Review Casts More Doubts on a Lung Cancer Study

 

But the doctors who conducted a controversial, widely publicized lung cancer study involving more than 50,000 patients at numerous hospitals were unable to locate 90 percent of the consent forms, according to a confidential review provided to The New York Times.

The finding casts further doubt on a clinical trial that made headlines in 2006 when it concluded that fully 80 percent of lung cancer deaths could be prevented through wide use of CT scans.

That trial, led by Dr. Claudia I. Henschke at Weill Cornell Medical College in New York City, drew sharp criticism from skeptics of cancer screening; the criticism intensified when The Times reported in March 2008 that the research was being financed in part by $3.6 million in grants from the parent company of the Liggett Group, a cigarette maker.

The confidential report on patient consent, dated Oct. 7, 2008, recommended that the trial be stopped. But it continues to this day, although not at Weill Cornell.

Several ethicists said the hospital was legally required to disclose the ethical problems documented by the secret review. That has not happened either.

The confidential report was commissioned by Weill Cornell after The Times’s 2008 article and other revelations about the study in the newsletter The Cancer Letter. The hospital hired four prominent professors from other universities to undertake an independent review of Dr. Henschke’s research, known as the International Early Lung Cancer Action Program, or I-Elcap.

In their report, the reviewers scolded Weill Cornell administrators for failing to supervise the research more closely, “especially knowing that scientific controversy has surrounded I-Elcap almost from its inception.”

One reviewer, Dr. David P. Carbone, a professor of medicine and cancer biology at Vanderbilt, said in an interview that he and the other reviewers never found out “whether these consents were obtained and lost or whether they weren’t obtained at all.”

He said that Dr. Henschke acted with the best of intentions, “but there’s no way for me to justify any of the problems” documented by the group’s review.

Dr. Henschke, who has since left Weill Cornell for Mount Sinai Medical Center in New York, declined to respond to the findings of the 2008 review, saying it was confidential. But in an e-mail, she said the responsibility for keeping track of consent forms lay with all the hospitals where the experiments were done.

“I-Elcap is a non-federally funded academic consortium of independent, autonomous sites that share certain data,” she wrote.? “Accountability and responsibility for human protection lie at the local level.”

But Dr. Henschke’s research has been supported by grants from the National Institutes of Health, and federal rules governing research conducted at multiple sites have long required that the coordinating center either collect copies of patient consent forms or ensure that they are being kept appropriately.

“The responsible conduct of a study requires that informed consent documents be kept on file,” said Dr. P. Pearl O’Rourke, director of human research affairs at Partners HealthCare, part of Harvard University. “There should be a system so that every consent form can be found no matter if individuals were enrolled at a single site or multiple sites.”

John D. Rodgers, a spokesman for Weill Cornell, wrote in an e-mail that the medical school followed federal research regulations “and there were no issues regarding the safety of the research subjects.”

Dr. Bruce A. Chabner, director of clinical research at Massachusetts General Hospital Cancer Center and editor in chief of The Oncologist journal, said he would ask Weill Cornell for an explanation of the problems outlined in the 2008 scientific review, as well as a follow-up to the report. His journal has published research by Dr. Henschke, and “if we find there was no informed consent for those patients, the paper would have to retracted,” he said.

The American Cancer Society helped finance Dr. Henschke’s research, and some of her work was published in cancer journals owned by the society. Dr. Otis W. Brawley, the society’s chief medical officer, said any study underwritten by the organization must conform to federal research rules, including those that require that problems with informed consent be reported to federal science agencies.

He added that the society’s journals might have to correct or retract any study that proved unable to document that patients had given informed consent. “But I don’t want to prejudge the case,” Dr. Brawley said.

In November, a huge federal study found that annual CT scans of current and former heavy smokers reduced their risk of death from lung cancer by 20 percent and, even more surprising, seemed to reduce the risks of death from other causes as well.

Although the scale of the benefit was substantially less than Dr. Henschke claimed her research showed, the federal study was widely interpreted as confirming her longtime contention that CT screening can save lives from lung cancer, which kills more than 150,000 people each year in the United States. Most patients discover their disease too late for treatment, and 85 percent die from it.