My supplemental comment submitted to FDA.
Food and Drug Administration
[Docket No. FDA-2012-N-1148]
FDA Actions Related to Nicotine Replacement Therapies and Smoking Cessation Products; Report to Congress on Innovative Products and Treatments for Tobacco Dependence
January 16, 2013
Comments Submitted
by
William T. Godshall, MPH
Executive Director
Smokefree Pennsylvania
1926 Monongahela Avenue
Pittsburgh, PA 15218
412-351-5880
FAX 351-5881
SMOKEFREE@COMPUSERVE.COM
These comments supplement testimony Smokefree Pennsylvania and I submitted to this docket on December 10, 2012 and presented at the FDA’s December 17, 2012 public hearing.
I’m Bill Godshall, founder and executive director of Smokefree Pennsylvania, a nonprofit organization that since 1990 has been advocating local, state and federal policies to ban smoking in workplaces, reduce tobacco marketing to youth, hold cigarette companies accountable in civil litigation, increase cigarette tax rates, fund tobacco education and smoking cessation services, inform smokers that smokefree tobacco/ nicotine products are far less hazardous alternatives to cigarettes, and ensure that smokefree alternatives remain legal and affordable to smokers. In 2007, I convinced Sen. Mike Enzi to amend to FSPTCA to require graphic warnings on cigarette packs. And two decades ago, we urged the FDA to approve NRT for OTC sales.
For disclosure, neither I nor Smokefree Pennsylvania have ever received any funding from any tobacco, drug or electronic cigarette company or trade association.
Chantix Poses Severe Adverse Health and Safety Risks
Since there have been many reports of suicide, suicidal thoughts, violence and adverse cardiovascular events associated with use of Chantix, and since 2,600 lawsuits have been filed against Pfizer (the first two of which were recently settled with undisclosed settlements)
Pfizer settles Alabama man's lawsuit against the company's smoking cessation drug Chantix | al.com
the FDA should consider removing Chantix from the market, or at least require a black box warning on Chantix packages informing consumers about suicide risks.
Additionally, the FDA should NOT fast-track the approval process for any new drug for “treating tobacco dependence”.
Nicotine Replacement Therapy (NRT) products
Although the FDA has approved many NRT products to “treat tobacco dependence” for more than two decades, the scientific evidence indicates that NRT products have >90% failure rate after six months (for treating tobacco dependence and as smoking cessation aids) and have
>95% failure rate after twelve months.
A meta-analysis found that an average of just 7% of those using over-the-counter NRT products remained cigarette free after six months, a 93% relapse rate.
A meta-analysis of the efficacy of over-the-counter nicotine replacement, Hughes JR, Shiffman S, Callas P, Zhang Z, Tobacco Control, 2003, Vol. 12, 21-27.
A meta-analysis of the efficacy of over-the-counter nicotine replacement -- Hughes et al. 12 (1): 21 -- Tobacco Control
Another meta-analysis also found that 7% of NRT remain cigarette free after six months, and that just 2% remain cigarette free after 20 months (a 98% relapse rate).
Effectiveness and safety of nicotine replacement therapy assisted reduction to stop smoking: systematic review and meta-analysis, David Moore, Paul Aveyard, Martin Connock, Dechao Wang, Anne Fry-Smith, Pelham Barton, BMJ 2009;338:b1024
Effectiveness and safety of nicotine replacement therapy assisted reduction to stop smoking: systematic review and meta-analysis | BMJ
A meta analysis of seven placebo controlled randomised controlled trials involving different NRT products found that just 6.75% of those receiving NRT had quit smoking after six months. Effectiveness and safety of nicotine replacement therapy assisted reduction to stop smoking: systematic review and meta-analysis, David Moore, Paul Aveyard, Martin Connock, Dechao Wang, Ann Fry-Smith, Pelham Burton, BMJ 2009; 338:b1024
http://www.sciencedirect.com/science/article/pii/S0306460311001572
While supposedly double-blind clinical trials have found that NRT products double the chances of quitting when compared to using a placebo, skepticism has been raised about the accuracy and reliability of these studies, since it is likely that many participants who were assigned to placebos realized they were not getting nicotine.
The blind spot in the nicotine replacement therapy literature: Assessment of the double-blind in clinical trials, Mooney M, White T, Hatsukami D, Addictive Behaviors, 2004 Vol. 29, 673-684.
http://whyquit.com/studies/NRT_Blinding_Failures.pdf
Precessation treatment with nicotine patch significantly increases abstinence rates relative to conventional treatment, Jed E. Rose, Joseph E. Herskovic, Frederique M. Behm and Eric C. Westman, Nicotine & Tobacco Research 2009 11(9):1067-1075; doi:10.1093/ntr/ntp103.
Precessation treatment with nicotine patch significantly increases abstinence rates relative to conventional treatment
Skin patches appear to be ineffective smoking cessation aids for those who fail to quit smoking during their first use of NRT, as two published studies on the use of NRT skin patches to quit smoking after an initial failure with NRT found six-month smoking cessation rates of 0% and 1.4%, respectively.
