Academy of Diagnostics & Laboratory Medicine - Scientific Short

A New Pharmacogenetics Resource From the FDA

Will It Change Demand for Testing?

Gwendolyn A. McMillin

It is well recognized that serious adverse drug reactions (ADRs) are a common and preventable cause of death. Pharmacogenetics, which associates genetics with discrete aspects of drug response, is one of many possible tools for predicting risk, and ideally preventing ADRs. For many years the FDA has published a “Table of Pharmacogenomic Biomarkers in Drug Labeling” that lists both somatic and germline biomarkers,based on information contained within the approved drug labeling.(1) The new table, a “Table of Pharmacogenetic Associations” is also based largely on information contained within the approved drug labeling, but it is focused on categorizing clinical value of germline drug/gene associations. (2) The table includes three lists, the first of which provides 51 drug/gene associations with therapeutic management recommendations, followed by a list of 19 drug/gene associations with potential impact on safety or response, and finally a list of 37 drug/gene associations with pharmacokinetic relevance only. Wow! What an impressive resource to orient clinicians and patients to more than 100 known associations! But as a laboratorian, I wonder if this resource will translate into increased demand for pharmacogenetic testing?

There are only a handful of examples wherein FDA labeling requires testing. These labeling annotations are archived along with labeling from other countries by the PharmGKB. (3) One example of a well characterized drug/gene association that requires testing is abacavir with HLA-B*57:01. Testing for this variant allele is relatively simple and the time to result required to impact clinical management decisions is several days to weeks. As such, this application is very manageable for laboratories to support. The interpretation and clinical implementation is also well defined. However, this straight forward scenario is not shared by most of the drug/gene associations in the new FDA table. Genes such as the CYP2D6 are extremely complicated and may require extensive expertise to perform adequate testing. If testing demand does increase, are laboratories prepared to deal with the potential complexities of testing and interpretation? How should the contributions of multi-gene associations be weighted, and how do non-genetic associations influence drug and dose selection decisions when genetic factors impact clinical decision making? Many global and local challenges and opportunities exist for the future of pharmacogenetic testing. (4) While I strongly believe that pharmacogenetics is an incredible tool and can be used wisely to inform pharmacy decisions, successful clinical outcomes depend on a multi-disciplinary approach to guide ordering, providing, or interpreting pharmacogenetic testing.

REFERENCES

  1. Table of Pharmacogenomic Biomarkers in Drug Labeling, https://www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling
  2. Table of Pharmacogenetic Associations, https://www.fda.gov/medical-devices/precision-medicine/table-pharmacogenetic-associations
  3. Pharmacogenomics Knowledge Base, https://www.pharmgkb.org
  4. Chenoweth MJ, Giacomini KM, Pirmohamed M, Hill SL, van Shaik RHN, Scwab M, Shuldiner AR, Rellying MV, Tyndale RF. Global Pharmacogenomics Within Precision Medicine: Challenges and Opportunities. Clin Pharm Ther 107:57-61, 2020.

Scientific Shorts are brought to you by the

The Academy of Diagnostics & Laboratory Medicine logo

Academy of Diagnostics & Laboratory Medicine Designation

Fellows of the Academy use the designation of FADLM. This designation is equivalent to FACB and FAACC, the previous designations used by fellows of the National Academy of Clinical Biochemistry and AACC Academy. Those groups were rebranded as Academy of Diagnostics & Laboratory Medicine in 2023.