A Critique of Mitch Zeller’s Tenure at the FDA Center for Tobacco Products

 

Mitch Zeller, director of the FDA Center for Tobacco Products for the past nine years, is scheduled to retire this month.  The agency released an interview with Zeller on April 20, in which he “reflects on the time he spent helping to make tobacco-related disease and death part of America’s past…”

One focus of the interview was Zeller’s account of the center’s accomplishments under his direction.  He said, “I stand by having a long list of efforts and accomplishments,” noting the following:

• “It starts with continuing to stand up the Center.  When I started as Director of CTP, it had its doors open for a little over three years, and we were 426 people. We’re now over 1,110.” 
  
• “incredible ongoing work from a compliance enforcement standpoint through our state contracts.” 
• “our remarkable public education efforts and accomplishments in the Office of Health Communication and Education.” 
• “I saw us as a Center work hard for many, many years on the nicotine reduction product standard.” 
• “we are using the product standard authority to prohibit menthol in cigarettes, and all characterizing flavors, including menthol, in cigars.” 
• “We’ve done an incredible job in the face of receiving applications for 6.7 million products under that court ordered deadline…We’ve taken action on just over 99 percent of those applications but of the approximately fifty thousand that remain, there are important decisions that still need to be made…the challenge will be in getting through those remaining applications as quickly as possible.”

I don’t doubt the increase in CTP staff or the agency’s compliance enforcement efforts, however, its public education efforts were far short of “remarkable.”  They were, in fact, abysmal, as reflected in the fact that numerous studies demonstrate that Americans are horribly misinformed about nicotine health risks.  For example, a 2018 study, using federal survey data, reported that over half of American adults incorrectly believed that nicotine causes cancer.  The study was conducted by Pinney Associates, which provides consulting services on tobacco harm reduction to tobacco manufacturers.  (Prior to joining the FDA in 2013, Zeller was employed by Pinney, which at that time had no tobacco clients.) 

In 2020, I noted in the American Journal of Public Health, “The [second] largest FDA Center for Tobacco Products budget item ($159.5 million, or 22%) supports public education campaigns and communications to ‘reduce tobacco use’ and tell ‘target audiences’ about the ‘harms of tobacco product use.’ (here)  In this category, ‘The Real Cost’ Youth E-Cigarette Prevention Campaign (http://bit.ly/2IWTSWj ) shows e-cigarettes invading adolescent bodies as worms and a magician converting e-cigarettes into combustible cigarettes. The FDA has acknowledged, apparently without concern, that the campaign convinces adult smokers that e-cigarettes are equally or more harmful than cigarettes, thus suppressing quitting.”  In 2018, I called American smokers’ misperception of e-cigarettes’ relative harm a nation disgrace (here).

During Zeller’s tenure, the FDA misinformation campaign consistently targeted smokeless tobacco, without substantiation, as I discussed previously (here, here and here). Zeller boasts of implementing a standard reducing nicotine in cigarettes to near zero, a flawed smoking cessation prescription that I first criticized 28 years ago (here and here).  He also touts the agency’s menthol and flavor bans (here), which are destined to fail (here).    

Zeller is effusive in his praise for his “incredible” CTP colleagues and their “dedication” and “commitment to the mission,” which is an apparent reference to “a world free of tobacco use” (here).  Zeller twice characterizes CTP staff as having “a never-say-die attitude,” which is ironic, given that during Zeller’s nine-year tenure, four million Americans died from smoking-caused illnesses.  The annual death toll in 2013 was 443,000; today it is 480,000. 

As Clive Bates recently noted: “It remains hard to identify a single thing FDA's Center for Tobacco Products has done that has a demonstrable public health benefit. The priority should be to reform this failing and bloated institution.”

Bates continued, “FDA needs to find a better way to embrace harm reduction and make that work for public health.  At present, FDA regulates nearly 3,000 cigarette brands that are pervasively available and uniquely harmful. But it is hard at work squeezing the life out of the vaping industry with ridiculously disproportionate regulatory burdens.  The problem is a lack of vision and a failure to grasp fundamentals about youth risk behaviours, flavors, and the way most of what it does has the effect, if not the intention, of protecting the incumbent cigarette trade from competition.”

