Researchers Fail to Disclose Conflicts of Interest with Big Pharma and Appear to Hide their Financial Relationships

In an article published in the current issue of the journal Addiction regarding effective treatment for smoking cessation, all co-authors except one denied having received any funding from pharmaceutical companies. Their declaration of interests statement reads: "The authors have received no direct or indirect funding from, nor do they have a connection with, the tobacco, alcohol, pharmaceutical or gaming industries or anybody substantially funded by one of these organizations."

In a related article also published in the journal Addiction regarding effective treatment for smoking cessation, the same authors (again except one) again denied having received any funding from pharmaceutical companies. That declaration of interests statements reads: "The authors have received no direct or indirect funding from, nor do they have a connection with the tobacco, alcohol, pharmaceutical or gaming industries or anybody substantially funded by one of these organizations."

In two additional related articles published in the same January issue of Addiction, the same authors make the identical declaration, claiming that they "have received no direct or indirect funding from, nor do they have a connection with the tobacco, alcohol, pharmaceutical or gaming industries or anybody substantially funded by one of these organizations." 

Two of the authors of the Addiction articles also published an article in the current issue of JAMA regarding the effectiveness of smoking cessation drugs. In that article, co-authors Dr. Michael Fiore and Dr. Timothy Baker have apparently declared that they have no conflicts of interest to disclose.

The Rest of the Story

Unless I am mistaken, it appears that the above disclosure statements are false and that several of the co-authors have indeed received funding from the pharmaceutical industry.

Dr. Fiore

The truth is that Dr. Fiore actually has a long history of significant financial relationships with pharmaceutical companies that manufacture smoking cessation drugs, none of which are acknowledged in his disclosure. Here is what is being hidden from readers:

1. According to his own 2008 JAMA article: "In the past 5 years, Dr Fiore reports that he has lectured and consulted for Pfizer and has served as an investigator on research studies at the University of Wisconsin (UW) that were supported by GlaxoSmithKline, Nabi, Pfizer, and sanofi-aventis."

2. According to his own sworn testimony, at the time of his chairing in 2008 of an expert NIH panel to make recommendations about the recommended clinical strategies for promoting smoking cessation, Dr. Fiore received up to $50,000 in annual resources from GlaxoSmithKline to support his educational, research, and policy activities.

3. In 2006, Dr. Fiore acknowledged that "I have done some consulting work for pharmaceutical companies over the years. Over the past five years, my outside consulting work on an annual basis has ranged between about $10,000 and $30,000 or $40,000 per year."

4. In 1998, the University of Wisconsin appointed him to a named chair, made possible by an unrestricted gift to the University from GlaxoWellcome.

5. In the past, "Dr. Fiore has served as a consultant for, given lectures sponsored by, or has conducted research sponsored by Ciba-Geigy, SmithKline Beecham, Lederle Laboratories, McNeil Consumer Products, Elan Pharmaceutical, Pharmacia, and Glaxo Wellcome."

6. Dr. Fiore directs a tobacco research center that received nearly $1 million in funding from makers of quit-smoking medicine in 2004 and $400,000 in 2005.

7. In a recent set of two articles on treatment for smoking cessation published in the Annals of Behavioral Medicine in April 2011 (article 1; article 2), the conflict of interest statement regarding Dr. Fiore acknowledges that: "Over the last 3 years, Michael C. Fiore served as an investigator on research studies at the University of Wisconsin that were funded by Nabi Biopharmaceuticals."

8. In a December 2010 article on treatment for smoking cessation published in the Wisconsin Medical Journal, the conflict of interest statement regarding Dr. Fiore acknowledges that: "Over the last 3 years, Dr Fiore has served as an investigator in research studies at the University of Wisconsin that were funded by Pfizer and Nabi Biopharmaceuticals."

Amazingly, none of these conflicts of interest are reported in the paper and the reader has no way of knowing this long history of financial conflicts of interest with Big Pharma. I imagine that most readers would be shocked to find out about this intense and long history of financial conflict with Big Pharma, given that Dr. Fiore reported no conflicts of interest and that he specifically stated that he has received no funding from pharmaceutical companies.

Specifically, Dr. Fiore stated that he has "received no direct or indirect funding from ... the ... pharmaceutical ... industr[y]...". This seems to be inaccurate, as Dr. Fiore acknowledges that he has received funding from GlaxoSmithKline, Nabi, Pfizer, sanofi-aventis, Ciba-Geigy, SmithKline Beecham, Lederle Laboratories, McNeil Consumer Products, Elan Pharmaceutical, and Pharmacia.

Thus, the disclosure statement appears to be quite false, as Dr. Fiore states that he has not received funding from any pharmaceutical companies, but the truth is that he appears to have received funding from a minimum of 10 pharmaceutical companies.

Dr. Baker

The truth is that Dr. Baker also has a long and significant history of financial relationships with pharmaceutical companies that manufacture smoking cessation drugs. Here is what is being hidden from readers:

1. In 2008, Dr. Baker reported that: "he has served as a co-investigator on research studies at the University of Wisconsin that were sponsored by four pharmaceutical companies."

2. In 2000, Dr. Baker disclosed as follows: "Timothy Baker has served as a consultant for, given lectures sponsored by, or has conducted research sponsored by Elan Pharmaceutical, SmithKline Beecham, Glaxo Wellcome, and Lederle."

3. As recently as 2012, Dr. Baker disclosed in an article that his research involved financial support from GlaxoSmithKline in the form of free medication provided to study participants.

4. In another 2012 paper, Dr. Baker also acknowledged that GlaxoSmithKline provided financial support in the form of free study medication. The same disclosure was made in another 2012 paper. And in another paper as well.

5. According to a 2011 paper: "Timothy B. Baker has served as a consultant, given lectures sponsored by, or has conducted research sponsored by GlaxoSmithKline, Nabi Biopharmaceuticals, Pfizer, and Sanofi-Synthelabo."

6. In a 2010 paper, Dr. Baker acknowledged "research grants from Pfizer, GlaxoSmithKline, Nabi Biopharmaceuticals, and Sanofi."That paper itself involved research with financial support from GlaxoSmithKline in the form of free study medication.

Again, amazingly, none of these conflicts of interest are reported in the paper and the reader has no way of knowing this long history of financial conflicts of interest with Big Pharma. I imagine that most readers would be shocked to find out about this intense and long history of financial conflict with Big Pharma, given that Dr. Baker reported no conflicts of interest and that he specifically stated that he has received no funding from pharmaceutical companies.

Specifically, Dr. Baker stated that he has "received no direct or indirect funding from ... the ... pharmaceutical ... industr[y]...". This seems to be inaccurate, as Dr. Baker acknowledges that he has received funding from Elan Pharmaceutical, SmithKline Beecham, Glaxo Wellcome, Lederle, Nabi Biopharmaceuticals, Pfizer, GlaxoSmithKline, and Sanofi-Synthelabo. Thus, the disclosure statement appears to be quite false, as Dr. Baker states that he has not received funding from any pharmaceutical companies, but the truth is that he appears to have received funding from a minimum of 8 pharmaceutical companies.

Dr. Douglas Jorenby

The truth is that despite claiming that he has not received funding from pharmaceutical companies, Dr. Jorenby has received "research support from Pfizer, Nabi Biopharmaceutical, Sanofi-Aventis and consulting fees from Nabi Biopharmaceutical." In addition, as recently as 2012, Dr. Jorenby disclosed in an article that his research involved financial support from GlaxoSmithKline in the form of free medication provided to study participants. In a 2011 publication, Dr. Jorenby disclosed that the study was funded by Nabi Biopharmaceuticals.

Dr. Megan Piper

According to her disclosure in a 2012 paper, Dr. Piper participated in a research study in which a research agreement was entered into with GlaxoSmithKline in which the company provided free study medications in a clinical trial of one of its smoking cessation drugs.

Dr. Tanya Schlam
According to her disclosure in a 2012 paper, Dr. Piper participated in a research study in which a research agreement was entered into with GlaxoSmithKline in which the company provided free study medications in a clinical trial of one of its smoking cessation drugs.

Summary

In summary, although all of these co-authors declared in multiple recent publications that they "have received no direct or indirect funding" from pharmaceutical companies, five of these co-authors appear to have received either direct or indirect funding, or both, from pharmaceutical companies.

The only possible argument for why this funding should not have been disclosed would be that the funding occurred in the past. However, this argument does not work because that's not what the disclosure states. It states that the authors "have received no indirect or direct funding." There is no time limitation on this disclosure. It clearly implies that the authors have never received funding from pharmaceutical companies.

Certainly, readers of these articles are being led to believe that these authors have not received funding from pharmaceutical companies. But this is not true. Thus, readers are being greatly deceived by these failed disclosures.

Moreover, as I have argued previously, I do not believe that conflicts of interest end the moment a grant from a pharmaceutical company terminates. Certainly, if a researcher had received tobacco industry funding in the past, we would demand that he or she disclose such funding, even if it occurred in the past. And if that researcher failed to make the disclosure, we would certainly criticize him or her for deceiving journal readers. And I have no doubt that if the disclosure stated that he or she has received no funding from tobacco companies, it would be uniformly be viewed in the tobacco control movement as a false disclosure. I pity the researcher who would find himself in that situation. The attacks from Stan Glantz alone would be devastating. And for good reason.

