FDA Holds Scientific Workshop on Youth E-Cigarette Cessation Treatment Strategies
By Samuel Jockel, Keller and Heckman LLP
Edited by Beth Oliva, Fox Rothschild LLP
Combatting youth use of tobacco, including electronic cigarettes (e-cigarettes), was a centerpiece of former U.S. Food and Drug Administration (FDA or the Agency) Commissioner Dr. Scott Gottlieb’s tenure, with the Agency taking significant enforcement action over the past two years to tackle what it calls a “growing epidemic” of youth e-cigarette use.
Prior to Gottlieb’s departure in early April 2019, the Agency produced a flurry of regulatory actions intended to prevent youth access to tobacco and e-cigarettes. In early March 2019, FDA requested a meeting with Walgreen Co.’s corporate management to discuss the company’s policy on selling tobacco products to youth. FDA has cited the company for repeated violations of restrictions on the sale and distribution of tobacco products to minors. The Agency also sent warning letters to several companies for, among other things, selling e-cigarettes with labeling and/or advertising that failed to include the required nicotine warning statement and for using labeling and/or packaging that was overly appealing to youth. Moreover, on March 13, 2019, FDA proposed to revise its current premarket review compliance policy on flavored e-cigarettes (other than tobacco, mint, and menthol-flavored), which permits e-cigarettes and other non-combustible deemed tobacco products on the market on August 8, 2016 to remain on the market until August 8, 2022 without premarket authorization. In its new draft guidance, FDA would require manufacturers of all flavored e-cigarette and e-liquid products (other than tobacco, mint, and menthol-flavored) to submit premarket applications to the Agency by August 8, 2021—one year earlier than previously proposed.
In conjunction with the Agency’s enforcement actions against retailers and manufacturers of e-cigarettes, as explained by former Commissioner Gottlieb, “the rapid growth in popularity of e-cigarettes among youth…necessitates that we explore all options,” including “potential drug therapies to support youth e-cigarette use.” Toward that end, on January 18, 2019, FDA held a public hearing to gather information regarding the potential role drug therapies could play in eliminating youth e-cigarette use. See our previous post for our complete coverage of that hearing. Relatedly, FDA has recently issued grants to the Institute for Advanced Clinical Trials for Children (I-ACT for Children) and the Duke Clinical Research Institute (DCRI) to establish a Global Pediatric Clinical Trials Network to facilitate clinical trials of new drugs and devices for children.
As a follow up to the January 2019 public meeting, on May 15, 2019, in collaboration with I-ACT and the DCRI, FDA held a public hearing and a scientific workshop to discuss challenges associated with youth tobacco addiction and cessation, and the current science regarding youth tobacco use and addiction as well as treatment strategies to support youth tobacco cessation.
Dr. Janet Woodcock, Director of FDA’s Center for Drug Evaluation and Research (CDER), opened the workshop stressing the Agency’s commitment to addressing the “alarming problem” of youth e-cigarette use and the importance of the workshop to continue to better understand the science behind youth addition and what interventions are needed to support youth cessation. Dr. Woodcock presented a detailed overview of the Center for Tobacco Products (CTP) efforts in enforcement and policy on the youth use of e-cigarettes. Ultimately, Dr. Woodcock insisted that “science is our best way forward” in addressing this issue. Her introduction was followed by a number of presenters and panelists, including various representatives from FDA, the U.S. Centers for Disease Control and Prevention (CDC), the National Institute on Drug Abuse (NIDA), medical researchers, industry representatives, and tobacco control organizations. Acting Commissioner Ned Sharpless also offered remarks during the second portion of the workshop.
