Tuesday, July 22, 2014

Federal Judge to FDA: Tobacco Advisory Panel Tainted by Conflicts of Interest



“The presence of conflicted members on [FDA Tobacco Products Scientific Advisory Committee, TPSAC] irrevocably tainted its very composition and its work product” and “the Committee’s findings and recommendations…are, at a minimum, suspect, and, at worst, untrustworthy.”  So ruled federal judge Richard Leon this week (here).

A lawsuit by Lorillard et al. claimed that the FDA appointment of TPSAC members Neal Benowitz, Jack Henningfield and Jonathan Samet was “arbitrary, capricious, an abuse of discretion, and otherwise not in compliance with the law” because they had conflicts of interest.  The evidence was abundant and uncontested.  Here are excerpts from the judge’s opinion:

“Since the 1980s, Dr. Benowitz has consulted for numerous pharmaceutical companies about the design of the NRT and other smoking-cessation drugs.  He consulted for affiliates of Pfizer, Inc. and GlaxoSmithKline (GSK) as to such products, even while serving on the TPSAC…Dr. Benowitz has also served as a paid witness for lawyers suing tobacco-product manufacturers.  He testified as a paid expert witness while serving on the TPSAC, and…he was designated to testify in 585 pending tobacco cases.”

“Before and while serving on the TPSAC, Dr. Henningfield consulted for GSK and other drug companies as to NRT and other smoking-cessation drugs.  He also had ownership interest in a company that was developing a patented NRT drug.  Dr. Henningfield has testified as an expert for GSK and for lawyers suing tobacco-product manufacturers… he was designated to testify in 350 pending tobacco cases.”

“Dr. Samet received grant support from GSK at least six times, including in 2010.  He also led the Institute for Global Tobacco Control, funded by GSK and Pfizer.  Dr. Samet also testified for lawyers suing tobacco-product manufacturers…he was designated to testify in two pending tobacco cases.”

Judge Leon’s ruling notes that the composition of TPSAC is different from other FDA advisory committees, because the enabling legislation bans any expert “who received ‘any salary, grants, or other payment or support’ from any tobacco company in the 18-month period prior to serving on the TPSAC.”  

TPSAC was structured to exclude qualified authorities who have had industry support.  Experts with industry support are not precluded from serving on other FDA advisory committees, in which scientific issues are more important than industry demonization.   

Judge Leon noted that the provision should apply evenly to any conflict of interest: “If Congress deemed that past remuneration from tobacco companies constituted a conflict of interest, it stands to reason that past remuneration from direct competitors of those companies, such as manufacturers of smoking-cessation drugs, would also constitute a conflict of interest.”

Judge Leon’s ruling bars the FDA from using a 2011 TPSAC report on menthol, and it also “enjoins the FDA to reconstitute TPSAC’s membership so that it complies with the applicable ethics laws.”  Dr. Samet is the only conflicted member remaining on TPSAC, as chair (until 2016).  Another member, Claudia Barone, may have a conflict, because she received a Pfizer Educational Grant through 2013 and was appointed to the TPSAC on April 1, 2014 (here).

Although the ruling applies specifically to committee actions on menthol cigarettes and dissolvable products, it is relevant to all TPSAC activities until conflicted members are removed.

It is common for experts to be co-opted by financial support from organizations committed to a tobacco free society, a euphemism for the obliteration of the tobacco industry (an objective that is at odds with the principle of regulation).  Any individual who is funded by organizations such as the American Cancer Society, the American Heart Association, the American Lung Association, the National Cancer Institute, the Centers for Disease Control and Prevention, or the Robert Wood Johnson Foundation should be ineligible for membership on TPSAC.

(Updated July 23)

Friday, July 18, 2014

How Many Americans Smoke?



This blog answered that question a few years ago, saying it was “either 45.3 million or 52.7 million in 2010, depending on which federal agency does the counting. This wide variance [among adults 18+ years] of age underscores the discordant findings from government smoking data.” (here)

I wrote, “It is unacceptable that two federal surveys differ by over 7 million in their adult smoking counts. Even worse is the way the government uses the divergent data to spin different stories about smoking.  They use the lower [National Health Interview Survey] numbers [43.5 million] to boast about declining smoking rates, which they attribute to higher taxes and smoking bans. They use the higher [National Survey on Drug Use and Health] numbers [52.7 million] to argue for even more onerous anti-tobacco measures.”