This is why journals have conflict of interest policies in the first place. The point is that readers need to be aware of potential conflicts of interest in order to appropriately evaluate the study validity. A past conflict does not alter the underlying point that the existence of that relationship could be perceived as to have influenced the conduct, interpretation, or reporting of the study.

As the instructions to authors of Addiction state: "Declarations of interest do not indicate wrongdoing but they must be declared in the interests of full transparency. ... Declaring a conflict of interest is the responsibility of authors and authors should err on the side of inclusiveness."

There are two important points here. First, there is absolutely nothing wrong with having a conflict of interest. If pharmaceutical companies did not fund research, the drug development process would be greatly hindered, and it would be devastating to the public's health. So there is nothing wrong with pharmaceutical companies funding university research, nor is there anything wrong with university researchers accepting pharmaceutical company funding. The key is that the funding needs to be disclosed. And furthermore, the interest being served is not some technical definition of what needs to be disclosed, but instead, it is the interest of full transparency. It hardly seems that readers of these articles in Addiction would agree that full transparency has been achieved if they found out about the extensive list of pharmaceutical funding of many of the co-authors of these articles as I have outlined above.

Second, authors should err on the side of inclusiveness. The guidelines to authors do not specify any particular date by which a conflict of interest becomes null and void. They do not state, for example, that authors should declare any funding from pharmaceutical companies that occurred in the past X number of years. Erring on the side of inclusiveness would seem to indicate that any past funding relationships should be disclosed. Moreover, the plain language of the disclosure statement (i.e., authors have not received funding from...) would seem to indicate that there is no history of funding, not simply no current funding. If what was meant is that there is no current funding, then that is what should have been stated. It would still have been an incomplete disclosure, but at least it would not have deceived readers into believing that there was no past funding either.

While the failed disclosures in this case serve mainly to deceive readers, in some cases, conflicts of interest can have important ramifications for the protection of the public's health. Just yesterday, Senator Bernie Sanders blocked the Senate confirmation of President Obama's nominee for FDA commissioner because he has a long history of financial relationships with pharmaceutical companies. Sanders stated: "Dr. Califf's extensive ties to the pharmaceutical industry give me no reason to believe that he would make the FDA work for ordinary Americans, rather than just the CEOs of pharmaceutical companies."

My point is not that Dr. Califf is inappropriate to serve as FDA commissioner (although that may well be the case), but simply that if these conflicts of interest were not disclosed to the Senate, then our policy makers would not have even had the opportunity to consider whether this nominee is best positioned to protect the public's health.

The purpose of conflict of interest disclosures is not to suggest that there is any wrongdoing, but to provide full transparency to journal readers, and ultimately, to the public.

NEJM Commentary Written by Anti-Tobacco Researchers Hides Conflicts of Interest with Big Pharma

An article published last week in the New England Journal of Medicine discusses strategies for reducing smoking, including the use of pharmaceutical products such as nicotine replacement therapy and other drugs. The article argues that every patient who wishes to quit should be provided with smoking cessation drugs, as opposed to relying upon other approaches, such as counseling or cold turkey quitting.

Because the advice given to physicians in this column conflicts with scientific evidence and undermines the principle of physician autonomy, readers may naturally be curious whether the authors of this commentary have any history of financial conflicts of interest with pharmaceutical companies that products the products discussed in the article.

Fortunately, readers can be rest assured that there were no relevant conflicts to disclose. All three of the co-authors - Dr. Michael Fiore, Dr. Steven Schroeder, and Dr. Timothy Baker - completed disclosure forms indicating that they have nothing to disclose, which implies that there is no relevant history of financial relationships of any of these authors with pharmaceutical companies.

Specifically, in completing section 5 of the form, each of the authors proclaimed that there were: "No other relationships/conditions/circumstances that present a potential conflict of interest." This section refers to financial interests that were not disclosed earlier in the form. The disclosures earlier in the form relate to financial interests present during the past 36 months. Importantly, however, the additional disclosures in section 5 do not have any stated time frame. The directions indicate that authors must "use this section to report other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing, what you wrote in the submitted work."

Since all three authors indicated in section 5 that there are no other relationships or activities that readers could perceive to have influenced their work, we can conclude that none of these authors has any significant history of financial relationships with Big Pharma.

The Rest of the Story

The rest of the story is that two of the three authors are hiding relevant financial conflicts of interest with Big Pharma that I believe should have been disclosed in the paper.

Dr. Fiore

The truth is that Dr. Fiore actually has a long history of significant financial relationships with pharmaceutical companies that manufacture smoking cessation drugs, none of which are acknowledged in his disclosure. Here is what is being hidden from readers:

1. According to his own 2008 JAMA article: "In the past 5 years, Dr Fiore reports that he has lectured and consulted for Pfizer and has served as an investigator on research studies at the University of Wisconsin (UW) that were supported by GlaxoSmithKline, Nabi, Pfizer, and sanofi-aventis."

2. According to his own sworn testimony, at the time of his chairing in 2008 of an expert NIH panel to make recommendations about the recommended clinical strategies for promoting smoking cessation, Dr. Fiore received up to $50,000 in annual resources from GlaxoSmithKline to support his educational, research, and policy activities.

3. In 2006, Dr. Fiore acknowledged that "I have done some consulting work for pharmaceutical companies over the years. Over the past five years, my outside consulting work on an annual basis has ranged between about $10,000 and $30,000 or $40,000 per year."

4. In 1998, the University of Wisconsin appointed him to a named chair, made possible by an unrestricted gift to the University from GlaxoWellcome.

5. In the past, "Dr. Fiore has served as a consultant for, given lectures sponsored by, or has conducted research sponsored by Ciba-Geigy, SmithKline Beecham, Lederle Laboratories, McNeil Consumer Products, Elan Pharmaceutical, Pharmacia, and Glaxo Wellcome."

6. Dr. Fiore directs a tobacco research center that received nearly $1 million in funding from makers of quit-smoking medicine in 2004 and $400,000 in 2005.

7. In a recent set of two articles on treatment for smoking cessation published in the Annals of Behavioral Medicine in April 2011 (article 1; article 2), the conflict of interest statement regarding Dr. Fiore acknowledges that: "Over the last 3 years, Michael C. Fiore served as an investigator on research studies at the University of Wisconsin that were funded by Nabi Biopharmaceuticals."

8. In a December 2010 article on treatment for smoking cessation published in the Wisconsin Medical Journal, the conflict of interest statement regarding Dr. Fiore acknowledges that: "Over the last 3 years, Dr Fiore has served as an investigator in research studies at the University of Wisconsin that were funded by Pfizer and Nabi Biopharmaceuticals."

Amazingly, none of these conflicts of interest are reported in the paper and the reader has no way of knowing this long history of financial conflicts of interest with Big Pharma. I imagine that most readers would be shocked to find out about this intense and long history of financial conflict with Big Pharma, given that Dr. Fiore reported no conflicts of interest.

Dr. Baker

The truth is that Dr. Baker also has a long and significant history of financial relationships with pharmaceutical companies that manufacture smoking cessation drugs. Here is what is being hidden from readers:

1. In 2008, Dr. Baker reported that: "he has served as a co-investigator on research studies at the University of Wisconsin that were sponsored by four pharmaceutical companies."

2. In 2000, Dr. Baker disclosed as follows: "Timothy Baker has served as a consultant for, given lectures sponsored by, or has conducted research sponsored by Elan Pharmaceutical, SmithKline Beecham, Glaxo Wellcome, and Lederle."

3. As recently as 2012, Dr. Baker disclosed in an article that his research involved financial support from GlaxoSmithKline in the form of free medication provided to study participants.

4. In another 2012 paper, Dr. Baker also acknowledged that GlaxoSmithKline provided financial support in the form of free study medication. The same disclosure was made in another 2012 paper. And in another paper as well.

5. According to a 2011 paper: "Timothy B. Baker has served as a consultant, given lectures sponsored by, or has conducted research sponsored by GlaxoSmithKline, Nabi Biopharmaceuticals, Pfizer, and Sanofi-Synthelabo."

6. In a 2010 paper, Dr. Baker acknowledged "research grants from Pfizer, GlaxoSmithKline, Nabi Biopharmaceuticals, and Sanofi."That paper itself involved research with financial support from GlaxoSmithKline in the form of free study medication.

Again, amazingly, none of these conflicts of interest are reported in the paper and the reader has no way of knowing this long history of financial conflicts of interest with Big Pharma.

Here, not only does it appear that Dr. Baker has failed to disclose conflicts that should have been revealed in section 5 of the form, but I have to question whether he has also hidden information that should have been disclosed in section 3. The instructions to that section clearly indicate that research involving drugs provided by pharmaceutical companies is to be included in this section. Since the research was ongoing in 2012 (that is the year in which papers were continuing to be published), it appears to me that this financial conflict falls within the 36 month period about which the form inquires.

Either way, Dr. Baker's participation in research that was financiallly supported by GlaxoSmithKline should have been reported in his disclosure.

3. Dr. Schroeder

Dr. Schroeder is the only one of the three authors who does not appear to be hiding a significant financial ionflict of interest. However, it is worth noting that Dr. Schroeder's center lists Pfizer as a partner. It is not clear to me what this means. If Pfizer is a financial partner, then this should have been disclosed in the article. But even if Pfizer is just a partner in terms of working together on a project, I would still view that as a conflict of interest that should have been disclosed.

