We use cookies to improve our service and to tailor our content and advertising to you.More infoYou can manage your cookie settings via your browser at any time. To learn more about how we use cookies, please see our cookies policy.
NOT PEER REVIEWED
More than 1,000 participants were exposed to IQOS in our clinical studies. The authors of the letter “Possible hepatotoxicity of IQOS" based their analysis on approximatively 10% of the data instead of examining the data as a whole. For example, for the five-day exposure studies in confinement, they stated that the percentage of participants with elevated bilirubin in IQOS arm was more than three times higher than that observed in the smoking abstinence (SA) arm in the European study (8.8% [7 participants] in IQOS arm, 2.6% [1 participant] in SA arm). However, they missed reporting that this percentage was lower in the IQOS arm than in the cigarette smoking (CC) arm in the Japanese study (10% [8 participants] in IQOS arm, 15% [6 participants] in CC arm). They also stated that the mean increase in alanine aminotransferase (ALT) was higher with IQOS than with CC or SA in the Japanese study but did not report that in the European study, the mean increase in ALT was lower in the IQOS arm than in the CC or SA arm.
Similarly, for the 90-day exposure studies in an ambulatory setting, they mentioned that the percentage of participants with increased ALT levels after 60 days of exposure was higher within the IQOS arm (6.3% [5 participants] in IQOS arm, 0% in CC arm, 2.6% [1 participant] in SA arm) in the U.S. study. However they omitted to mention that in the Japanese study, this percentage was lower in IQOS arm compared with CC or SA arms after 3...
NOT PEER REVIEWED
More than 1,000 participants were exposed to IQOS in our clinical studies. The authors of the letter “Possible hepatotoxicity of IQOS" based their analysis on approximatively 10% of the data instead of examining the data as a whole. For example, for the five-day exposure studies in confinement, they stated that the percentage of participants with elevated bilirubin in IQOS arm was more than three times higher than that observed in the smoking abstinence (SA) arm in the European study (8.8% [7 participants] in IQOS arm, 2.6% [1 participant] in SA arm). However, they missed reporting that this percentage was lower in the IQOS arm than in the cigarette smoking (CC) arm in the Japanese study (10% [8 participants] in IQOS arm, 15% [6 participants] in CC arm). They also stated that the mean increase in alanine aminotransferase (ALT) was higher with IQOS than with CC or SA in the Japanese study but did not report that in the European study, the mean increase in ALT was lower in the IQOS arm than in the CC or SA arm.
Similarly, for the 90-day exposure studies in an ambulatory setting, they mentioned that the percentage of participants with increased ALT levels after 60 days of exposure was higher within the IQOS arm (6.3% [5 participants] in IQOS arm, 0% in CC arm, 2.6% [1 participant] in SA arm) in the U.S. study. However they omitted to mention that in the Japanese study, this percentage was lower in IQOS arm compared with CC or SA arms after 30 days of exposure (1.3% [1 participant] in IQOS arm, 4.8% [2 participants] in CC arm, 7.5% [3 participants] in SA arm).
Taken together, the changes reported by the authors concern a small number of participants across all arms and most likely represent normal fluctuations of these parameters.
Finally, the grade 2 ALT increase in IQOS arm that was mentioned in the letter corresponds to a participant with an isolated increase at Day 30, which is explained by the use of concomitant medication. This information was also part of the publicly available information but was not taken into account by the authors.
In conclusion, the data submitted to the FDA as well as the data gathered in the context of our post-market safety surveillance system, based on pharmaceutical industry best practices, show unquestionably that there is no increased risk of developing hepatotoxicity after switching to IQOS.
NOT PEER REVIEWED
This study has some important findings that could, if replicated, guide FDA decision making on applications from manufacturers to make modified risk tobacco product claims. However, while it does not detract from the study’s findings, the article does not accurately describe the standards FDA must apply when evaluating those applications. The abstract inaccurately suggests that tobacco products in the U.S. may make reduced-risk or reduced-exposure claims so long as they are not misleading, and does not mention that any explicit or implicit reduced-exposure or reduced-risk claims may not be legally made without first submitting an application to FDA and receiving a permissive order, which considers various other factors, as well.
The introduction of the paper does a bit better, accurately stating that the Tobacco Control Act requires prior review by FDA before making lower-exposure or lower-risk claims. But it then suggests that manufacturers can receive that permission if they either demonstrate that the product lowers harm or risk compared with other tobacco products or if they demonstrate that the product is free of or contains reduced levels of harmful chemicals and the related claims don’t mislead consumers to believe that the reduced-exposure means lower risk. While that description is accurate as far as it goes, it leaves off the enormously important requirement, in both cases, that a manufacturer’s application for permission to...