Recycling with nicotine patches in smoking cessation. Tonnesen P, Norregaard J, Sawe U, Simonsen K, Addiction. 1993 Apr;88(4):533-9.
Recycling with nicotine patches in smoking cessation. [Addiction. 1993] - PubMed - NCBI
Double blind trial of repeated treatment with transdermal nicotine for relapsed smokers. Gourlay SG, Forbes Q, Marriner T, et al. British Medical Journal, 1995, Vol. 311, No 7001 363-366.
A survey of 500 U.S. smokers found only 16% agreed that NRT helps people quit smoking.
Attitudes toward nicotine replacement therapy in smokers and ex-smokers in the general public. Etter JF, Perneger TV, Clinical Pharmocol Therapy 2001 Volume 69, 175-83.
Therefore, the FDA should disapprove all currently approved NRT products as treatments for tobacco dependence, and should not approve NRT products for treating tobacco dependence or as smoking cessation aids unless clinical trials find a 20% or higher success rate, or to at least require manufacturers to notify consumers of the six and twelve month success rates the product was found to have for both smoking cessation and for achieving nicotine abstinence.
This submitter is not aware of any other drug ever approved by the FDA that has a 95% failure rate for achieving the intent/purpose for which it was approved. By approving NRT products for “treating tobacco dependence” and by approving manufacturer advertisements touting NRT as an effective smoking cessation aid, the FDA has grossly misled smokers and the public about NRT’s effectiveness.
But since NRT products are far less hazardous alternatives to cigarettes, and since most NRT products are consumed for “off label” use as either temporary substitutes (when/where smoking isn’t permitted) or as long term substitutes for cigarettes, the FDA should approve all NRT products as “temporary” and “long term” “harm reduction alternatives” to cigarettes.
A 2003 study of NRT sales transactions found that an estimated 36.6% of current nicotine gum users have consumed the product for longer than six months.
Persistent use of nicotine replacement therapy: analysis of actual purchase patterns in a population based sample, Shiffman S, Hughes JR, Pillitteri JL, Burton SL, Tobacco Control, Vol. 12, 310-316, 2003.
http://tc.bmjjournals.com/cgi/content/full/12/3/310
Since clinical trials aren’t necessary for the FDA to approve NRT products as “temporary” and “long term” “harm reduction alternatives” to cigarettes, manufacturers of electronic cigarettes and/or other smokefree tobacco/nicotine products may also consider applying to the FDA for their products to be similarly approved as “temporary” and “long term” “harm reduction alternatives” to cigarettes.
Smokefree Tobacco/Nicotine Products Are Far Less Hazardous
Alternatives to Cigarettes
To improve consumer and public health, it is critically important for the FDA to stop protecting cigarettes from market competition by far less hazardous smokefree alternatives, to correct or clarify FDA’s many inaccurate and misleading claims about low risk smokefree tobacco and nicotine alternatives, and to keep all smokefree alternatives legal and affordable for smokers.
>99% of all tobacco attributable mortality and health care costs in the US are caused by repeated inhalation of tobacco smoke, while <1% are caused by the use of noncombustible tobacco and nicotine products. Epidemiological evidence indicates that cigarettes are at least 100 times more hazardous than smokefree nicotine and tobacco products marketed in the US, including smokeless tobacco, electronic cigarettes and NRT products.
While cigarettes and smokefree tobacco products are similarly addictive (i.e. creating daily dependence), published epidemiology research finds that daily cigarette smoking imposes about 100 times greater mortality risks than does daily use of smokefree tobacco products marketed in the U.S. and Sweden. On a continuum of tobacco mortality risk from 1 to 100 (whereby Nicotine Replacement Products are 1 and cigarettes are 100), smokefree tobacco products are below 2.
In 2006, I coauthored a comprehensive evaluation of epidemiology research on smokeless tobacco products, which found that smokeless tobacco products used in the U.S. and Sweden are exponentially less hazardous than cigarette smoking, and recommended that smokers be provided with truthful information about the comparable health risks of different tobacco products and encouraged to switch to smokefree tobacco alternatives if they cannot or don’t want to quit using tobacco.
Tobacco harm reduction: an alternative cessation strategy for inveterate smokers, Brad Rodu and William T Godshall, Harm Reduction Journal 2006, 3:37doi:10.1186/1477-7517-3-37.
HRJ | Full text | Tobacco harm reduction: an alternative cessation strategy for inveterate smokers
In 2007, the Royal College of Physicians published a report on the comparable health risks of smokeless tobacco products and cigarettes, that similarly concluded smokeless tobacco products are far less hazardous than cigarettes, and that smokers who cannot or won’t quit tobacco use should be encouraged to switch to smokeless alternatives.
Harm reduction in nicotine addiction; Helping people who can't quit, Royal College of Physicians, 2007.
