The pro-vaping assault on the World Health Organization

The Framework Convention on Tobacco Control is the treaty negotiated among members of the World Health Organization to establish international standards for tobacco control interventions. Negotiations began at the turn of the century, and the treaty came into force in February 2005. The vast majority (182 of 194) countries which participate in the World Health Organization have joined this treaty process,

The governments and civil society organizations that are involved in the treaty process are now preparing for the FCTC's 9th Conference of the Parties, which will be held virtually during the second week of November. The item that seems to be gaining the most attention, however, is one that the FCTC Bureau (its management committee) has removed from this year's agenda: discussion of how to manage new nicotine products, like e-cigarettes and heated tobacco products. Removing this issue from the agenda has not, however, stopped the attacks on the WHO for the background work it has done on this topic.

This post reports on some recent activities by the World Health Organization related to electronic nicotine delivery systems (ENDS) and on activities by those opposing these efforts.

1 The action:
WHO's evolving knowledge and recommendations on alternative nicotine products 

The FCTC has grappled with how to address e-cigarettes (electronic nicotine delivery systems, ENDS) for several years, and countries have repeatedly sought advice from WHO on how to respond to the new products. Examples of these are consensus decisions taken in the 2014 and 2016 meetings of the Conference of Parties ( FCTC/COP/6/10 Rev.1, FCTC/COP7(9)). 

In 2018, the parties requested WHO to engage independent scientists to study the issue of e-cigarettes and other "novel and emerging tobacco products" and their potential benefits and risks  (FCTC/COP8(22)). They also asked the FCTC secretariat to prepare suggestions on how to adjust the treaty in response to this changing market. It was expected that these documents would provide a foundation for a negotiation during COP 9 (originally scheduled for 2020 and then delayed to 2021) on whether or how to include these products in the treaty.

As requested, the WHO, the secretariat and its advisory committee on tobacco regulation (TobReg) commissioned a series of scientific reviews and hosted a meeting of approximately 50 regulators and experts to discuss the findings (including some from Canada). The meeting took place a year ago (September 28-October 2 2020). The first indication of the advice that would be provided from this review came in an overview of expert meetings that was circulated to WHO's Executive Board in December. (EB148/47). 

The recommendations circulated in advance of this meeting covered two categories of electronic products: heated tobacco products and vapour products. The recommendations for heated tobacco products (such as the IQOS product now sold in Canada) were for them to be regulated as strictly as other tobacco products, that manufacturers be barred from making health claims and that advertisements be banned. Recommendations specific to e-cigarettes included banning open systems (where users can modify the liquids), regulatory requirements which prohibited e-cigarettes from providing more nicotine than conventional tobacco and a prohibition on the sale of other pharmacologically active substances (eg cannabinoids) in vaping liquids. 

In May 2021, the full report of WHO's scientific advisors and the background research was made public. In over 300 pages, this eighth report of the WHO study group on tobacco product regulation (Tob Reg) addressed evidence concerning product toxicants, addictive potential, patterns of use, individual and population risk, flavours and forms of nicotine. In addition to the recommendations that had circulated earlier, there was detailed policy advice in each of the 12 separate chapters.

In July, WHO released its 8th MPOWER report, which included, for the first time, data on e-cigarettes (electronic nicotine delivery systems, ENDS). The report reviewed WHO's involvement in the issue (see figure below), and clearly recommended that e-cigarettes and "new and emerging products should be included in a comprehensive approach to tobacco control". The WHO concludes that children who use ENDS are more likely to later smoke tobacco, and that the "evidence on the potential role for ENDS in cessation is still inconclusive."

Also in July, the FCTC Secretariat provided countries with its assessment of the situation in two background documents. One (FCTC/COP/9/9) outlined the key findings of the 8th TobReg report with respect to heated tobacco products (HTP, eg IQOS). The other (FCTC/COP/9/10), addressed specific challenges in regulation. The Secretariat's unequivocal advice was that HTP products should be regulated in the same way as conventional tobacco products, and that Parties should be mindful of their FCTC obligations in making this happen.

By the time these documents were released, however, the decision had been reached that "substantive discussions" on the topic should be postponed until COP10, likely in 2023.

2. The re-action:
Calls for WHO to be de-funded and for an independent review of its scientific review.  

The circulation of WHO's recommendation on e-cigarettes in December 2020 triggered attacks on the institution in several in important quarters. 