NOT PEER REVIEWED
This study has some important findings that could, if replicated, guide FDA decision making on applications from manufacturers to make modified risk tobacco product claims. However, while it does not detract from the study’s findings, the article does not accurately describe the standards FDA must apply when evaluating those applications. The abstract inaccurately suggests that tobacco products in the U.S. may make reduced-risk or reduced-exposure claims so long as they are not misleading, and does not mention that any explicit or implicit reduced-exposure or reduced-risk claims may not be legally made without first submitting an application to FDA and receiving a permissive order, which considers various other factors, as well.
The introduction of the paper does a bit better, accurately stating that the Tobacco Control Act requires prior review by FDA before making lower-exposure or lower-risk claims. But it then suggests that manufacturers can receive that permission if they either demonstrate that the product lowers harm or risk compared with other tobacco products or if they demonstrate that the product is free of or contains reduced levels of harmful chemicals and the related claims don’t mislead consumers to believe that the reduced-exposure means lower risk. While that description is accurate as far as it goes, it leaves off the enormously important requirement, in both cases, that a manufacturer’s application for permission to make a modified-risk claim must also show that the proposed claim will benefit the health of the population as a whole (taking into consideration impacts of the product and its marketing with the modified-risk claim on implementation, cessation, relapse, etc.).
This study’s findings could have been presented even more powerfully if the article had also discussed their relevance to FDA’s consideration of how reduced-risk or reduced-exposure claims would impact the public health based on the claims likely influence on youth and adult consumer behaviors.
The "serious criticism" that Mr. Bates refers to is from him (on another website).
In order for the FDA to issue an order allowing Philip Morris International to market IQOS in the United States as a reduced risk tobacco product, the law required that, among other things, FDA "determines that the applicant [PMI] has demonstrated that such product [IQOS], as it is actually used by consumers will significantly reduce harm and the risk of tobacco- related disease to individual tobacco users."
That is why PMI provided the information of biomarkers of potential harm to the FDA. and how they compare to values observed in smokers. My paper shows that, using PMI's own data, IQOS will not significantly reduce risk to consumers compared with cigarettes.
Bates ignores this reality and instead talks about biomarkers of exposure, which is a different question.
NOT PEER REVIEWED The main problem with the claim of equivalence between smoking and switching to iQOS is that some biomarkers of potential harm change over a much longer timeframe than the 90-day duration of the trials. Biomarkers of potential harm can reflect years of accumulated physical changes arising from smoking and only improve slowly after smoking cessation. The trial did, of course, pick up very substantial reductions in biomarkers of exposure, which would, over time, emerge as reductions in biomarkers of potential harm.
This would have been apparent and obvious to readers if the paper had also shown the results for the third arm of the trial, smoking abstinence. The biomarkers of potential harm for smoking abstinence and for switching to iQOS are quite similar in this trial. This is a curious omission. Furthermore, biomarkers of exposure turned quite similar for both switching to iQOS and smoking abstinence - both are greatly reduced, which is an encouraging finding about the iQOS product.
It is unlikely that anyone would argue against smoking abstinence on the basis of the biomarkers of potential harm in the original PMI study. However, the author has selectively used the iQOS data from these trials without the context of the smoking abstinence data to oppose the Modified Tobacco Product Application that PMI made to the U.S. FDA - the author's attempt to block this reduced-risk product from entering the US market. ...
NOT PEER REVIEWED The main problem with the claim of equivalence between smoking and switching to iQOS is that some biomarkers of potential harm change over a much longer timeframe than the 90-day duration of the trials. Biomarkers of potential harm can reflect years of accumulated physical changes arising from smoking and only improve slowly after smoking cessation. The trial did, of course, pick up very substantial reductions in biomarkers of exposure, which would, over time, emerge as reductions in biomarkers of potential harm.
This would have been apparent and obvious to readers if the paper had also shown the results for the third arm of the trial, smoking abstinence. The biomarkers of potential harm for smoking abstinence and for switching to iQOS are quite similar in this trial. This is a curious omission. Furthermore, biomarkers of exposure turned quite similar for both switching to iQOS and smoking abstinence - both are greatly reduced, which is an encouraging finding about the iQOS product.
It is unlikely that anyone would argue against smoking abstinence on the basis of the biomarkers of potential harm in the original PMI study. However, the author has selectively used the iQOS data from these trials without the context of the smoking abstinence data to oppose the Modified Tobacco Product Application that PMI made to the U.S. FDA - the author's attempt to block this reduced-risk product from entering the US market. https://tobacco.ucsf.edu/pmi’s-own-data-biomarkers-potential-harm-americans-show-iqos-not-detectably-different-conventional-cigs
NOT PEER REVIEWED
The potential presence of formaldehyde cyanohydrin in the polylactic acid (PLA) filter of Marlboro Heatstick when heated was reported by Davis and al. PLA is a biodegradable thermoplastic derived from renewable resources such as corn starch. This tentative identification is based on the GC-MS analysis of the headspace of a heated piece of PLA, and the subsequent compound identification by mass spectra matching (acceptance criteria >85%) with the spectra library of the National Institute of Standard and Technology (NIST). However, this was not confirmed by injecting a purchased analytical grade reference standard, in order to unambiguously prove the presence of formaldehyde cyanohydrin. Therefore, we decided to repeat the experiment using headspace injection gas chromatography coupled to high resolution mass spectrometry under similar conditions as described in the publication. Our headspace GC-HR-MS analyses showed four peaks, at retention times of 16.38, 16.47, 17.14, and 18.58 min, in good agreement with the reported data reported (figure 4).
