Journal of the National Cancer Institute Advance Access originally published online on May 13, 2008
JNCI Journal of the National Cancer Institute 2008 100(10):690-691; doi:10.1093/jnci/djn170
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© Oxford University Press 2008.
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Lung Cancer Screening Trial Financed by Tobacco-Funded Foundation, Sparks Debate
For those who are worried about conflicts of interest in medical research, the news that a cigarette company helped fund a major lung cancer screening study, revealed in a front page story in the New York Times and in the Cancer Letter, represented a perfect storm of ethical issues that could further erode public confidence in the value of academic science.
The story highlighted how two discrete issues that research institutions grapple with—financial conflict of interest and use of tobacco company money to fund research—came together in a highly unusual way, complicating the interpretation of results from internationally known researchers and a major medical institution.
The Times and the Cancer Letter reported that Weill Cornell Medical College researchers Claudia Henschke, M.D., Ph.D., and David Yankelevitz, M.D., its dean, Antonio Gotto, M.D., D.Phil., and the vice chairman of the college board of overseers, Arthur J. Mahon, were officers of a charity called the Foundation for Lung Cancer: Early Detection, Prevention, and Treatment. That charity was almost exclusively funded by $3.6 million in funds donated by the Vector Group, the holding company for Liggett Tobacco, which makes several different brands of cigarettes.
Henschke and Yankelevitz used the funds as seed money to help launch studies to test whether computed tomography (CT) screening of patients at risk for lung cancer can lead to early detection of the disease. Published studies from the group have shown a connection between CT screening and improved detection, and results from the Cornell-led International Early Lung Cancer Action Program (I-ELCAP), published in the New England Journal of Medicine in 2006, demonstrate that CT screening saves lives, according to Henschke. The findings created controversy among lung cancer researchers, some of whom said that the nonrandomized study did not prove that such screening could reduce mortality.
But the connection between Liggett Tobacco and the researchers was not transparent in the journals that published results of I-ELCAP and earlier studies. The foundation was listed as one of 32 funding sources in the NEJM publication, but not the fact that it contained Liggett Tobacco funds and little else.
Angry Reactions
The news stories on the foundation prompted immediate reaction. Otis Brawley, M.D., the chief medical officer for the American Cancer Society, called the foundation's funding "blood money" that needs to be disclosed. Jerome Kassirer, M.D., editor of NEJM from 1991 to 1999, said that people need to ask themselves, "Why would a tobacco company fund a study that shows lung cancer caused by cigarette smoking is treatable? Conflicts of interest happen all the time; using a foundation to obscure a funding relationship is just a new twist on a big problem."
In a statement to JNCI, Greg Donaldson, the American Cancer Society's national vice president for corporate communications, said that Henschke's statements misled the society in 2005 when it asked her, as well as all other researchers that it funds, to disclose in writing any potential conflicts and specific tobacco-related funding sources. "The investigator in question acknowledged in writing that there were no such conflicts and that she had no tobacco sources of funding," Donaldson wrote. "She has signed several similar documents to that effect in the years since."
The American Cancer Society has "taken steps to eliminate all perceived ties with the investigators associated with this particular trial and, by extension, any questionable sources of funding," Donaldson said. "The society is also revisiting and reviewing society policies and procedures related to seeking such funding disclosures, monitoring and, when necessary, enforcing them."
Catherine DeAngelis, M.D., editor in chief of JAMA, said in the news stories that she would not have accepted the Weill Cornell CT scanning studies if she had known of the tobacco funding. NEJM's journal editors, including its chief editor, Jeffrey Drazen, M.D., wrote in their April 2 issue that it is "appropriate to ask whether a study on clinical outcomes in lung cancer should be directly underwritten in part by the tobacco industry. Given the enormous burden of smoking-related illness and the ongoing sale of cigarettes and other forms of tobacco, one might question the advisability of research entities’ accepting funding from tobacco companies except through the American Legacy Foundation, which distributes funds received through the Master Settlement Agreement with U.S. tobacco companies."
Henschke told the Times that the implication that Cornell was trying to conceal the gift is "entirely false" and that the original $2.4 million pledge by the Vector Group was disclosed in a 2000 press release that was reported by several media outlets. Cornell's Gotto said that the researchers established the foundation without university approval, which is allowed at the institution, and that he joined the foundation later to ensure that the grants were handled correctly. There was no attempt to "hide tobacco money," he said.
After the news stories appeared, Weill Cornell Medical College released a statement saying that the gift was "used appropriately for the public good" and that it "was originally made as part of a grand plan and vision on the part of public health and lung cancer advocacy groups and Vector/Liggett to provide screening research centers throughout the country." There was also an expectation that other major tobacco companies would contribute—but they didn’t.