Not "fit for purpose"

United Kingdom politicians working under the banner "All-Party Parliamentary Group for Vaping Inquiry" hosted hearings in the winter, with an objective to "collect evidence and issue a report on the FCTC's Conference of Parties 9". (copinquiry.co.uk) In it's report this unofficial parliamentary committee concluded that the FCTC is " no longer fit for purpose" and called on the British government to cut funding to the WHO unless a more pro-vaping position was adopted. In their report (and subsequent Twitter posts), they have exhorted the United Kingdom to flex its post-Brexit muscle and push for a pro-vaping resolution at COP9. 

The "fit for purpose" attack has been joined by several industry-friendly groups. These include the Consumer Choice Centre, which says the "the FCTC protocol [sic] has become more of a tool for political power and control rather than considerate public health policies."

In a report focused at the upcoming COP, the UK Institute of Economic Affairs repeated this assertion. "The FCTC Secretariat and the COP meetings are not fit for purpose. In their relentless opposition to vaping and other reduced risk products, they have become a threat to global health."  (In support of this position, the IEA directly attributes the decline in smoking in Canada to increased vaping.) 

As COP9 approaches, the campaign to up-end WHO's advice has intensified, with a particular focus on encouraging the U.K. government to flex its post-Brexit independence to influence FCTC decisions.  

In September, the Global Tobacco and Nicotine Forum held a session on "Transforming the FCTC". (The GTNF is an annual meeting established by tobacco companies to promote communication between government and industry)  At a press conference the next day, speakers from the conference accused the WHO of being "negligent and incompetent" and called for the British government to have a “big independent voice” at COP9 and to push for e-cigarettes to be treated as an acceptable tobacco alternative. 

Another event in the pre-COP9 campaign took place this past week, when a letter signed by 100 "experts" was sent to country representatives to the FCTC meeting. Among these were individuals who are known to be funded by the tobacco industry and also some who are known to not be associated with it. These individuals called for an independent audit of WHO's scientific analysis of heated tobacco and ENDS: "Initiate an independent review of WHO and the FCTC approach to tobacco policy ...the interpretation and use of science, the quality of policy advice, stakeholder engagement, and accountability and governance."  

The letter is an apparent follow-up to a letter to WHO leadreship sent on World No Tobacco Day by the same organizers.  

Next week, another pro-industry group, the Global State of Tobacco Harm Reduction, will launch another attack on WHO's approach to e-cigarette and on FCTC decisions. "Fighting the Last War challenges the direction of travel of the Framework Convention on Tobacco Control (FCTC) ahead of the forthcoming Conference of the Parties (COP 9). Over recent years, these meetings have moved away from the fundamental aim of the treaty, which was to prevent disease and death linked to tobacco smoking. Instead, leaders in tobacco control have sought to undermine the growing evidence supporting the efficacy and effectiveness of safer nicotine products and their public health potential."

3. The road ahead

When delegates to COP9 meet in early November, they will do so on computer screens. Face-to-face meetings (with the ability to negotiate in informal settings and to gain information through corridor chats) will be postponed until COP10 in 2023. 

Only a few FCTC members have adopted policies which promote harm reduction and e-cigarette use. The majority of member states see these products as part of the problem, not part of the solution. Many interpret the FCTC obligations in Article 5.2 as guidance to maintain a focus on reducing nicotine addiction, not just tobacco use. (As shown below, parties are obliged to adopt measures for "preventing and reducing tobacco consumption, nicotine addiction and exposure to tobacco smoke.")

Because the FCTC operates by consensus and because a consensus does not appear to be in the cards, there is little advantage for either vaping enthusiasts or vaping doubters to force the issue to come to the floor for discussion.

Meanwhile, tobacco and vaping companies will continue to amplify the voices of those who want a permissive regulatory approach to these products. Less certain is whether the silent majority of governments and tobacco control activists will continue to remain silent as WHO continues to come under attack.

Recent events highlight contrasting regulatory approaches for market access: US FDA vs. Canada

This week, the Canadian subsidiary of Philip Morris International (Rothmans, Benson and Hedges) announced the launch of their new vaping product, VEEV. 

On the same day, the U.S. Food and Drug Administration granted permission to Reynolds American (a subsidiary of British American Tobacco) to sell a version of its VUSE e-cigarette in that market.