From the analysis of reference standards, we have confirmed the presence of both e-caprolactone (CAS# 502-44-3) and (S,S)-lactide (CAS# 4511-42-6) eluting at 16.47 and 17.14 min, respectively. We identified triacetin (CAS# 102-76-1) at 18.58 min, based on the reference standard, instead of 1,2-diacetin (their EI mass spectra are very similar).
However, we have demonstrated unambiguously the a...
NOT PEER REVIEWED
The potential presence of formaldehyde cyanohydrin in the polylactic acid (PLA) filter of Marlboro Heatstick when heated was reported by Davis and al. PLA is a biodegradable thermoplastic derived from renewable resources such as corn starch. This tentative identification is based on the GC-MS analysis of the headspace of a heated piece of PLA, and the subsequent compound identification by mass spectra matching (acceptance criteria >85%) with the spectra library of the National Institute of Standard and Technology (NIST). However, this was not confirmed by injecting a purchased analytical grade reference standard, in order to unambiguously prove the presence of formaldehyde cyanohydrin. Therefore, we decided to repeat the experiment using headspace injection gas chromatography coupled to high resolution mass spectrometry under similar conditions as described in the publication. Our headspace GC-HR-MS analyses showed four peaks, at retention times of 16.38, 16.47, 17.14, and 18.58 min, in good agreement with the reported data reported (figure 4).
From the analysis of reference standards, we have confirmed the presence of both e-caprolactone (CAS# 502-44-3) and (S,S)-lactide (CAS# 4511-42-6) eluting at 16.47 and 17.14 min, respectively. We identified triacetin (CAS# 102-76-1) at 18.58 min, based on the reference standard, instead of 1,2-diacetin (their EI mass spectra are very similar).
However, we have demonstrated unambiguously the absence of formaldehyde cyanohydrin by injecting the reference standard (Sigma, CAS# 107-16-4, ref. 50640). The formaldehyde cyanohydrin is eluting at 11.53 min and does not correspond to the peak eluting just before e-caprolactone that the authors tentatively identified as formaldehyde cyanohydrin (17.97 min under their conditions). This peak has been confirmed, using the purchased reference standard (NatureWorks, CAS # 13076-19-2), to be meso-lactide, the third isomers of lactide. The experimental details are available on PMIScience.com (https://www.pmiscience.com/library/publication/analysis-of-polylactic-ac...).
It is well known among analytical chemists that unit mass matching with a single data base is insufficient to prove the identity of a compound. Therefore, we typically use commercially available reference standards to verify our findings. This is important to us, as we are focused on developing reduced risk alternatives to combustible cigarettes. In this context, it is key that our science is always verified to the highest possible standards.
NOT PEER REVIEWED
Euromonitor International is a privately held, independent provider of strategic market research with no agenda other than to present the most realistic illicit trade data impartially and within its wider industry context. Subscribers to Euromonitor’s Passport Tobacco database are varied and include tobacco control/ public health groups, academia, retailers, manufacturers of raw materials as well as tobacco brand owners and banks/ consultancies, amongst others.
These same stakeholders are approached by Euromonitor for comment on industry trends, including those of illicit sales. Euromonitor’s stated sources for illicit cigarettes sales thus include trade press, customs offices, interviews with manufacturers and retailers, government and academic organisations. This is reconciled against local knowledge of the market and illicit trade’s wider context – eg national economic performance, trends in taxation, unit prices and duty paid sales, porosity of borders, law enforcement efforts, and so on. There is no reliance on any one source.
By its very nature, illicit trade in tobacco products is a contentious area and one that is difficult to quantify – there are often wide discrepancies between various sources on illicit trade, reflecting vested interests in either deflating or inflating figures. In these circumstances, Euromonitor strives to present the most widely accepted and realistic estimate of the illicit market, based on a holistic...
NOT PEER REVIEWED
Euromonitor International is a privately held, independent provider of strategic market research with no agenda other than to present the most realistic illicit trade data impartially and within its wider industry context. Subscribers to Euromonitor’s Passport Tobacco database are varied and include tobacco control/ public health groups, academia, retailers, manufacturers of raw materials as well as tobacco brand owners and banks/ consultancies, amongst others.