Summary

For years, we in tobacco control have attacked tobacco industry-funded scientists or researchers who consulted for tobacco companies for not disclosing their conflicts of interest. It is therefore quite unfortunate, and ironic, that tobacco control researchers do not appear to take their own conflicts of interest seriously and that they, too, are hiding these conflicts from the public.

As I previously articulated, the hiding of these conflicts of interest damages public health in four ways:

1. It violates public health ethics and could be damaging to the entire field of tobacco control;
2. It degrades the research integrity of tobacco control;
3. It makes us hypocrites when we criticize failed tobacco industry disclosures; and
4. It hides the influence of Big Pharma money on the field of tobacco control and hinders smoking cessation efforts.

NEJM Commentary Written by Anti-Tobacco Researchers Hides Conflicts of Interest with Big Pharma

An article published today in the New England Journal of Medicine discusses the results of a clinical trial of low-nicotine cigarettes for reducing smoking. The article recommends that low-nicotine cigarettes should be a part of a national strategy to reduce tobacco use. However, it fails to recommend that electronic cigarettes be considered as a part of this strategy, even though e-cigarettes are much more effective in getting smokers to cut down on the amount they quit, much more effective in getting smokers to quit completely, and much safer. But e-cigarettes are a threat to pharmaceutical companies that manufacture smoking cessation drugs. Therefore, readers may naturally be curious whether the authors of this commentary have any history of financial conflicts of interest with pharmaceutical companies.

Fortunately, readers can be rest assured that there were no relevant conflicts to disclose. Both of the co-authors - Dr. Michael Fiore and Dr. Timothy Baker - completed disclosure forms indicating that they have nothing to disclose, which implies that there is no relevant history of financial relationships of any of these authors with pharmaceutical companies.

Specifically, in completing section 5 of the form, each of the authors proclaimed that there were: "No other relationships/conditions/circumstances that present a potential conflict of interest." This section refers to financial interests that were not disclosed earlier in the form. The disclosures earlier in the form relate to financial interests present during the past 36 months. Importantly, however, the additional disclosures in section 5 do not have any stated time frame. The directions indicate that authors must "use this section to report other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing, what you wrote in the submitted work."

Since both authors indicated in section 5 that there are no other relationships or activities that readers could perceive to have influenced their work, we are led to believe that neither of these authors has any significant history of financial relationships with Big Pharma.

The Rest of the Story

The rest of the story is that both authors are hiding relevant financial conflicts of interest with Big Pharma that I believe should have been disclosed in the paper.

Dr. Fiore

The truth is that Dr. Fiore actually has a long history of significant financial relationships with pharmaceutical companies that manufacture smoking cessation drugs, none of which are acknowledged in his disclosure. Here is what is being hidden from readers:

1. According to his own 2008 JAMA article: "In the past 5 years, Dr Fiore reports that he has lectured and consulted for Pfizer and has served as an investigator on research studies at the University of Wisconsin (UW) that were supported by GlaxoSmithKline, Nabi, Pfizer, and sanofi-aventis."

2. According to his own sworn testimony, at the time of his chairing in 2008 of an expert NIH panel to make recommendations about the recommended clinical strategies for promoting smoking cessation, Dr. Fiore received up to $50,000 in annual resources from GlaxoSmithKline to support his educational, research, and policy activities.

3. In 2006, Dr. Fiore acknowledged that "I have done some consulting work for pharmaceutical companies over the years. Over the past five years, my outside consulting work on an annual basis has ranged between about $10,000 and $30,000 or $40,000 per year."

4. In 1998, the University of Wisconsin appointed him to a named chair, made possible by an unrestricted gift to the University from GlaxoWellcome.

5. In the past, "Dr. Fiore has served as a consultant for, given lectures sponsored by, or has conducted research sponsored by Ciba-Geigy, SmithKline Beecham, Lederle Laboratories, McNeil Consumer Products, Elan Pharmaceutical, Pharmacia, and Glaxo Wellcome."

6. Dr. Fiore directs a tobacco research center that received nearly $1 million in funding from makers of quit-smoking medicine in 2004 and $400,000 in 2005.

7. In a recent set of two articles on treatment for smoking cessation published in the Annals of Behavioral Medicine in April 2011 (article 1; article 2), the conflict of interest statement regarding Dr. Fiore acknowledges that: "Over the last 3 years, Michael C. Fiore served as an investigator on research studies at the University of Wisconsin that were funded by Nabi Biopharmaceuticals."

8. In a December 2010 article on treatment for smoking cessation published in the Wisconsin Medical Journal, the conflict of interest statement regarding Dr. Fiore acknowledges that: "Over the last 3 years, Dr Fiore has served as an investigator in research studies at the University of Wisconsin that were funded by Pfizer and Nabi Biopharmaceuticals."

Amazingly, none of these conflicts of interest are reported in the paper and the reader has no way of knowing this long history of financial conflicts of interest with Big Pharma. I imagine that most readers would be shocked to find out about this intense and long history of financial conflict with Big Pharma, given that Dr. Fiore reported no conflicts of interest.

Dr. Baker

The truth is that Dr. Baker also has a long and significant history of financial relationships with pharmaceutical companies that manufacture smoking cessation drugs. Here is what is being hidden from readers:

1. In 2008, Dr. Baker reported that: "he has served as a co-investigator on research studies at the University of Wisconsin that were sponsored by four pharmaceutical companies."

2. In 2000, Dr. Baker disclosed as follows: "Timothy Baker has served as a consultant for, given lectures sponsored by, or has conducted research sponsored by Elan Pharmaceutical, SmithKline Beecham, Glaxo Wellcome, and Lederle."

3. As recently as 2012, Dr. Baker disclosed in an article that his research involved financial support from GlaxoSmithKline in the form of free medication provided to study participants.

4. In another 2012 paper, Dr. Baker also acknowledged that GlaxoSmithKline provided financial support in the form of free study medication. The same disclosure was made in another 2012 paper. And in another paper as well.

5. According to a 2011 paper: "Timothy B. Baker has served as a consultant, given lectures sponsored by, or has conducted research sponsored by GlaxoSmithKline, Nabi Biopharmaceuticals, Pfizer, and Sanofi-Synthelabo."

6. In a 2010 paper, Dr. Baker acknowledged "research grants from Pfizer, GlaxoSmithKline, Nabi Biopharmaceuticals, and Sanofi."That paper itself involved research with financial support from GlaxoSmithKline in the form of free study medication.

Again, amazingly, none of these conflicts of interest are reported in the paper and the reader has no way of knowing this long history of financial conflicts of interest with Big Pharma.

Summary

For years, we in tobacco control have attacked tobacco industry-funded scientists or researchers who consulted for tobacco companies for not disclosing their conflicts of interest. It is therefore quite unfortunate, and ironic, that tobacco control researchers do not appear to take their own conflicts of interest seriously and that they, too, are hiding these conflicts from the public.

As I previously articulated, the hiding of these conflicts of interest damages public health in four ways:

1. It violates public health ethics and could be damaging to the entire field of tobacco control;
2. It degrades the research integrity of tobacco control;
3. It makes us hypocrites when we criticize failed tobacco industry disclosures; and
4. It hides the influence of Big Pharma money on the field of tobacco control and hinders smoking cessation efforts.

Chair of NIH Smoking Cessation Panel May Have Made Incomplete Conflict of Interest Disclosures

According to his own sworn testimony, the chair of the expert panel which in 2008 released national recommendations for the use of smoking cessation medications by physicians received (at the time) up to $50,000 in annual resources from GlaxoSmithKline to support his educational, research, and policy activities.

In addition, according to his own 2008 JAMA article: "In the past 5 years, Dr Fiore reports that he has lectured and consulted for Pfizer and has served as an investigator on research studies at the University of Wisconsin (UW) that were supported by GlaxoSmithKline, Nabi, Pfizer, and sanofi-aventis."

The Rest of the Story

Despite this huge financial conflict of interest with Big Pharma, the panel chair - Dr. Michael Fiore - failed to recuse himself from the panel and the panel organizers failed to remove him from the panel.

But perhaps even worse, Dr. Fiore apparently failed to disclose all of his financial conflicts of interest in his initial financial disclosure required for his participation on the panel. The disclosure form asks for "complete" disclosure of all conflicts over the past 5 years. On the form, Dr. Fiore denied any current honoraria or consulting arrangements with pharmaceutical companies, but apparently failed to disclose the fact (based on his own testimony) that: "I have done some consulting work for pharmaceutical companies over the years. Over the past five years, my outside consulting work on an annual basis has ranged between about $10,000 and $30,000 or $40,000 per year."

The financial disclosure form asked for disclosure of all conflicts of interest in the past five years. The financial disclosure form for the Clinical Practice Guideline was signed in 2006, meaning that Dr. Fiore should have disclosed any and all consulting work with pharmaceutical companies dating back to 2001. Dr. Fiore's testimony in the DOJ lawsuit was in 2005, meaning that he admitted doing pharmaceutical consulting work during the period 2001-2005 ranging between $10,000 and $40,000 per year. I do not find this consulting work disclosed on the primary financial disclosure form signed by Dr. Fiore on September 5, 2006.