This post looks at the different regulatory pathways that led to these decisions.

No permission is needed in Canada to launch new e-cigarette designs in Canada.

In Canada, there is no process for tobacco or vaping products to be reviewed by public health officials efore they can be marketed. As long as they meet the requirements set out in the Tobacco and Vaping Products Act and the Canada Consumer Product Safety Act (eg. maximum nicotine concentration and labelling) the company is free to market them.

Canada's open door policy for new tobacco and vaping products is in contrast to that in the United States, where pre-market authorization is now required.

The FDA now controls market access for e-cigarette manufacturers in the USA

When the U.S. federal government adopted the Family Smoking Prevention and Tobacco Control Act in 2009, it included provisions measures to prohibit the sale of any new types of tobacco products which had not been authroized by the Food and Drug Administration (Section 910 of the Federal Food, Drug and Cosmetic Act). The law directs the FDA to authorize these products only if it is determined that doing so is "appropriate for the protection of public health." It also directs the organization to consider whether allowing this product on the market will result in fewer people quitting or more people starting to use tobacco when it makes that decision.

Until this week, the FDA had issued 15 premarket authorizations based on such applications. These were to allow the sale of the IQOS brand of heated tobacco, of a brand of denicotinized cigarettes and some snus brands. (A separate FDA regulatory review is involved if these products are to be marketed as being less harmful - "modified risk" - as has been done for 8 snus products.)

It was only in 2016 that this requirement was extended to manufacturers of e-cigarettes (now considered to be tobacco products under U.S. law). E-cigarettes were already on the market when this happened, and the FDA did not require them to be immediately withdrawn even though no review had been conducted to determine whether their sale was appropriate for the protection of public health.

Instead, despite a series of changing deadlines, it established a market authorization process that culminated last month with millions of products being ordered off the market while others are allowed to remain on sale until the application review process is completed. This week it announced the results of its first completed review.

The first authorization - a tobacco-flavoured Cigalike

FDA's first authorization for e-cigarettes was issued for the VUSE SOLO cigalike and its replacement cartridges. This is a 'cigalike' design that was introduced to the U.S. market by BAT's subsidiary around 2013.

A similar designed product, the VYPE/VUSE e-STICK, was introduced by the Canadian BAT branch in 2018, but which was subsequently withdrawn (presumably because of low sales). It is different than the VUSE ePOD which is the only VUSE product now marketed north of the border.

The FDA explained it decided to permit the sale of this e-cigarette design because it had "determined that the potential benefit to smokers who switch completely or significantly reduce their cigarette use would outweigh the risk to youth."

At this point, only the tobacco-flavoured version is authorized for sale. The FDA turned down the compay's request to sell 20 other flavours and ordered any that were on the market to be withdrawn. The decision on menthol flavourings is pending, and by inference the company can continue to sell that flavour until that happens.

Also pending are the FDA's decisions on JUUL, VUSE ALTO and other e-cigarette products that are closer to those that are currently for sale in Canada. Philip Morris has not yet publicized any agreement with its U.S. partner, ALTRA, for VEEV to be submitted to the FDA for review.

The FDA requires manufacturers to submit massive amounts of information before and after products are marketed

Last week the FDA released requirements for future submissions from manufacturers, including those wanting to introduce a new design (through the Premarket Tobacco Product Application, PMTA process) and those wishing to market a new version of existing design (through the Substantial Equivalent, SE process). Both sets of requirements come into effect next month.

(These rules were originally planned for release in January, but were suspended as a result of the transfer from the Trump to the Biden administrations. This delay resulted in the seemingly odd sequence whereby the FDA announced its new application process AFTER it dispensed with millions of applications and directed manufacturers to remove millions of products from the market.)

The final rules published this week give more indication of the issues that the FDA will consider when assessing whether approving new tobacco products is appropriate for the protection of public health. The list of items that companies are required to submit covers almost 20 pages of small print. Documents that must be submitted for review include:

• detailed descriptions of the design, manufacture and ingredients
• details on their marketing plans (and how young people will be protected from them)
• an environmental impact assessment
• an assessment of the health risks to users and non-users
• an assessment of the perception of the product and impact of "human factors" on usage
• an analysis of the population effect
• the impact the product will have on other tobacco use.
• comprehensive results from any studies

Once the U.S. FDA has authorized the sale of a new tobacco product by issuing a "marketing order", it maintains the right to withdraw that order at any time. Manufacturers are obliged to keep records and to file reports with the FDA that will be used to assess their marketing privileges.