These same stakeholders are approached by Euromonitor for comment on industry trends, including those of illicit sales. Euromonitor’s stated sources for illicit cigarettes sales thus include trade press, customs offices, interviews with manufacturers and retailers, government and academic organisations. This is reconciled against local knowledge of the market and illicit trade’s wider context – eg national economic performance, trends in taxation, unit prices and duty paid sales, porosity of borders, law enforcement efforts, and so on. There is no reliance on any one source.
By its very nature, illicit trade in tobacco products is a contentious area and one that is difficult to quantify – there are often wide discrepancies between various sources on illicit trade, reflecting vested interests in either deflating or inflating figures. In these circumstances, Euromonitor strives to present the most widely accepted and realistic estimate of the illicit market, based on a holistic view of the wider national context and the factors that contribute towards it (as described above) – no single source or figure is taken as definitive and all figures undergo this wider review. Furthermore, this wider context is discussed at length in the attendant analysis in each country report where the trends behind the figures are laid out.
Given Euromonitor’s exhaustive geographic coverage of this dataset – at 100 markets researched in-field for illicit trade, there is no other source like it – as well as our annual revisiting of this dataset, it is inevitable that some changes between editions will be necessary. Euromonitor is transparent about its reasons for change and welcomes any discussion on what can be a opaque area - we are always happy to engage with all concerned stakeholders and review their own sources, on a country-by-country basis, should they exist.
NOT PEER REVIEWED
Coleman et al’s important report [1] on transitions in the vaping and smoking status of a nationally representative cohort of American 18+ adults who use electronic cigarettes (EC) from the PATH study provides rich data that can greatly advance our understanding of the natural history of EC use and their potential in harm reduction.
However, we were struck by the absence of emphasis in the report of what is perhaps its most important finding. If we examine the report’s data and consider the net impact of vaping on the critical goals of having vapers stopping smoking and vaping non-smokers not starting to smoke, the findings are very disturbing and should strong reason for pause among those advocating e-cigarettes as a game-changing way of stopping smoking.
At Wave 2, 12 months on from Wave 1, of the cohort of 2036 dual users (EC + smoking) only 104 (5.1%) had transitioned to using only EC and another 143 (7%) had quit both EC and smoking for a combined total of 247 or 12.1%. Of the 896 exclusive EC users at Wave 1, 277 (30.9%) had stopped vaping at Wave 2. Together, 524 out of the 2932 EC users (17.9%) followed from Wave 1 might be considered to have had positive outcomes at Wave 2.
The other side of the coin however, shows that of the 2036 dual users at Wave 1, 886 (43.5%) relapsed to using cigarettes exclusively. In addition, among the 896 exclusive EC users from Wave 1, 109 (12.2%) had stopped vaping and were now smoking, wit...
NOT PEER REVIEWED
Coleman et al’s important report [1] on transitions in the vaping and smoking status of a nationally representative cohort of American 18+ adults who use electronic cigarettes (EC) from the PATH study provides rich data that can greatly advance our understanding of the natural history of EC use and their potential in harm reduction.
However, we were struck by the absence of emphasis in the report of what is perhaps its most important finding. If we examine the report’s data and consider the net impact of vaping on the critical goals of having vapers stopping smoking and vaping non-smokers not starting to smoke, the findings are very disturbing and should strong reason for pause among those advocating e-cigarettes as a game-changing way of stopping smoking.
At Wave 2, 12 months on from Wave 1, of the cohort of 2036 dual users (EC + smoking) only 104 (5.1%) had transitioned to using only EC and another 143 (7%) had quit both EC and smoking for a combined total of 247 or 12.1%. Of the 896 exclusive EC users at Wave 1, 277 (30.9%) had stopped vaping at Wave 2. Together, 524 out of the 2932 EC users (17.9%) followed from Wave 1 might be considered to have had positive outcomes at Wave 2.
The other side of the coin however, shows that of the 2036 dual users at Wave 1, 886 (43.5%) relapsed to using cigarettes exclusively. In addition, among the 896 exclusive EC users from Wave 1, 109 (12.2%) had stopped vaping and were now smoking, with another 121 having resumed smoking as well as using EC (i.e. became dual users). Importantly, 502 of 896 (56%) exclusive e-cigarette users were those who had never been established smokers prior to using e-cigarettes. Alarmingly, of these 502 adults, 120 (23.9%) progressed from using only e-cigarettes to either dual use (54 or 10.8%) or smoking only (66 or 13.2%).
Taken together, 886 dual users in Wave 1 relapsed to become exclusive cigarette smokers in Wave 2, and 230 exclusive vapers in Wave 1 took up cigarette smoking in Wave 2 (dual use or exclusively cigarettes). Undoubtedly, these should be considered as negative outcomes.
The table below shows that for every person vaping at Wave 1 who benefited across 12 months by quitting smoking, there are 2.1 who either relapsed to or took-up smoking. Most disturbingly, in this adult cohort nearly one in four of those who had never been established smokers took up smoking after first using EC. Concern about putative gateway effects of ECs to smoking have been dominated by concerns about youth. These data showing transitions from EC to smoking in nearly a quarter of exclusive adult EC users with no histories of established smoking should widen this debate to consider adult gateway effects too.
