco product to the market, but these concerns should be considered against the backdrop of the science that is known about smoking. People who smoke and regulators will best be served by informing them of the relative risks of such products compared to continuing to smoke. This requires an unbiased review of the existing science whilst continuing to study the impact on individual and public health. Such actions will help and inform those who currently smoke to transition away from cigarettes and non-smokers not to start to use any nicotine or tobacco product.
(𝟱) 𝗥𝗲𝗳𝗲𝗿𝗲𝗻𝗰𝗲
1.) Braznell S, Van Den Akker A, Metcalfe C, et alCritical appraisal of interventional clinical trials assessing heated tobacco products: a systematic review. Tobacco Control Published Online First: 08 November 2022. doi: 10.1136/tc-2022-057522
2.) Tattan-Birch_H, Hartmann-Boyce_J, Kock_L, Simonavicius_E, Brose_L, Jackson_S, Shahab_L, Brown_J. Heated tobacco products for smoking cessation and reducing smoking prevalence. Cochrane Database of Systematic Reviews 2022, Issue 1. Art. No.: CD013790. https://doi.org/10.1002/14651858.CD013790.pub2
3.) Food and Drug Administration (2020) Scientific Review of Modified Risk Tobacco Product Application (MRTPA) STNs MR0000059 - MR0000061, MR0000133 -Technical Project Lead Document (https://www.fda.gov/media/139796/download)
4.) Food and Drug Administration (FDA) (2012): Modified Risk Tobacco Product Applications. Guidance for Industry (https://www.fda.gov/media/83300/download).
5.) NCT05569005 (https://www.clinicaltrials.gov/ct2/show/NCT05569005?spons=Philip+Morris&...)
6.) NCT05566678 (https://www.clinicaltrials.gov/ct2/show/NCT05566678?spons=Philip+Morris&...)
7.) NCT05385055 (https://www.clinicaltrials.gov/ct2/show/NCT05385055?spons=Philip+Morris&...)
8.) Choi, S., Lee, K., Park, S.M., (2021) Combined associations of changes in noncombustible nicotine or tobacco product ad combustible cigarette use habits with subsequent short-term cardiovascular disease risk among South Korean men. Circulation, 144: 1521-1538. doi: 10.1161/CIRCULATIONAHA.121.054967
9.) van der Plas A, Antunes M, Romero-Kauss A, Hankins M and Heremans A (2022) Ischemic Heart Disease and Chronic Obstructive Pulmonary Disease Hospitalizations in Japan Before and After the Introduction of a Heated Tobacco Product. Front. Public Health 10:909459. doi: 10.3389/fpubh.2022.909459
10.) Philip Morris International 2021 Annual Report (p42) published on 24.03.2022
11.) Gilmore A B, Braznell S. US regulator adds to confusion around heated tobacco products BMJ 2020; 370 :m3528 doi: 10.1136/bmj.m3528
12.) Bero LA. Tobacco industry manipulation of research. Public Health Rep 2005;120:200–8. doi: 10.1177/003335490512000215
Clive Bates’ commentary on our paper repeats claims we previously addressed [1]. Here, we address seven points, the first is contextual and the remaining are raised in his letter.
1. We note the failure of the author to acknowledge Māori perspectives, in particular their support for endgame measures, concerns in relation to harm minimisation [2] as outlined in his “all in” strategy, and ethical publishing of research about Indigenous peoples. [3]
2. We reject the assertion that the basis of our modelling is “weak”. While there is uncertainty around the potential effect of denicotinisation, as this policy hasn’t been implemented, there are strong grounds to believe that it will have a profound impact on reducing smoking prevalence. This is based on both theory and logic (i.e., nicotine is the main addictive component of cigarettes and why most people smoke), and the findings of multiple randomized controlled trials (RCTs) showing that smoking very low nicotine cigarettes (VLNCs) increases cessation rates for diverse populations of people who smoke [4-7].
Our model’s estimated effect on smoking prevalence had wide uncertainty, namely a median of 85.9% reduction over 5 years with a 95% uncertainty interval of 67.1% to 96.3% that produced (appropriately) wide uncertainty in the health impacts. The derivation of this input parameter through expert knowledge elicitation (EKE) is described in the Appendix of our paper. Univariate se...
Clive Bates’ commentary on our paper repeats claims we previously addressed [1]. Here, we address seven points, the first is contextual and the remaining are raised in his letter.