The obligations on Philip Morris to continue marketing IQOS, and those for VUSE SOLO, show that these reports cover a wide range of concerns, including:

• any changes made to the product or manufacturing process and the rationale for each change
• reports on health impact or related scientific investigations
• data on sales and distribution
• demographic characteristics of purchasers
• information on age verification procedures and their effectiveness
• summaries of findings from consumer research
• details on marketing activities, including copies of all advertisements, PR and consumer engagement activities and marketing reach.

Other U.S. government agencies impose reporting requirements on tobacco manufacturers. The U.S. Federal Trade Commission requires reports on commercial activities and earlier this year released a report on cigarette and smokeless tobacco sales and expenditures. It recently ordered 5 e-cigarette manufacturers to also provide such information.

The European Union requires pre-market and post-market information from e-cigarette manufacturers

The European Union Directive on tobacco (Directive 2014/40/EU) requires EU countries to permit the sale of e-cigarettes, and to pass laws which impose certain requirements on manufacturers or products. These include an obligation on manufacturers to give provide post-market information on "sales volumes, preference of various consumer groups and mode of sales" and also on toxicological data. The directive requires that "this information is made available to the general public, taking the need to protect trade secrets duly into account."

In a study to support the European Commission's review of the first 5 years of this process, researchers found that the notification and reporting requirements were costly to enforce.

Many EU countries collaborate in managing these obligations through the EU Joint Action on Tobacco Control (JATC), and the European Union manages a Common entry gate (EU-CEG) for some reporting.

Information provided during pre- and post-market reporting is on (seemingly rare) occasion made public as a result of government agency reports. In France, for example, ANSES (agence nationale de securite sanitaire) allows the public to download data files with the ingredients and other design elements of tobacco products and some information on vaping products. It has published its own analysis of that data in separate reports on tobacco and vaping products. (It also reported significant non-compliance with these reporting obligations).

Canada currently has few pre- or post-market reporting obligations for e-cigarette manufacturers, although post-market reports on tobacco products must be submitted.

E-cigarette manufacturers need only get authorization from the Canadian federal government if they intend to sell vaping products as a cessation aid or other therapeutic product. In such cases, the process is set under the Food and Drugs Act.

Although provincial governments have the constitutional right to control market access for these products, few have chosen to do so. Those which require reporting include British Columbia, [which has required pre-market notification of vaping products for over a year] (https://www2.gov.bc.ca/gov/content/health/keeping-bc-healthy-safe/tobacco-vapour/notice-of-intent-vapour-products) and Nova Scotia, where it is a component of their vaping tax law.

Health Canada has imposed extensive reporting requirements for manufacturers of cigarettes, with somewhat lesser requirements for other tobacco products. The federal Tobacco and Vaping Products Act also gives Health Canada the authority to request similar information from vaping product manufacturers and for the past 4 years the department has indicated that such regulations are in development. Under the Canadian Consumer Product Safety Act, manufacturers are currently required to inform the department of any adverse incidents.
Considerations for Canadian public health

By scrutinizing the marketing plans and designs for e-cigarettes and novel tobacco products before allowing their sale, the United States is pioneering approaches to tobacco regulation that have not yet been tried in Canada. The U.S. experience may provide examples for future approaches in Canada, as may the regulatory requirements in Europe.

Implications for new Canadian regulations:

• Requiring that new tobacco products be authorized by government health authorities before they can be marketed.
• Requiring a separate regulatory review for each product before government views on reduced harm can be claimed.
• Putting the burden of proof on manufacturers to show that their new tobacco products are appropriate for the protection of public health, instead of putting the burden on regulators to say they are not.
• Requiring extensive reporting by manufacturers both before and after products are marketed.
• Establishing a common portal for receipt of data by different jurisdictions, and collaboration in the use of the data.