By far the largest proportion of those with negative outcomes are those dual users who relapsed to smoking (886 or 43.5% of dual users). As the authors note in their discussion, many of these were infrequent EC users, possibly involved in transitory experimentation at Wave 1. If we add the 902 who were still dual using at Wave 2, then 1788 of 2036 dual users (87.8%) in this sample might be said to have been held in smoking (dual using or exclusive smoking) 12 months later compared to 12.1% dual users who may have benefitted by using ECs.
We would expect commercial interests in both the tobacco and EC industries would be more than delighted with these findings. However, from a public health harm reduction perspective these results argue against EC being an effective harm reduction strategy, and point to their far stronger potential to both recruit smokers and hold many smokers in smoking.
Reference
1. Coleman B et al Transitions in electronic cigarette use among adults in the Population Assessment of Tobacco and Health (PATH) Study, Waves 1 and 2 (2013-2105). Tobacco Control 2018; doi:10.1136/tobaccocontrol-2017-054174
NOT PEER REVIEWED
The potential presence of formaldehyde cyanohydrin in the polylactic acid (PLA) filter of Marlboro Heatstick when heated was reported by Davis and al. PLA is a biodegradable thermoplastic derived from renewable resources such as corn starch. This tentative identification is based on the GC-MS analysis of the headspace of a heated piece of PLA, and the subsequent compound identification by mass spectra matching (acceptance criteria >85%) with the spectra library of the National Institute of Standard and Technology (NIST). However, this was not confirmed by injecting a purchased analytical grade reference standard, in order to unambiguously prove the presence of formaldehyde cyanohydrin. Therefore, we decided to repeat the experiment using headspace injection gas chromatography coupled to high resolution mass spectrometry under similar conditions as described in the publication. Our headspace GC-HR-MS analyses showed four peaks, at retention times of 16.38, 16.47, 17.14, and 18.58 min, in good agreement with the reported data reported (figure 4).
From the analysis of reference standards, we have confirmed the presence of both e-caprolactone (CAS# 502-44-3) and (S,S)-lactide (CAS# 4511-42-6) eluting at 16.47 and 17.14 min, respectively. We identified triacetin (CAS# 102-76-1) at 18.58 min, based on the reference standard, instead of 1,2-diacetin (their EI mass spectra are very similar).
However, we have demonstrated unambiguously the a...
NOT PEER REVIEWED
The potential presence of formaldehyde cyanohydrin in the polylactic acid (PLA) filter of Marlboro Heatstick when heated was reported by Davis and al. PLA is a biodegradable thermoplastic derived from renewable resources such as corn starch. This tentative identification is based on the GC-MS analysis of the headspace of a heated piece of PLA, and the subsequent compound identification by mass spectra matching (acceptance criteria >85%) with the spectra library of the National Institute of Standard and Technology (NIST). However, this was not confirmed by injecting a purchased analytical grade reference standard, in order to unambiguously prove the presence of formaldehyde cyanohydrin. Therefore, we decided to repeat the experiment using headspace injection gas chromatography coupled to high resolution mass spectrometry under similar conditions as described in the publication. Our headspace GC-HR-MS analyses showed four peaks, at retention times of 16.38, 16.47, 17.14, and 18.58 min, in good agreement with the reported data reported (figure 4).
From the analysis of reference standards, we have confirmed the presence of both e-caprolactone (CAS# 502-44-3) and (S,S)-lactide (CAS# 4511-42-6) eluting at 16.47 and 17.14 min, respectively. We identified triacetin (CAS# 102-76-1) at 18.58 min, based on the reference standard, instead of 1,2-diacetin (their EI mass spectra are very similar).
However, we have demonstrated unambiguously the absence of formaldehyde cyanohydrin by injecting the reference standard (Sigma, CAS# 107-16-4, ref. 50640). The formaldehyde cyanohydrin is eluting at 11.53 min and does not correspond to the peak eluting just before e-caprolactone that the authors tentatively identified as formaldehyde cyanohydrin (17.97 min under their conditions). This peak, based on existing literature [1] and high resolution mass spectra, is highly likely to be meso-lactide, the third isomers of lactide. The experimental details are available on PMIScience.com (https://www.pmiscience.com/library/publication/analysis-of-polylactic-ac...)
It is well known among analytical chemists that unit mass matching with a single data base is insufficient to prove the identity of a compound. Therefore, we typically use commercially available reference standards to verify our findings. This is important to us, as we are focused on developing reduced risk alternatives to combustible cigarettes. In this context, it is key that our science is always verified to the highest possible standards.
