Testing Trends: AMP Creates New Quality Guidelines for PGx Laboratory Testing

Pharmacogenetic (PGx) testing has recently come under fire from both the scientific and regulatory community for its lack of self-policing. But the new Association for Molecular Pathology (AMP) position statement outlining best practices for PGx testing may help calm the storm.

Concerns Over PGx Testing

PGx testing provides information to predict the likelihood of medication response and/or risk for adverse medication reactions based on a person’s genetic makeup. This information can be useful in guiding medication and dosing decisions. But while PGx testing continues to grow, it remains relatively new and unproven. And as with any new forms of testing, there are concerns about the clinical validity of particular PGx tests and the quality of PGx laboratory testing. The AMP guidelines are an attempt to allay those concerns by setting out four standards for laboratories providing PGx tests to follow to ensure that testing is carried out in accordance with best practices.

1. PGx Health-Related Claims Must Have Well-Established Clinical Validity

“[PGx] tests that are offered clinically should demonstrate evidence of clinical validity before being offered to patients,” the AMP guidelines state. “The drug-gene association must be robust and supported by strong scientific evidence,” which may include peer-reviewed literature, FDA drug labels and/or clinical practice guidelines, such as the PGx evidence level standards created by the Clinical Pharmacogenetics Implementation Consortium (CPIC).

2. PGx Test Labs Must Follow CLIA

PGx test providers must comply with the same CLIA standards that are required for all other clinical laboratory tests, the guidelines say, including those requiring that tests be verified under the supervision of, and interpreted and reported by, board-certified molecular laboratory professionals, and that details regarding analytical methodology, validity and quality be readily available to providers upon request.

3. Standards for Test Reporting

The AMP says that laboratories must ensure that the PGx test report can be comprehended by the provider, including those who do not have medical genetics or PGx training. The report should include the interpretation of the findings, the significance of the results and the limitations of the test and list the following information:

• A statement of the metabolizer status determined by the genotype for the genes that affect drug metabolism;

• A list of the drugs for which responsiveness may be affected by the genotype;
• A generalized statement to alert providers when alternate dosage or drug treatment may be considered based on the results;

• A list of resources and references that the provider can utilize to learn more about the genotyping result, the drug-gene association and how to incorporate the result into actionable decisions.

4. Standards for Use of PGx Testing Results

The AMP “strongly recommends” that patients who have direct access to their PGx testing results not change their treatment plan on the basis of those results without first talking to their provider. “Any result of a pharmacogenomic test should be discussed with the patient’s healthcare provider to determine whether changes to the patient’s medication plan are recommended,” according to the guidelines.

The Practical Impact of the AMP Guidelines

To appreciate the significance of the AMP guidelines, you need to consider the context and current state of PGx testing. The AMP is hardly alone in harboring concerns about the clinical validity and quality of PGx testing. Regulators feel the same way, including the FDA. Although the FDA has approved the inclusion of PGx information in the labels of hundreds of medications, it has also trained its enforcement sights on test makers for making unproven claims about the capabilities of tests that have not received agency clearance.

Thus, on Nov. 1, 2018, the FDA issued a Safety Communication alerting patients and physicians that claims about the capabilities of unreviewed PGx tests to predict response to specific medications may not be supported by sufficient scientific or clinical evidence. As an example, the Safety Communication cites genetic tests purporting to be capable of predicting whether certain medications used to treat depression may be less effective or have an increased chance of side effects. The relationship between variations and the effectiveness of antidepressant medication has never been established, the Safety Communication states.

Soon after issuing the Safety Communication, the FDA began issuing warning letters to PGx test makers for allegedly making unwarranted claims. At least one recipient of such a letter, Inova Genomics Laboratory, has reportedly stopped offering PGx tests in response.

The laboratory industry has called on the FDA to end the crackdown, which it contends is exercising a chilling effect on PGx and Laboratory Developed Test (LDT) development and innovation and compromising medication decisions. In a recent letter, the American Clinical Laboratory Association (ACLA) claimed that the “FDA’s actions have the practical effect of taking away valuable tools that physicians rely on for making informed prescribing decisions. . . [and] 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 says the FDA and its constituents would be better served if the agency focused its energies on encouraging “responsible” LDT development by adopting recommendations such as those offered by professional groups. It then cites the AMP guidelines as an example.

Takeaway: Nobody disputes the enormous potential value of PGx testing in empowering better medication decisions. But as with just about any other innovative new testing field, PGx science and technology is moving faster than the clinical and government regulators. That puts a burden on PGx test makers and laboratories to police themselves until the regulators catch up. Complying with the new AMP guidelines should serve as a significant step in that direction.