Documents and resources referenced in this post:

1. British Columbia. E-substances Regulation. 2020.
2. Canada. Tobacco Reporting Regulations (SOR/2000-273), 2000.
3. European Commission. Tobacco Products Directive 2014/40/EU b
4. European Commission. Report on the application of Directive 2014/40/EU concerning the manufacture, presentation and sale of tobacco and related products.
5. European Commission: Final report: Support Study to the report on the application of Directive 2014/40/EU.
6. European Union. Joint Action for Tobacco Control
7. France. Agence national de securité sanitaire. Déclaration des produits du tabac et produits connexes en France. Produits du tabac - Bilan 2016-2020
8. France. Agence national de securité sanitaire Déclaration des produits du tabac et produits connexes en France. Produits du vapotage - Bilan 2016-2020
9. United Kingdom: The Tobacco and Related Products Regulations 2016
10. US FDA: Premarket Tobacco Product Applications and Recordkeeping Requirements. Final Rule. 2021
11. US FDA: Content and Format of Substantial Equivalence Reports; Food and Drug Administration Actions on Substantial Equivalence Reports. Final Rules. 2021
12. US FTC. Order to File Special Section 6(b) Report on E-Cigarette Products in Calendar Year 2021
13. USA. Federal Food, Drug and Cosmetic Act, s. 910 Application for Review of Certain Tobacco Products.

Meta-analyses find vaping leads to smoking among young people and former smokers

This post highlights scientific reviews about the relationship between vaping and smoking that have been published since our previous summaries (in January 2021 and April 2021). 

More evidence that vaping puts young people at greater risk of smoking

An Australian team of researchers has provided a new systematic review and meta-analysis of studies exploring whether e-cigarette use is a risk factor for subsequent cigarette smoking in young people. In this study, published in PLOS one last month, Sze Lin Yoong and colleagues restricted their analysis to longitudinal studies only, thus strengthening the certainty of the findings. Their meta-analysis of 17 such studies of e-cigarette use at baseline and subsequent ever cigarette use (published before October 2020) found a relative risk of cigarette uptake of 3.01. All 17 studies showed a positive relationship. 

This study builds on the conclusions of other recent meta-analyses, including those published last year by British researchers (Kouja et al. based on evidence up to November 2018) and another Australian team (Baenziger et al. based on evidence up to April 2020). Multiple studies have now confirmed that adolescents who use e-cigarettes are at least three times more likely to take up smoking than non-users of e-cigarettes.

And newer studies provide consistent results ...

After the October 2020 cut-off date for the Yoong meta-analysis, three more longitudinal studies appeared were published that provide consistent conclusions.

In July 2021, Jeremy Staff and colleagues reported on their study using longitudinal data on British youth who were questioned at age 14 and followed at age 17. They found that young people who were using e-cigarettes at age 14, but not smoking, were more than five times more likely to have started smoking tobacco cigarettes by age 17.  The reverse was true too. Those who started smoking tobacco cigarettes at age 14 were three times more likely take up e-cigarettes by age 17.  Their results counter the proposition that the young people who vape would otherwise be smokers (the 'common liability' theory) as they found distinct risk factors for tobacco-use and vaping.

Also in July 2021, a paper written by the Netherlands' research team lead by Thomas Martinelli  reported on e-cigarette use and tobacco smoking among Dutch-speaking high school students in the Netherlands and Belgium. This longitudinal study collected follow-up information after six and twelve months and found that those who were using e-cigarettes were 5.63 times more likely to be using tobacco a year later.  They also found that those who were smoking tobacco were 3 times more likely to be using e-cigarette at the year's end. These findings are very like those of British youth reported by Staff et al., cited above. 

A few weeks earlier, Elizabeth Hair and colleagues reported on a longitudinal study of youth and young adutls (15-21 year-olds in 2017) who were contacted after one year. This study found that users of e-cigarettes in 2017 were more than three times more likely to become users of cigars, little cigars or cigarillos (CLCCs) by 2018.  Young people who were cigarette smokers or marijuana users in 2017 were also more likely to become users of CLCCs by 2018.

Evidence that vaping puts former smokers at greater risk of relapsing 

Health authorities hold differing views on whether or not e-cigarettes help smokers quit. For example, Health Canada advises that vaping products are "linked to improved rates of success", but U.S. health authorities (eg U.S. Surgeon General) has found there is "inadequate evidence to conclude that e-cigarettes, in general, increase smoking cessation." Since our last review of this topic in April , the Cochrane review has updated its review and concluded there are reasons to be "moderately confident" that e-cigarettes outperformed NRT in helping people quit for at least 6 months. Because this review considered only random clinical trials and did not look at studies of real-world conditions, it is consistent with the conclusions of recent meta-analyses which found e-cigarettes are effective in clinical settings, but not when sold as consumer products.

