Friday, March 28, 2008

Weill Cornell Medical College Researcher Hides Tobacco Industry Funding of Study on Use of CT Scans for Lung Cancer Screening

In an October 26, 2006 article in the New England Journal of Medicine, Dr. Claudia Henschke of Weill Cornell Medical College and a group of other investigators reported the results of a study of the use of low-dose spiral CT scans as a screening tool to detect lung cancer among asymptomatic individuals. The article reported that 85% of patients with lung cancer detected had stage I cancer and the estimated 10-year survival among these patients was 88%. The study concluded that: "Annual spiral CT screening can detect lung cancer that is curable" and that "such screening could prevent some 80% of deaths from lung cancer."

The paper listed its funding sources at the end, one of which was the Foundation for Lung Cancer: Early Detection, Prevention & Treatment.

The New England Journal of Medicine has a policy of not publishing any paper supported with funds from the tobacco industry. Not seeing any disclosure of funding from the industry, the Journal published the paper.

The Rest of the Story

The rest of the story is that the Foundation for Lung Cancer: Early Detection, Prevention, & Treatment "was, according to a New York Times article, "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. The foundation got four grants from the Vector Group, Liggett's parent, from 2000 to 2003."

According to the New York Times article and a concurrent article in The Cancer Letter, the Journal of the American Medical Association was also deceived by the absence of disclosure of Dr. Henschke's tobacco funding and would never have published her paper had they known that Henschke received tobacco industry money for her CT screening research.

To make matters worse, the Times reported that Dr. Henschke "failed to disclose in articles and educational lectures a patent and 10 pending patents related to CT screening and follow-up." By virtue of these financial interests, Dr. Henschke stands to benefit personally (financially) if her recommendations for the widespread adoption of CT scan screening for lung cancer are adopted.

Moreover, the Cancer Letter reports that "medical journals and providers and accreditors of continuing medical education are investigating her failure to disclose patents and royalties from commercial sponsors, including GE Healthcare. As the leading manufacturer of CT scanners, GE stands to benefit from Henschke's campaign to screen asymptomatic former and current smokers."

If it is true that Dr. Henschke has a significant financial interest in GE Healthcare, such as royalties, consultant fees, or licensing payments, and that financial interest was present in October 2006, then she did fail to disclose that interest in her New England Journal article as that article states: "No potential conflict of interest relevant to this article was reported."


I am not, in this post, criticizing Dr. Henschke for either accepting tobacco industry funding or for having financial interests relating to the use of CT screening for lung cancer. What I am being critical of is the failure to disclose the tobacco industry funding of her research and the potential conflicts of interest.

Most disturbing to me is her failure to disclose the tobacco industry funding of her research. Clearly, this failure to disclose led to the deception of editors at two major journals which published her work about the nature of the funding sources for her research. Neither was aware of her funding by the tobacco industry; thus, her failure to disclose was substantial.

I do not believe that Dr. Henschke can hide behind the excuse that she disclosed funding from the Foundation for Lung Cancer: Early Detection, Prevention & Treatment, and so that she did indeed disclose her funding sources. The intent of disclosure of funding is to provide editors, reviewers, and the public with relevant information about the source of funding, not merely to provide the name of the foundations or entities set up to receive that funding. Thus, I view the failure to disclose her funding from Liggett as a significant violation of ethical standards of conduct.

Unfortunately, the reputation and validity of this important research has been tainted by these events. It should lead the public to question the objectivity of the conclusions of the research. In fact, as I have argued in detail (before knowing that the work was tobacco-funded), I believe that the current evidence does not support the use of CT scans as a screening tool for lung cancer and that widespread adoption of this approach at this time would be a public health disaster.

I also believe that the conclusions of the research are biased and do not reflect an appropriate, broad-based perspective on the criteria that are necessary to be met before a screening tool is adopted on a population basis. While the ELCAP researchers have jumped to recommend CT screening be adopted (perhaps not surprising in light of the financial conflicts of interest disclosed in this week's articles), they have not sufficiently addressed the important concerns regarding the false positives that result from screening and the harm that might be done by invasively investigating harmless nodules. In addition, I do not feel that they have addressed the potential harm inherent in exposing millions of people to the substantial radiation doses associated with CT scans (most of whom would be exposed unnecessarily).

Spiral CT screening for lung cancer has not yet been shown to be an effective and appropriate screening tool. The specificity of the test is very low, and combined with a very low prevalence of lung cancer in the population, the positive predictive value of CT screening is dismally low. This means that the overwhelming majority of patients who have lung nodules detected on CT scan will not have lung cancer. But these patients will require follow-up monitoring, and some will even require further invasive procedures to obtain a definitive diagnosis. These procedures carry a morbidity and even a mortality risk themselves and a number of the diagnostic procedures will result in morbidity or possibly mortality unnecessarily (by which I mean morbidity or mortality in patients who do not have lung cancer).

Another important consideration is the anxiety that could be produced in a huge number of patients who have nodules detected on CT scan but who do not have lung cancer. The protocol calls on these patients to either have invasive diagnostic procedures, which can be physically damaging, or to simply wait for 3 months for a follow-up test, which can be psychologically damaging. Imagine the anxiety a patient would have if told that they have an abnormal nodule in their lung that could be cancerous and what the doctor wants them to do is sit around for 3 months and try not to think about it.

In the ELCAP study, 4186 patients were identified as having abnormal lung nodules at baseline CT screening. Of these patients, only 405 were found to have lung cancer. Thus, 3781 patients had false positive results. The positive predictive value of the test was therefore only 10%. This means that a positive test result (the finding of a lung nodule) only indicates lung cancer 10% of the time. Ninety percent of the time, the test is wrong. That's usually viewed as being unacceptable for a screening test.

In this case, having 90% of your patients with nodules worrying unnecessarily for 3 months hardly seems acceptable to me.

If there were some gold standard, definitive test that could be performed immediately following the baseline CT scan to determine whether or not a patient has lung cancer, then this initial screening test might be acceptable. But I find it quite troubling that patients are being told that they may have cancer - please come back in 3 months and we'll either tell you how much it's grown or we'll tell you never mind, false alarm.

Also concerning is the fact that in this study, 43 patients had some form of invasive or surgical procedure, presumably ranging from fine-needle aspiration to bronchoscopy to mediastinoscopy to open lung biopsy, but ended up having nothing wrong with them.

In other words, what I'm trying to say is that without a doubt, instituting such a screening procedure is guaranteed to cause harm to some patients. It is likely to cause psychological harm to many, and physical harm to a smaller, but not negligible number of people.

On the other hand, we cannot say with certainty that instituting this screening procedure will result in benefit because it has not yet been demonstrated definitively that spiral CT screening for lung cancer does save lives.

For further reading about this story, see the article at the Time Magazine web site and at the Columbia Journalism Review.

No comments: