R Street Comments on the Proposed FDA/CTP Flavor Guidance

May 07, 2026

Dr. Bret Koplow  
Director Center for Tobacco Products (CTP)  
United States Food and Drug Administration  
Rockville, MD 20852

Re: Docket No. FDA-2026-D-1817

My name is Dr. Jeffrey S. Smith, and I am a Resident Senior Fellow at the R Street Institute, a nonprofit, nonpartisan public policy research organization headquartered in Washington, D.C. R Street supports pragmatic, evidence-based policy solutions that emphasize free markets, limited government, and individual liberty. In that capacity, I have conducted extensive research on tobacco harm reduction, nicotine regulation, and the role of reduced-risk nicotine products in public health. I submit this comment in response to the Food and Drug Administration’s (FDA) March 2026 draft guidance, “Flavored Electronic Nicotine Delivery Systems (ENDS) Premarket Applications, Considerations Related to Youth Risk” (hereinafter “the Guidance”).[1]

At the outset, I wish to acknowledge several positive elements of the Guidance. The adoption of a graduated, risk-proportionate evaluation framework represents a meaningful step forward in FDA’s approach to ENDS regulation. The Guidance correctly recognizes that flavored ENDS may benefit adult smokers who are attempting to transition away from combustible cigarettes. Its sliding-scale concept, under which flavors with less youth appeal face a correspondingly lower evidentiary burden, is a reasonable structural principle. The mention of novel device access restriction (DAR) technologies further reflects a commendable willingness to consider innovative, technology-driven solutions to the challenge of youth access.

However, while this framework represents progress, the Guidance as drafted imposes disproportionate evidentiary burdens on flavored ENDS products that could deny adult smokers access to the very products most likely to help them quit. In particular, the high evidentiary burden applied to fruit, candy, and sweet flavors, the categories most preferred by adult switchers, risks functioning as a de facto prohibition. This comment draws on the best available scientific evidence to argue that flavored ENDS play a critical role in adult smoking cessation, that restricting them will produce serious unintended consequences, and that international experience demonstrates the viability of a harm reduction approach that includes flavor availability. I offer six concrete recommendations to strengthen the Guidance and better serve the 480,000 Americans who die from smoking-related illness each year.

The Scientific Case for Flavored ENDS in Adult Smoking Cessation

The evidence base supporting nicotine e-cigarettes as effective smoking cessation tools has grown substantially in recent years. The most recent Cochrane review on this topic found high-certainty evidence that nicotine e-cigarettes increase quit rates compared to nicotine replacement therapy (NRT), with a risk ratio (RR) of 1.55 (95% CI 1.28–1.88), drawn from nine randomized controlled trials (RCTs) involving 2,703 participants.[2] The earlier iteration of this review reported a comparable RR of 1.63 (95% CI 1.30–2.04). These are not marginal effects.[3] They represent a roughly 55–63% improvement in quit rates over the current frontline pharmacotherapy for smoking cessation. Other research demonstrated that e-cigarettes were nearly twice as effective as NRT for sustained smoking cessation, with quit rates of 18.0% versus 9.9% at one year.[4] This trial remains one of the most rigorous evaluations of e-cigarettes as cessation aids ever conducted, and its findings are consistent with the broader Cochrane synthesis.

Critically, a growing body of evidence indicates that non-tobacco flavors are central to the cessation advantage of e-cigarettes. This study, analyzing data from a large, nationally representative U.S. survey conducted in 2018–2019, found that adults using nontobacco-flavored ENDS had an adjusted odds ratio (AOR) of 2.9 for making a quit attempt and 1.7 for achieving quit success, compared to nonusers.[5] Among frequent users of nontobacco-flavored ENDS, the AOR for quit success rose to 4.0. These findings suggest that flavor is not merely a preference but a functional driver of the switching process.

