The Problem with Pharmacogenetic Testing
By Adrienne Mueller, PhD
January 27, 2021
Your genetics can determine how you respond to medications. Knowing more about your genetics can help your doctor decide which medication to prescribe, and even inform the dosage. Over the last few decades, the genetic testing industry has boomed, and currently over a dozen companies offer personal genetic reports with information about your predicted response to different classes of drugs. The companies that provide pharmacogenetic testing each look at a panel of genes and determine which version, or variant, of those genes you possess. Your report will include not just a list of your genetic variants, but also a description of your likely gene-drug interactions that then guides your doctor’s therapeutic decisions. And that is where the problem lies.
In an article recently released in the Journal of Personalized Medicine, first author Sally Luvsantseren, MD and senior author Latha Palaniappan, MD describe the case of a 65-year-old woman seeking treatment for anxiety and depression. Her experience highlights the issues with the current state of pharmacogenetic testing. The patient received genetic reports from two different companies and although they agreed in their analysis of which genetic variants she possessed, they disagreed in their interpretation of that information. One company’s report stated that she would have a poor response to selective serotonin reuptake inhibitors (SSRIs), a common class of antidepressant medication, and the other company’s report stated that her response to SSRIs would be normal. This ambiguity regarding her genetics and treatment increased the patient’s anxiety and also made deciding on her medication very challenging for her physician. Luvsantseren et al further investigated why these reports differed and how to resolve those differences.
The investigators found that the companies were using different evidence – different sets of scientific studies and different algorithms to analyze the genetic information – to inform their interpretation of the genetic data. Unfortunately, this field is still so new that the FDA does not have strong policies on how to interpret pharmacogenetic information. However, there is an international consortium of volunteers, the Clinical Pharmacogenetics Implementation Consortium (CPIC), who have devoted themselves to providing guidelines to help inform therapeutic decisions.
CPIC’s guidelines are evidence-based, peer-reviewed, open-access and endorsed by numerous clinicians, scientists and professional societies. In the case of this patient, the CPIC guidelines aligned with the report of the company that stated she would have a normal response to SSRIs, and her physician therefore used those recommendations to inform her treatment.
Although this patient ultimately received appropriate care; it was a stressful, confusing and challenging process. Unfortunately, her case is not unique, and many patients will experience similar difficulties regarding therapeutic recommendations. Pharmacogenetic information can certainly improve patient care, but the pharmacogenetics industry needs to move towards standardization of genetic variant testing and interpretation. Companies should conform to evidence-based, open-access, and internationally peer-reviewed guidelines, such as those provided by CPIC.
Additional Stanford Cardiovascular Institute-affiliated authors who contributed to this study include Michelle Whirl-Carrillo, Katrin Sangkuhl, Nancy Shin, Alice Wen, and Russ Altman.