The American Clinical Laboratory Association (ACLA) is urging the FDA to halt its recent crackdown on laboratory developed tests (LDTs) and other pharmacogenomics (PGx) tests that reference specific drugs or drug classes unless approved by the agency.
In a letter to FDA Acting Commissioned Ned Sharpless, M.D., signed by ACLA President Julie Khani, the Association urged the agency to instead FDA encourage “responsible” LDT development by adopting recommendations such as those offered by professional groups, and formally recognizing existing peer-reviewed, evidence-based guidelines as a basis for establishing clinical validity of a PGx test
ACLA cited the Association for Molecular Pathology (AMP)’s position statement for pharmacogenomic testing, published September 4, that spells out “best practices” criteria for laboratories to follow. The three-page statement included criteria that are designed to ensure responsible use of the tests, while preserving broad access and improving patient care, according to AMP.
The ACLA also requested a meeting with FDA leaders to discuss the issue.
“FDA’s actions have the practical effect of taking away valuable tools that physicians rely on for making informed prescribing decisions,” the ACLA argued in the letter. “Given that physicians will be forced to revert to older methodologies (such as try and fail, try and maybe succeed) in order to make prescribing decisions without actionable genomic information, it is likely that FDA’s new policy will result in more patients receiving less than optimal medications or doses, with consequent safety and cost ramifications.
“What FDA is doing will result in more patients getting a less effective or the wrong medication, with negative consequences for patient care and health care costs,” the ACLA asserted. “Additionally, by implementing an effective ban, FDA will chill investment and innovation in the PGx space.”
The FDA has said it is acting to ensure patient safety.
“Claims for many genetic tests to predict a patient’s response to specific medications have not been reviewed by the FDA, and may not have the scientific or clinical evidence to support this use for most medications,” the agency said when it launched its crackdown on PGx testing on October 31, 2018. “Changing drug treatment based on the results from such a genetic test could lead to inappropriate treatment decisions and potentially serious health consequences for the patient.”
Contacting Test Developers
The FDA’s enforcement initiative began with a “Safety Communication” that warned patients and healthcare providers not to change patient medication regimens based on results from genetic tests claiming to predict a patient’s response to specific medications, but which are not supported by scientific or clinical evidence.
The FDA followed up by contacting companies that offer PGx tests, demanding that they revise their test reports and labeling, or withdraw such tests. “Most firms addressed the FDA’s concerns by removing specific medication names from patient test reports and informational material,” the ACLA noted.
When one test developer, Inova Genomics Laboratory, declined to follow suit, according to the ACLA, the FDA accused Inova in a “Warning Letter” of “illegally” marketing genetic tests that had not been reviewed by the agency for safety and effectiveness. Initially, Inova noted that it had been offering MediMap tests under what it termed “FDA’s policy of enforcement discretion for [LDTs], as previously described in the FDA’s publicly available statements and documents.” But in April, Inova ended MediMap testing.
“Without necessary context about the relationship of genetic variants to specific drugs, prescribers and patients are left without clinically vital information,” the ACLA contended. “Patients whose genetic makeup indicates that a specific drug will be effective –or will cause an adverse reaction –will be directly and immediately harmed by FDA’s actions.”
That harm, the Association added, has been compounded by the FDA extending its crackdown by requiring the laboratories to withhold information about drug classes.
The FDA has defended its heightened scrutiny of the PGx tests.
“Consumers are increasingly embracing genetic testing to better understand their individual risk for developing diseases. With this rise in popularity and availability, we’re also seeing significant activity in the field of pharmacogenetics,” Jeff Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health, said in the agency’s April 4 press release announcing the Warning Letter to Inova.
“Without appropriate evaluation to determine whether these tests work, patients are being put at risk—potentially impacting treatment decisions by providing false promise that they will respond well to a certain medicine or keeping them from using therapies that may benefit them,” Shuren added.