In a secondary analysis of a nationwide clinical trial, researchers found that non-tobacco flavors led to substantially greater e-cigarette uptake (74% vs. 55%) and a markedly higher rate of achieving at least a 50% reduction in cigarette consumption (34% vs. 14%) compared to tobacco flavor alone.[6] These are large, clinically meaningful differences. When adult smokers are given a product that tastes like tobacco, far fewer adopt it; when given a product with a flavor they prefer, significantly more make the switch and sustain meaningful reductions in combustible cigarette use.

A secondary analysis reinforced these findings.[7] Quit rates were notably lower among tobacco-flavor users than among users of other flavors (20.2% vs. higher rates for non-tobacco flavors), corresponding to a risk ratio of 0.56 for tobacco flavor relative to other flavor categories. Put simply, choosing tobacco flavor nearly halved a smoker’s probability of quitting. Flavor switching also occurred among long-term e-cigarette users: only 36–44% of users maintained their original flavor preference, and exclusive e-cigarette users overwhelmingly gravitated toward sweet flavors over time.[8] Nearly half of respondents reported that they would find a way to obtain their preferred flavors even if those flavors were banned.

The National Academies of Sciences, Engineering, and Medicine reached two conclusions of direct relevance.[9] First, there is “conclusive evidence that completely substituting e-cigarettes for combustible tobacco cigarettes reduces users’ exposure to numerous toxicants and carcinogens.” Second, population dynamic modeling indicated that “under likely scenarios, the use of e-cigarettes will result in a net public health benefit over the next 30 years.” The United Kingdom’s Royal College of Physicians estimated that the harm from e-cigarettes is unlikely to exceed 5% of the harm from combustible cigarettes.[10] These assessments place e-cigarettes firmly within a harm reduction framework that the FDA’s own Guidance purports to embrace.

Flavors Drive Adult Switching: Tobacco Flavor is Not Enough

The central tension in the Guidance is between youth protection and adult access. The Guidance resolves this tension by applying progressively higher evidentiary burdens to flavors with higher youth appeal, effectively placing fruit, candy, and sweet flavors in the most restrictive category. In principle, a graduated approach is sound. In practice, however, the evidence strongly suggests that the flavors most appealing to youth are also the flavors most effective at helping adults quit smoking. This creates a policy dilemma that the Guidance does not adequately address.

Users of tobacco-flavored e-cigarettes quit at roughly half the rate of users of other flavors (RR 0.56).[11] If a pharmaceutical company submitted a drug that was half as effective as an alternative formulation, regulators would not approve only the inferior version. Yet that is precisely the outcome the Guidance risks producing.

Flavor preference is not static. Adult vapers who initially choose tobacco flavor frequently migrate toward sweet and fruit flavors as they become more experienced.[12] This migration pattern suggests that non-tobacco flavors serve an important role in sustaining long-term use of the reduced-risk product and preventing relapse to combustible cigarettes. Restricting flavor availability at the point of initial adoption may therefore reduce switching, and restricting it after adoption may increase reversion to smoking.

Additional real-world data from the JUUL2 actual use study demonstrated that menthol-flavored users had significantly higher switching rates than tobacco-flavored users, with an odds ratio of 1.36 (95% CI 1.04–1.78) for past-30-day switching.[13] This finding, drawn from a naturalistic use environment rather than a clinical trial, suggests that the flavor-cessation relationship holds across different product platforms and study designs.

Taken together, these data make a compelling case that restricting flavored ENDS to tobacco flavor would substantially reduce the cessation benefit of e-cigarettes for adult smokers. The Guidance must grapple with this trade-off directly, rather than treating the youth-appeal dimension of flavors in isolation from their adult-cessation dimension.