The irregular counting continues today, and the discrepancy between NHIS and NSDUH is actually growing.  Earlier this year the CDC released its count for 2012, which is 42.1 million (here), based on NHIS.  My analysis of the 2012 NSDUH, which is sponsored by the federal Substance Abuse and Mental Health Services Administration (SAMHSA), indicates that there are at least 51.6 million adult smokers.  That’s a difference of nearly 10 million smokers! 

My research sheds light on this discrepancy (here).  It’s time for the federal government to acknowledge their data conflict, and resolve it.

Wednesday, July 9, 2014

Dishonoring Tony Gwynn



The loss of American sports heroes is often accompanied by an outpouring of grief.  But the death of San Diego Padre star Tony Gwynn from salivary gland cancer was dishonored by a federal official (here) and other uneducated or unprincipled opportunists (here, herehere  and here) who used it to further an irresponsible campaign against smokeless tobacco.

The fact is that salivary gland cancer is extremely rare, about 23 cases per million men each year.  Epidemiologic studies have not established a definitive cause, but they show that radiation therapy, alcohol and hair dyes are possible risk factors (more information here).  Tobacco use is NOT. 

Stretching the facts to demonize smokeless products, Brian King, scientific advisor in the U.S. Center for Disease Control’s office of smoking and health, told Fox News, “…with smokeless use, it’s primarily in the oral region, [which is] why we’re seeing a lot of cancers associated with smokeless tobacco around the oral cavity.”

This is completely false.  King surely knows that the vast majority of mouth cancers are associated with smoking, alcohol abuse and/or human papillomavirus infection.  Numerous epidemiologic studies have documented that there is no mouth cancer risk associated with American moist snuff, chewing tobacco or Swedish snus.

In another attack on smokeless tied to Mr. Gwynn’s untimely death, periodontist Dr. Sanda Moldovan took to The Huffington Post with total disregard for science and fact (here).  “Nicotine is a silent killer with any number of different kinds of cancers,” she wailed.  Decades of scientific studies have established that nicotine does not cause cancer at all.  In fact, nicotine is not the cause of any disease related to smoking.

Moldovan claimed that, “As an oral health professional, I see the initial stages of oral, gum, throat and salivary gland cancers all too often,” but this is near impossible unless she defines “all too often” as twice in her entire career.  In a published study using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program, I calculated that “If every oral cancer was detected by 1 of the 128,000 general dentists in the United States, then on average each dentist would make 1 diagnosis every 12 years.”

Moldovan is grossly wrong in claiming that “There are even studies that show that smokeless tobacco is more carcinogenic than smoked tobacco!”  A 2004 National Cancer Institute-funded study concluded: … “[smokeless] products pose a substantially lower risk to the user than do conventional cigarettes.  This finding raises ethical questions concerning whether it is inappropriate and misleading for government officials or public health experts to characterize smokeless tobacco products as comparably dangerous with cigarette smoking.”   
  
I don’t blame Tony Gwynn for desperately trying to find a cause for the cancer that took his life.  In blaming smokeless tobacco, he was wrong, but that doesn’t attenuate the sense of loss all of us feel when a legend’s life comes to a close.  However, Gwynn’s life and last struggle are dishonored when extremists torture the truth and disrespect science.                                                                                    

Monday, June 30, 2014

Swedish Study: After a Heart Attack, Quitting Tobacco Better Than No Tobacco


A recent study by Gabriel Arefalk and colleagues at the University of Uppsala in Sweden, published in the American Heart Association flagship journal Circulation (abstract here), was purported by the authors, the AHA (here) and the media (here) to show that continuing snus use or smoking after a heart attack (myocardial infarction, MI) is twice as harmful as quitting.   

These conclusions are questionable.  Using the Arefalk numbers, Carl Phillips and I found that snus users, and perhaps even some smokers, are better off than non-users. 

