The U.S. Food and Drug Administration granted de novo marketing authorization for the Invitae Common Hereditary Cancers Panel, an in vitro diagnostic test that can help detect hundreds of genetic variants associated with an elevated risk of developing certain cancers. The test can also help identify potentially cancer-associated hereditary variants in individuals with already-diagnosed cancer.
The test—which is the first of its kind to be granted FDA marketing authorization—evaluates DNA extracted from a blood sample to identify variants in 47 genes known to be associated with an elevated risk of developing certain types of cancer.
“This test can assess multiple genes in a single test by using next-generation sequencing, which has proven helpful in providing insight into genetic variants with sensitivity and speed,” said Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health. “Today’s action can provide an important public health tool that offers individuals more information about their health, including possible predisposition for certain cancers, which can help guide physicians to provide appropriate monitoring and potential therapy, based on discovered variants.”
How does the new cancer screening panel work?
The Invitae Common Hereditary Cancers Panel can be used as a tool to help identify inherited causes of various types of cancers. Patients should speak with a healthcare professional or a genetic counselor to discuss any personal/family history of cancer, as such information can be helpful in interpreting test results. Importantly, this test is not intended to identify or evaluate all known genes that may predispose an individual to cancer.
For this prescription test, the specimen is collected at the point of care, such as a doctor’s office, and sent to a laboratory for testing. The clinical interpretation of the variants is based on evidence from published literature, public databases, prediction programs, and Invitae’s internal curated variants database using Invitae's variant interpretation criteria consistent with those established by appropriate professional organizations or accredited boards. Some of the most clinically significant genes that the test identifies are:
BRCA1 and BRCA2, which are genes with known associations to hereditary breast and ovarian cancer syndrome,
MLH1, MSH2, MSH6, PMS2, and EPCAM (Lynch syndrome-associated genes),
CDH1 (mainly associated with hereditary diffuse gastric cancer and lobular breast cancer), and
STK11 (associated with Peutz-Jeghers Syndrome).
Safe, reliable, and robust cancer screening
The FDA reviewed the Invitae Common Hereditary Cancers Panel under the FDA’s De Novo premarket review pathway—a regulatory pathway for low- to moderate-risk devices of a new type. To validate the performance, Invitae tested over 9,000 clinical samples and achieved ≥99.0 percent accuracy for all tested variant types.
The risks associated with the test are mainly the possibility of false positive and false negative test results, as well as possible misunderstanding of the results. False negative test results may provide a false sense of assurance and these patients may not receive appropriate surveillance or clinical management. False positive test results could lead to inappropriate decision-making regarding healthcare and lifestyle, which can be associated with other undesirable clinical consequences.
Further, since this test is not intended to identify or evaluate all known genes associated with a predisposition for cancer, and genetics are not the only factor in the development of cancer, there is a risk of patients misunderstanding that they still have some risk of developing cancer following a negative test result. These risks are mitigated by the analytical performance validation, clinical validation, and appropriate labeling of this test.
Why is this authorization significant?
Along with this de novo authorization, the FDA is establishing special controls that define the requirements related to labeling and performance testing. For example, accuracy for reporting of substitutions, insertions/deletions, and copy number variants must be ≥99.0 percent for positive agreement and ≥99.9 percent for negative agreement with a validated orthogonal method. When met, the special controls, in combination with general controls, provide a reasonable assurance of safety and effectiveness for tests of this type.
This recent action creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through the FDA’s 510(k) premarket process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a predicate device, saving a developer time and expense compared to other review pathways.
- This press release was originally published on the U.S. Food and Drug Administration website