Although the form does note that Dr. Fiore was named to an endowed Chair position made possible by an unrestricted gift from GlaxoWellcome, the disclosure fails to mention that receives up to $50,000 in annual resources from GlaxoSmithKline to support his educational, research, and policy activities.

According to his testimony in the Department of Justice tobacco lawsuit: "GlaxoSmithKline gave a grant to the University of Wisconsin that established a chair for the treatment of tobacco dependence. That donation by GlaxoSmithKline was to the University. Named chairs at the University of Wisconsin provide the person who sits in that chair to access to the revenue generated from the investment on the initial grant. So in this instance, I have access to up to $50,000 per year to support my University approved and sanctioned educational, research, and policy activities."

A Wall Street Journal article of February 8, 2007 reports that: "Between 1999 and 2004, Dr. Fiore personally pocketed $10,000 to $40,000 a year from the quitting-aid industry for honorariums and consulting work. He says he stopped such work in 2005." This article corroborates the information from other sources that Dr. Fiore had pharmaceutical-related consultancy income for the years 2002-2004 that should have been reported on the Clinical Practice Guideline initial disclosure form.

Thus, in the five-year period asked about in the primary disclosure form for the panel, it appears that Dr. Fiore should, at very least, have reported his lectures and consultation for Pfizer. In addition, it appears that he also should have reported his serving as an investigator on research grants funded by four pharmaceutical companies.

I do not understand why it appears that Dr. Fiore failed to disclose his consultant work for pharmaceutical companies on the primary disclosure form. In his testimony, he acknowledges receiving between $10,000 and $40,000 annually from pharmaceutical companies for consulting work during the period 2001-2005. However, I would interpret his primary financial disclosure form to indicate that he has not done any consultant work for the pharmaceutical companies for the past 5 years (that is, from 2002-2006). This appears to be inconsistent with the testimony, and therefore it appears to be inaccurate.

The disclosure form states: "In keeping with recent JAMA recommendations, Dr. Fiore does not accept honorarium nor do consulting work for the pharmaceutical industry."

Since the form requires disclosure of all financial interests during the past 5 years, the interpretation of this disclosure statement is that Dr. Fiore does not currently do consulting work for the pharmaceutical industry, and has not done such consulting work for the past 5 years.

Based on Dr. Fiore's testimony, this appears not to be true. Thus, this appears to be a dishonest, or at very least, a severely flawed and incomplete disclosure.

The fact that Dr. Fiore later disclosed 2005 consultant payments from one pharmaceutical company does not compensate for the failure to disclose similar conflicts during the years 2002-2006, which were specifically asked about in the primary disclosure form.

A second apparent failed disclosure of Dr. Fiore's financial conflicts of interest is an article in a 2008 issue of the American Journal of Public Health. Dr. Fiore and co-authors examine the effect of smoking cessation media campaigns among socioeconomically advantaged and disadvantaged populations (see: Niederdeppe J., Fiore MC, Baker TB, Smith SS. Smoking-cessation media campaigns and their effectiveness among socioeconomically advantaged and disadvantaged populations. Am J Public Health 2008; 98:916-924).

In the paper, the authors make a push for increased access to pharmaceutical treatment for smoking cessation. They point out that access to these pharmaceuticals is a major barrier for less-educated populations: "Less-educated populations face more barriers in turning a quit attempt into smoking abstinence, including fewer smoking restrictions at work, greater nicotine dependence, and less access to evidence-based treatments. Future campaigns should keep these barriers in mind when developing campaigns to promote quitting among lower-SES populations."

The paper's push for greater access to pharmaceuticals does not come from authors who are objective. In fact, Dr. Fiore has a history of very close financial connections to a number of pharmaceutical companies which manufacture smoking cessation products and thus stand to gain financially if his advice is heeded. However, these financial relationships are not disclosed anywhere in the paper.

The paper does acknowledge financial support from the Robert Wood Johnson Foundation and from the National Institutes of Health. However, it does not disclose the financial conflicts of interest of Dr. Fiore. It appears that there is really no way for article readers to know that Dr. Fiore has had severe conflicts of interest which could lead them to question his objectivity in making a recommendation for the greater use of pharmaceuticals. I find this to be quite unfortunate.

Whether Dr. Fiore has important conflicts of interest that ought to be disclosed does not seem to be at issue here. Because in an article published on almost the exact same day as the AJPH article, Dr. Fiore discloses in a 2008 JAMA article that he does indeed have important conflicts of interest. That article states: "In the past 5 years, Dr Fiore reports that he has lectured and consulted for Pfizer and has served as an investigator on research studies at the University of Wisconsin (UW) that were supported by GlaxoSmithKline, Nabi, Pfizer, and sanofi-aventis. In 1998, the UW appointed him to a named chair, made possible by an unrestricted gift to the UW from GlaxoWellcome."

Does it not seem important for readers of his AJPH article to also know that Dr. Fiore has lectured and consulted for companies which manufacture smoking cessation products and that his chair position was endowed by one such pharmaceutical company?

In my opinion, this is unfortunate. I believe it represents a failed disclosure of an important conflict of interest. I suppose it is possible that Dr. Fiore did disclose the conflict but AJPH chose not to publish it. However, it seems to me that an author can insist that the journal include such a disclosure statement in the Acknowledgments section of the article.

To be clear, I am not suggesting that there was anything more than a mistake - a failed disclosure - made in these two situations. I'm not arguing that there was wrongdoing or violation of any policy or rule. However, the fact that the readers of the AJPH article are not immediately aware of the conflict of interest is problematic. As is the fact that the initial disclosure for the expert panel appears to be incomplete.

While I do not necessarily think there is anything wrong with accepting money from pharmaceutical companies to examine the use and effectiveness of their products, I do think it is wrong when such conflicts of interest are not disclosed to the public. And I think these conflicts need to be disclosed in all relevant publications, not just some of them.

Because of the importance of this issue, I would certainly hope that Dr. Fiore would correct these two failed or incomplete conflict of interest disclosures. Everyone makes mistakes (I have made my share) and mistakes may be particularly common with conflict of interest disclosures. However, the most important thing is that once a mistake is identified, the individual promptly corrects that mistake. I do not hold these apparent mistakes against Dr. Fiore. I do, however, think that they must be corrected. And I think that such complete transparency and honesty is necessary not because of any individual wrongdoing, but because the integrity of our national policy regarding smoking cessation depends on it.

Financial Conflict of Interest Not Disclosed in Article on Smoking Cessation; Another Example of Failed Disclosure in Tobacco Control Research

In an article in this month's issue of the American Journal of Public Health, Dr. Michael Fiore of the Center for Tobacco Research and Intervention at the University of Wisconsin and co-authors examine the effect of smoking cessation media campaigns among socioeconomically advantaged and disadvantaged populations (see: Niederdeppe J., Fiore MC, Baker TB, Smith SS. Smoking-cessation media campaigns and their effectiveness among socioeconomically advantaged and disadvantaged populations. Am J Public Health 2008; 98:916-924).

In the paper, the authors make a push for increased access to pharmaceutical treatment for smoking cessation. They point out that access to these pharmaceuticals is a major barrier for less-educated populations: "Less-educated populations face more barriers in turning a quit attempt into smoking abstinence, including fewer smoking restrictions at work, greater nicotine dependence, and less access to evidence-based treatments. Future campaigns should keep these barriers in mind when developing campaigns to promote quitting among lower-SES populations."

The Rest of the Story

The paper's push for greater access to pharmaceuticals does not come from authors who are objective. In fact, Dr. Fiore has a history of very close financial connections to a number of pharmaceutical companies which manufacture smoking cessation products and thus stand to gain financially if his advice is heeded. However, these financial relationships are not disclosed anywhere in the paper.

The paper does acknowledge financial support from the Robert Wood Johnson Foundation and from the National Institutes of Health. However, it does not disclose the financial conflicts of interest of Dr. Fiore. It appears that there is really no way for article readers to know that Dr. Fiore has had severe conflicts of interest which could lead them to question his objectivity in making a recommendation for the greater use of pharmaceuticals. I find this to be quite unfortunate.

Whether Dr. Fiore has important conflicts of interest that ought to be disclosed does not seem to be at issue here. Because in an article published on almost the exact same day as the AJPH article, Dr. Fiore discloses in a JAMA article that he does indeed have important conflicts of interest. That article states: "In the past 5 years, Dr Fiore reports that he has lectured and consulted for Pfizer and has served as an investigator on research studies at the University of Wisconsin (UW) that were supported by GlaxoSmithKline, Nabi, Pfizer, and sanofi-aventis. In 1998, the UW appointed him to a named chair, made possible by an unrestricted gift to the UW from GlaxoWellcome."

Does it not seem mildly important for readers of his AJPH article to know that Dr. Fiore has lectured and consulted for companies which manufacture smoking cessation products and that his chair position was endowed by one such pharmaceutical company?

In my opinion, this is inappropriate. I believe it represents another failed disclosure of conflict of interest in tobacco control research.

While I do not necessarily think there is anything wrong with accepting money from pharmaceutical companies to examine the use and effectiveness of their products, I do think it is wrong when such conflicts of interest are not disclosed to the public. And I think these conflicts need to be disclosed in all relevant publications, not just some of them.

