How the FDA Can Improve Public Health — Helping People Stop Smoking

“Cigarette smoking remains the leading preventable cause of illness and death in the United States. One in eight U.S. adults smoke, with the highest prevalence among some of the groups that are affected by the greatest health inequities. Although most people who smoke are aware of the associated health risks and want to quit, many are unable to do so because of nicotine dependence. [..]

Although studies show higher rates of successful quitting among people who use a medication approved for smoking cessation by the Food and Drug Administration (FDA), only one third of people use evidence-based cessation treatments when making a quit attempt. Even when people use cessation medications and use them correctly (which is often not the case), most don’t successfully quit smoking. Given the magnitude of this problem, we believe the FDA should make helping people quit smoking a priority. [..]

Under the Tobacco Control Act, tobacco products that were commercially marketed as of February 15, 2007, are considered “preexisting tobacco products” and have been subject to limited regulation by the CTP [Center for Tobacco Products, a FDA division]. Tobacco products introduced after this date are subject to premarketing review by the FDA and are supposed to be authorized only if authorization is “appropriate for the protection of the public health,” considering the effects on people who use, and people who don’t use, tobacco products. By contrast, new smoking-cessation products that fall within CDER’s [Center for Drug Evaluation and Research, a different FDA division] jurisdiction have been subject to rigorous scientific review to assess their safety and efficacy. The result has been a counterintuitive approach in which cigarettes — the deadliest form of nicotine delivery — have been subject to limited oversight, whereas products marketed to help people quit smoking face far more substantial regulatory barriers. [..]

The FDA has approved only three types of drugs (nicotine-replacement therapy [NRT], bupropion, and varenicline) for helping people quit smoking. The first NRT product and bupropion were approved for smoking cessation in 1984 and 1997, respectively, and varenicline was approved in 2006; there have been no substantial advances in FDA-approved smoking-cessation products in the past 17 years. [..]

First, when evaluating new therapies, CDER could adjust its risk–benefit analysis to consider how a new product compares with existing approved therapies. Under such an approach, the new therapy would need to have at least similar efficacy for smoking cessation as existing therapies and would have to expand the population of people who are expected to use smoking-cessation therapies to successfully quit smoking. Identifying and promoting new therapies could increase the overall impact (effectiveness multiplied by reach) of approved smoking-cessation products. [..]

Second, and closely related, evaluation of new therapies could take into account the unacceptable status quo: continued widespread use of cigarettes, products that kill up to half of users and are associated with an average loss of 7 to 10 years of life. Given this context, CDER could assess whether it has the legal capability and the tools to support the approval of new smoking-cessation products that may have broader appeal, but possibly greater addiction potential and moderately higher toxicity, than those already authorized. Regulators would have to ensure that a product’s increased effectiveness for promoting smoking cessation outweighed its potential risks.

Third, CDER could explore providing incentives to support innovation and encourage manufacturers to put promising cessation products through its review process. One option would be to consider alternatives to long-term clinical trials for demonstrating evidence of safety and efficacy for promising new products. CDER could also support the establishment of new indications for existing products when there is sufficient evidence to fulfill the FDA’s safety and efficacy criteria. For example, the FDA could consider the sale of over-the-counter combination therapy (a single box containing nicotine patches and gum with use instructions) to be in keeping with best practices. CDER could evaluate real-world evidence on the use, safety, and effectiveness of CTP-regulated products that are already available to consumers, including e-cigarettes, in cases in which manufacturers submit applications for treatment designation. [..]

Fourth, CDER could proactively reach out to companies that may be interested in developing smoking-cessation products to open a forum to foster innovation. CDER could issue guidance clarifying its expectations for demonstrating safety and effectiveness, and it could work with companies — and in some cases with the CTP — to determine what steps can be taken to ensure that products provide the maximum possible benefit to people who smoke, while minimizing risks to others (e.g., adolescents). In coordination with the CTP, CDER could assess what safeguards (including product regulations and sales and marketing limitations) are needed to limit abuse of smoking-cessation products and address concerns about use of products by people who don’t use tobacco, especially young people.

Finally, CDER could use “fast track” designation and the accelerated approval pathway, as it does for products intended for treating serious and life-threatening conditions, in situations in which there is substantial real-world evidence on safety, effectiveness, and patterns of use for a smoking-cessation product. Working transparently with interested companies, CDER could evaluate strategies for establishing “fast track” and accelerated approval procedures for smoking-cessation products.”

Full editorial, NL Benowitz, KE Warner, ML Myers, et al. New England Journal of Medicine, 2023.4.24