Last Friday, two tobacco companies - Lorillard and R.J. Reynolds - filed a lawsuit against the Food and Drug Administration (FDA) to enjoin the agency from relying upon any recommendations that come out of the Tobacco Products Scientific Advisory Committee (TPSAC). The suit alleges that the composition of the TPSAC is unlawful because three of the panelists have severe conflicts of interest which violate federal law, including the Federal Advisory Committee Act (FACA) regarding the presence of conflicts of interest among members of federal advisory bodies.
The tobacco companies argue that three members of the advisory panel - Dr. Neal Benowitz, Dr. Jack Henningfield, and Dr. Jon Samet - have severe conflicts of interest which preclude the panel from conducting a balanced and objective review of the scientific and policy issues it is charged with addressing.
The Federal Advisory Committee Act holds that all federal advisory panels (including TPSAC) must be "fairly balanced in terms of the points of view represented and the functions to be performed," and its members cannot have severe financial conflicts of interest such that the committee's assessments, reports, or recommendations and decisions will be "inappropriately influenced . . . by any special interest."
The plaintiff tobacco companies argue that Drs. Benowitz, Henningfield, and Samet have two severe conflicts of interest which put the committee's composition in violation of the Federal Advisory Committee Act:
First, the companies allege that these three members are conflicted because "they have made tens of thousands of dollars as paid expert witnesses in litigation against tobacco products manufacturers."
Second, the companies allege that Drs. Benowitz, Henningfield, and Samet are conflicted because of "their continuing financial relationships with pharmaceutical companies that make smoking-cessation products."
Regarding the financial conflicts of interests of these committee members with pharmaceutical companies that manufacture smoking cessation drugs, the plaintiffs allege as follows:
Dr. Benowitz: "Dr. Benowitz, as a paid consultant for pharmaceutical companies, has assisted them with the design, development, and marketing of smoking-cessation products. Among the companies for which he has consulted on such products are GlaxoSmithKline plc and its affiliates (collectively, “GSK”); Pfizer, Inc. and its affiliates (collectively, “Pfizer”); Novartis AG and its affiliates (collectively, “Novartis”); Sanofi-Aventis U.S. LLC and its affiliates (collectively, “Sanofi-Aventis”); and Aradigm Corp. and its affiliates (collectively, “Aradigm”). During the last ten years, he has received at least approximately $10,000 per year for such consulting. He has also received grant support for research and writing from GSK and/or Pfizer on at least five occasions. In 2010, he co-authored a study, funded by Pfizer, on the use of its drug, Chantix, for smoking cessation."
Dr. Henningfield: "Dr. Henningfield is a Principal at, and derives most of his income from, Pinney Associates, a firm that currently provides to GSK on an exclusive basis consulting services regarding smoking-cessation products. His formal title is: Vice President, Research & Health Policy. Through his association with Pinney Associates, Dr. Henningfield advises GSK specifically on the development of nicotine-replacement therapies and treatments for tobacco dependence. Pinney Associates has received on average more than $2 million per year in revenue from pharmaceutical companies, more than half of which relates to smoking-cessation products. In addition, during the last decade, Dr. Henningfield has received grant support for research and writing from GSK on at least eight occasions. Dr. Henningfield is also a partner in a company that holds patents for a nicotine replacement-therapy product. He has estimated that, if thess patents are successfully licensed, they could be worth more than $1 million to him as a partner in that company. Thus, Dr. Henningfield has a financial interest in bringing about regulatory policies that will drive current smokers to use nicotine-replacement-therapy products."
Dr. Samet: "During the last decade, Dr. Samet has received grant support for research and writing from GSK on at least six occasions, including in 2010. In addition, he formerly led the Institute for Global Tobacco Control, which is funded by GSK and Pfizer. Moreover, until 2009, Dr. Samet received regular honoraria from Pfizer for his service on the Pfizer Global Tobacco Advisory Board."
The plaintiffs then argue that "the continuing roles of Drs. Benowitz, Henningfield, and Samet as consultants to manufacturers of nicotine-replacement-therapy products and other smoking cessation products constitute circumstances that demonstrate their lack of impartiality, or at least raise questions regarding their impartiality, in particular matters that have been, are, and/or will be presented to them as voting members of the TPSAC, or as members of the Constituents Subcommittee. As to those expressed views, a reasonable person with knowledge of the relevant facts would perceive the appearance of a conflict of interest."
