Thursday, March 27, 2008

Smoked Out: Funding Lung Cancer Screening Research with Tobacco Money

A few weeks ago, we posted about conflicts of interest affecting a widely publicized study of using CT scans to screen for lung cancer. The study, basically a large case-series, was susceptible to multiple kinds of study bias that challenged its validity. Yet its authors used this limited and flawed data to strongly advocate such screening. Two lead study investigators, Dr Claudia Henschke and Dr David Yankelevitz of Weill Medical College of Cornell University, held multiple patents on technology used for the screening, and had licensed one patent to General Electric, a manufacturer of CT scans, and exchanged another for rights in a start-up manufacturer of lung biopsy devices. They did not disclose these conflicts in the articles they published describing study results, including one in the New England Journal of Medicine. We noted that perhaps these conflicts were related to the investigators' great enthusiasm for CT scan based lung cancer screening that went well beyond the data from their study.

Since then, the plot has thickened. A follow up article in the Cancer Letter(1) noted that the New England Journal of Medicine article which failed to disclose the authors' patents and licensing agreement also was a vehicle for continuing medical education (CME). Ethics rules for US CME require full disclosure of all authors' conflicts of interest. Futhermore, the authors had given multiple CME talks. Their disclosure of these conflicts was inconsistent across these talks. Thus, on the GoozNews blog, Merrill Goozner announced that "The Center for Science in the Public Interest later this week will ask the ACCME [Accreditation Council for Continuing Medical Education] to order all the CME providers where Henschke failed to disclose to send proper disclosures to anyone who participated in those activities."

Henschke and Yankelewitz wrote a letter to JAMA in which they acknowledged they had failed to disclose "potential conflicts of interest" in a previous JAMA article and letter.(2) The letter was rather defensive, in my humble opinion, declaring that "The license agreement was between General Electric and Cornell, the institution listed on the title page. A portion of the royalties are distributed to both of us and to the other co-inventors pursuant to Cornell policy, which in turn is consistent with the Bayh-Dole Act." The letter also asserted the authors' very narrow interpretation of conflicts of interest, "we believe that none of the patent applications or the license agreement played any role in the design of the study, interpretation of the data, or drafting of the publications in JAMA and therefore did not disclose them."

A recent AP article noted that even getting to Henschke and Yankelevitz to write this much was not easy.


Dr. Catherine DeAngelis, editor in chief of JAMA, the Journal of the American Medical Association, said she contacted Henschke months ago after others pointed out patents not disclosed in a July 2006 study. DeAngelis said Henschke didn't believe the patents were relevant to the research and resisted disclosing them.

'We'd been working with Dr. Henschke trying to get her to write a letter of apology — which is our policy — and to take responsibility,' DeAngelis said. 'It was not easy to get her to do anything.'

But you ain't seen nothing yet.

This week, Gardiner Harris writing in the New York Times revealed that the same study which was reported in the New England Journal of Medicine article(3), was substantially funded by money from a tobacco company.




Small print at the end of the study, published in The New England Journal of Medicine, noted that it had been financed in part by a little-known charity called the Foundation for Lung Cancer: Early Detection, Prevention & Treatment. A review of tax records by The New York Times shows that the foundation was underwritten almost entirely by $3.6 million in grants from the parent company of the Liggett Group, maker of Liggett Select, Eve, Grand Prix, Quest and Pyramid cigarette brands [Vector Group Ltd].

Moreover, Henschke and Yankelevitz could hardly deny knowing about this source of their funding. They were the ones running the foundation.




Dr. Henschke was the foundation president, and her longtime collaborator, Dr. David Yankelevitz, was its secretary-treasurer.

It turns out that the leadership of Weill Medical College of Cornell University were in on this.




Dr. Antonio Gotto, dean of Weill Cornell, and Arthur J. Mahon, vice chairman of the college board of overseers, were directors.

The Cornell leadership denied that the intent was hiding tobacco money. On the other hand, the purpose of the foundation, other than to serve as a conduit for this money to the research project, was not exactly clear.




In an e-mail message, Drs. Henschke and Yankelevitz wrote, 'It seems clear that you are trying to suggest that Cornell was trying to conceal this gift, which is entirely false.'