Flavor Restrictions Produce Unintended Consequences

The risks described above are not hypothetical. Empirical evidence from U.S. state-level flavor restrictions demonstrates that these policies produce measurable, harmful unintended consequences. A recent study analyzed the effects of state flavor restrictions on tobacco use among young adults aged 18–29.[14] The researchers found that flavor restrictions were associated with a 3.6 percentage point decrease in daily vaping, but a 2.2 percentage point increase in daily smoking. The net effect was approximately three additional daily smokers for every five fewer daily vapers. This is a deeply troubling trade-off. Any regulatory framework that reduces vaping only to increase the far more harmful behavior of combustible cigarette smoking has failed to optimize for public health. This study is particularly relevant because it measures exactly the cross-product substitution effect that the Guidance should, but does not, account for. When adult smokers and dual users lose access to flavored e-cigarettes, a substantial proportion do not quit nicotine altogether. Instead, they revert to or increase their use of combustible cigarettes. The Guidance’s framework evaluates each ENDS product in isolation, assessing its youth-appeal risk against its adult-benefit evidence. But cigarettes are never part of that equation, even though they remain freely available in every flavor restriction jurisdiction and represent an exponentially greater health risk.

The Guidance should explicitly require applicants and FDA reviewers to consider cross-product substitution effects when evaluating flavored ENDS applications. A standard that focuses exclusively on whether a product might appeal to youth, without weighing the public health consequences of that product’s absence from the market, will systematically underestimate the net harm of restrictive decisions.

International Evidence Demonstrates That Harm Reduction with Flavors Works

The United States is not operating in a vacuum. Several nations have pursued tobacco harm reduction strategies that include flavored alternatives to combustible cigarettes, and the results are instructive.

In late 2024, after smoking rates had declined by 55 percent over the preceding decade, Sweden became the first country in the world to achieve “smoke-free” status, defined as fewer than 5% daily smokers among the adult population.[15] To achieve this, Sweden combined high cigarette taxes with broadly accessible reduced-risk alternatives, including snus, nicotine pouches, and e-cigarettes, many of which are available in a wide range of flavors. The public health returns have been extraordinary: Sweden’s cancer incidence is 41% lower than the rest of the European Union. This is not a coincidence. It is the predictable result of policies that incentivize lower-risk products over combustible cigarettes.

The United Kingdom has historically pursued one of the most proactive vaping policies in the world. As of 2024, the smoking rate had fallen to approximately 9.1%, and the number of vapers (approximately 10% of the adult population) now exceeds the number of smokers.[16] The Royal College of Physicians’ landmark 2016 report concluded that e-cigarette harm is unlikely to exceed 5% of smoking harm, and the National Health Service (NHS) actively endorses vaping as a cessation tool within clinical settings.[17] Flavored e-cigarettes are widely available throughout the UK. The UK’s success demonstrates that it is possible to simultaneously reduce smoking, expand vaping as a cessation tool, and manage youth uptake through enforcement and age-verification measures.

Japan provides a distinctive case study. Following the introduction of heated tobacco products, cigarette sales declined by 52% between 2011 and 2023.[18] Millions of Japanese smokers switched to heated tobacco products without flavor restrictions driving the policy environment. Japan’s experience illustrates that when reduced-risk products are accessible and appealing, smokers will switch voluntarily and at scale.

All three of these nations achieved dramatic reductions in smoking while maintaining flavor availability. None imposed comprehensive flavor bans as a precondition for harm reduction progress. The Guidance should draw on this international evidence, not as a mandate to replicate any single country’s regulatory model, but as a demonstration that flavor availability and public health improvement are compatible.

Youth Use Is Declining Without a National Flavor Ban

The Guidance is framed, in large part, as a response to the youth e-cigarette epidemic. It is therefore essential to examine the current state of youth use. According to the National Youth Tobacco Survey (NYTS), youth e-cigarette use fell to 5.9% in 2024, representing approximately 1.63 million middle and high school students.[19] This figure is down from a peak of 27.5% in 2019. Youth e-cigarette use has declined to roughly one-third of its peak level. The Centers for Disease Control and Prevention (CDC) reported in 2024 that youth tobacco product use had reached a 25-year low.[20] Youth cigarette smoking fell to 1.4% in 2024, the lowest level ever recorded. These are not modest improvements. They represent a generational shift in youth tobacco use patterns that is already well underway.