The reasons why these financial conflicts of interest would be expected to affect these panelists' consideration of, and opinions on, specific business before the advisory committee, is stated as follows:
"Manufacturers of nicotine-replacement-therapy products and other smoking cessation products, including the pharmaceutical companies, GSK, Pfizer, Novartis, Sanofi-Aventis, and Aradigm, are in direct competition with tobacco-product manufacturers for the purchasing choices of adult smokers. This competitive dynamic is reflected in the discussion at the March 31, 2010 meeting of the Committee of whether banning menthol from cigarettes would result in smokers trying to quit smoking, rather than switching to a non-menthol brand (Tr. 92 (public comment), 199-200 (committee discussion)). A ban or restriction on the sale of menthol cigarettes might increase the sales of nicotine-replacement-therapy products and other smoking-cessation products. Similarly, FDA regulations banning or further restricting the availability of dissolvable or other smokeless tobacco products might increase the sales of such products. The opportunities for Drs. Benowitz, Henningfield, and Samet to continue to obtain income from consulting with pharmaceutical companies with respect to nicotine replacement-therapy products and/or other smoking-cessation products depend on the continuing sales and profitability of such products. Therefore, these individuals have an interest in protecting and enhancing the sales and profitability of such products, and may consciously or unconsciously influence the other members of the TPSAC inappropriately to recommend bans on, or unduly strict regulation of, the smokeless tobacco products with which they compete. Even if these individuals did not influence the TPSAC in such a manner, their mere presence on the committee poses (and appears to pose) severe financial conflicts of interest because their remunerative relationships with pharmaceutical companies will prevent them from being (and from being perceived as) open-minded and from considering impartially the submissions and presentations to the TPSAC or Constituents Subcommittee by tobacco-product manufacturers and others."
The Rest of the Story
While I do not believe that the first grounds for the court declaring an impermissible conflict of interest among these three panelists is compelling because all scientists have existing opinions on issues and are entitled to serve as expert witnesses without precluding their participation in national scientific and policy issues, I believe that the second grounds - the existence of severe financial conflicts of interest by virtue of these panelists financial connections to pharmaceutical companies that manufacture smoking cessation products - is entirely compelling.
In fact, I revealed these conflicts of interest and called for the resignation of Drs. Henningfield, Benowitz, and Samet from the TPSAC panel in the first few days after the TPSAC members were announced by the FDA.
On March 1 of last year (the day the panel members were announced), I wrote a commentary entitled "GlaxoSmithKline Given a Seat on FDA Tobacco Products Scientific Advisory Committee" in which I argued that the presence of Dr. Henningfield on the committee rendered it impossible of conducting an objective review of any issue relating to harm reduction.
Specifically, I wrote: "The last individual in the world who you would want to serve on such a panel would be a Big Pharma consultant, especially one who consults specifically in the area of smoking cessation medications. The fact that this individual also has a personal financial interest in such medication and who also has testified in court on behalf of Big Pharma simply adds insult to the public's injury."
I argued that the appointment of Dr. Henningfield to TPSAC undermines the "entire point of the panel and turns the whole thing into a joke, rather than a serious scientific and policy undertaking for the benefit of the public's health."
I concluded: "These type of panels should consist of individual scientists who are impartial and do not have personal financial conflicts of interest with industry, especially if that industry is to be directly regulated by the FDA and if the use and profitability of its products will be directly affected by the national policy decisions that the Agency makes. For example, one issue that the FDA is going to have to deal with immediately is the regulation of electronic cigarettes. As these products are a tremendous threat to GlaxoSmithKline profits ... there is no way that the Scientific Advisory Committee can have an objective discussion about this issue. Unfortunately, the FDA has chosen to invite Big Pharma to the table. So much for an objective scientific panel."
On September 29, I called for the resignation of Drs. Henningfield, Benowitz, and Samet from the TPSAC panel because of their financial conflicts of interest with pharmaceutical companies that manufacture smoking cessation drugs, arguing that "it is inexcusable to have individuals on the Tobacco Products Scientific Advisory Committee (TPSAC) who have financial conflicts of interest with Big Pharma."