'The gift was announced publicly, the advocacy and public health community knew about it, it is quite easy to look it up on the Internet, its board has independent Cornell faculty on it, and it was fully disclosed to grant funding organizations,' they wrote, adding that the Vector grant represented a small part of the study’s overall cost. The foundation no longer accepts grants from tobacco companies, they wrote.

In the Vector press release, Dr. Henschke was quoted as saying that, thanks to the Vector grants, 'we have raised the initial funding needed to support this important research and data collection on the effectiveness of spiral CT screening.'

Dr. Gotto said in an interview that Dr. Henschke, Dr. Yankelevitz and another colleague set up the foundation initially without the university’s approval, which he said faculty members are allowed to do. He and Mr. Mahon joined the board some weeks or months after its creation to ensure that the Vector grants were handled correctly, he said.

'If we had been approached, we would not have set up the foundation,' Dr. Gotto said. 'We would have accepted the gift directly. We think we behaved honorably. There was no attempt to set up a foundation to hide tobacco money.'

Days earlier, Andrew Ben Ami, assistant secretary of the foundation, said in an interview he would not disclose the source of the charity’s financing at the request of the university.

In another interview before Dr. Gotto agreed to speak, Mr. Mahon, another foundation director, said he did not know the source of the funds.


Note that the Foundation for Lung Cancer: Early Detection, Prevention, & Treatment seems quite obscure. It has no web-site. Its address and email address, as reported by SourceWatch, are for Dr Henschke's office. What it has done other than transfer tobacco money to the research project is unknown.

You just can't make this stuff up.

So we have yet another case which illustrates how pervasive is the web of conflicts of interest that entangles physicians, researchers, academic medical institutions, and industry. Moreover, the web increasingly appears to involve not only industries that make products meant to do patients more good than harm, that is drugs and medical devices, but also industries whose products have no medical use, and even now tobacco, certainly one of the major man-made health scourges.

So this case has actually produced some outrage. Per the New York Times article,



Prominent cancer researchers and journal editors, told of the foundation by The Times, said they were stunned to learn of Dr. Henschke’s association with Liggett. Cigarette makers are so reviled among cancer advocates and researchers that any association with the industry can taint researchers and bar their work from being published.

'If you’re using blood money, you need to tell people you’re using blood money,' said Dr. Otis Brawley, chief medical officer of the American Cancer Society. The society gave Dr. Henschke more than $100,000 in grants from 2004 to 2007, money it would not have provided had it known of Liggett’s grants, Dr. Brawley said.


Also,



Dr. Jerome Kassirer, a former editor of The New England Journal of Medicine and the author of a book about conflicts of interest, said he believed that Weill Cornell had created the foundation to hide its receipt of money from a cigarette company. 'You have to ask yourself the question, ‘Why did the tobacco company want to support her research?’' Dr. Kassirer said. 'They want to show that lung cancer is not so bad as everybody thinks because screening can save people; and that’s outrageous.'


The case also illustrates the messiness of relationships among researchers, academic medical leaders, and industry. As Gardiner Harris wrote in the NY Times,



Universities are responsible for policing conflicts of interest and, in many cases, the required disclosures of their faculty. But Weill Cornell shared in the proceeds of Dr. Henschke’s patent and pending patents, and university officials were on the foundation board.

'We have a very strict oversight policy' for conflicts of interest, Dr. Gotto of Weill Cornell said. He dismissed any suggestion that the university could not police and benefit from faculty members’ financial deals.

But Dr. Kassirer said, 'The problem is that universities, because they’re so conflicted themselves, ignore the conflicts of interest of their faculty.'


To illustrate Dr Kassirer's last point, a quick Google search revealed that Dr Gotto, in addition to being dean of the medical school, is a top leader of two pharmaceutical companies. He is on the board of directors of Aegerion Pharmaceuticals and of Arisaph Pharmaceuticals. So where do his interests lie? - promoting the integrity of the medical school, promoting more funding to the medical school, promoting the profits of these two companies, or promoting the interests of the power elite who simultaneously can run medical schools and run health care corporations? Who can tell?

And that is, as we have said before, the curse of conflicts of interest in health care. Conflicts lead to confused thought, speech, and action. One cannot tell what interests lie behind the speech and actions of the conflicted. So clinical research designed, implemented, analyzed, and discussed by the conflicted rather than leading to further clarity about how to care for patients, just leaves us in a fog of doubt.