But what about those who successfully quit smoking and have remained non-smokers for a year or more? Are some of them tempted to try e-cigarettes? If they do so, are they more or less likely to relapse to tobacco use?

These questions were recently addressed by a Brazilian research team led by Laura Barufaldi. Their search for all papers which examined this phenomenon resulted in only three studies which met their inclusion criteria.

The largest (and thus most influential) of these was by American researchers Hongying Dai and Adam Leventhal who used data from the U.S. longitudinal study on smoking behaviour (the Population Assessment of Tobacco and Health, or PATH Study). From this study they identified people who at the time of the interview had quit smoking more than 12 months previously and then looked for their smoking status one year later. They found that those who had taken up vaping after quitting smoking were 2- 4 times more likely to have relapsed to tobacco smoking.

The other papers confirmed and reinforced those conclusions: Smoking relapse was twice as likely among people who had quit smoking but subsequently started using e-cigarettes.

Implications for public health

Adolescents who never smoked but start vaping are at least three times more likely to start smoking than adolescents who don't try vaping.
• Some former smokers take up e-cigarettes.  If they do so, they are twice as likely to relapse to smoking as former smokers who don't vape.
• E-cigarettes may help some people quit smoking as part of a supervised intervention. In the majority of cases, when acquired and used as consumer products, they do not increase the likelihood of successful quitting

Publications cited:

Baenziger ON, Ford L, Yazidjoglou A, et al. E-cigarette use and combustible tobacco cigarette smoking uptake among non-smokers, including relapse in former smokers: umbrella review, systematic review and meta-analysis, BMJ Open 2021

https://bmjopen.bmj.com/content/11/3/e045603

Barufaldi LA, Guerra RL, de Albuquerque RCR, et al. Risk of smoking relapse with the use of electronic cigarettes: A systematic review with meta-analysis of longitudinal studies. Tob Prev Cessat. 2021;29:29. Published 2021 Apr 27. doi:10.18332/tpc/132964

Dai H, Leventhal AM. Association of electronic cigarette vaping and subsequent smoking relapse among former smokers. Drug Alcohol Depend. 2019;199:10-17. 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743978/

Hair EC, Kreslake JM, Mowery P et al. A longitudinal analysis of e-cigarette use and cigar, little cigar or cigarillo initiation among youth and youth adults: 2017–2019. Drug and Alcohol Dependence,

Volume 226, 2021.
https://pubmed.ncbi.nlm.nih.gov/34218009/

Hartmann-Boyce J, McRobbie H, Butler AR, Lindson N, Bullen C, Begh R, Theodoulou A, Notley C, Rigotti NA, Turner T, Fanshawe TR, Hajek P. Electronic cigarettes for smoking cessation. Cochrane Database Syst Rev. 2021 Sep 14;9(9) https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010216.pub6/full

Khouja JN, Suddell SF, Peters SE, Taylor AE, Munafò MR. Is e-cigarette use in non-smoking young adults associated with later smoking? A systematic review and meta-analysis. Tob Control. 2020 Mar 10;30(1):8–15. doi: 10.1136/tobaccocontrol-2019-055433. https://pubmed.ncbi.nlm.nih.gov/32156694/

Martinelli T, Candel MJJM, de Vries H, et al. Exploring the gateway hypothesis of e-cigarettes and tobacco: a prospective replication study among adolescents in the Netherlands and Flanders. Tobacco Control Published Online First: 05 July 2021. https://tobaccocontrol.bmj.com/content/early/2021/08/18/tobaccocontrol-2021-056528

Staff, J., Kelly, B. C., Maggs, J. L., and Vuolo, M. (2021) Adolescent electronic cigarette use and tobacco smoking in the Millennium Cohort Study. Addiction, https://onlinelibrary.wiley.com/doi/10.1111/add.15645

Yoong SL,  Hall A, Turon H et al. Association between electronic nicotine delivery systems and electronic non-nicotine delivery systems with initiation of tobacco use in individuals aged < 20 years. A systematic review and meta-analysis. Plos One September 8, 2021

https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0256044