1. We note the failure of the author to acknowledge Māori perspectives, in particular their support for endgame measures, concerns in relation to harm minimisation [2] as outlined in his “all in” strategy, and ethical publishing of research about Indigenous peoples. [3]
2. We reject the assertion that the basis of our modelling is “weak”. While there is uncertainty around the potential effect of denicotinisation, as this policy hasn’t been implemented, there are strong grounds to believe that it will have a profound impact on reducing smoking prevalence. This is based on both theory and logic (i.e., nicotine is the main addictive component of cigarettes and why most people smoke), and the findings of multiple randomized controlled trials (RCTs) showing that smoking very low nicotine cigarettes (VLNCs) increases cessation rates for diverse populations of people who smoke [4-7].
Our model’s estimated effect on smoking prevalence had wide uncertainty, namely a median of 85.9% reduction over 5 years with a 95% uncertainty interval of 67.1% to 96.3% that produced (appropriately) wide uncertainty in the health impacts. The derivation of this input parameter through expert knowledge elicitation (EKE) is described in the Appendix of our paper. Univariate sensitivity analyses comparing the 67.1% and 96.3% estimates (all other input parameters held at their median value) produced HALY gains ranging from 545,000 to 653,000. Our paper presents this uncertainty transparently.
3. The assertion that the effect size estimate of denicotinisation is based on one randomized trial is incorrect. The author has been informed that this assertion is false on several occasions but even so continues to repeat this claim. We used an EKE process, which is described in the Appendix of our paper. The experts considered many ‘inputs’ to their estimation, of which just one was the evidence from the multiple existing RCTs.
4. We disagree with the author’s characterisation of the EKE process as “arbitrary guesswork”. As Bates himself has noted, expert judgement can provide valuable insight in situations of uncertainty and can “provide a risk-perception ‘anchor’ … following assessment of the evidence that exists.” [8] We believe that ≥ 5 RCTs demonstrating a relationship between VLNCs and increased smoking cessation constitute a reasonable evidence base to draw upon, particularly when supported by theory/logic and other lines of evidence.[9]
Policy-making often occurs in a context of uncertainty. Denicotinisation is one such example, as we will not know its ‘real world’ impact until it has been implemented. To inform that policy making, it is astute to have estimates of the likely health impact – which requires EKE. Over time, as evidence accrues, such modelling should be updated.
5. As stated in our paper, we did not explicitly model an illicit market. Tight border security in an island nation with no land borders within 1,000 km, reduces the potential of a significant illicit tobacco market. Furthermore, the Aotearoa/New Zealand (A/NZ) Government announced new measures against tobacco smuggling in preparation for the introduction of its ‘endgame’ legislation. [10] The impact of an illicit tobacco market may be greater in other countries. In A/NZ, the illicit market is small (around 5-6% max) and has not increased greatly despite 10 years of above inflation tobacco excise increases and the introduction of plain packs – interventions which the tobacco industry routinely claims will result in an explosion in the illicit market. This suggests enforcement measures work well in the A/NZ context. Furthermore, given the widespread availability and use by people who smoke of nicotine-containing vaping products in A/NZ, seeking to replace VLNCs with illicit cigarettes is likely to be significantly less common than in jurisdictions where vaping products are not available.
6. It is possible – as Bates asserts – that we have overestimated the health gains from denicotinisation and other endgame policies because the smoking prevalence since 2020, appears to be falling more rapidly than we modelled (meaning the ‘room’ for health gains from an endgame policy is less). We discussed this in our paper.
7. Discussing the public health philosophy of denicotinisation was beyond the scope of our paper. Our focus was only on evaluating the potential health and equity impacts of four interventions included the A/NZ Smoke-free Action Plan 2025.
[2] Waa A, Robson B, Gifford H, Smylie J, Reading J, Henderson JA, Henderson PN, Maddox R, Lovett R, Eades S, Finlay S. Foundation for a smoke-free world and healthy Indigenous futures: an oxymoron?. Tobacco Control. 2020 Mar 1;29(2):237-40.
[3] Maddox R, Drummond A, Kennedy M, et al. Ethical publishing in ‘Indigenous’ contextsTobacco Control Published Online First: 13 February 2023. doi: 10.1136/tc-2022-057702
[4] Donny EC, Denlinger RL, Tidey JW, Koopmeiners JS, Benowitz NL, Vandrey RG, Al’Absi M, Carmella SG, Cinciripini PM, Dermody SS, Drobes DJ. Randomized trial of reduced-nicotine standards for cigarettes. New England Journal of Medicine. 2015 Oct 1;373(14):1340-9.