[1] Arrieta MP, Parres-Garcia F, Lopez-Martinez J et al. Pirólisis de residuo de bioplásticos : Productos obtenidos del ácido poliláctico (PLA). Dyna Ingenieria e Industria, 2012 ; 87(4):395-399. doi:10.6036/4673
NOT PEER REVIEWED
The reporting of the results of this study is far from complete, which is concerning given the highly politicised controversy that surrounds this product. I hope the authors should respond to this comment by publishing supplementary material with all the data they collected in a an accessible form such a CSV file and summarised in tables in a supplementary memo.
In particular, the authors should provide all data on the following:
+ Vaping and JUUL current use (used in past 30-days) prevalence stratified by age, clearly differentiating between 18 and over and under-18s
+ Frequency of use of vaping products and JUUL within the 30 days among current (past-30 days) users, ideally using the same frequency breakdown used in the National Youth Tobacco Survey
+ Breakdown of vaping status by smoking status and frequency of vaping and JUUL use - to help determine the extent to which regular JUUL use is concentrated among smokers
+ Smoking prevalence and frequency
There is a rare opportunity to gain insights into a live controversy, yet the reporting of the survey is so incomplete it is difficult to draw any serious conclusions from it about the overall effect. For example, JUUL maybe displacing other vaping products used by youth as it is in the market overall. JUUL may be functioning as an alternative to smoking in both adolescents and adults and contributing to achieving smoke-free public health objectives.
NOT PEER REVIEWED
The reporting of the results of this study is far from complete, which is concerning given the highly politicised controversy that surrounds this product. I hope the authors should respond to this comment by publishing supplementary material with all the data they collected in a an accessible form such a CSV file and summarised in tables in a supplementary memo.
In particular, the authors should provide all data on the following:
+ Vaping and JUUL current use (used in past 30-days) prevalence stratified by age, clearly differentiating between 18 and over and under-18s
+ Frequency of use of vaping products and JUUL within the 30 days among current (past-30 days) users, ideally using the same frequency breakdown used in the National Youth Tobacco Survey
+ Breakdown of vaping status by smoking status and frequency of vaping and JUUL use - to help determine the extent to which regular JUUL use is concentrated among smokers
+ Smoking prevalence and frequency
There is a rare opportunity to gain insights into a live controversy, yet the reporting of the survey is so incomplete it is difficult to draw any serious conclusions from it about the overall effect. For example, JUUL maybe displacing other vaping products used by youth as it is in the market overall. JUUL may be functioning as an alternative to smoking in both adolescents and adults and contributing to achieving smoke-free public health objectives.
The Truth Initiative is proud of its advocacy for young people, but as far as presentation and interpretation of data are concerned, such activist commitment amounts to a competing interest. For that reason, everyone, including Truth, is served by full disclosure of the survey data in an appropriate and accessible form and answers to key data questions that would help understand the JUUL phenomenon.
NOT PEER REVIEWED
The authors state "These stores have largely stopped carrying e-cigarettes at the same time as starting to stock IQOS HEETS (HEATSTICKS), the cigarette-like component that is smoked in the IQOS device,..." but provide no insight into why that is. Are these retailers being incentivised to stop selling e-cigs by PMI?
While the risk profile of IQOS is uncertain, the product is highly likely to be much more harmful than vaping e-cigs. Commercial tactics that promote IQOS over vaping devices, excluding the latter from retail chains, would be of major concern for tobacco control.
NOT PEER REVIEWED
Show MoreMore than 1,000 participants were exposed to IQOS in our clinical studies. The authors of the letter “Possible hepatotoxicity of IQOS" based their analysis on approximatively 10% of the data instead of examining the data as a whole. For example, for the five-day exposure studies in confinement, they stated that the percentage of participants with elevated bilirubin in IQOS arm was more than three times higher than that observed in the smoking abstinence (SA) arm in the European study (8.8% [7 participants] in IQOS arm, 2.6% [1 participant] in SA arm). However, they missed reporting that this percentage was lower in the IQOS arm than in the cigarette smoking (CC) arm in the Japanese study (10% [8 participants] in IQOS arm, 15% [6 participants] in CC arm). They also stated that the mean increase in alanine aminotransferase (ALT) was higher with IQOS than with CC or SA in the Japanese study but did not report that in the European study, the mean increase in ALT was lower in the IQOS arm than in the CC or SA arm.
Similarly, for the 90-day exposure studies in an ambulatory setting, they mentioned that the percentage of participants with increased ALT levels after 60 days of exposure was higher within the IQOS arm (6.3% [5 participants] in IQOS arm, 0% in CC arm, 2.6% [1 participant] in SA arm) in the U.S. study. However they omitted to mention that in the Japanese study, this percentage was lower in IQOS arm compared with CC or SA arms after 3...