 

 

FDA Blunders Again, Endorsing Reduced Nicotine Cigarettes Today…and 27 Years Ago

 

The Well News on January 25 published my commentary on the FDA’s recent regulatory blunder of approving a cigarette that provides all of the smoke but almost none of the nicotine of a traditional cigarette. 

Upon its publication, I received a number of critical emails suggesting that I had failed to properly research the issue.  In fact, those critics failed to do their due diligence on me.  To help them, here is another analysis I published on the subject – back in 1995.

A group of tobacco reformers, led by the Food and Drug Administration Commissioner, has a new regulatory strategy: reduce the amount of nicotine in cigarettes. The theory is that the nicotine concentration of cigarettes will be too low to allow nicotine addiction to be established in new smokers. In the meantime the strategy is intended to serve as a (mandatory) national withdrawal program for the nation’s current smokers.

 

The FDA commissioner has collaborators in this regulatory quest at the highest levels of academia and government. Two well known experts on nicotine addiction, Dr. Neal Benowitz from the University of California at San Francisco and Dr. Jack Henningfield from the National Institute on Drug Abuse, wrote an editorial in the New England Journal of Medicine essentially endorsing the fadeout plan. Although they admitted that “a threshold for nicotine addiction is a theoretical concept ...,” these researchers still postulated a safe concentration of nicotine in cigarettes that would prevent addiction in new smokers. To reach this level, the FDA would have to order a reduction in nicotine content from about eight milligrams per cigarette to about one-half of a milligram, representing a 94 percent reduction.

 

Although the fadeout idea has not been tested with regard to prevention, the plan has been studied for many years as a smoking cessation option. It is basically a drawn-out variation of a strategy called nicotine fading, in which the smoker’s exposure to nicotine is gradually reduced to very low levels. The concept was first introduced in 1979, and numerous trials, usually combining nicotine fading with other behavioral modifications, were conducted throughout the 1980’s.

 

In a recent review of 21 different quit-smoking strategies, nicotine fading came in with an unsurprising success rate — about 25 percent. Dr. Michael C. Fiore, director of the Center for Tobacco Research and Intervention at the University of Wisconsin, questioned the effectiveness of this strategy in helping current smokers quit. Of course if the FDA has its way, this program will not be optional. In other words, a large percentage of current smokers may not find this forced nicotine withdrawal a pleasant experience. What will they do?

 

As they did with low tar low nicotine cigarettes and those with filters, smokers will initially respond to the nicotine phase-out plan by smoking more often and more intensely. Benowitz and Henningfield acknowledged this problem in their editorial. They responded by saying that these smokers’ “short-term (ten-year) risk may be offset by the long-term benefit of a greater likelihood that they will quit smoking (as cigarettes become less satisfying) and by the enormous benefit of preventing nicotine addiction in future generations.”  In other words, they are sorry if your risks increase for ten years because you can't quit, but maybe you'll quit anyway and besides, maybe your children won't get hooked.

 

Another drawback to the fadeout plan is its potential to spawn another huge illicit drug problem. The FDA commissioner commented that “even if we don’t ban cigarettes, we could create a black market by removing the nicotine too quickly.” He seems to believe that the problem is avoidable simply by reducing the nicotine slowly. He is undaunted: “We need to withdraw it at just the right pace, letting the addiction fade as we reduce the nicotine.”

 

There are other fundamental problems with the strategy. For example, setting a threshold level of nicotine exposure below which it is not addictive is an extremely speculative tactic. This would imply that there may be a “safe” level of consumption for all addictions including alcohol, cocaine, and heroin.  A caffeine comparison serves us well here. Utilizing the same rationale concerning effect on body function (addictive potential) and intent (ability to manipulate levels), the FDA has ruled that caffeine is a food additive at concentrations up to 0.02 percent. This amounts to 72 milligrams of caffeine in a twelve-ounce soda. The FDA designates over-the-counter products containing caffeine (up to 200 milligrams per dose) as stimulants. Consistency is not a strong feature of the FDA’s caffeine policy, because a twelve-ounce serving of coffee can have as much as 400 milligrams of caffeine.