[5] Smith TT, Koopmeiners JS, Tessier KM, Davis EM, Conklin CA, Denlinger-Apte RL, Lane T, Murphy SE, Tidey JW, Hatsukami DK, Donny EC. Randomized trial of low-nicotine cigarettes and transdermal nicotine. American journal of preventive medicine. 2019 Oct 1;57(4):515-24.
[6] Walker N, Howe C, Bullen C, Grigg M, Glover M, McRobbie H, Laugesen M, Parag V, Whittaker R. The combined effect of very low nicotine content cigarettes, used as an adjunct to usual Quitline care (nicotine replacement therapy and behavioural support), on smoking cessation: a randomized controlled trial. Addiction. 2012 Oct;107(10):1857-67.
[7] Higgins ST, Tidey JW, Sigmon SC, Heil SH, Gaalema DE, Lee D, Hughes JR, Villanti AC, Bunn JY, Davis DR, Bergeria CL. Changes in cigarette consumption with reduced nicotine content cigarettes among smokers with psychiatric conditions or socioeconomic disadvantage: 3 randomized clinical trials. JAMA network open. 2020 Oct 1;3(10):e2019311-.
NOT PEER REVIEWED
I read with interest the article "Global tobacco advertising, promotion, and sponsorship regulation: what’s old, what’s new, and where to next?[1]" published in Tobacco Control. As a psychiatrist specializing in addiction treatment at Taoyuan Psychiatric Center in Taiwan, I wish to share our institution's experience in implementing a successful smoke-free hospital program, which may serve as a model for other psychiatric centers.
Since 2014, Taoyuan Psychiatric Center has made significant progress in promoting a smoke-free environment through a comprehensive tobacco control program. Our program's objectives include creating a smoke-free hospital, increasing smoking cessation services for outpatients and inpatients, and improving patient smoking status documentation. Furthermore, we prioritize smoking cessation counseling for adolescents, pregnant women, and their families.
In psychiatric settings, smoking cessation is crucial as tobacco use can influence the blood concentration of psychotropic medications, potentially destabilizing psychiatric symptoms. Assisting patients in quitting smoking not only lowers the risk of tobacco-related diseases but also contributes to stabilizing their psychiatric conditions.
Our program encompasses various initiatives, including staff training, community tobacco harm prevention promotion, provision of second-generation smoking cessation treatments for outpatients and inpatien...
Show MoreNOT PEER REVIEWED
We acknowledge receipt of a private e-mail message from JLI regarding our paper (Yassine et al., 2022). Given the industry‘s long history of industry obfuscation, interference, and deception regarding research on tobacco products, we decided that the most transparent approach to the private e-mail that we received from an employee of a tobacco product manufacturer would be for us to report our results independently and respond to any public discussion of our work if and when it arose. Now that public discussion has arisen, we are pleased to respond to it.
We very recently analyzed the menthol and nicotine content of samples of liquid from six menthol flavor pods purchased in 2020. Three of these were liquids extracted from the pods in June 2021 for our paper and had been stored since in sealed amber glass containers at 5°C in the dark. The other three pods had been stored in their original sealed packages and were taken from the same batches as the pods analyzed in June 2021. These unopened packages were stored in the dark at room temperature over the intervening 18 months. The data from this small sample demonstrate a 24% reduction in menthol content over that period (12.01±0.46 vs 9.15±0.22 mg/ml), which helps to explain the results we reported (Yassine et al., 2022). We also found a 5% reduction in nicotine content (62.47±0.63 vs 59.52±0.49 mg/ml), as well as discoloration of the liquid in the pods that were stored at room temperatur...
Show MoreNOT PEER REVIEWED
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,...
Show MoreNOT PEER REVIEWED
I would like to make three comments by way of a brief post-publication review.
1. The impacts of vaping tax on smoking have been completely overlooked
For a study of e-cigarette taxation to have any public health relevance, it must consider the impact of e-cigarette prices on *cigarette* demand. Cigarettes and e-cigarettes are economic substitutes. The demand for one responds to changes in the price of the other, an idea well understood in economics and quantified through the concept of cross-elasticity. The paper appears to pay no regard to the impact of vaping taxes on cigarette demand, Yet such effects might easily overwhelm any benefits from reduced e-cigarette use - in fact, impact on demand for other tobacco products and the development of informal markets are by far the most important impacts of a vaping tax. By way of example, a 2020 paper by Pesko et al. [1] concluded:
"Our results suggest that a proposed national e-cigarette tax of $1.65 per milliliter of vaping liquid would raise the proportion of adults who smoke cigarettes daily by approximately 1 percentage point, translating to 2.5 million extra adult daily smokers compared to the counterfactual of not having the tax."
