A radiology technologist looks at a CT scan of a lung.
When cancer doctors read about the latest research findings in their journals, they expect two things — that the studies are scientifically sound, and that the results are not biased by any personal or institutional interests. But in a stunning revelation Wednesday, the latter expectation was apparently violated in a widely read lung cancer trial published in 2006 by researchers at Weill Cornell Medical College.
The study, conducted by Dr. Claudia Henschke and published in the New England Journal of Medicine, found impressively that 80% of lung cancer deaths could be prevented through greater use of relatively simple CT scans, which can detect small tumors early and get patients into treatment before the disease takes hold. According to an investigation by the New York Times, funding for the trial came from the Foundation for Lung Cancer: Early Detection, Prevention & Treatment — an entity created by Dr. Henschke and her collaborators, and supported in part by the cigarette maker Liggett Group.
Conflicts of interest in medical research certainly aren't new: doctors serve as consultants to pharmaceutical companies; researchers establish start-ups and seek funding to commercialize promising devices or therapies emerging from their work; and, increasingly, larger trials involving hundreds or thousands of patients are funded by companies or industries that may have an interest, direct or indirect, in the outcome. Major medical journals now require that authors disclose all potential conflicts, including payments, consultancies, board positions and personal enterprises that might impinge on the validity of their results; such conflicts are so widespread that if journals refused submissions from researchers who had them, the number of publishable articles would shrink to almost nothing.
So, the question is: does the source of funding affect the scientific soundness of a study? That depends — on a number of factors. The answer is yes when it comes to trials of new drugs that pharmaceutical companies want to test; in those cases, industry money supports the studies, usually conducted by researchers at academic institutions, and the companies have input into how the trial is designed, and what clinical endpoint it will measure — a huge factor in the trial's outcome. In other cases, primarily involving private or foundation-based grants, the financial support is completely irrelevant to the study, and donors have little to no impact on how the study is designed or how the data is analyzed.
In the case of Henschke's study, Henschke and her team were well aware that the money for the trial — about $3.5 million — had originated from Liggett. In fact, according to Dr. Antonio Gotto, dean of Weill Cornell, the idea for the Foundation originated at a meeting some time in the late 1990s in which Henschke, representatives from the American Cancer Society and the National Cancer Institute as well as anti-smoking activists were present. At the time, there was no national or international lung cancer screening effort in place, and the group decided that such a program was needed, and that tobacco companies should contribute funding to support the project. Liggett was the first to agree, and, to Gotto's understanding, the company promised to convince other cigarette makers to donate as well. "We made a public announcement along with Liggett that they were making a gift to Weill Cornell to support this activity," says Gotto, who was not involved in the study. "We made no effort to cover up the fact that the money was coming from Liggett. It is patently false that we set up the Foundation to cover up the fact that we were getting tobacco money."
Though funds from other cigarette makers never materialized, Henschke and Weill Cornell secured the funding from Liggett, and from other sources to support the project, including money from the 1998 Tobacco Master Settlement, which came through New York State, and private donors.
Unlike other institutes, Weill Cornell does not have restrictions on accepting gifts from tobacco companies, and while it is unusual that Henschke was president of a foundation that was funding her own research project, Gotto says, "We do not encourage faculty to form foundations, but we don't have a restriction that keeps them from doing that."
The publication and publicizing of Henschke's study likely prompted more smokers, or former smokers, to get screened for potential lung tumors — a practice that could come under harsher review, with the revelation of Liggett's involvement. Although the trial involved 31,000 subjects, the Cornell team followed them for only up to 18 months. Their conclusion that 80% of lung cancer deaths could be prevented with CT screening was based on an extrapolation of how many subjects would have survived 10 years later — a calculation involving assumptions about death rates and interpretations about the benefit of CT scans that, in theory, could be open to bias. "If those projections were more robust than they should have been," says Dr. Raymond DuBois, provost of MD Anderson Cancer Center, "it makes all the numbers different. That's where bias could come in."
And that's the problem with conflicts of interest: even if the study results were scientifically sound, if the interpretations and projections made by the researchers defensible, and if there was no connection at all between Liggett and the researchers, the fact that a cigarette manufacturer was even remotely involved taints the findings and leaves the results open to question. Fortunately, in this case, that question may be answered in a few years. A comprehensive, multi-year trial looking at the ability of CT screening to prevent lung cancer deaths is currently under way, with results expected in 2010. Rather than estimating data to calculate a death rate, that trial — funded by the National Cancer Institute, part of the federal government's National Institutes of Health — will record actual deaths from lung cancer in two groups of subjects, those who are screened and those who are not.
If anything, this incident exposes the extent to which the medical field still relies on the integrity of its members to maintain patient confidence. But as economic and other interests continue to seep into the doctor's office, that may have to change. It may no longer be enough for journals to ask researchers to disclose potential conflicts of interest, for example; now editors may have to begin asking for records detailing how a study was funded. In the end, that may be just as important as analyzing the study itself.