IOM
The fallout from the Duke case includes 27 papers that Duke expects to be partially or completely retracted, three canceled clinical trials, and a lawsuit against Duke by patients in the trials. What happened reflects "a rush" to pass tests based on genomics in the clinic and market, said Chairman of the Board Gilbert Omenn, a biologist computing at the University of Michigan, Ann Arbor. "There are many lessons here probably apply to other places," says Omenn.
The controversy began after Duke researchers led by Anil Potti and his mentor, geneticist Joseph Nevins cancer has reported that the patterns of gene activity or gene expression in tumor cell lines could be used to predict how individual patients responded to various chemotherapeutic drugs. Their results were published first in a Nature medicine paper in 06 and later in other journals. the university has launched three clinical trials in which patients with breast cancer and lung were to receive medications appropriate to their expression results gene.
Meanwhile, two biostatistician at MD Anderson Cancer Center in Houston, Texas, Keith Baggerly and Kevin Coombes, found apparent errors in Nature Medicine paper and related publications review published in September 09. The National Cancer Institute (NCI), which had questions about the results of a genetic signature Duke, he wanted to use in a new trial, also began to investigate. Duke stopped testing for examination, but restarted a few months later.
Then, in July 2010, after Letter cancer , Washington, DC, a newsletter, reported that Potti had falsely claimed to be a Rhodes Scholar, over 30 statisticians and bioinformatics wrote to NCI Director Harold Varmus asking to investigate NCI. Varmus asked the IOM study, and Duke has launched a new investigation and arrested the test a second time.
IOM found many potential problems inherent in tests based on omics, which he defines as a search that looks for patterns in large sets of molecules such as proteins, DNA, the RNA, or metabolites. These tests offer great potential to guide patient care but because they can be difficult to reproduce, less than expected have reached the clinic, the report notes.
A major problem, according to the report, is "overfitting" Because studies often wear models in hundreds of biomolecules using a relatively small sample of patients, it is easy to find correlations that do not reflect the biology of the disease patients. The report recommends a series of measures to validate tests such as repeat the test on blind samples in a different institution. Magazines and donors should also require data and document templates are available free of charge so that other researchers can verify results.
Before evaluating the test at the clinic, researchers need to "lock" or freeze the calculation model used so that it can not be changed, the report said. Researchers should also consult with the Food and Drug Administration (FDA) long before they use the test in a clinical trial-that Duke did not. And the FDA needs to clarify its requirements.
The IOM committee also found problems with control at Duke, where "several systems in place ... to ensure the integrity and rigor of the scientific process has failed." A 31-page annex provides piecemeal account of what happened to the Duke. She notes that financial conflicts of interest (Duke investigators had patents on the technology and links with developing societies, testing) and deference to a senior professor may have influenced the university to dismiss concerns about papers. Duke attributed his failure to "missed signals."
To avoid these problems, the institutions need to strengthen their oversight of interests and conflicts process to answer questions on published research.
Baggerly MD Anderson said his report of initial reading is "quite positive." If all the recommendations had been implemented, "I think a lot of the problems could have been short-circuited," said -he.
The NCI Lisa McShane, who spent months trying itself to validate the results of Duke, said the IOM committee "did work really well" by asking the questions. NCI now plans to require its cooperative groups that want to use omics tests follow a checklist similar to that in the IOM report. NCI has not yet decided whether to add new requirements for omics tests in its review process Peer Grants Initiative researchers. But "we hope that this report will increase making everyone aware," says McShane.
In a statement, the duke said he "appreciate [s] reflected the work and depth carried out by the IOM committee "and expects to incorporate the recommendations in" ongoing efforts to reinforce the rigor of our research enterprise. We have learned of our situation, "the statement said.
Potti left Duke in 2010 and later joined a medical practice in South Carolina, but after 60 Minutes aired a segment on the controversy in February, he was released. an investigation of scientific misconduct Duke is underway, according to the university.
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