Public Health Impact of FDA's Request for Additional Safety Data on Cytisine for Tobacco Cessation.

Importance: No new tobacco cessation medication has been licensed in the US since 2006. Cytisine, a plant-based partial agonist of nicotinic acetylcholine receptors, has demonstrated safety and efficacy in several randomized clinical trials and is currently available in many countries. However, the drug is not commercially available in the US. A New Drug Application to license cytisine as a smoking cessation medication in the US is being prepared for review by the US Food and Drug Administration, whose request for additional safety data will delay submission of the application by approximately 1 year. Objective: To project the potential public health impact of cytisine, and delays in its availability, as a smoking cessation aid in the US. Design, Setting, and Participants: This mathematical model estimated life expectancy gains from smoking cessation for people aged 18 to 99 years in the US, reflecting the civilian, noninstitutionalized population. The model also accounted for cytisine uptake and effectiveness, as well as potential relapse among people who stop smoking. Exposure: Cytisine availability as a tobacco cessation treatment immediately or after 1 year. Main Outcomes and Measures: The main outcomes were the number of adults able to stop smoking and sustain long-term abstinence and aggregate life-years gained. Results: The base case includes an estimated 29.4 million US civilian noninstitutionalized adults who smoke cigarettes (age distribution, 18-24 years: 5.5%; 25-44 years: 37.3%; 45-64 years: 41.8%; ≥65 years: 15.5%). With a conservative assumption that 3.8% of these individuals would use cytisine in the first year of availability, immediate cytisine availability could lead 71 000 more people to quit smoking over 1 year and maintain long-term abstinence. This would produce more than 500 000 additional life-years compared to the status quo in which cytisine is unavailable and fewer people stop smoking. Each additional year of delay in the availability of cytisine might reduce population-level life expectancy by 10 000 years. The model results were most sensitive to changes in cytisine uptake and effectiveness. Conclusions and Relevance: Smoking cessation generates large gains in life expectancy. This mathematical model demonstrated that immediate cytisine availability, even if used successfully by only a small fraction of people who smoke, could produce major public health benefits. Given the need for new tobacco cessation pharmacotherapy options, the magnitude of cytisine's potential public health benefits, and the morbidity and mortality associated with delay in its availability, a timely review of cytisine for approval in the US is warranted.