Conflict of Interest Controversy Casts Cloud Over Research Into CT Scanning for Lung Cancer

Zosia Chustecka

March 28, 2008

March 28, 2008 — The controversy surrounding computed tomography (CT) screening for lung cancer has reached new heights, with revelations this week that the research was funded by a tobacco company and earlier revelations that the researchers involved held patents on the technology used.

Principal proponent of the CT scanning approach for lung cancer, Claudia Henschke, MD, PhD, from the New York Presbyterian/Weill Cornell Medical Center, has claimed that her research provides compelling evidence that CT scanning saves lives, and that it can reduce mortality from lung cancer by 80%. These claims, based on data from the International Early Lung Cancer Action Project (I-ELCAP) reported in October 2006 in the New England Journal of Medicine (2006;355:1763-1771), were widely publicized in the lay media. They also led to calls from advocacy groups for widespread use of CT scanning for smokers and others at high risk for lung cancer.

However, other experts in the field have not agreed, and claims that CT scanning saves lives were refuted by a large study published in the Journal of the American Medical Association (JAMA) in March 2007 (297:953-961), as previously reported by Medscape Oncology.

Now, on top of the disagreement over the clinical value of CT scanning for lung cancer, comes fresh controversy related to conflicts of interest.

Dr. Henschke and colleagues declared in their I-ELCAP report that funding for the study came from the Foundation for Lung Cancer: Early Detection, Prevention, and Treatment. It was not until this week, however, that a link to a cigarette manufacturer was revealed in a front page article in the New York Times. The newspaper reviewed tax records for the foundation and found that it was underwritten almost entirely by $3.6 million in grants from the Vector Group, a parent company of the Liggett Group, which produces several brands of cigarettes, including Pyramid and Quest.

Dr. Henschke pointed out that the Vector grants were made public, and that they were only a small proportion of the total funding received. However, the link from the foundation to a tobacco company has cast a cloud. "Now her research is tainted," Dr. Paul Bunn, executive director of the International Association of the Study of Lung Cancer, told the New York Times. Former editor of the New England Journal of Medicine and author of a book about conflicts of interest, Dr. Jerome Kassirer, told the newspaper that he believed Weill Cornell created the foundation to hide the fact that the money came from a cigarette manufacturer. "You have to ask yourself the question, 'Why did the tobacco company want to support her research?'...They want to show that lung cancer is not as bad as everyone thinks because screening can save people, and that's outrageous."

"How can you, as an institution that is based on promoting public health and medical research, take money from an industry that produces a product that causes health problems in the world?" commented Ruth Fadden, director of the John Hopkins Berman Institute of Bioethics, in a report on ABC News.

More questions about conflicts of interest were raised a few weeks ago, when Cancer Letter (2008;34[2]) detailed patents issued to Dr. Henschke and colleagues for technology used in CT screening, for which royalties are paid to Cornell. Among these patents are 2 held by General Electric, a company listed among the sources that funded the research in the 2006 I-ELCAP paper. However, no mention was made of patents or royalties.

Earlier this week, Dr. Henschke and colleague David Yankelevitz, MD, provided details of these patents and the royalties in a letter to JAMA, published online March 24. They referred to earlier JAMA publications in which they had not disclosed these details, and added that they believed the patents and licensing agreements played no role in their research or in the drafting of their papers. However, JAMA editor Catherine DeAngelis, MD, MPH, noted that these financial disclosures would have been published had they been disclosed at the time, and believes that they are relevant. They have now been added to the original publications as corrections.

Weill Cornell Medical College has issued a detailed statement about these conflict-of-interest issues. It points out that the grant from Vector to the foundation was "fully and publicly disclosed at the time through a press release, and was substantially covered in the lay media."

Vector Group, the holding company for Liggett Tobacco, provided funding in the form of an unrestricted gift, and "the gift was used appropriately for the public good," the statement reads. "The gift 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. The Foundation was organized by Dr. Claudia Henschke and Dr. David Yankelevitz and other advocacy-individuals associated with the I-ELCAP program, with the expectation that other major tobacco companies, in addition to Vector/Liggett, would contribute to this national effort. The initial decision to establish a foundation was thought by them to be the most appropriate and effective fundraising vehicle to achieve such a national research plan."