NOT PEER REVIEWED
This study has some important findings that could, if replicated, guide FDA decision making on applications from manufacturers to make modified risk tobacco product claims. However, while it does not detract from the study’s findings, the article does not accurately describe the standards FDA must apply when evaluating those applications. The abstract inaccurately suggests that tobacco products in the U.S. may make reduced-risk or reduced-exposure claims so long as they are not misleading, and does not mention that any explicit or implicit reduced-exposure or reduced-risk claims may not be legally made without first submitting an application to FDA and receiving a permissive order, which considers various other factors, as well.
The introduction of the paper does a bit better, accurately stating that the Tobacco Control Act requires prior review by FDA before making lower-exposure or lower-risk claims. But it then suggests that manufacturers can receive that permission if they either demonstrate that the product lowers harm or risk compared with other tobacco products or if they demonstrate that the product is free of or contains reduced levels of harmful chemicals and the related claims don’t mislead consumers to believe that the reduced-exposure means lower risk. While that description is accurate as far as it goes, it leaves off the enormously important requirement, in both cases, that a manufacturer’s application for permission to...
Show MoreNOT PEER REVIEWED
The "serious criticism" that Mr. Bates refers to is from him (on another website).
In order for the FDA to issue an order allowing Philip Morris International to market IQOS in the United States as a reduced risk tobacco product, the law required that, among other things, FDA "determines that the applicant [PMI] has demonstrated that such product [IQOS], as it is actually used by consumers will significantly reduce harm and the risk of tobacco- related disease to individual tobacco users."
That is why PMI provided the information of biomarkers of potential harm to the FDA. and how they compare to values observed in smokers. My paper shows that, using PMI's own data, IQOS will not significantly reduce risk to consumers compared with cigarettes.
Bates ignores this reality and instead talks about biomarkers of exposure, which is a different question.
NOT PEER REVIEWED The main problem with the claim of equivalence between smoking and switching to iQOS is that some biomarkers of potential harm change over a much longer timeframe than the 90-day duration of the trials. Biomarkers of potential harm can reflect years of accumulated physical changes arising from smoking and only improve slowly after smoking cessation. The trial did, of course, pick up very substantial reductions in biomarkers of exposure, which would, over time, emerge as reductions in biomarkers of potential harm.
Show MoreThis would have been apparent and obvious to readers if the paper had also shown the results for the third arm of the trial, smoking abstinence. The biomarkers of potential harm for smoking abstinence and for switching to iQOS are quite similar in this trial. This is a curious omission. Furthermore, biomarkers of exposure turned quite similar for both switching to iQOS and smoking abstinence - both are greatly reduced, which is an encouraging finding about the iQOS product.
It is unlikely that anyone would argue against smoking abstinence on the basis of the biomarkers of potential harm in the original PMI study. However, the author has selectively used the iQOS data from these trials without the context of the smoking abstinence data to oppose the Modified Tobacco Product Application that PMI made to the U.S. FDA - the author's attempt to block this reduced-risk product from entering the US market.
...
NOT PEER REVIEWED
The potential presence of formaldehyde cyanohydrin in the polylactic acid (PLA) filter of Marlboro Heatstick when heated was reported by Davis and al. PLA is a biodegradable thermoplastic derived from renewable resources such as corn starch. This tentative identification is based on the GC-MS analysis of the headspace of a heated piece of PLA, and the subsequent compound identification by mass spectra matching (acceptance criteria >85%) with the spectra library of the National Institute of Standard and Technology (NIST). However, this was not confirmed by injecting a purchased analytical grade reference standard, in order to unambiguously prove the presence of formaldehyde cyanohydrin. Therefore, we decided to repeat the experiment using headspace injection gas chromatography coupled to high resolution mass spectrometry under similar conditions as described in the publication. Our headspace GC-HR-MS analyses showed four peaks, at retention times of 16.38, 16.47, 17.14, and 18.58 min, in good agreement with the reported data reported (figure 4).
From the analysis of reference standards, we have confirmed the presence of both e-caprolactone (CAS# 502-44-3) and (S,S)-lactide (CAS# 4511-42-6) eluting at 16.47 and 17.14 min, respectively. We identified triacetin (CAS# 102-76-1) at 18.58 min, based on the reference standard, instead of 1,2-diacetin (their EI mass spectra are very similar).
Show MoreHowever, we have demonstrated unambiguously the a...
NOT PEER REVIEWED
Euromonitor International is a privately held, independent provider of strategic market research with no agenda other than to present the most realistic illicit trade data impartially and within its wider industry context. Subscribers to Euromonitor’s Passport Tobacco database are varied and include tobacco control/ public health groups, academia, retailers, manufacturers of raw materials as well as tobacco brand owners and banks/ consultancies, amongst others.
These same stakeholders are approached by Euromonitor for comment on industry trends, including those of illicit sales. Euromonitor’s stated sources for illicit cigarettes sales thus include trade press, customs offices, interviews with manufacturers and retailers, government and academic organisations. This is reconciled against local knowledge of the market and illicit trade’s wider context – eg national economic performance, trends in taxation, unit prices and duty paid sales, porosity of borders, law enforcement efforts, and so on. There is no reliance on any one source.