Critically, this decline occurred without a national flavor ban. The primary drivers were Tobacco 21 (T21) legislation, increased enforcement against retailers selling to minors, and market-level changes, including changes in marketing and product format (i.e. cartoon characters) and the maturation of the market.[21] The Guidance’s own data acknowledge that youth use is declining. A regulatory framework designed to address a crisis that has substantially abated should calibrate its restrictions accordingly.

This is not an argument for complacency. Youth protection must remain a regulatory priority. However, the Guidance should not impose evidentiary burdens calibrated to a 2019-era crisis on a 2026-era market. The goal should be to sustain and accelerate the existing decline in youth use while preserving adult access to the products that are driving historically low smoking rates.

The Evidentiary Burden Must Be Achievable

A recurring theme in ENDS regulatory policy is the gap between the evidentiary standard articulated by FDA and the ability of applicants to meet that standard. As of the date of this comment, no fruit-flavored or sweet-flavored ENDS product has ever received a marketing order from FDA. This is not because applicants have failed to submit evidence of cessation benefits or harm reduction. It is because the evidentiary standard for high-youth-appeal flavors has been, in practice, impossible to satisfy.

The Guidance acknowledges a correspondingly high evidentiary burden for these flavors but does not specify what types of evidence, at what quantities or quality levels, would be sufficient. A standard that cannot be met in practice is indistinguishable from a ban. If the Guidance is to function as a genuine regulatory pathway rather than a functionally unattainable standard, FDA must provide concrete guidance on what a successful application for a fruit-flavored or sweet-flavored ENDS product would look like.

This clarity is not merely an administrative convenience. It is a due process imperative. Manufacturers and applicants are entitled to understand what is required of them before they invest the resources necessary to develop applications. The current ambiguity creates a chilling effect: companies that might otherwise invest in rigorous clinical trials and population studies are deterred by the perception that no amount of evidence will suffice.

The Guidance’s treatment of device access restriction (DAR) technologies illustrates this problem. The Guidance suggests that DAR technologies may be considered as part of a product’s youth-access mitigation strategy, but simultaneously signals that products with high-appeal flavors face the most stringent review. If a manufacturer develops a fruit-flavored product with robust age-verification technology, the Guidance should evaluate that product on the merits of its DAR system rather than dismissing it categorically because of its flavor profile. Innovation in access restriction should be rewarded, not penalized.

Recommendations

Based on the current status of the ENDS marketplace and the totality of the research in the reduced risk products space, I respectfully offer the following six recommendations for strengthening the Guidance:

1. Provide a clear, achievable evidentiary pathway for fruit, sweet, and candy flavored ENDS. The Guidance should specify the types, quantities, and quality levels of evidence that would satisfy the “correspondingly high evidentiary burden” for flavors with significant youth appeal. This may include, but should not be limited to, randomized controlled trials, observational switching studies, population-level modeling, and youth-access mitigation data.
2. Give greater weight to real-world switching data. The hierarchy of evidence in cessation research should not be limited to RCTs. Observational studies, quasi-experimental designs, and real-world evidence from market-level data provide critical context that RCTs alone cannot capture. The Guidance should explicitly acknowledge these study designs as valid components of a PMTA submission.
3. Require consideration of cross-product substitution effects. The Guidance should mandate that both applicants and FDA reviewers evaluate the likely consequences of denying a marketing order for a flavored ENDS product, including the probability that current users will switch to or revert to combustible cigarettes. Flavor restrictions can increase smoking, and this possibility must be part of the public health calculus.
4. Embrace innovative access control technologies. DAR technologies should be evaluated on their demonstrated effectiveness at restricting youth access, not dismissed preemptively because the product to which they are attached uses a high-appeal flavor. FDA should provide clear technical standards for DAR systems and treat effective age-verification as a meaningful factor in reducing the youth-risk side of the benefit-risk equation.
5. Adopt a truly risk-proportionate framework informed by international evidence. The successes of Sweden, the United Kingdom, and Japan demonstrate that harm reduction with flavor availability produces dramatic improvements in public health outcomes. The Guidance should draw on these international experiences to inform its risk-proportionate framework and avoid the assumption that flavor restriction is a necessary precondition for public health progress.
6. Calibrate the evidentiary burden to the current state of youth use. Youth e-cigarette use has declined to one-third of its 2019 peak and is at a 25-year low. The Guidance should reflect this improved landscape rather than applying crisis-era standards to a substantially changed environment. Evidentiary burdens should be recalibrated to account for the demonstrated effectiveness of existing youth-access measures.