I pointed out that "the next major issue that TPSAC will consider (after menthol), in fact, is dissolvable tobacco products. Now that GlaxoSmithKline has come out in strong opposition to these products and directly petitioned the FDA to remove these products from the market, it is not possible for any TPSAC member who has a financial conflict of interest with Glaxo (or similar companies that manufacture smoking cessation products) to impartially participate in discussions on this matter. Due to the FDA's ignoring financial conflicts of interest in appointing the TPSAC panel, however, it turns out that Glaxo essentially has a seat on the panel." ...
"To make matters worse still, the chair of the Committee - Dr. Jonathan Samet - has received grant support from GlaxoSmithKline. In addition, the organization that he directed - the Institute for Global Tobacco Control - is funded by GlaxoSmithKline and Pfizer.
And to make matters even more unacceptable, a third member of the panel - Dr. Neal Benowitz - has consulted for GlaxoSmithKline. Dr. Benowitz also co-authored a study on the use of Chantix in smoking cessation which was funded by Pfizer and has served as a Pfizer consultant. In particular, Dr. Benowitz served as a Pfizer consultant on how to develop a scientific base to support the use of Chantix in smoking cessation. In addition to consulting for Glaxo, Benowitz has also consulted for Nabi Pharmaceuticals." ...
"Given GlaxoSmithKline's direct request to the FDA and given these ... panel members' significant conflicts of interest with Big Pharma, I call on these panel members to withdraw from the Tobacco Products Scientific Advisory Committee. Short of that, I call on the FDA to remove these members from the Committee and to replace them with unconflicted scientists who can make unbiased decisions about federal regulatory policy."
I think that Lorillard and R.J. Reynolds have put forward a very compelling argument that the TPSAC panel is not balanced and fair and that it cannot conduct an objective review of multiple specific areas before it because of severe, impermissible, financial conflicts of interest of Drs. Henningfield, Samet, and Benowitz.
Thus, although I am not swayed by the argument that Henningfield, Samet, and Benowitz should have been disqualified from the panel because they have served and continue to serve as expert witnesses in litigation against tobacco companies, I believe that the conflicts of interest with respect to pharmaceutical company funding are sufficient to render all three individuals ineligible for participation on the panel under federal law.
I therefore agree with the following major declarations that the plaintiffs are seeking from the Court:
"1. That the presence of Drs. Benowitz, Henningfield, and Samet as voting members of the TPSAC creates financial conflicts of interest that violate 18 U.S.C. §§ 202(a), 208; FDCA § 712, 21 U.S.C. § 379d-1; and 5 C.F.R. pts. 2635, 2640 (2010) because these individuals have financial interests that are disqualifying under these provisions of law."
2. "That the financial conflicts of interest of Drs. Benowitz, Henningfield, and Samet incapacitate the TPSAC from preparing a report on menthol in cigarettes that is unbiased and untainted by financial conflicts of interest."
3. "That the current voting membership of the TPSAC prevents the TPSAC from properly performing its broad statutory function of advising the Defendants with respect to issues relating to dissolvable tobacco products and other smokeless tobacco products because it does not represent the view of those members of the public-health and tobacco-control communities who have no financial or other ties to tobacco-product manufacturers (and so are not industry representatives of tobacco-product manufacturers), but who believe that current scientific knowledge about smokeless tobacco products shows that, now and in the future, at least some smokeless tobacco products can play a beneficial role in reducing the harm from tobacco in the United States."
4. "That, therefore, the current voting membership of the TPSAC violates 5 U.S.C. app. 2 § 5."
While I called for the resignation or dismissal of these panelists because of their conflicts of interest immediately after the TPSAC panel was announced, the FDA failed to pay heed to these concerns. Now, I'm afraid that the situation is exactly as Lorillard and R.J. Reynolds allege: the TPSAC is impermissibly constituted under federal law, it is not balanced and cannot make an objective recommendation regarding several specific issues before it, and it is unduly influenced by severe financial conflicts of interest among these three panelists.
For my complete commentaries on this issue, please see the following:
1. GlaxoSmithKline Given a Seat on FDA Tobacco Products Scientific Advisory Committee
2. Washington Ethics Group Calls for Investigation into Conflicts of Interest of Two FDA Tobacco Panelists, Citing Their Financial Ties to Big Pharma
3. GlaxoSmithKline Urges FDA to Take Dissolvable Tobacco Products Off the Market; Rest of the Story Calls on Four TPSAC Panel Members to Resign
4. FDA Guidelines for Determining Eligibility for Advisory Committees are Ridiculous and Ensure that Conflicts of Interest Will Continue to Plague Agency