that a recent draft guidance on presubmission for devices outlines current FDA recommendations about clinical assay development and provides information on how to contact the appropriate FDA offices (FDA, 2012a). If the results of an assay are not used in treatment decisions in a clinical trial, the test does not pose significant risk and an IDE is not required, Jessup explained. However, biomarker tests used for eligibility criteria, treatment assignment, or dose modification may require a presubmission IDE review.
In summary, Jessup suggested that investigators include in their trial protocols a section that documents the risk of false positive or false negative assay results and the potential consequences of false results in the context of the disease. Investigators should also indicate whether they think an IND (Investigational New Drug) application or IDE is required. Jessup added that the potential consequences of false results from biomarker assays should be described for patients in the informed consent documents. “The FDA wants to know exactly what patients are being told about the markers and the consequences of the assay results,” he said. He concluded that “principal investigators, assay developers and performers, and sponsors need to collaborate and partner closely.”
Garraway noted that “just because something is done in a CLIA lab doesn’t automatically mean that it’s done with high quality. It just means that it’s done the exact same way every single time.” Garraway is part of a consortium that is currently trying to define appropriate metrics for sequencing standards that could cut across various types of platforms and approaches and offer objective performance comparators (National Human Genome Research Institute, 2013).
Solit stressed that biomarker validity is more important for late-stage clinical trials. He suggested that there should be a lower bar for biomarkers used in early-stage clinical trials. “Oftentimes, patients have no other treatment options. I don’t see any risks in the trials that we’re running in advanced metastatic cancer patients, who typically have a life expectancy of less than a year,” he said. But Miller countered that “the field was set back substantially by misinterpretation of EGFR assays, so even if multiple platforms are contemplated, there should be a common playing field with minimal criteria.”
Comis noted that testing a companion diagnostic concurrently with an intervention in a registration trial can be limiting as it “locks onto a specific assay, when the whole dynamics of understanding mutations and their interactions” is continually evolving. “It can inhibit the kinds of clinical