FDA holds court on post hoc data linking KRAS status to drug response (original) (raw)

Nature Biotechnology volume 27, pages 110–112 (2009)Cite this article

Post hoc re-evaluation of clinical data runs counter to conventional statistical practice at the FDA. According to the agency's standard line of thinking, biomarker and therapeutic should be developed in parallel and endpoints designed prospectively in order for the validity of a hypothesis (and a related null hypothesis) to be tested. For its part, the FDA acknowledges that the science of drug development tied to prognostic indicators is moving at breakneck speed and that new developments may provide reasons for re-evaluating its stance—for example, in situations where patients could be spared futile treatment on the basis of biomarkers identified after a clinical trial has begun or even after a product has been approved for marketing. As a result, the FDA is gathering information on how to assess retrospective biomarker usefulness, and the members of the ODAC panel seemed to be using the confab with Amgen and ImClone scientists as a sounding board to air their questions.

The FDA panel was upfront with its concerns and cited problems intrinsic to retrospective studies. The greatest angst was over “re-analysis of failed clinical trials” in search of alleged efficacy in subsets of biomarker-patient groups that may be undertaken without consideration for missing data and questionable assay techniques. This was a clear warning shot intended to discourage drug developers from rummaging through their discarded and well-worn products with the idea of manipulating data to make a drug fit some selectively back-tested and redistilled class of patient, biomarker and disease. “We are in agreement with that,” says Hagop Youssoufian, senior vice president of clinical research and development at ImClone Systems, now a wholly owned subsidiary of Eli Lilly of Indianapolis, Indiana. “But that was never the purpose of the KRAS analysis anyway,” he says. Both Erbitux and Vectibix won FDA approval as second-line therapies in the US without regard to biomarker status.

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  1. Columbia, South Carolina
    George S. Mack

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Mack, G. FDA holds court on post hoc data linking KRAS status to drug response.Nat Biotechnol 27, 110–112 (2009). https://doi.org/10.1038/nbt0209-110c

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