Lessons from Combustible Cigarette Prevention and Cessation Efforts
As a starting point, several presenters highlighted the importance of understanding lessons learned from cigarette smoking cessation and their application to youth e-cigarette prevention and cessation efforts. Dr. Brian King, Office on Smoking and Health, CDC, noted the success of prevention strategies for cigarette smoking, including smoke-free policies, taxation, and age restriction requirements. Applying these strategies to e-cigarette use, Dr. King stated that currently eight states tax e-cigarettes (as well as Washington, DC and a number of localities), and 12 states now have smoke-free policies that include the use of e-cigarettes. Moreover, Dr. King highlighted that what led youth to smoke cigarettes (advertising, use of flavors, nicotine), has some applicability to the trends seen with e-cigarette use today.
In devising a public health policy plan for e-cigarette cessation, Dr. Allison Hoffman, Office of the Commissioner, FDA, outlined the now-defunct Youth Tobacco Cessation Collaborative’s National Blueprint for Action as a reference point for goals and research objectives.
Current State of Youth Cessation Strategies
While lessons learned from prevention and cessation efforts in the context of combustible cigarettes use may be helpful as a guide, many presenters noted that those lessons cannot necessarily be interchanged with solutions to prevent and stop youth e-cigarette use. This is due to both the recognition that treatment strategies are likely to differ in the youth population as opposed to adults and the differences in products, including the different active ingredients used in combustible cigarettes compared to vaporized nicotine.
While FDA has approved several nicotine replacement therapy (NRT) products, as well as prescription drugs, such as Chantix, for adult smoking cessation, there is very limited safety and efficacy data for these products in the youth population. Dr. Thomas McRae, Pfizer, highlighted the failure of varenicline (Chantix), a prescription drug used to help adult smokers quit, when the drug was studied in a clinical trial for purposes of youth smoking cessation. Dr. Celia Winchell, CDER FDA, confirmed that this was the only failed trial of Chantix for the purpose of smoking cessation. Dr. John Alexander, CDER FDA, noted that existing studies and data on drug trials for the adult population cannot simply be extrapolated to apply to youth. Dr. Carlos Peña, Center for Devices and Radiological Health (CDRH) FDA, highlighted CDRH’s experience approving medical devices for the purpose of addiction generally but noted the complete lack of approved medical device products for tobacco cessation and encouraged industry to work with CDRH on this front.
Beyond the pharmacological approach, presenters offered other psychological, socio-cultural, and technological approaches to prevent youth from initiating use and to address issues of addiction. Kathleen Crosby, CTP FDA, shared FDA’s “The Real Cost” e-cigarette prevention campaign, using social media to engage youth and teens to communicate the risk of harm from regular use, and Dr. Amanda Graham, Truth Initiative, shared the Truth Initiative’s text message program for youth that are seeking to quit vaping. Given the lack of safety and efficacy support for NRTs and other pharmaceutical approaches in youth, Dr. Suchitra Krishnan-Sarin, Yale School of Medicine, stressed the need for behavioral approaches as a first step toward addressing addiction, and Dr. Paula Riggs, University of Colorado, emphasized the importance of prevention mentoring and cognitive behavioral therapy treatment for those youth already using e-cigarettes.
Gaps in Information
As the Agency and interested stakeholders worked to identify potential strategies to both prevent and stop youth e-cigarette use, the “waterfront of possible interventions,” as characterized by Dr. Winchell, CDER FDA, requires further exploration and understanding. Dr. Winchell remarked that she had “come away with as many questions as I had before,” referencing the number of gaps in information that the workshop brought forth, including:
- What are the use patterns of e-cigarette use for youth? As a foundational question, Dr. Krishnan-Sarin noted that use patterns, such as why youth are using e-cigarettes, what exactly is being used, etc., needs to be better understood. Relatedly, Dr. Cathy Backinger, CTP FDA, highlighted the phenomenon of youth using nicotine-containing e-cigarettes and marijuana products in conjunction with each other, which should factor into the understanding surrounding the actual use of nicotine-containing e-cigarettes among youth.
- How are e-cigarette products changing and how can we track what products youth are using? Many presenters noted the ascension of the use of pod-based e-cigarettes, where nicotine is in a protonated form (referred to as nicotine salts), which can deliver nicotine at higher levels. With the changing marketplace for vaping products, Dr. Wilson Compton, NIDA, stressed the need to track these products and the differences that may impact youth addiction.