New Study Shows that Quitline Cessation Counseling is of No Value for Young Adult Smokers

An article published in the May issue of Nicotine & Tobacco Research reports the results of a clinical trial of a quitline-based smoking cessation counseling intervention among young adult smokers ages 18-24. The article reports no significant effect of the intervention on attempted quitting or successful quitting.

(See: Sims TH, McAfee T, Fraser DL, Baker TB, Fiore MC, Smith SS. Quitline cessation counseling for young adult smokers: a randomized clinical trial. Nicotine & Tobacco Research 2013; 15(5): 932-941.)

The study's methods are described as follows: "This was a 2-group randomized clinical trial. The quitline-based counseling intervention (CI) included up to 4 proactive telephone counseling sessions; participants in the self-help (SH) group received only mailed cessation materials. Participants included 410 young adults who had smoked at least 1 cigarette in the past 30 days and who called the Wisconsin Tobacco Quit Line (WTQL) for help with quitting. Primary study outcomes included whether or not a quit date was set, whether or not a serious quit attempt was undertaken, and self-reported 7-day point-prevalence abstinence at 1-, 3-, and 6-month postenrollment."

The results were as follows: "Relative to self-help, quitline counseling motivated young adults to set a quit date but abstinence rates were not improved."

The Rest of the Story

Although quitlines are the mainstay of current tobacco control approaches to smoking cessation, this study shows no evidence that this approach has any value for the young adult smoking population. Yong adults who participated in the quitline counseling program were no more likely to try to quit and were no more likely to actually quit.

It is interesting that rather than concluding that more effective methods of motivating young adult smokers to quit are necessary, the study concludes that: "Research is needed on how to motivate young adult smokers to seek cessation treatment including quitline services."

If quitline services don't work for this population, then why do we need better ways of getting young adult smokers to use quitline services?

The answer appears to be simple:

We don't. However, one of the study authors has a conflict of interest by virtue of having owned stock in Free & Clear, the quitline vendor used by the vendor in this study. This study author was also employed by Free & Clear in the past. And the University of Wisconsin paid Free & Clear through a grant subcontract during the study, which supported this co-author.

Thus, this conflict of interest has the appearance of creating a bias in the paper's recommendations. Rather than stick with the study findings, the paper ignores those findings and recommends that we continue to focus on quitlines as a smoking cessation intervention for young adults. This flies in the face of the evidence presented within the paper itself, which shows no benefit, even with a rather intensive counseling intervention.

It is also interesting that two of the co-authors (Dr. Fiore and Dr. Baker) report no conflicts of interest.

However, in a 2008 article, Dr. Fiore acknowledged: "In the past 5 years, Dr Fiore reports that he has lectured and consulted for Pfizer and has served as an investigator on research studies at the University of Wisconsin (UW) that were supported by GlaxoSmithKline, Nabi, Pfizer, and sanofi-aventis. In 1998, the UW appointed him to a named chair, made possible by an unrestricted gift to the UW from GlaxoWellcome."

Also in 2008, Dr. Baker reported that: "reported that he has served as a co-investigator on research studies at the University of Wisconsin that were sponsored by four pharmaceutical companies."

Why weren't these financial conflicts of interest with Big Pharma disclosed in the current article? Certainly they represent a conflict because Big Pharma stands to lose substantially if quitlines drop out of favor as a focus for the nation's smoking cessation strategy. And although it appears that neither of these co-authors has maintained pharmaceutical company funding or consulting over the past 5 years, I see no reason why these prior conflicts are not relevant to readers of the study.

If a former tobacco industry consultant published an article, would anti-smoking advocates be comfortable with that individual not disclosing his prior financial relationship with Big Tobacco? I doubt it.

The rest of the story is that: (1) this article provides evidence that quitline-based cessation counseling is of no value for young adult smokers; (2) that there is an apparent bias in the article's recommendation that appears to be related to a financial conflict of interest of one of the study authors; and (3) that two of the study authors are failing to report a prior conflict of interest that is very relevant to the current study.

More on Failed Disclosures: Even Former Tobacco Industry-Funded Scientists Disclose their Past History of Financial Conflicts

In 2014, Dr. Roger Jenkins was co-author of an article published in the European Journal of Applied Physiology on acute cardiovascular reactions to inhaled particles. The study tested exposures to a variety of pollutants, including tobacco smoke. This journal uses the ICJME conflict of interest disclosure form (similar to that used by JAMA).

Background Information: Dr. Jenkins officially retired in 2004 from the Oak Ridge National Laboratory, where he conducted research that was funded, in part, by tobacco companies. Until 2008, he served as an expert witness to the tobacco industry. However, during the five years prior to publication of this article, he did not testify in litigation and was no longer employed at Oak Ridge. Thus, he had no personal conflicts of interest for the past five years.

Question: Should Dr. Jenkins have disclosed his history of past conflicts, dating back to 2008, in this 2014 article?

As I revealed over the past two days, in a similar situation, a number of smoking cessation drug researchers who had a history of funding from pharmaceutical companies failed to disclose those relationships, presumably because they were not active for the past 36 months, and item 3 of the ICJME form asks for a disclosure of conflicts within the past 36 months.

So according to this reasoning, there was no requirement for Dr. Jenkins to disclose his past history of tobacco industry funding and his having served as an expert witness for the industry in litigation.

To be sure, failure to disclose these past financial interests would be deceptive to journal readers, and without a doubt, anti-smoking groups would attack Dr. Jenkins for hiding this important information from the public. We certainly expect that past relationships with tobacco companies should be disclosed, even if they are no longer in place and have not been in place for several years.

The Rest of the Story

In contrast to the anti-smoking researchers, who failed to disclose their extensive history of funding from pharmaceutical companies, Dr. Jenkins did disclose the potential conflicts that were present more than five years earlier, but were not currently active, since he had retired 10 years earlier and had not testified for the past five years. Nevertheless, he disclosed that he "acted as an expert witness in tobacco industry-related litigation from 1997 to 2008."

Contrast this with the disclosures of several of the co-authors of articles published in 2016 in Addiction and JAMA:

1. In a recent set of two articles on treatment for smoking cessation published in the Annals of Behavioral Medicine in April 2011 (article 1; article 2), the conflict of interest statement regarding Dr. Fiore acknowledges that: "Over the last 3 years, Michael C. Fiore served as an investigator on research studies at the University of Wisconsin that were funded by Nabi Biopharmaceuticals."

However, in the recently published JAMA article, Dr. Fiore states that he has no conflicts of interest to disclose. And in the Addiction articles, he states that he has "received no direct or indirect funding from ... the tobacco, alcohol, pharmaceutical or gaming industries."

2. In a 2010 paper, Dr. Baker acknowledged "research grants from Pfizer, GlaxoSmithKline, Nabi Biopharmaceuticals, and Sanofi." That paper itself involved research with financial support from GlaxoSmithKline in the form of free study medication.

However, in the recently published JAMA article, Dr. Baker states that he has no conflicts of interest to disclose. And in the Addiction articles, he states that he has "received no direct or indirect funding from ... the tobacco, alcohol, pharmaceutical or gaming industries."

3. As recently as 2012, Dr. Jorenby disclosed in an article that his research involved financial support from GlaxoSmithKline in the form of free medication provided to study participants, and in a 2011 publication, Dr. Jorenby disclosed that the study was funded by Nabi Biopharmaceuticals.

However, in the recently published Addiction articles, Dr. Jorenby states that he has "received no direct or indirect funding from ... the tobacco, alcohol, pharmaceutical or gaming industries."

Why This is So Important

For decades, we in tobacco control have attacked tobacco industry-funded researchers for failing to disclose their relationships with tobacco companies. But it goes much further than that. The tobacco companies were found guilty of violating the RICO statute in large part because of industry-funded scientists failing to disclose these relationships.

In fact, in her final opinion in the DOJ lawsuit against the tobacco companies, Judge Kessler included an entire section entitled: "The Industry's ETS Consultants Cited and/or Published Without Disclosure of Tobacco Industry Ties." Judge Kessler wrote a 43-page section on scientists' failed disclosures of conflicts of interest.

In the case of the tobacco industry, these failed disclosures seriously undermined the public's health. They led to many policy makers believing that secondhand smoke was not harmful, which delayed or prevented the adoption of smoke-free policies to protect the public from exposure to secondhand smoke.

In large part, the reason why virtually all scientific journals have conflict of interest policies now is this past history of failed disclosures of scientists' ties to the tobacco companies.

It is for this reason that it becomes so imperative for us, as scientists in the tobacco control movement, to disclose our own conflicts of interest. It would seem highly hypocritical for us to demand that past relationships with tobacco companies need to be disclosed but that past relationships with pharmaceutical companies can remain hidden. No one is suggesting that the public health implications are the same; however, the principle is.

Ultimately, if we want the public to take seriously our efforts to protect the integrity of science from influence by corporations which have a vested interest in influencing the public's opinion about the safety of their products, then it becomes critical that we set the example by being transparent about our own conflicts of interest.

NIH Expert Panel Recommends Smoking Cessation Pharmaceuticals for Every Smoking Patient; Panel Chair and 8 Members Have Financial Ties to Big Pharma

An NIH expert panel this week released a 2008 update of the clinical practice guideline regarding the treatment of tobacco use and dependence (see: Fiore MC, Jaén CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. May 2008).

