Since entering the field of pharmacogenomics (PGx) in 2000, I’ve witnessed firsthand the transformative potential of genetic testing to personalize medication management and reduce avoidable harm. We’ve evolved from sporadic testing focused on specific drug-gene pairs to comprehensive panels that can inform treatment for over one hundred commonly prescribed medications across numerous specialties, including mental health, pain management, cancer care, and cardiovascular health.
Research shows significant reductions in emergency department visits, hospitalizations, adverse drug events, healthcare costs, and even mortality rates with the use of PGx. Given that adverse drug reactions rank as the fourth leading cause of death in the U.S. and that non-optimized medications incur higher costs than any chronic disease or the drugs themselves, the case for PGx is clear. Yet, a persistent fallacy among providers seems to remain; they can wait for FDA requirements or guidelines from bodies like National Comprehensive Cancer Network before implementing genetic testing.
Integrating PGx testing is not just a matter of improving patient care; it’s also a crucial step in mitigating medical liability risk. Medication-related harm ranks among the top three causes of malpractice claims, with a staggering 75% resulting in paid indemnity. Moreover, a review of genomic malpractice cases in the United States suggested that 57% of the genomic medical malpractice cases could have been avoided if genetic testing had been performed.
When taught about PGx as part of a diverse community dialogue, patients believe that their healthcare providers have the responsibility to tell them if PGx could impact their medication management and let the patient decide whether to test or not, even when insurance may not cover the testing. This proactive approach not only fosters trust but can also be a safeguard against legal repercussions.
Courts ordered Oregon Health & Science University to pay $1 million to a widower who lost her husband to avoidable toxicity from capecitabine. Both 5-FU and capecitabine are commonly given after cancer surgery, especially colorectal, to knock out any residual cancer cells. A simple cheek swab PGx test would have revealed that a standard dose was twice that for David McIntyre. Like up to 8% of patients, he had a PGx variation that increased his chance of treatment-related death at a standard dose over 25X, requiring lower doses for safety. His wife also asked that OHSU start discussing testing with patients exposed to these medications as part of the settlement. Notably, testing was not required by the FDA nor bodies such as NCCN, but the science clearly demonstrates that testing can help avoid harm, and the Clinical Pharmacogenomics Implementation Consortium provides management guidance. After hearing about the case, a number of cancer centers finally started implementing this life-saving testing, many as part of comprehensive panels that also provide guidance for other medications needed during cancer care and beyond.
Karen Merritt, a member of Advocates for Universal DPD/DPYD Testing, who lost her mother in similar circumstances, is aware of five similar cases currently pending litigation. She noted that many cases like this end up settling out of court under non-disclosure agreements, so the stories often never reach the public or healthcare providers that need to hear about them. Notably, none of the deaths in these cases were tracked as adverse drug events in healthcare records. This is the tip of the iceberg in underscoring the urgent need for systematic integration of PGx testing to reduce patient harm and subsequent litigation.
While PGx testing for individual genes such as DPYD offers valuable insights, it fails to capture the full picture. One study showed that almost 60% of patients were taking medications with evidence-based drug or dose change guidance in more than one clinical area, based on medications taken at the time of PGx panel testing. Another study of almost 500,000 patients in the U.K. showed that one in 11 prescriptions have an evidence-based drug or dose change guidance based on PGx panel testing, further validating the need to apply this information across disease states and for life. This is where the Right Drug Dose Now Act of 2024 comes in. This bipartisan legislation, re-introduced by Swalwell and Crenshaw, aims to eliminate barriers to the widespread implementation of these critical tests, addressing the alarming statistic that an American loses their life every two minutes due to adverse drug events, many preventable.
A brave young college student, Abby Yoder, testified in support of the act. She was tested as a child, but her results were lost as a PDF in the EHR of her ordering provider. The escitalopram (Lexapro) she was prescribed in college led to suicidal thoughts she thankfully knew were not normal, leading to quick discontinuation. A chance encounter with her old healthcare provider resurfaced her test results, showing this drug should have been avoided. Patients with certain PGx variations, like Abby, are 34% more likely to become victims of suicide on escitalopram (Lexapro) or citalopram (Celexa). This oversight not only jeopardized her health but also points to the critical need for prioritizing discrete storage and reuse of PGx results in the EHR.
Abby’s same PGx variation means that Plavix (clopidogrel), a medication used to prevent heart attacks and strokes, will likely not work for her. The same is true for about 15% of white patients and 40% to 50% of patients with Asian and Pacific Islander ancestry. In a 2024 retrial, the makers of Plavix lost a case for $916 million in Hawaii for not making it more clear that non-white patients were more likely to fail therapy. Again, this aids in making the case for comprehensive, disease-agnostic testing and prioritizing the integration of PGx in the clinical workflow.
Steps to Mitigate Risk
For healthcare executives and providers, the time is now to commit to safer, more personalized patient care. Here are some actionable steps:
- Educate Your Team: Familiarize yourself and your staff with the basics of pharmacogenomics. Resources like the FDA’s pharmacogenetic associations and CPIC guidelines on actionable, evidence-based drug-gene pairs provide essential knowledge.
- Adopt PGx Panel Testing: Implement broad PGx testing panels that can inform medication decisions across specialties.
- Leverage Pharmacists. As medication experts, they can assist busy providers in implementing programs and being sure results are applied holistically.
- Invest in Clinical Decision Support: Utilize integrated clinical decision support systems that flag the need for genetic testing and provide real-time, evidence-based guidance on drug and dose optimization.
- Advocate for Legislative Support: Get involved in legislative efforts like the Right Drug Dose Now Act to promote policies that support the integration of PGx testing to enhance patient safety.
The evidence is compelling, and the need for action is urgent. By embracing pharmacogenomics, healthcare organizations can significantly improve patient outcomes and satisfaction and reduce the risk of medical liability.
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Kristine Ashcraft
Kristine Ashcraft has worked in pharmacogenomics since 2000 and was named one of the 25 leading global voices in precision medicine. She is the Founder and President of YouScript (an Aranscia Company), an award-winning clinical decision support tool that has integrated PGx-guided personalized prescribing in the clinical workflow for over a decade. Kristine has 25+ years of experience in various C-level, board, customer success and business development roles. She has authored multiple publications on the clinical and economic benefits of pharmacogenomic testing and serves on numerous PGx advisory groups including the STRIPE Steering Committee, the FDA collaborative community for pharmacogenomics, CPIC, and the American Cancer Society Cancer Action Network PGx task force.