Publication - Harm reduction in nicotine addiction
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(07)61482-2/fulltext#article_upsell
A comprehensive evaluation of epidemiological research on Swedish snus published in 2007 at
http://nzhta.chmeds.ac.nz/publications/smokeless_tobacco.pdf similarly concluded that Swedish snus poses exponentially fewer health risks than cigarettes.
In 2008, the American Association of Public Health Physicians published a white paper at
http://www.aaphp.org/Resources/Documents/20081026HarmReductionResolutionAsPassedl.pdft
that evaluated the existing epidemiological research, and similarly concluded that smokeless tobacco products are exponentially less hazardous than cigarettes, and that vast public health gains could be achieved by eliminating the federally required (since 1986) warning on smokeless tobacco products that misleadingly states “This product is not a safe alternative to cigarettes.”
In 2010, the American Association of Public Health Physicians updated the new scientific evidence published since its 2008 white paper at
American Association of Public Health Physicians - Tobacco Update
The Tobacco Harm Reduction 2010 yearbook published by TobaccoHarmReduction.org at
THR2010. (tobaccoharmreduction.org) similarly evaluated the published research and concluded that the health risks posed by smokeless tobacco products are exponentially fewer than the health risks posed by cigarettes.
At the FDA’s 2010 workshop entitled: Risks and Benefits of Long-Term Use of Nicotine Replacement Therapy (NRT) Products; Public Workshop at:
Regulations.gov, many presenters and commenters (including two FDA Tobacco Product Scientific Advisory Committee members) cited the strikingly similar health risk and benefit profiles between Swedish snus and Nicotine Replacement Therapy (NRT) gums and lozenges when recommending FDA approve longterm usage of NRT products (since epidemiology studies on NRT aren’t available because the products have only been on the market for several decades).
A report by the American Council on Science and Health and Brad Rodu The Scientific Foundation for Tobacco Harm Reduction, 2006-2011 at
http://www.harmreductionjournal.com/content/pdf/1477-7517-8-19.pdf evaluated all published studies (during the past five years) on the health risks of smokeless tobacco products, confirmed that they are far less hazardous than cigarettes, and that increasingly more smokers have quit smoking by switching to smokeless tobacco alternatives.
Authors of a published meta analysis of North American and European epidemiological cohort and case-control studies relating any form of cancer to smokeless tobacco use (i.e. 62 US and 18 Scandinavian studies) reported the following results:
“Random-effects meta-analysis estimates for most sites showed little association. Smoking-adjusted estimates were only significant for oropharyngeal cancer (1.36, CI 1.04–1.77, n = 19) and prostate cancer (1.29, 1.07–1.55, n = 4). The oropharyngeal association disappeared for estimates published since 1990 (1.00, 0.83–1.20, n = 14), for Scandinavia (0.97, 0.68–1.37, n = 7), and for alcohol-adjusted estimates (1.07, 0.84–1.37, n = 10). Any effect of current US products or Scandinavian snuff seems very limited. The prostate cancer data are inadequate for a clear conclusion.” and “Smokeless tobacco-attributable deaths would be 1,102 (1.1%) if as many used smokeless tobacco as had smoked, and 2,081 (2.0%) if everyone used smokeless tobacco.”
Systematic review of the relation between smokeless tobacco and cancer in Europe and North America, Peter N Lee and Jan Hamling, BMC Medicine 2009, 7:36doi:10.1186/1741-7015-7-36
BMC Medicine | Full text | Systematic review of the relation between smokeless tobacco and cancer in Europe and North America
Another comprehensive meta analyses of 150 studies on various diseases found no association with snus use and cancer of the oropharynx (meta-analysis RR 0.97, 95% CI 0.68-1.37), oesophagus (1.10, 0.92-1.33), stomach (0.98, 0.82-1.17), pancreas (1.20, 0.66-2.20), lung (0.71, 0.66-0.76) or other sites, or with heart disease (1.01, 0.91-1.12) or stroke (1.05, 0.95-1.15). The author concluded: “Using snus is clearly much safer than smoking. While smoking substantially increases the risk of cancer and cardiovascular diseases, any increase from snus use is undemonstrated, and if it exists is probably about 1% of that from smoking.”
Summary of the epidemiological evidence relating snus to health, Peter N Lee, Regul Toxicol Pharmacol 2011, Mar, 59(2):197-214
Summary of the epidemiological evide... [Regul Toxicol Pharmacol. 2011] - PubMed - NCBI
A previously published and widely reported meta analysis of 11 studies found that snus use was associated with slightly elevated risk of fatal myocardial infarction and fatal stroke, but was NOT associated with all myocardial infarctions or strokes, casting doubt on its findings about fatal heart attacks and strokes.
Use of smokeless tobacco and risk of myocardial infarction and stroke: systematic review with meta-analysis, Paulo Boffetta, Kurt Straif, BMJ 2009; 339:b3060
Use of smokeless tobacco and risk of myocardial infarction and stroke: systematic review with meta-analysis | BMJ