The guideline recommends that every patient who wishes to quit be treated with pharmaceuticals, unless medically contraindicated. The guideline also recommends the use of Chantix, despite concerns about its potential suicide risk, a risk that is currently being investigated by the FDA. Among the pharmaceuticals recommended by the panel are:

• buproprion;
• nicotine gum;
• nicotine patch;
• nicotine nasal spray;
• nicotine lozenge;
• nicotine inhaler;
  
• Chantix; and
  
• combinations of the above.

The Rest of the Story

Far from being an objective review and assessment of the best possible strategy to enhance smoking cessation among smokers in the United States, the guideline is a heavily biased analysis that is plagued by the presence of severe financial conflicts of interests among the panel's chair and at least 8 of its other members.

These 9 panel members have received, or are currently receiving, funding from pharmaceutical companies. Most of the involved companies stand to gain from the clinical practice guideline's recommendations, because these companies manufacture drugs recommended by the panel.

Here is the long list of financial conflicts of interest among this supposedly objective panel of expert scientists:

Michael C. Fiore: "reported that he served as an investigator on research studies at the University of Wisconsin (UW) that were supported wholly or in part by four pharmaceutical companies, and in 2005 received compensation from one pharmaceutical company. In addition, he reported that, in 1998, the UW appointed him to a named Chair, which was made possible by an unrestricted gift to the UW from GlaxoWellcome."

William C. Bailey: "reported significant financial interests in the form of compensation from three different pharmaceutical companies in 2006 and two in 2007 for speaking engagements."

Timothy B. Baker: "reported that he has served as a co-investigator on research studies at the University of Wisconsin that were sponsored by four pharmaceutical companies."

Neal L. Benowitz: "reported significant financial interest in the form of compensation from one pharmaceutical company for each of the years 2005-2007, as well as stock ownership in one pharmaceutical company."

Michael G. Goldstein: "reported that his employer received support from Bayer Pharmaceutical prior to 2005 and that he was employed by Bayer Pharmaceutical Corporation prior to January 1, 2005. His organization received payments for his professional services from two pharmaceutical companies and one commercial Internet smoking cessation site during the period 2005-2007."

Harry A. Lando: "reported serving on an advisory panel for a new tobacco use cessation medication and attending 2-day meetings in 2005 and 2006 as a member of this panel."

C. Tracy Orleans: "reported significant financial interests in the form of a dependent child who owns pharmaceutical stock... ."

Maxine L. Stitzer: "reported participation on a pharmaceutical scientific advisory panel for a new tobacco use cessation medication."

Sally Faith Dorfman: "reported her employment by Ferring Pharmaceuticals, Inc., a company whose business does not relate to treating tobacco dependence."

GlaxoWellcome, which apparently endowed the Chair position that the chair of the panel enjoys, is the manufacturer of Wellbutrin, Commit lozenge, Committed Quitters, NiQuitin/Nicoderm, Nicabate, and Nicorette. The use of all of these drugs is recommended by the panel.

What this means is that we basically have a group of experts who are largely financially linked with pharmaceutical companies, and who stand to gain personally if they recommend the use of pharmaceuticals as part of their smoking cessation guidelines. The more use of pharmaceuticals they recommend, the more they stand to gain.

This is a conflict of interest in the ugliest way that I can imagine. It is precisely the type of thing that needs to be stopped.

Ironically, it is the Department of Health and Human Services, the Public Health Service, and NIH itself which are regulating conflicts of interest among America's medical researchers. To have such a huge conflict of interest in its own supported work is unconscionable.

While I find it objectionable that these agencies would allow experts with these type of financial conflicts of interest to serve on the panel, I find it equally troubling that such individuals would agree to serve. I believe that based on these conflicts, these experts should have recused themselves from service on the panel.

The conflict in this case is not just a hypothetical one. It reveals itself in the extreme bias of the guideline. The analysis over-estimates the benefit of drugs in smoking cessation and overlooks population-based evidence showing that most people who quit smoking do so without pharmaceutical aids.

As my colleague Dr. Lois Biener of the University of Massachusetts Boston argued in an Associated Press article about the guideline, there is little if any "real-world evidence" that when used outside the context of clinical trials, drugs produce any long-term enhancement of smoking cessation, and certainly not the magnitude of benefit as suggested by those who are touting the importance of these drugs.

According to the article: "Lois Biener, a researcher of tobacco use and control efforts at the University of Massachusetts in Boston, said most people who quit do so without smoking-cessation drugs. There's little evidence that these drugs are superior in the long run to quitting without help, and while a few studies have shown some benefit, it's 'way less than what is claimed' by medication advocates, Biener said."

One national expert on smoking cessation who was not on the panel - John Polito - suggested in the article that the guideline is basically a "sales pitch" for the pharmaceutical industry, that the benefits of pharmaceuticals are overstated, that the value of quitting cold turkey is not considered, and that the recommendation to promote Chantix use is misguided and could cause harm.

According to the article: "Fiore's views are shaped by his past ties to the drug industry, and those ties still pose a conflict, at least one consumer advocate said. John Polito, a smoking cessation educator who runs the WhyQuit.com site advocating quitting 'cold turkey,' called the revised guidelines 'a sales pitch' for the drug industry. The task force overlooked research showing that quitting cold turkey works, Polito said, and studies showing Chantix is superior don't reflect how it's used 'in the real world.' 'People are quitting smoking to save their lives,' Polito said. If Chantix's risks outweigh its benefits, 'then it's insane for people to risk their lives' by using it, he said."

Polito has really stated it better than I could and he is right on the mark. The guideline is basically a sales pitch for the pharmaceutical industry, and it demonstrates what corporations can buy through their payments to scientific experts.

What's most disturbing to me is that while the medical field continues to move to decrease the influence of pharmaceutical companies on physicians by restricting financial benefits for doctors, the tobacco control field seems to be increasingly plagued by this pharmaceutical influence. The problem is being ameliorated in medicine, but in tobacco control, it continues to get worse.

The ultimate irony of all of this is that we in tobacco control have been so vehement in decrying the tobacco industry's influence on science. We have attacked and berated scientists for having financial ties to tobacco companies. We have discredited scientific conclusions based solely on the financial connections of the authors to Big Tobacco. But now, our national policies are being set by individuals who have equally strong connections to Big Pharma.

It may come as a surprise to many in tobacco control, but this type of science is just as bad. Bad science is bad science. Conflicts of interest are conflicts of interest. Believe me, the science doesn't get any stronger just because it is a less detestable industry. As a field which has literally helped to ruin the careers of scientists with tobacco industry connections, we should be beyond reproach in not allowing similar conflicts of interest to degrade and poison our science.

Why Do Anti-Smoking Groups and Researchers Recommend Pharmaceutical Cessation Aids for Every Patient When Unaided Quitting is More Effective?

Not long ago, an NIH expert panel released a 2008 update of the clinical practice guideline regarding the treatment of tobacco use and dependence (see: Fiore MC, Jaén CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. May 2008).

The guideline recommends that every patient who wishes to quit be treated with pharmaceuticals, unless medically contraindicated. The guideline also recommends the use of Chantix, despite concerns about its potential suicide risk, a risk that is currently being investigated by the FDA. Among the pharmaceuticals recommended by the panel are:

• buproprion;
• nicotine gum;
• nicotine patch;
• nicotine nasal spray;
• nicotine lozenge;
• nicotine inhaler;
  
• Chantix; and
  
• combinations of the above.

The expert panel was supposedly guided by scientific evidence in drawing its conclusions. It chose to recommend the use of pharmaceutical aids for every individual trying to quit smoking, presumably, due to research showing that drug-aided cessation is more effective than unaided cessation.

Many national anti-smoking groups have echoed the expert panel's recommendations. To be sure, pharmaceutical-aided smoking cessation is at the core of the national tobacco control movement's strategy and recommendations.

The Rest of the Story

But what does the scientific evidence show?

Those who have read the Clinical Practice Guideline on smoking cessation treatment may be shocked to find out that the scientific evidence clearly shows that unaided smoking cessation is substantially more effective than pharmaceutical-aided cessation.

For example, Larabie found that smokers who quit unaided were 2.3 times more likely to succeed than those who quit using pharmaceutical aids. Contrary to the dogma expressed in the smoking cessation expert panel report, unplanned quit attempts were found to be more successful than planned quit attempts. The paper concludes that in light of this finding: "the current guidelines may be hindering, rather than assisting successful smoking cessation." This research has important implications for the type of advice that health professionals deliver to patients regarding smoking cessation. The appropriate recommendations, however, are completely at odds with those presented in the expert panel report.

In a similar study by West and Sohal, unplanned quit attempts were found to be 2.5-2.6 times more likely to be successful than planned quit attempts.

To be sure, nicotine replacement therapy is known to be dismally effective in treating smoking dependence. Among smokers who are not particularly motivated to quit, the six-month success rate for nicotine replacement therapy is a dismal 6.8%.

Why would the NIH expert panel and major anti-smoking groups recommend drug-aided cessation when this strategy has been shown to be less effective than unaided cessation, and when even short-term success rates among unmotivated smokers are as low as 7%? This means that our national experts are recommending a treatment that fails 93% of the time! Even worse, they are recommending a treatment that fails 93% of the time when there is an alternative which has been clearly shown to be more than twice as effective.

The Answer

The answer to the question posed above, and in this post's title, is actually quite simple.