2. The case for reducing adult vaping by taxation has not been made
The authors have based their paper on an unexamined assumption that it is a justifiable goal of policy to lower rates of adult e-cigarette use. Why should...
Show MoreNOT PEER REVIEWED
I have a number of concerns with the paper as currently written.
1) The authors write: “Besides, none of the previous studies except Pesko et al (15) that examined the associations between vaping product excise tax adoption and ENDS use has accounted for the clustering of respondents within the same localities…” This is not accurate, as citation 19 also clusters standard errors at the locality level in all specifications.
2) The authors write: "A working paper reported reduced ENDS sales, but not ENDS use prevalence or behaviours, after implementation of a vaping product excise tax policy. (19)” This is not accurate, as the cited study uses the magnitude of e-cigarette tax values, rather than an indicator variable for tax implementation. States have adopted e-cigarette taxes of different magnitudes and a number of them (such as California) have changed the magnitudes of these taxes after adoption. All of this variation is used in citation 19, contrary to the current study’s description. It's also unclear from the sentence whether citation 19 studied use and found imprecise estimates, or did not study use. It's the latter and this should be clarified. It's also unclear why the authors did not use magnitude of e-cigarette taxes themselves in the current paper, as has been commonly done in the referenced literature.
3) Authors write they use a “nationally representative sample of US young adults.” I do not beli...
Show MoreNOT PEER REVIEWED
We appreciate the comments from Bates and the opportunity for us to respond and clarify.
First, Bates' argument heavily relies on the assumption that e-cigarettes and combustible cigarettes are substitutes, which is theoretically possible as some consider vaping as a harm reduction alternative to combustible cigarettes. Empirically, however, there have been mixed findings about whether e-cigarettes and combustible cigarettes are substitutes (or complements). Bates cited Pesko et al. (2020) that concludes e-cigarettes and combustible cigarettes are substitutes, whereas other studies have shown that they are complements. For example, Cotti et al. (2018) found that higher cigarette excise taxes, in fact, decrease sales of both e-cigarettes and combustible cigarettes, suggesting that they are complements. Such mixed results abate Bates' argument that taxing ENDS could lead to more use of combustible cigarettes.
Second, Bates might have ignored that our study focused on young adults aged 18-24 years rather than general adults when examining the effect of vaping product tax on e-cigarette use. Although Pesko et al. (2020) suggests that e-cigarettes and combustible cigarettes are substitutes, the findings are based on the general adult population (average age: 55 years) which may not be generalizable to the young adult population. In fact, one study conducted by Abouk and Adams (2017) indicates that e-cigarettes and combustible ci...
Show MoreNOT PEER REVIEWED
We thank Pesko for his comments and the opportunity for us to respond and clarify.
First, we appreciate Pesko’s clarification that Cotti et al. (2020) clustered standard errors to account for clustering. In the present study, we used multilevel analysis not only to account for clustering of respondents (i.e., design effects) but also to incorporate different error terms for different levels of the data hierarchy which yields more accurate Type I error rates than nonhierarchical methods where all unmodeled contextual information ends up pooled into a single error term of the model.
Second, we understand that Cotti et al. (2020) evaluated the magnitude of e-cigarette tax values, which does not contradict to our statement because our study focused on the effects of e-cigarette excise tax policies on individual e-cigarette use and prevalence rather than aggregated sales at state or county levels. We also clearly described the reason why we examined the e-cigarette excise tax policy implementation indicator rather than its magnitude in our paper’s discussion section.
Third, our study used a nationally representative sample of young adults (rather than a nationally representative sample of general adult population). While we understand Pesko’s concern that a sample’s representativeness might be lost when subgroups are explored, we believe our use of sampling weights in analysis has reduced such a concern.
Fourth, in Table 3,...
Show MoreNOT PEER REVIEWED
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...
