Nicotine Reduction in Cigarettes: Literature Review and Gap Analysis.

BACKGROUND: The US Food and Drug Administration (FDA) is considering reducing nicotine levels in cigarettes to "minimally or non-addictive levels." However, important research gaps remain, and the FDA must determine when the available research is sufficient to support moving forward.
METHODS: The authors conducted a systematic review of research articles in PubMed relating to nicotine reduction. Building on a review of risk assessment best practices, the authors also developed a risk assessment framework for tobacco regulation and used it to guide a gap analysis of nicotine reduction research.
RESULTS: The final sample consisted of 78 articles. The majority examined either nicotine dependence on very low nicotine cigarettes (VLNCs) or markers of potential health effects of using VLNCs. One-third of the identified articles reported results from four large randomized controlled trials (RCTs). While these studies report promising results and suggest that a nicotine reduction rule would be a powerful tool to reduce cigarette smoking, our gap analysis suggests that there is a need for studies that better reflect the use and availability of a wide range of tobacco/nicotine products and the potential for dual- or multi-product use.
CONCLUSION: The current body of research on nicotine reduction is weighted towards RCTs, which is appropriate for a policy that has not yet been implemented anywhere in the world. The FDA must consider a wide range of factors that may impact a product standard's public health impact, including those difficult to assess in RCTs, such as a nicotine reduction rule's impact on smoking initiation and relapse. IMPLICATIONS: This systematic review presents a gap analysis based on a risk assessment framework to help identify remaining research priorities to inform FDA's potential product standard to reduce nicotine levels in cigarettes. Quickly addressing those gaps would support the FDA's effort to develop a nicotine reduction product standard that will be effective and withstand legal challenges.