Conclusion

The FDA’s March 2026 draft guidance on flavored ENDS represents a meaningful step toward a more nuanced, risk-proportionate approach to nicotine regulation. The graduated evaluation framework, the acknowledgment of adult switching benefits, and the consideration of DAR technologies are all welcome developments. However, the Guidance as currently drafted risks imposing evidentiary burdens on flavored ENDS that are functionally prohibitive, denying adult smokers access to the products most likely to help them quit.

The scientific evidence is clear. Flavored e-cigarettes are more effective cessation tools than tobacco-flavored alternatives. Restricting flavors drives some users back to combustible cigarettes. International experience demonstrates that flavor availability and public health progress are compatible. Youth use is already declining sharply without a national flavor ban.

The 480,000 Americans who die from smoking each year deserve a regulatory framework that matches the urgency of their situation. I urge the FDA to adopt the recommendations outlined in this comment and to ensure that the final guidance provides a genuine, achievable pathway for flavored ENDS products that can help millions of adult smokers transition away from combustible tobacco. The science supports it. The evidence demands it. The public health stakes require it.

Respectfully submitted,

Jeffrey Smith
Senior Fellow, Healthier Communities
R Street Institute
jsmith@rstreet.org

[1] U.S. Food and Drug Administration. (2026, March 11). ENDS premarket applications considerations related to youth risk (Draft guidance, Docket No. FDA-2026-D-1817). https://www.fda.gov/regulatory-information/search-fda-guidance-documents/flavored-electronic-nicotine-delivery-systems-ends-premarket-applications-considerations-related

[2] Lindson, N., Theodoulou, A., Ordóñez-Mena, J. M., Fanshawe, T. R., Sutton, A. J., Livingstone-Banks, J., … & Hartmann-Boyce, J. (2025). Electronic cigarettes for smoking cessation. Cochrane Database of Systematic Reviews, (11). https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010216.pub8/full

[3] Hartmann-Boyce, J., Lindson, N., Butler, A. R., McRobbie, H., Bullen, C., Begh, R., … & Hajek, P. (2022). Electronic cigarettes for smoking cessation. Cochrane Database of Systematic Reviews, (11). https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010216.pub7/full

[4] Pesola, F., Myers Smith, K., Przulj, D., Ladmore, D., Phillips-Waller, A., McRobbie, H., & Hajek, P. (2025). Patterns of e-Cigarette Use and Smoking Cessation Outcomes: Secondary Analysis of a Large Randomised Controlled Trial to Inform Clinical Advice. Nicotine and Tobacco Research, ntaf240. https://academic.oup.com/ntr/advance-article/doi/10.1093/ntr/ntaf240/8374747

[5] Mok, Y., Jeon, J., Levy, D. T., & Meza, R. (2023). Associations between e-cigarette use and e-cigarette flavors with cigarette smoking quit attempts and quit success: Evidence from a U.S. large, nationally representative 2018–2019 survey. Nicotine & Tobacco Research, 25(3), 541–552. https://academic.oup.com/ntr/article/25/3/541/6761959

[6] Smith, T. T., Wahlquist, A. E., Wagener, T. L., Cummings, K. M., & Carpenter, M. J. (2025). The impact of non-tobacco e-cigarette flavoring on e-cigarette uptake, cigarette smoking reduction, and cessation: A secondary analysis of a nationwide clinical trial. Addictive Behaviors, 163, 108240. https://www.sciencedirect.com/science/article/abs/pii/S0306460324002892?via%3Dihub=