The April 2 online edition of NEJM issued a "clarification" from Henschke, acknowledging that $3.6 million—"virtually all of the foundation's funding"—was contributed in 2000–2003 as an unrestricted gift by the parent company of Liggett Tobacco. Henschke and Yankelevitz also published a correction on a different conflict-of-interest issue that has created more controversy—the fact that they received royalties from Cornell Research Foundation as inventors of methods to assess tumor growth and regression in imaging tests for which pending patents are held by Cornell Research Foundation and licensed to General Electric.
Foundations Need Scrutiny
The story caught researchers who examine issues of conflict of interest by surprise because foundation funding wasn’t widely viewed as a pressing problem. In fact, the February 28 release of new guidelines on managing conflicts of interest, issued by the Association of American Medical Colleges and the Association of American Universities, never mentions foundation funding at all.
"This one is under the radar," said Julie Gottlieb, assistant dean for policy coordination at the Johns Hopkins University School of Medicine and a leader of the advisory committee that assembled the new guidelines. "Foundations have been discussed informally, but there are so many issues of conflict of interest in academic and medical research that they haven’t been front and center." Gottlieb said that some of her colleagues have wondered about foundation support "because some are heavily supported by industry, but it is often hard to know" if conflicts of interest exist. Now, as a result of the Times story, she said, foundation funding is an emerging issue.
A study published in JAMA by Eric Campbell, Ph.D., an associate professor of medicine at Harvard Medical School, found that 70% of medical schools participating in his survey have policies related to the financial interests of senior and mid-level institutional officials, but only about a third have policies addressing the interests held by the institution itself. "This raises questions about the potential effect of institutional conflicts of interests on the missions of academic medical centers," Campbell said of the study results.
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"The first question that comes to mind from the Weill Cornell story is to ask how often faculty establish these foundations, and if an institution doesn’t know, it needs to find out," Campbell said.
Institutional Policies
The potential, or even perceived, conflict of interest caused by the Vector Group funding would not have arisen in Henschke's research if Weill Cornell Medical College had banned the use of tobacco money for research, as a few medical schools have done. Among them are Johns Hopkins and Harvard, according to Gottlieb and Campbell, who also say that their institutions do not allow researchers to set up private foundations.
"If an institution stepped up and said tobacco money has no place in research to begin with, it will set the tone for the institution not to accept that money in any form, foundation or otherwise," said Chi Dang, M.D., Ph.D., vice dean for research at Johns Hopkins School of Medicine. "We have reached the conclusion that tobacco use causes morbidity and mortality and has no place in funding medical research."
But it can be difficult to convince nonmedical researchers that a ban on tobacco funding is necessary, said Philip Pizzo, M.D., dean of the school of medicine at Stanford University. In February 2007, professors of history, law, and medicine introduced a resolution through the university faculty senate, recommending a prohibition on accepting tobacco industry research money—which would have made Stanford the first to pass such a campuswide ban. After several contentious debates, the resolution was withdrawn. Even though there is "virtually universal disdain for the tobacco industry practices," Pizzo said, "many faculty are concerned about setting a precedent that could have inadvertent consequences for the university's research mission."
Even though Pizzo felt that the tobacco funding issue was "more one of professional ethics than of academic freedom," he said that Stanford has a strong conflict-of-interest committee that can ensure funding transparency. Nonetheless, even though foundations such as Henschke's appear unusual, Pizzo said, "in light of the Cornell situation, we are reviewing our data to be certain that we do not have such foundations in our school or in the university."
This problem needs to be addressed at every university, he added. "The real issue is that reviewers of the publications—whether they are journal editors or readers—would not know there was a potential bias because of the funding source."
Others urge caution as institutions address these issues. Dang said that he does not think that the Cornell Weill study indicates systemic problems. "My belief is that this is a singular event, which is very unfortunate," he said. "Something like this always casts a negative light on the good deeds we do, but we have to be careful to make sure this whole conflict-of-interest issue doesn’t go overboard, tainting everything with an assumption of guilt."
In that light, there has also been some pushback against the idea that tobacco cannot fund research like Henschke’s. "The idea that this study is somehow going to encourage people to smoke is ridiculous," said Thomas Stossel, M.D., a professor of medicine at Harvard Medical School and author of a commentary in the March 1 issue of the British Medical Journal that argues that the hunt for conflicts of interest has gone too far. "If there is a problem with the merits of the study, that is one thing—and it wouldn’t have been published in top journals if that were true," he said. "Who cares who funded it? Give the benefit of the doubt to the researcher."
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