Wednesday, August 23, 2017

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.


3 comments:

Chris Lalonde said...

Let’s review: they spent $93,300,000 to discover that giving smokers regular cigarettes for free increases the number of cigarettes they smoke, and that giving smokers free cigarettes with radically reduced nicotine causes them to smoke the same number of RNR cigarettes but also to compensate by smoking regular cigarettes. By my math, that’s just shy of $120,000 per participant. Your tax dollars at work.

Bill Godshall said...

Thanks for posting. In the past 25 years, the US DHHS has wasted hundreds of millions of taxpayer dollars on biased junk studies to lobby to ban cigarettes (under the deceptive guise of a regulation to make cigarettes nonaddictive).

US DHHS has also wasted tens of millions of dollars subsidizing (i.e. preventing bankruptcy of) 22nd Century, the company that makes and sells very low risk nicotine cigarettes (as DHHS is the company's only customer, as cigarette smokers won't buy their useless cigarettes).

And since the TCA was enacted in 2009, FDA, NIH, CDC, NIDA, US PHS and other DHHS agencies have wasted many hundreds of millions of addition dollars on biased junk studies that demonize and lobby for the Deeming Rule to ban very low risk vapor products, dissolvables and flavorings, and lower risk (than daily cigarette smoking) pipe tobacco and many/most cigars (which pose significantly lower risks than daily cigarette smoking), as well as a regulatory standard to ban 95% of smokeless tobacco products.

While Scott Gottlieb's four year delay (until August 8, 2022) of vapor prohibition day in America and his stated endorsement of reduced risk products was a critically important temporary public health victory, the Deeming Regulation must be repealed and replaced with reasonable and responsible vapor product standards and truthful statements by FDA about the vastly different risk/benefit profiles of all tobacco/nicotine products (like what Rep. Duncan Hunter recently introduced in Congress).

I don't think Gottlieb's proposal to mandate low nicotine cigarettes will ever become the law of the land, especially after state officials realize that doing so will deprive them of $25 billion in annual tax revenue and MSA payments, and after members of Congress realize that the doing so will deprive them a $12 billion in annual tax revenue (most of which is appropriated for the State Child Health Insurance Program).


Black.Ink.On.Paper said...

Low nicotine cigarettes I think will cause smokers to smoke more, not less. When I used to be a smoker, my favorite brand became American Spirit, which generally had higher nicotine (which I don't think I knew at the time) and burned twice as long (because of no additives). I noticed that I would smoke only a half a pack a day with the American Spirits, but when I smoked any other commercial brand, usually camel, the cigs burned away faster and I would smoke nearly twice as much.