Show MoreNOT PEER REVIEWED
The objective of the systematic review by Braznell et al. was “𝘵𝘰 𝘤𝘳𝘪𝘵𝘪𝘤𝘢𝘭𝘭𝘺 𝘢𝘴𝘴𝘦𝘴𝘴 𝘵𝘩𝘦 𝘮𝘦𝘵𝘩𝘰𝘥𝘰𝘭𝘰𝘨𝘪𝘤𝘢𝘭 𝘤𝘩𝘢𝘳𝘢𝘤𝘵𝘦𝘳𝘪𝘴𝘵𝘪𝘤𝘴 𝘢𝘯𝘥 𝘲𝘶𝘢𝘭𝘪𝘵𝘺 𝘰𝘧 𝘪𝘯𝘵𝘦𝘳𝘷𝘦𝘯𝘵𝘪𝘰𝘯𝘢𝘭 𝘤𝘭𝘪𝘯𝘪𝘤𝘢𝘭 𝘵𝘳𝘪𝘢𝘭𝘴 𝘪𝘯𝘷𝘦𝘴𝘵𝘪𝘨𝘢𝘵𝘪𝘯𝘨 𝘵𝘩𝘦 𝘦𝘧𝘧𝘦𝘤𝘵𝘴 𝘰𝘧 𝘩𝘦𝘢𝘵𝘦𝘥 𝘵𝘰𝘣𝘢𝘤𝘤𝘰 𝘱𝘳𝘰𝘥𝘶𝘤𝘵𝘴 (𝘏𝘛𝘗𝘴).” ¹ The review was intended to examine the quality of HTP clinical trials “𝘣𝘦𝘧𝘰𝘳𝘦 𝘤𝘰𝘯𝘴𝘶𝘮𝘦𝘳𝘴 𝘢𝘯𝘥 𝘳𝘦𝘨𝘶𝘭𝘢𝘵𝘰𝘳𝘴 𝘮𝘢𝘬𝘦 𝘪𝘮𝘱𝘰𝘳𝘵𝘢𝘯𝘵 𝘥𝘦𝘤𝘪𝘴𝘪𝘰𝘯𝘴 𝘣𝘢𝘴𝘦𝘥 𝘰𝘯 𝘵𝘩𝘦 𝘳𝘦𝘴𝘶𝘭𝘵𝘴 𝘰𝘧 𝘵𝘩𝘦𝘴𝘦 𝘴𝘵𝘶𝘥𝘪𝘦𝘴.” 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) 𝗥𝗲𝗴𝘂𝗹𝗮𝘁𝗼𝗿𝘆 𝗱𝗲𝗰𝗶𝘀𝗶𝗼𝗻𝘀 𝗵𝗮𝘃𝗲 𝗯𝗲𝗲𝗻 𝗺𝗮𝗱𝗲 𝗯𝗮𝘀𝗲𝗱 𝗼𝗻 𝗣𝗠𝗜’𝘀 𝗰𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝘀𝘁𝘂𝗱𝗶𝗲𝘀, 𝘄𝗵𝗶𝗰𝗵 𝘄𝗲𝗿𝗲 𝗷𝘂𝗱𝗴𝗲𝗱 𝘁𝗼 𝗯𝗲 𝗮𝘁 𝗹𝗼𝘄 𝗿𝗶𝘀𝗸 𝗼𝗳 𝗯𝗶𝗮𝘀
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. ²
We agree that regulatory decisio...
Show MoreNOT PEER REVIEWED
Clive Bates’ commentary on our paper repeats claims we previously addressed [1]. Here, we address seven points, the first is contextual and the remaining are raised in his letter.
1. We note the failure of the author to acknowledge Māori perspectives, in particular their support for endgame measures, concerns in relation to harm minimisation [2] as outlined in his “all in” strategy, and ethical publishing of research about Indigenous peoples. [3]
2. We reject the assertion that the basis of our modelling is “weak”. While there is uncertainty around the potential effect of denicotinisation, as this policy hasn’t been implemented, there are strong grounds to believe that it will have a profound impact on reducing smoking prevalence. This is based on both theory and logic (i.e., nicotine is the main addictive component of cigarettes and why most people smoke), and the findings of multiple randomized controlled trials (RCTs) showing that smoking very low nicotine cigarettes (VLNCs) increases cessation rates for diverse populations of people who smoke [4-7].
Our model’s estimated effect on smoking prevalence had wide uncertainty, namely a median of 85.9% reduction over 5 years with a 95% uncertainty interval of 67.1% to 96.3% that produced (appropriately) wide uncertainty in the health impacts. The derivation of this input parameter through expert knowledge elicitation (EKE) is described in the Appendix of our paper. Univariate se...
Show MorePages