Impact of Missing Science on FDA-CTP Decisions
The U.S. Food and Drug Administration’s Center for Tobacco Products (FDA-CTP) was founded in 2009 in order to regulate the manufacturing, distribution and marketing of tobacco products as designated by the Family Smoking Prevention and Tobacco Control Act. Between the years of 2009 and 2023, the government estimates that the FDA-CTP collected and spent $8 billion of user fees directly from the manufacturers and importers of tobacco and nicotine products. However, the impact of this fee collection and spending is unclear: In 2009, it was estimated that 437,400 Americans died due to smoking-related disease and that number has changed little with the Centers for Disease Control and Prevention reporting 480,000 tobacco-related deaths in 2022.
Across the 14-year history of the FDA-CTP, manufacturers and public health authorities have intensely scrutinized the establishment of regulatory policies and actions, resulting in a litany of lawsuits. While the FDA-CTP has established some guidelines and processes for applications, many of these lack the typical standards and practices that are included in other regulatory guidelines. The result of these deficits is confusion throughout the application process with numerous failed applications even prior to being reviewed. The net result of this activity is that there are hundreds of combustible products that have been approved for sale but only 45 reduced-risk products have been approved by the FDA-CTP, netting only six electronic nicotine delivery systems, one heat-not-burn and a few oral tobacco/nicotine products in the legal U.S. marketplace. Millions of applications have been submitted and rejected at different phases of review and thousands remain in regulatory purgatory, well beyond the required 180-day statutory review period.
There are two clear outcomes from the FDA-CTP’s activities over the last decade and a half. The first is that a tremendous amount of money has been spent (from the pockets of American citizens) with outcomes that are still reflecting nearly half a million tobacco-related deaths per year in our country. The second is that an often-used excuse for the lack of marketing orders for reduced-risk tobacco and nicotine products is the need for more science. The FDA-CTP continues to ignore the need to establish standards that science can be applied against in the development of new products that may act to greatly reduce the health burdens associated with the use of traditional combustible tobacco products.
If gaps in science exist, what has the FDA-CTP accomplished that will help with attempts to close those gaps?
In 2013, the FDA and the National Institutes of Health partnered to establish the Tobacco Centers of Regulatory Science (TCORS). In the first series of awards (TCORS 1.0), 14 academic and independent institutions received a total of $273 million in grants distributed over a 5-year award period. The stated goal of the initial series of projects was to generate critical research to inform the regulation of tobacco products. In 2018, the second wave (TCORS 2.0) received $151 million in funds for an additional nine institutions to develop science in areas of toxicology, addiction, health impacts, behaviors and marketing related to tobacco products. Finally, the current 2023 round of awards (TCORS 3.0) gives another seven grants of $140 million to support additional research in the eight scientific domains identified as a high priority for the FDA-CTP.
Even with these major awards, hundreds of other non-TCORS grants, and peer-reviewed publications by industry and independent investigators, the FDA-CTP still claims that significant gaps exist in the science related to reduced-risk products. These gaps are the FDA-CTP’s primary rationale for the lack of awarding marketing orders for novel nicotine delivery products, which have been shown to greatly reduce the health impact of their use (as compared to combustible cigarettes).
The FDA-CTP has recently announced several new grants focused on “filling the gaps” in tobacco and nicotine science. The first two grants were awarded to two investigators to determine how a menthol ban may affect cessation rates or switching behavior and further clarify the role of flavors and electronic nicotine delivery systems (ENDS, also referred to as e-cigarettes or vapes) on switching behavior.
The first study ($3.9 million) is listed as having a start date of May 2023 and an end date of April 2028. The intended objectives are: 1) to determine the impact of menthol products on use patterns; and 2) to determine how the availability of these products impacts changes in tobacco use patterns. Additionally, the lead investigator stated that data from the study will clarify how any ban on menthol products will impact all consumers who use menthol products. What is interesting about this award is that in five years, the studies should be completed, yet the FDA-CTP is in the final stages of establishing a national ban on menthol. It therefore seems counterintuitive to create a national ban on an area that is designated to have insufficient scientific background, and which the FDA-CTP are currently funding a scientific study on to eliminate that issue. As an organization that is led by science, it would make more sense for the FDA-CTP to hold any activity on menthol until data collection is complete.
The second study ($3.9 million) also started in May 2023 and ends in April 2028. This study focuses on ENDS product uptake, changes in craving for traditional cigarette products, and whether the use of flavored ENDS products leads to sustained and complete switching behavior. This will be one of the longest studies that will evaluate both the role of flavors and how using ENDS products (with and without flavors) impacts participant health. Scientists are expecting to provide novel outcomes to clarify the importance (or lack thereof) of flavored ENDS products and to use this data to help consumers make informed decisions about their use of reduced-risk products and to provide data to the FDA-CTP that will guide them in regulating such products. In this case, there have been numerous studies over the past decade that show the effectiveness of reduced-risk products as well as the importance of options (flavors, etc.) in helping people who smoke move away from cigarette use. So, though many agree that replication is an essential step in validating scientific principles, the continued delay of awarding marketing orders to products that will save lives seems to be a sacrifice that is too large to continue to make.
The overall takeaway is that uncertainty best describes the actions and activities of the FDA-CTP. There has been very little change in the health outcomes related to tobacco use in over a decade. The agency has spent billions of dollars with almost nothing to show from the investment. Most concerning is the fact that there are numerous published reports of how reduced-risk products help people who smoke switch, and by doing so, improve their health, yet the FDA-CTP is still delaying the entry of these products into the U.S. marketplace. This lack of effective regulatory oversight has led to confusion in the consumer base, decreased competition and innovation in the industry, and the continuation of deaths that could have been avoided if only proper educational messaging and a wide range of reduced-risk products were available in the United States. It is worrisome to think that there could be another half a million preventable deaths every year until the FDA-CTP figures it out.