- What are the harms associated with e-cigarette use for youth? The extent to which e-cigarettes harm children is not well understood. Dr. Sharon Levy, Boston Children’s Hospital, noted that the impact nicotine and other chemicals have on the neurodevelopmental stage for children are unknown and needs further exploration. This includes the possible release of chemicals at higher levels than conventional cigarettes and the effect e-cigarettes have on the airways.
- How can those harms be best communicated to youth? How can messaging reflect the motivators to quit? Graham, Truth Initiative, noted the importance of nuance in targeting messages to the youth e-cigarette smoker, who is less likely to identify themselves as an addict needing help. Dr. Theresa Michele, CDER FDA, also raised the issue surrounding stigma associated with quitting and addiction and how messaging should take this into account.
- How to best recruit and retain youth for long-term clinical trial terms? As highlighted by Dr. McRae, Pfizer, the 312 youth participants in the Chantix trial took almost six years to recruit, and the study struggled to retain youth participants. Identifying youth that were willing to participate in a drug treatment trial and navigating parental consent were significant challenges faced. Determining the appropriate end points and selecting the particular vape product used are additional considerations for clinical trials for potential drug therapies.
- From a policy perspective, how do regulators balance the need to curb youth e-cigarette use with the potential for electronic nicotine delivery systems (ENDS) to present a less harmful alternative for adult smokers of combustible cigarettes? While discussion centered around prevention and treatment strategies for youth cessation, many presenters recognized the need to preserve a pathway for adult smokers to transition to e-cigarettes.
In some of his first substantive remarks on the Agency’s work to tackle youth e-cigarette use as Acting FDA Commissioner, Dr. Sharpless repeated one of Dr. Gottlieb’s signature lines, “[w]e cannot and will not risk a generation of youth to a lifetime of nicotine addiction.” As the public face of these efforts for the past two years, Dr. Gottlieb’s resignation from his post as FDA Commissioner raised questions of whether the Agency would continue the efforts championed by Dr. Gottlieb to curb youth e-cigarette use. In his remarks at the workshop, Acting Commissioner Sharpless made clear that “[u]nder my leadership at FDA, we will maintain this energy and focus.” In light of the research gaps and outstanding questions on the best way forward to address youth prevention and use of e-cigarettes, the Agency and interested stakeholders have much more work ahead. Whether Acing Commissioner Sharpless can in fact maintain FDA’s energy and focus on combating youth access and use of e-cigarettes will ultimately be seen moving forward.
 Letter to Walgreen Co., FDA.gov (March 4, 2019).
 Statement from FDA Commissioner Scott Gottlieb, M.D., on forceful new actions focused on retailers, manufacturers to combat youth access to e-cigarettes as part of FDA’s Youth Tobacco Prevention Plan, FDA.gov (March 4, 2019).
 It is worth noting that on May 15, 2019 the U.S. District Court for the District of Maryland vacated FDA’s August 2017 Guidance Document which extended the premarket review compliance policy deadline to August 8, 2022. In short, the court held that the guidance was effectively a binding rule that was subject to the Administrative Procedure Act and should have gone through notice and comment rulemaking. FDA has 60 days to appeal the decision. American Academy of Pediatrics et al. v. FDA, No. PWG-18-883 (D. Md.) (May 15, 2019).
 Modifications to Compliance Policy for Certain Deemed Tobacco Products, FDA.gov (March 2019).
 Statement from FDA Commissioner Scott Gottlieb, M.D., on the agency’s continued efforts to address growing epidemic of youth e-cigarette use, including potential new therapies to support cessation, FDA.gov (Nov. 2, 2018).
 Notice of public scientific workshop; request for comments, 84 FR 12619 (April 2, 2019).
 Remarks to the Youth Tobacco Cessation Public Scientific Workshop, FDA.gov (May 15, 2019).