By its very nature, illicit trade in tobacco products is a contentious area and one that is difficult to quantify – there are often wide discrepancies between various sources on illicit trade, reflecting vested interests in either deflating or inflating figures. In these circumstances, Euromonitor strives to present the most widely accepted and realistic estimate of the illicit market, based on a holistic...
Show MoreNOT PEER REVIEWED
Coleman et al’s important report [1] on transitions in the vaping and smoking status of a nationally representative cohort of American 18+ adults who use electronic cigarettes (EC) from the PATH study provides rich data that can greatly advance our understanding of the natural history of EC use and their potential in harm reduction.
However, we were struck by the absence of emphasis in the report of what is perhaps its most important finding. If we examine the report’s data and consider the net impact of vaping on the critical goals of having vapers stopping smoking and vaping non-smokers not starting to smoke, the findings are very disturbing and should strong reason for pause among those advocating e-cigarettes as a game-changing way of stopping smoking.
At Wave 2, 12 months on from Wave 1, of the cohort of 2036 dual users (EC + smoking) only 104 (5.1%) had transitioned to using only EC and another 143 (7%) had quit both EC and smoking for a combined total of 247 or 12.1%. Of the 896 exclusive EC users at Wave 1, 277 (30.9%) had stopped vaping at Wave 2. Together, 524 out of the 2932 EC users (17.9%) followed from Wave 1 might be considered to have had positive outcomes at Wave 2.
The other side of the coin however, shows that of the 2036 dual users at Wave 1, 886 (43.5%) relapsed to using cigarettes exclusively. In addition, among the 896 exclusive EC users from Wave 1, 109 (12.2%) had stopped vaping and were now smoking, wit...
Show MoreNOT PEER REVIEWED
The potential presence of formaldehyde cyanohydrin in the polylactic acid (PLA) filter of Marlboro Heatstick when heated was reported by Davis and al. PLA is a biodegradable thermoplastic derived from renewable resources such as corn starch. This tentative identification is based on the GC-MS analysis of the headspace of a heated piece of PLA, and the subsequent compound identification by mass spectra matching (acceptance criteria >85%) with the spectra library of the National Institute of Standard and Technology (NIST). However, this was not confirmed by injecting a purchased analytical grade reference standard, in order to unambiguously prove the presence of formaldehyde cyanohydrin. Therefore, we decided to repeat the experiment using headspace injection gas chromatography coupled to high resolution mass spectrometry under similar conditions as described in the publication. Our headspace GC-HR-MS analyses showed four peaks, at retention times of 16.38, 16.47, 17.14, and 18.58 min, in good agreement with the reported data reported (figure 4).
From the analysis of reference standards, we have confirmed the presence of both e-caprolactone (CAS# 502-44-3) and (S,S)-lactide (CAS# 4511-42-6) eluting at 16.47 and 17.14 min, respectively. We identified triacetin (CAS# 102-76-1) at 18.58 min, based on the reference standard, instead of 1,2-diacetin (their EI mass spectra are very similar).
Show MoreHowever, we have demonstrated unambiguously the a...
NOT PEER REVIEWED
The reporting of the results of this study is far from complete, which is concerning given the highly politicised controversy that surrounds this product. I hope the authors should respond to this comment by publishing supplementary material with all the data they collected in a an accessible form such a CSV file and summarised in tables in a supplementary memo.
In particular, the authors should provide all data on the following:
+ Vaping and JUUL current use (used in past 30-days) prevalence stratified by age, clearly differentiating between 18 and over and under-18s
+ Frequency of use of vaping products and JUUL within the 30 days among current (past-30 days) users, ideally using the same frequency breakdown used in the National Youth Tobacco Survey
+ Breakdown of vaping status by smoking status and frequency of vaping and JUUL use - to help determine the extent to which regular JUUL use is concentrated among smokers
+ Smoking prevalence and frequency
There is a rare opportunity to gain insights into a live controversy, yet the reporting of the survey is so incomplete it is difficult to draw any serious conclusions from it about the overall effect. For example, JUUL maybe displacing other vaping products used by youth as it is in the market overall. JUUL may be functioning as an alternative to smoking in both adolescents and adults and contributing to achieving smoke-free public health objectives.
T...
Show MoreNOT PEER REVIEWED
The authors state "These stores have largely stopped carrying e-cigarettes at the same time as starting to stock IQOS HEETS (HEATSTICKS), the cigarette-like component that is smoked in the IQOS device,..." but provide no insight into why that is. Are these retailers being incentivised to stop selling e-cigs by PMI?
While the risk profile of IQOS is uncertain, the product is highly likely to be much more harmful than vaping e-cigs. Commercial tactics that promote IQOS over vaping devices, excluding the latter from retail chains, would be of major concern for tobacco control.
Can the authors enlighten us?
Pages