Far from being an objective review and assessment of the best possible strategy to enhance smoking cessation among smokers in the United States, the guideline is a heavily biased analysis that is plagued by the presence of severe financial conflicts of interests among the panel's chair and at least 8 of its other members.

These 9 panel members have received, or are currently receiving, funding from pharmaceutical companies. Most of the involved companies stand to gain from the clinical practice guideline's recommendations, because these companies manufacture drugs recommended by the panel.

Here is the long list of financial conflicts of interest among this supposedly objective panel of expert scientists:

Michael C. Fiore (panel chair): "reported that he served as an investigator on research studies at the University of Wisconsin (UW) that were supported wholly or in part by four pharmaceutical companies, and in 2005 received compensation from one pharmaceutical company. In addition, he reported that, in 1998, the UW appointed him to a named Chair, which was made possible by an unrestricted gift to the UW from GlaxoWellcome."

William C. Bailey: "reported significant financial interests in the form of compensation from three different pharmaceutical companies in 2006 and two in 2007 for speaking engagements."

Timothy B. Baker: "reported that he has served as a co-investigator on research studies at the University of Wisconsin that were sponsored by four pharmaceutical companies."

Neal L. Benowitz: "reported significant financial interest in the form of compensation from one pharmaceutical company for each of the years 2005-2007, as well as stock ownership in one pharmaceutical company."

Michael G. Goldstein: "reported that his employer received support from Bayer Pharmaceutical prior to 2005 and that he was employed by Bayer Pharmaceutical Corporation prior to January 1, 2005. His organization received payments for his professional services from two pharmaceutical companies and one commercial Internet smoking cessation site during the period 2005-2007."

Harry A. Lando: "reported serving on an advisory panel for a new tobacco use cessation medication and attending 2-day meetings in 2005 and 2006 as a member of this panel."

C. Tracy Orleans: "reported significant financial interests in the form of a dependent child who owns pharmaceutical stock... ."

Maxine L. Stitzer: "reported participation on a pharmaceutical scientific advisory panel for a new tobacco use cessation medication."

Sally Faith Dorfman: "reported her employment by Ferring Pharmaceuticals, Inc., a company whose business does not relate to treating tobacco dependence."

GlaxoWellcome, which apparently endowed the Chair position that the chair of the panel enjoys, is the manufacturer of Wellbutrin, Commit lozenge, Committed Quitters, NiQuitin/Nicoderm, Nicabate, and Nicorette. The use of all of these drugs is recommended by the panel.

What this means is that we basically have a group of experts who are largely financially linked with pharmaceutical companies, and who stand to gain personally if they recommend the use of pharmaceuticals as part of their smoking cessation guidelines. The more use of pharmaceuticals they recommend, the more they stand to gain.

This is a conflict of interest in the ugliest way that I can imagine. It is precisely the type of thing that needs to be stopped.

Ironically, it is the Department of Health and Human Services, the Public Health Service, and NIH itself which are regulating conflicts of interest among America's medical researchers. To have such a huge conflict of interest in its own supported work is unconscionable.

While I find it objectionable that these agencies would allow experts with these type of financial conflicts of interest to serve on the panel, I find it equally troubling that such individuals would agree to serve. I believe that based on these conflicts, these experts should have recused themselves from service on the panel.

The conflict in this case is not just a hypothetical one. It reveals itself in the extreme bias of the guideline. The analysis over-estimates the benefit of drugs in smoking cessation and overlooks population-based evidence showing that most people who quit smoking do so without pharmaceutical aids.

As my colleague Dr. Lois Biener of the University of Massachusetts Boston argued in an Associated Press article about the guideline, there is little if any "real-world evidence" that when used outside the context of clinical trials, drugs produce any long-term enhancement of smoking cessation, and certainly not the magnitude of benefit as suggested by those who are touting the importance of these drugs.

One national expert on smoking cessation who was not on the panel - John Polito - has suggested that the guideline is basically a "sales pitch" for the pharmaceutical industry, that the benefits of pharmaceuticals are overstated, that the value of quitting cold turkey is not considered, and that the recommendation to promote Chantix use is misguided and could cause harm.

Polito has really stated it better than I could and he is right on the mark. The guideline is basically a sales pitch for the pharmaceutical industry, and it demonstrates what corporations can buy through their payments to scientific experts.

What's most disturbing to me is that while the medical field continues to move to decrease the influence of pharmaceutical companies on physicians by restricting financial benefits for doctors, the tobacco control field seems to be increasingly plagued by this pharmaceutical influence. The problem is being ameliorated in medicine, but in tobacco control, it continues to get worse.

The ultimate irony of all of this is that we in tobacco control have been so vehement in decrying the tobacco industry's influence on science. We have attacked and berated scientists for having financial ties to tobacco companies. We have discredited scientific conclusions based solely on the financial connections of the authors to Big Tobacco. But now, our national policies are being set by individuals who have equally strong connections to Big Pharma.

It may come as a surprise to many in tobacco control, but this type of science is just as bad. Bad science is bad science. Conflicts of interest are conflicts of interest. Believe me, the science doesn't get any stronger just because it is a less detestable industry. As a field which has literally helped to ruin the careers of scientists with tobacco industry connections, we should be beyond reproach in not allowing similar conflicts of interest to degrade and poison our science.

Rest of the Story Calls for Removal of Chantix from the Market: FDA, Pfizer, and Anti-Smoking Groups Have Done Enough Damage to People's Lives

Today, I am calling for the FDA to remove Chantix from the market and for anti-smoking groups and researchers to demand that the FDA take such action.

It has become clear to me that the current black box warning is simply insufficient to protect the public from the significant and severe adverse side effects of Chantix.

The FDA responded to the more than 100 reports of suicides, more than 400 reports of violence, and more than 11,000 other cases of severe side effects associated with Chantix by requiring Pfizer to place a "black box" warning label on the medication. The label warns physicians to monitor their patients for adverse psychiatric effects, such as severe depression, violent behavior, and suicidality.

However, it has become clear to me that this black box warning is simply not sufficient. The severe and often deadly effects of Chantix can occur quickly and without warning. Many of the individuals who have died as a result of Chantix use committed suicide suddenly, without warning, and within just days after initiating therapy with this medication. Clearly, the black box warning was not sufficient. With a drug that can have such severe adverse effects in such a short time, it is simply impossible to appropriately monitor and prevent these effects from becoming lethal through physician monitoring. The effects appear too quickly and medical practice is not set up to conduct psychological testing every day for a one- to two-week period following initiation of medical therapy for smoking cessation.

Evidence published in January demonstrates that Chantix is most definitely not a safe drug. A study published in PLoS One reported that Chantix is the worst drug offender in terms of being associated with suicidal behavior and violence towards others. According to the research, Chantix has been associated with more than 400 cases of violence and more than 11,000 serious adverse effects. Chantix was associated with 18 times the number of violence cases as one would have expected by chance.

The study controlled for the possible increased tendency towards aggression among the population being treated with Chantix and the relationship between varenicline use and violence was still enormous. Thus, these effects seem to be a real side effect of Chantix use.

The article concludes: "Acts of violence towards others are a genuine and serious adverse drug event associated with a relatively small group of drugs. Varenicline, which increases the availability of dopamine, and antidepressants with serotonergic effects were the most strongly and consistently implicated drugs."

This research has led some to conclude that: "the message is clear that while Chantix can prove to be an effective weapon for chronic quitters (smokers who try various magic bullets to kick the habit, only to fail…), the costs to some in terms of Chantix aggression and other Chantix side effects can be potentially devastating."

According to a news article published in the March 2009 issue of the Journal of the American Medical Association (JAMA), evidence was already mounting at that time supporting the conclusion that use of the smoking cessation drug varenicline (Chantix) is associated with suicidal ideation and behavior in a substantial number of treated patients (see: Kuehn BM. Studies linking smoking-cessation drug with suicide risk spark concern. JAMA 2009;301(10):1007-1008).

According to the article: "A new analysis by the US Food and Drug Administration (FDA) adds to evidence that varenicline might be associated with an increased risk of suicidal thoughts and behavior, including among patients with no psychiatric history. The results, which were published in January, follow warnings from the agency that such a link is likely, as well as label changes noting a possible risk. ... An analysis of adverse event reports submitted to the FDA between May 2006 (when varenicline was approved) and November 2007 found 116 cases of suicidal ideation and 37 cases of suicidal behavior, more than half resulting in death. Half of the patients reporting either suicide ideation or suicidal behavior had a history of psychiatric problems, 26% had no such history, and 24% had an unknown psychiatric history."

Because there are many other treatments available for smoking cessation with similar effectiveness, I believe that the cost-benefit ratio for Chantix is now clearly on the side of the costs to society - even with the black box warning - and the drug should therefore be pulled from the market.

According to an article in Lawyers USA, there are now at least 200 lawsuits that have been filed by the families of plaintiffs who allege that their loved ones committed suicide as a result of taking the smoking cessation drug Chantix (varenicline) or by plaintiffs who attempted suicide after starting Chantix. These cases were filed by a single law firm, which is investigating another 1,200 cases. Another firm is investigating 175 similar cases.

The plaintiff's attorney was quoted in the article as describing the cases as follows: ""Tragically, almost without explanation, these people commit suicide, often without any prior diagnosis of family or individual history of depression, psychosis or any other type of psychological conditions."