[7] Hajek, P., Phillips-Waller, A., Przulj, D., Pesola, F., Myers Smith, K., Bisal, N., … & McRobbie, H. J. (2019). A randomized trial of e-cigarettes versus nicotine-replacement therapy. New England Journal of Medicine, 380(7), 629–637. https://www.nejm.org/doi/10.1056/NEJMoa1808779

[8] Du, P., Bascom, R., Fan, T., Sinharoy, A., Yingst, J., Mondal, P., & Foulds, J. (2020). Changes in flavor preference in a cohort of long-term electronic cigarette users. Annals of the American Thoracic Society, 17(5), 573-581. https://academic.oup.com/annalsats/article/17/5/573/8419141?guestAccessKey=

[9] National Academies of Sciences, Engineering, and Medicine. (2018). Public health consequences of e-cigarettes. The National Academies Press. https://www.nationalacademies.org/projects/HMD-BPH-16-02/publication/24952

[10] Royal College of Physicians. (2016). Nicotine without smoke: Tobacco harm reduction. RCP. https://www.rcp.ac.uk/resources/nicotine-without-smoke-tobacco-harm-reduction/

[11] Hajek, P., Phillips-Waller, A., Przulj, D., Pesola, F., Myers Smith, K., Bisal, N., … & McRobbie, H. J. (2019). A randomized trial of e-cigarettes versus nicotine-replacement therapy. New England Journal of Medicine, 380(7), 629–637. https://www.nejm.org/doi/10.1056/NEJMoa1808779

[12] Du, P., Bascom, R., Fan, T., Sinharoy, A., Yingst, J., Mondal, P., & Foulds, J. (2020). Changes in flavor preference in a cohort of long-term electronic cigarette users. Annals of the American Thoracic Society, 17(5), 573-581. https://academic.oup.com/annalsats/article/17/5/573/8419141?guestAccessKey=

[13] Goldenson, N. I., Shiffman, S., Sembower, M. A., Selya, A., Pype, S., & Black, R. A. (2025). Evaluating the effect of the JUUL2 system with 5 flavors on cigarette smoking and tobacco product use behaviors among adults who smoke cigarettes: 6-week actual use study. Interactive Journal of Medical Research, 14(1), e60620. https://i-jmr.org/2025/1/e60620

[14] Friedman, A. S., Sindelar, J. L., Engberg, J. B., & Ganz, O. (2024). Flavored e-cigarette sales restrictions and young adult tobacco use. JAMA Health Forum, 5(12), e244956. https://jamanetwork.com/journals/jama-health-forum/fullarticle/2828404

[15] Smoke Free Sweden. (2024). Missing the target. https://smokefreesweden.org/

[16] Action on Smoking and Health. (2025). Fall in smoking means more people now vape than smoke. https://ash.org.uk/

[17] Royal College of Physicians. (2016). Nicotine without smoke: Tobacco harm reduction. RCP. https://www.rcp.ac.uk/resources/nicotine-without-smoke-tobacco-harm-reduction/

[18] Global State of Tobacco Harm Reduction. (n.d.). Cigarette sales halved: Heated tobacco products and the Japanese experience. https://gsthr.org/resources/briefing-papers/

[19] Park-Lee, E., Jamal, A., Cowan, H., et al. (2024). Notes from the field: E-cigarette and nicotine pouch use among middle and high school students — United States, 2024. Morbidity and Mortality Weekly Report, 73, 774–778. https://www.cdc.gov/mmwr/volumes/73/wr/mm7335a3.htm?s_cid=mm7335a3_w

[20] Centers for Disease Control and Prevention. (2024, September 5). Youth e-cigarette use drops to lowest level in a decade [Press release]. https://www.cdc.gov/media/releases/2024/p0905-youth-ecigarette.html

[21] Prohibition of Sale of Tobacco Products to Persons Younger Than 21 Years of Age, 89 Fed. Reg. 70,484 (Aug. 30, 2024) (to be codified at 21 C.F.R. pt. 1140). https://www.federalregister.gov/documents/2024/08/30/2024-19481/prohibition-of-sale-of-tobacco-products-to-persons-younger-than-21-years-of-age