The statement also clarifies the patent situation: "Cornell Research Foundation, a subsidiary of Cornell University, licensed technology (some of which is now patented) related to detection and measurement of nodules developed by Henschke, Yankelevitz, and others to General Electric. As is typical at many institutions, the royalties were distributed to Cornell, which, in turn, provided a share to the inventors under Cornell intellectual property policy, which is in line with the Bayh-Dole Act. NIH [National Institutes of Health] Conflict of Interest regulations currently do not require individual disclosure of royalties paid to them by the employer institutions (see 42 CFR 50.603 — Definition of 'Significant Financial Interest'). Henschke and Yankelevitz did not use the GE products as part of the I-ELCAP and did not require participating I-ELCAP institutions to use the GE product."

In an interview with Medscape Oncology, Richard Gralla, MD, from the Monter Cancer Center North Shore-LIJ Health System, in Lake Success, New York, commented that the failure to disclose is a "disappointment," and predicted that it will now cast a pall over research into CT screening for lung cancer. He emphasized that this is a controversial area anyway, because the question of whether or not it saves lives has still not been answered. One of the major criticisms of Dr. Henschke's studies is that they are not controlled, he said, and many experts are awaiting results from large randomized trials.

There should have been full disclosure, Dr. Gralla said, but he asked: "How big a scandal is this? It's not like making up data." The tobacco industry has in the past funded "very questionable research" and has for years tried to suppress data on the link between cigarettes and lung cancer, so the taint is understandable. A lot of medical research is sponsored by the pharmaceutical industry, but even when this is fully disclosed, "it does not wash the bias," he commented.

"Tremendous credit should be given to Dr. Henschke for raising awareness of screening for lung cancer worldwide," Dr. Gralla said. She has done more than anybody to raise awareness of this issue, and it is an appropriate topic, he added, when lung cancer is a leading cause of death in the western world. "No one can fault her dedication and her real belief that this is important for patients," he continued, However, he added that "she is far from dispassionate" and suggested that "enthusiasm has gotten in the way of her objectiveness."

This suggestion was echoed by another cancer researcher commenting to Medscape Oncology, who asked to remain anonymous. "We generally expect "advocates," usually self-appointed, to become believers because of their lack of equanimity on a topic. When a "scientist" rapidly becomes a believer without high-quality evidence (high-quality evidence often requiring more than 1 convincing trial), one begins to smell a dead rat somewhere," he said. "Some issues rapidly degenerate into a science-versus-religion conflict, but there is no substitute or alternative with the power of a controlled trial to provide evidence from which to draw an inference."

Another lung cancer expert, Tom Lynch, MD, from the Massachusetts General Hospital, in Boston, and a member of the editorial board of Medscape Oncology, said: "Clearly, the authors should have disclosed their sources of research funding. However, despite this, I don't think the impact of this alters our impression of how reasonable screening is. Dr. Henschke and her colleagues are well known as strong advocates for screening, and the question of screening's role requires randomized clinical trial data, which should be forthcoming soon."

The Lung Cancer Alliance (LCA), an advocacy group that has campaigned to make CT screening for lung cancer more widely available, described the report in the New York Times "as another attempt to discredit I-ELCAP and lung cancer screening in general. Why else raise this now? The donation was made 8 years ago, was publicly reported, and was an unrestricted grant that allowed for no control by the donor."

In addition, the group publicized a letter written by its president and CEO, Laurie Fenton-Ambrose, to the newspaper, pointing out that: "In 1997, Liggett publicly admitted they and all the tobacco companies had known but covered up that smoking caused lung cancer. The breaking of ranks and release of key documents led to the $250 billion Master Settlement Agreement that has funded, among many things, many cancer and disease research programs around the country. Are you questioning these tobacco funded research programs as well?

"In 2000, Vector Ltd., whose holdings included Liggett, publicly announced a $2.4 million unrestricted gift for lung cancer screening research," the letter continues. "This was openly discussed at meetings, advocated for by LCA's management, and was widely reported in the media. It is my understanding that it was given to a foundation within Cornell Weill, the only consortia at that time doing early-detection research, to help advance screening research at institutions around the world. And it was set up to prevent big tobacco from controlling or manipulating this research to their advantage. At this time, many in the public-health field were calling for penalty payments from big tobacco in an attempt to right the human tragedy and social costs brought about by big tobacco's conduct.

"LCA’s long-held position is that big tobacco's deceitful marketing and cover-up of tobacco's harms has led directly to the underfunding of lung cancer research," the letter states, adding: "Is seeking these and other penalty payments to advance research to help victims then wrong?"