But financial ties to various industries, regardless of the conflicts they produce, fuel academic medical institutions and universities who want their faculty to become "taxpayers" rather than teachers and researchers (see post here). Such funding may be one reason why administrators now outnumber faculty in higher educational institutions. Such funding fuels the imperial pretensions of their leadership (see post here). So the universities will not give up their conflicts without quite a fight. But it's time for that fight to start.

ADDENDUM (28 March, 2008) - See also comments by Merrill Goozner on Gooznews, and by Gary Schwitzer on the Schwitzer Health News Blog.

References

1. Goldberg P. NEJM says Henschke conflicts irrelevant; propriety of granting CME questioned. Cancer Letter 2008; 34: 1.
2. Henschke CI, Yankelevitz DF. Unreported financial disclosures. JAMA 2008. (Link here.)
3. The International Early Lung Cancer Action Program Investigators. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006; 355: 1763-1771. (Link here.)

6 comments:

MedInformaticsMD said...

As Gardiner Harris wrote in the NY Times, Universities are responsible for policing conflicts of interest and, in many cases, the required disclosures of their faculty ... 'We have a very strict oversight policy' for conflicts of interest, Dr. Gotto of Weill Cornell said. He dismissed any suggestion that the university could not police and benefit from faculty members’ financial deals.

Universities policing faculty grants and COI's?

Yeah, right.

Daniel Goldberg said...

Wow. You would think I could no longer be surprised by this stuff, but, apparently, you'd be wrong.

Sean Kent said...

There is a huge difference between supporting tobacco companies and being supported by tobacco companies to undo the harm that tobacco is inflicting on society. This article implies that every city in all 46 states that benefitted from TOBACCO SETTLEMENTS is somehow unethical and using blood money, which is misleading and simply not true. A lot of the tobacco settlement money went towards smoking cessation programs, public education programs, and local hospital funding - how is it any different if the hospital uses the money to conduct life-saving research?

Roy M. Poses MD said...

But the tobacco settlements, to my knowledge, did not give the tobacco companies any say in how the money was spent. Furthermore, those receiving the money had no reason to feel indebted to the companies.

The current case is quite different.

The money that supported the CT scan screening research was given voluntarily by a tobacco company. Did the researchers thus feel any obligation to the company? It's not clear. But another question is why did the researchers set up their own foundation whose apparent only function was to serve as a conduit for that money? Doing so allowed them to list financial support as coming from this obscure foundation, which the researchers and the medical school in fact controlled, and not list the tobacco company as a sponsor. If this was not the reason for setting up the foundation, what was?

MarilynMann said...

"So where do [Gotto's] interests lie? - promoting the integrity of the medical school, promoting more funding to the medical school, promoting the profits of these two companies, or promoting the interests of the power elite who simultaneously can run medical schools and run health care corporations?"
Or maybe promoting his own profits?
Both of these companies are privately held, but Aegerion Pharmaceuticals has filed to do an IPO. Dr. Gotto also has a consulting agreement with Aegerion. From the Form S-1 (publicly available on www.sec.gov, EDGAR database)

"On April 4, 2006, we entered into a consulting agreement with Dr. Gotto, one of our directors. As of the date of this prospectus, we owed Dr. Gotto $45,000 for services rendered to us under this agreement. Under his consulting agreement, Dr. Gotto purchased 33,979 shares of restricted common stock for an aggregate purchase price of $50. This agreement will terminate effective upon completion of this initial public offering."

The consulting agreement has to terminate when the IPO is completed because the independent director of a public company can't have this kind of consulting agreement with the company. If the stock does well this arrangement could be quite profitable. Of course, it may not.


http://www.sec.gov/Archives/edgar/data/1338042/000119312508008887/ds1a.htm

http://www.sec.gov/Archives/edgar/data/1338042/000119312507250821/dex1012.htm

http://www.sec.gov/Archives/edgar/data/1338042/000119312507250821/dex1013.htm

Marilyn

Anonymous said...

Roy,

When one of your articles leaves me shaking my head, sighing, and thinking "I've seen it all," you present a sequel. STOP! I'm getting dizzy.

Frankly, did you ever think 'journalism' would be THIS easy. I do not imply that the writing and research you and your contributors do is easy . . . just that the landscape you cover is so bountiful you don't have to beat the bushes for material. You and your contributors do a truly fine job of writing, complete with substantiating references. Please keep writing . . . and I'll keep reading and shaking my head.

Melody