According to the article: "On Feb. 1, 2008, the Food and Drug Administration issued an alert that 'serious neuropsychiatric symptoms have occurred in patients taking Chantix.' The symptoms include 'changes in behavior, agitation, depressed mood, suicidal ideation, and attempted and completed suicides.' 'It appears increasingly likely that there is an association between Chantix and serious neuropsychiatric symptoms,' the FDA stated. ..."

"A study in May 2008 by the Institute for Safe Medication Practices, a prescription drug watchdog group based near Philadelphia, reported that in the fourth quarter of 2007, varenicline accounted for 988 serious injuries reported to the FDA, more than any other single drug. ... The Federal Aviation Administration has banned pilots and air traffic controllers from using Chantix; the drug has also been banned for use by commercial drivers." ...

"On Feb. 1, 2008, Pfizer strengthened its Chantix labeling to include stronger warnings about neuropsychiatric symptoms. In May 2008, it revised the warning again, advising physicians to discontinue Chantix immediately if patients become agitated, depressed or suicidal."

However, discontinuing Chantix as a result of patients becoming suicidal is ineffective. If patients are suicidal and they commit suicide, it is too late to withdraw the medication. No physician's office is equipped to conduct the kind of day-to-day, intensive psychological monitoring that would be needed to make Pfizer's recommendation effective in preventing these severe adverse side effects.

The FDA cannot allow this black box warning to remain the only protection for patients, as it is woefully inadequate. The time has come to pull Chantix from the market.

The Rest of the Story

How ironic it is that the FDA is spending more time trying to ban electronic cigarettes - which have not caused a single reported death or severe adverse effect in the U.S. - but is sitting on its hands with regards to Chantix, which continues to kill people due to its effects on violence, aggression, depression, and suicidality.

And ironically, while five anti-smoking groups have called for the removal of electronic cigarettes from the market, none have called for the removal of Chantix, although the latter drug is actually killing people while the former is not.

For this reason, I argue that both the FDA and the anti-smoking groups bear major responsibility in the tragedy of Chantix-related suicide.

Also bearing responsibility, I believe, are the anti-smoking researchers who have been recommending the use of Chantix as part of a national smoking cessation strategy, but who had or have severe conflicts of interest by virtue of their receiving money from pharmaceutical companies that manufacture smoking cessation drugs, in particular - from Pfizer, the manufacturer of Chantix.

The Chantix experience serves as a poignant (and tragic) reminder of exactly why it is that financial conflicts of interest are not to be tolerated in the formation of national clinical treatment policy. The presence of financial conflicts of interest produces a bias (even if subconscious) that is unacceptable when recommendations are being made that affect people's lives (i.e., clinical practice).

The bias in the Clinical Practice Guideline panel's analysis is apparent when one considers the research documenting that the overwhelming majority of successful quit attempts are unplanned. The planning of quit attempts by patients with medication provided by their physicians is, on a population basis, one of the least effective methods of smoking cessation.
Planned quit attempts are actually less successful than attempts that are unplanned. National smoking cessation policy and treatment of patients should therefore be based on efforts to motivate patients sufficiently to quit cold turkey, rather than to plan quit attempts for them.

The bias created by financial conflicts of interest with Big Pharma in tobacco control continues and can be seen in numerous research articles. For example, in response to the article documenting that unplanned quit attempts are the most successful, a researcher from the University of Vermont challenges the conclusions of that study. What is not disclosed is the fact that in 2006, the same researcher "accepted honoraria, fees or travel expenses from Academy for Educational Development, Atrium Healthcare, Cambridge Hospital, Celtic Pharmaceuticals/Xenova, Concepts in Medicine, Cowen and Companies, Cygnus, Edelman Bioscience, Exchange Supplies Ltd., Fagerstrom Consulting, Free and Clear, Health Learning Systems, Healthwise, JSR, Insyght, LEK Consulting, Maine Medical Center, Nabi Pharmaceuticals, New York Association of Substance Abuse Providers, Nabi Biopharmaceuticals, National Institutes on Health; Pfizer/U.S., Pfizer Canada, Pinney Associates, Sanofi-Aventis, Shire Health London, Temple University of Health Sciences, University of Wisconsin and ZS Associates."

What at first glance might appear to be an unbiased assessment of the state of the research turns out instead to be written by someone who has received money from a large number of pharmaceutical companies, including several that have a direct financial stake in consumers making planned rather than unplanned quit attempts.

Not long ago, an NIH expert panel released a 2008 update of the clinical practice guideline regarding the treatment of tobacco use and dependence (see: Fiore MC, Jaén CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. May 2008).

The guideline recommends that every patient who wishes to quit be treated with pharmaceuticals, unless medically contraindicated. The guideline also recommends the use of Chantix, despite concerns about its potential suicide risk.

Far from being an objective review and assessment of the best possible strategy to enhance smoking cessation among smokers in the United States, the guideline is a heavily biased analysis that is plagued by the presence of severe financial conflicts of interests among the panel's chair and at least 8 of its other members.

Nine of the panel members have received, or are currently receiving, funding from pharmaceutical companies. Most of the involved companies stand to gain from the clinical practice guideline's recommendations, because these companies manufacture drugs recommended by the panel.

Here is the long list of financial conflicts of interest among this supposedly objective panel of expert scientists:

Michael C. Fiore (panel chair): "reported that he served as an investigator on research studies at the University of Wisconsin (UW) that were supported wholly or in part by four pharmaceutical companies, and in 2005 received compensation from one pharmaceutical company. In addition, he reported that, in 1998, the UW appointed him to a named Chair, which was made possible by an unrestricted gift to the UW from GlaxoWellcome."

William C. Bailey: "reported significant financial interests in the form of compensation from three different pharmaceutical companies in 2006 and two in 2007 for speaking engagements."

Timothy B. Baker: "reported that he has served as a co-investigator on research studies at the University of Wisconsin that were sponsored by four pharmaceutical companies."

Neal L. Benowitz: "reported significant financial interest in the form of compensation from one pharmaceutical company for each of the years 2005-2007, as well as stock ownership in one pharmaceutical company."

Michael G. Goldstein: "reported that his employer received support from Bayer Pharmaceutical prior to 2005 and that he was employed by Bayer Pharmaceutical Corporation prior to January 1, 2005. His organization received payments for his professional services from two pharmaceutical companies and one commercial Internet smoking cessation site during the period 2005-2007."

Harry A. Lando: "reported serving on an advisory panel for a new tobacco use cessation medication and attending 2-day meetings in 2005 and 2006 as a member of this panel."

C. Tracy Orleans: "reported significant financial interests in the form of a dependent child who owns pharmaceutical stock... ."

Maxine L. Stitzer: "reported participation on a pharmaceutical scientific advisory panel for a new tobacco use cessation medication."

Sally Faith Dorfman: "reported her employment by Ferring Pharmaceuticals, Inc., a company whose business does not relate to treating tobacco dependence."

GlaxoWellcome, which apparently endowed the Chair position that the chair of the panel enjoys, is the manufacturer of Wellbutrin, Commit lozenge, Committed Quitters, NiQuitin/Nicoderm, Nicabate, and Nicorette. The use of all of these drugs is recommended by the panel.

What this means is that we basically have a group of experts who are largely financially linked with pharmaceutical companies, and who stand to gain personally if they recommend the use of pharmaceuticals as part of their smoking cessation guidelines. The more use of pharmaceuticals they recommend, the more they stand to gain.

While I find it objectionable that these agencies would allow experts with these type of financial conflicts of interest to serve on the panel, I find it equally troubling that such individuals would agree to serve. I believe that based on these conflicts, these experts should have recused themselves from service on the panel.

This is a conflict of interest in the ugliest way that I can imagine. It is precisely the type of thing that needs to be stopped.

Perhaps the most troubling conflict of all is that of the expert panel's chair - Dr. Michael Fiore. Dr. Fiore has reported "that he has lectured and consulted for Pfizer and has served as an investigator on research studies at the University of Wisconsin (UW) that were supported by GlaxoSmithKline, Nabi, Pfizer, and sanofi-aventis." Pfizer is the company that markets Chantix.

That this panel made a national recommendation that all physicians use Chantix (and other drugs) to treat every smoker without specific contraindications and that this recommendation was made by a panel whose Chair had received money from Pfizer, is inexcusable. It is even more troubling that the panel has not issued any kind of update or warning to modify its recommendation that Chantix be used as a smoking cessation drug in light of the many reports of the deadly side effects that this medication has had.

The rest of the story is that the many Chantix-associated suicides are truly a tragedy, and they are even more tragic because the deaths that have been caused by Chantix would possibly have been prevented had the national panel not consisted of members with such severe financial conflicts of interest. Any kind of objective review of the data, in my opinion, would have precluded a national panel from recommending the use of this drug, given the many alternatives available that have similar effectiveness. At very least, an objective panel would have returned to this issue after - at the latest - the January 2011 report and issued a modification of the Clinical Practice Guideline retracting the recommendation that patients be treated with Chantix.

The central tenet of medicine and public health is "to do no harm." Sadly, this is a story in which physicians and public health practitioners have caused harm. While mistakes occur, and are excusable because people are only human and cannot predict the future, clouding scientific and policy issues by financial conflicts of interest that result in poor national recommendations is not acceptable. We owe the public a greater degree of scientific, medical, and public health integrity.