We have submitted a letter to the editor of Circulation, and Carl has the full text of our letter in his CASAA blog post (here).    

The bottom line is that the authors tried to spin the results as suggesting that continuing snus use is dangerous after an MI.  In fact, continuing snus users actually had a lower death rate than people who used neither snus nor cigarettes. 

Whatever is happening in this population, it clearly does not support the simplistic “snus is bad” mantra.  There is a glaringly obvious explanation for why people who quit snus (or smoking) after an MI fare better than those who do not:  Those who are healthy (except for the recent MI, of course) and hope to recover are more likely to take steps to minimize their risks.  After being advised to give up snus, many also get physical therapy, exercise and maintain a healthier diet.  Meanwhile, those who are less healthy may not make changes in an attempt to regain long-term health.  The Arefalk analysis may not have adequately controlled for these confounding factors.

Of course, this would only partially explain the better outcomes of quitters compared to continuing users; it does nothing to explain why all of them (except those who continued to smoke) apparently fared better than non-users.  There are possible explanations for this in the form of statistical artifacts or real effects.  The key observation is that these unreported results do not support the authors’ main interpretation that snus use is dangerous after an MI.

With the publication of this article, peer review appears to have been woefully inadequate.   The prime statistical error we discovered is the key number reported in the first paragraph of the article’s results section.  Reviewers of this study failed to detect the glaring error.

Even without correcting that error or calculating the mortality rate for non-users, the (incorrect) number for the population as a whole the authors reported can still be compared to rates for people who used snus or cigarettes at the time of their MI.  This is enough to raise red flags about the analysis and conclusions, since it is still higher than the rate for those who kept using snus, and far higher than the rates for those who stopped using either product. 

In 2011 Arefalk was lead author on a study making dubious claims about snus use and heart failure.  I described that effort as “neither legitimate nor persuasive until the authors resolve the fundamental questions about the analysis.” (here).

The current article in Circulation is a classic example of anti-tobacco propaganda.  Credible epidemiologic studies do not report risks in exposed groups without reporting the comparable baseline risk among the unexposed.  The authors, and the journal editors and reviewers who enabled them, omitted this critical information.  Our letter to the editor gives them a chance to correct these deficiencies.


Thursday, June 26, 2014

Snus Nicotine Lowers Risk for Multiple Sclerosis, May be Therapeutic for Other Nerve Disorders



New research published in Multiple Sclerosis Journal (abstract here) and authored by Anna Hedström of Stockholm’s Karolinska Institute of Environmental Medicine confirms that snus users have a significantly lower risk for multiple sclerosis (MS) than nonusers of tobacco.  I discussed the researchers’ earlier findings on this subject five years ago in this blog (here).

Hedström’s study is based on some 7,900 Swedes with MS and 9,400 controls.  Compared with never users of tobacco, snus users had a lower risk for MS (odds ratio OR = 0.75, 95% confidence interval, CI= 0.63 – 0.90).  Hedström also showed an increased effect at higher duration-dose levels of snus.  For example, users with greater than ten packet-years (the number of snus doses per day and years of use) had an OR of 0.45 (CI= 028 – 0.68).  Smokers had modestly increased risk (OR= 1.49, CI= 1.40 – 1.59), a finding that is similar to that reported in Hedström’s previous study.

Scientific research is methodically unveiling the benefits of nicotine and smoke-free tobacco use with respect to degenerative brain diseases.  A finding that nicotine may improve performance in people with mild cognitive impairment (discussed here), has resulted in calls for more research on nicotine’s effect on dementia (reference here).

The impact of nicotine/tobacco use on Parkinson’s disease is well documented.  An American Cancer Society study (here) provides clear evidence that smokeless tobacco use may be protective for Parkinson’s disease (RR = 0.22, CI = 0.07 – 0.67).  In fact, nicotine is being discussed as therapy for this disorder (here, here  and here).

Alzheimer’s disease is the sixth leading cause of death in the United States, and Parkinson’s disease is the fourteenth.  The role of nicotine and smoke-free tobacco in reducing risk of or treating these disorders is of significant import.