 

The important lesson from the caffeine analysis is that the FDA can draw on a precedent for every aspect of the nicotine fading strategy. The plan seems to be bolstered by an elegant scientific rationale, and it superficially appears to be a new and creative approach to the problem of nicotine addiction. However, that's where the real problem lies. Because antitobacco groups have passed judgement on nicotine addiction, they have focused all of their energy on eradicating tobacco. The nicotine fade is simply a thinly veiled disguise for tobacco prohibition.

 

That was my view, published 27 years ago in my clearly timeless book, For Smokers Only: How Smokeless Tobacco Can Save Your Life. Dr. David Kessler was FDA Commissioner at the time.

At the FDA, despite dramatic advances in tobacco science, virtually nothing has changed.

 

 

 

Negligible Evidence of Radical Nicotine Reduction Benefit

An August 17 commentary in the New England Journal of Medicine (here) by FDA Commissioner Scott Gottlieb and Center for Tobacco Products Director Mitchell Zeller raises some concern about the agency’s new tobacco regulation strategy.

The piece touches on “less harmful tobacco products,” which Commissioner Gottlieb wrote favorably about earlier (here), but it includes descriptors – “potential” (four times) and “conceivable” (once) – that suggest the authors are not convinced that e-cigarettes are truly lower-risk. Smokeless tobacco, already demonstrated to be vastly safer than cigarettes, isn’t mentioned.

In their commentary, the FDA officials advocate for radical nicotine reduction (RNR) in cigarettes. 

RNR is a variation on a failed concept: supply-side elimination of popular products.  Full-on cigarette prohibition was adopted, then jettisoned, in 12 states from 1899 to 1909 (here). During Prohibition a decade later, brewers tried to market an alcohol-free product called near beer (here).  That bombed just as badly as Vector Group’s RNR cigarettes in 2003 (here).  Any new RNR products will likely be rejected as well, causing smokers to seek out higher-nicotine-level products, licit or otherwise.

Despite a significant expenditure of taxpayer dollars on RNR research, this approach has not been demonstrated to reduce adult smoking. For example, a $29 million clinical trial by Dr. Neal Benowitz, reported in 2015, produced dismal results (my review here).

The FDA commissioner and his co-author remain optimistic: “A recent 6-week study by Donny et al. showed that cigarettes with lower nicotine content reduced nicotine exposure and dependence, as well as the number of cigarettes smoked, as compared with cigarettes with standard nicotine levels.”  They are referring to another 2015 report (here), but that study’s results were unimpressive as well.

Dr. Eric Donny recruited 840 smokers uninterested in quitting, and randomly provided them with one of seven types of cigarettes to use for 6 weeks: their usual brand, a full-nicotine study cigarette and five others with varying low nicotine levels (2% to 33% of the full-nicotine cigarette).  Subjects were paid up to $835 for 10 clinic visits, which probably contributed to a 92% completion rate.

While it was not surprising that smokers using reduced nicotine cigarettes had lower nicotine levels in their urine, most of the low-nicotine smokers (73-81%) admitted that they smoked three or four “wildcat” cigarettes (products not distributed as part of the study) on 24-35% of days in the trial.

There was little consistency regarding changes in dependence.  On the Wisconsin scale, smokers in all groups had lower scores after six weeks than at baseline, with only one of the reduced nicotine groups significantly lower than the full-nicotine group.  On the Fagerström scale, three low-nicotine groups were significantly lower than the full-nicotine group, but the changes from baseline were not impressive.  In other words, it is not clear if the low-nicotine cigarettes reduced dependence.

The number of cigarettes smoked in the Donny study is interesting.  At baseline, every group was smoking about 15 cigarettes per day.  Although Commissioner Gottlieb and Mr. Zeller imply that low-nicotine groups smoked fewer cigarettes at the end of the study, they actually averaged 15-16 cigarettes per day.  Smokers of usual-brand and full-nicotine cigarettes smoked 21-22 per day after six weeks, an increase of 6-7.  Perhaps Donny contributed to this increased consumption by providing full nicotine cigarettes for free.

Like the Benowitz study, the Donny study does not prove that reduced-nicotine cigarettes produce meaningful benefits for smokers.

It should be noted that the Donny study was supported by $93.3 million in grants from the National Institute on Drug Abuse and the FDA.