Medical liability in pharmacogenetics - risk vs. benefit

Every prescription carries some risk of side effects or treatment failure. Prescribers have always considered age, weight, sex, kidney and liver function, and other medications. Pharmacogenetics (PGx) adds another piece of information: how a person's genes affect the way they process and respond to medications. As more drug labels and clinical guidelines include genetic information, prescribers increasingly ask what this means for their professional responsibility. This article summarizes what drug labels say, what the legal literature discusses and practical steps to use PGx results safely.

This article is general information, not legal advice. Physicians in Canada can contact the Canadian Medical Protective Association (CMPA) for advice on their specific situation.

Why does pharmacogenetics matter for prescribing safety?

For many commonly prescribed medications, a significant share of people are poor, intermediate, rapid or ultrarapid metabolizers and may need a different dose or a different drug to avoid side effects or treatment failure. Testing, ideally before starting treatment, can shorten the trial-and-error period and help prevent some adverse drug reactions. In a large European trial of nearly 7,000 patients, prescribing guided by a 12-gene panel reduced clinically relevant adverse drug reactions by about 30%.

The benefit depends on two things: a reliable test that covers the right genes and variants, and correct interpretation using evidence-based guidelines such as those from the Clinical Pharmacogenetics Implementation Consortium (CPIC). Pharmacogenetic testing is now part of routine care for some gene-drug pairs and is still emerging for others.

What do drug labels say about genetic testing?

Health Canada, the US Food and Drug Administration (FDA) and the European Medicines Agency include pharmacogenetic information in the labels of many medications. The FDA's Table of Pharmacogenetic Associations lists gene-drug pairs for which the FDA considers the evidence sufficient to support prescribing recommendations, pairs with a potential impact on safety or response, and pairs that affect drug levels only. Label wording varies:

• Testing required before use. For a few medications, labels require a genetic test before starting. For example, abacavir (an HIV medication) requires testing for HLA-B*57:01, and siponimod (for multiple sclerosis) requires CYP2C9 testing.
• Testing recommended for some patients. The carbamazepine label recommends testing for HLA-B*15:02 in patients with ancestry from populations where it is common, because of the risk of severe skin reactions.
• Genetic information to guide treatment. Many labels describe how genes affect dosing or response without requiring a test. For example, clopidogrel's boxed warning states that CYP2C19 poor metabolizers get less benefit, and the warfarin label includes a dosing table based on genetic variants. (Warfarin's boxed warning itself is about bleeding risk.)

Because genotype-specific recommendations are becoming more common, prescribers benefit from knowing the labels and guidelines for the medications they prescribe most often.

What does the legal literature say about liability?

Legal commentators, including Gary Marchant and Rachel Lindor in Genetics in Medicine, have described two main sources of potential liability as personalized medicine grows:

• Not considering available genetic information, for example when a drug label recommends testing or when a patient brings relevant results, and a preventable adverse reaction occurs.
• Misinterpreting or misapplying genetic results, for example acting on recommendations from a poorly validated test.

They also note that courts increasingly judge care by what a reasonable, informed practitioner would do, rather than only by local custom. In the United States, a lawsuit was filed in 2012 (Scholz v. Kaiser Foundation Hospital) by a patient who developed Stevens-Johnson syndrome after taking carbamazepine without being tested for HLA-B*15:02, as the label recommends for patients of Asian ancestry. In Canada, the CMPA has published guidance on the new obligations that genetic testing creates for physicians.

Lack of familiarity with PGx is one of the main barriers to using it. Training and decision support, such as pharmacist reviews, can help close this gap.

How can prescribers use PGx results safely?

• Check the test's quality. Use results from an accredited laboratory that tests the AMP-recommended variants, with recommendations based on CPIC, the Dutch Pharmacogenetics Working Group (DPWG) or drug labels.
• Consider results when they are available. If a patient brings PGx results, review them for the medications you are prescribing.
• Look at the whole picture. Drug interactions, age, kidney and liver function and other factors can change how a genetic result applies.
• Document your reasoning, including when you decide not to follow a recommendation and why.
• Ask for help. A pharmacist trained in pharmacogenetics can help interpret results and suggest options.

What happens in common scenarios?

Scenario A: a normal metabolizer. The patient learns they are a normal metabolizer for the medication being prescribed. The prescriber can proceed with standard dosing, with added confidence. The result is still valuable for life, because it can guide many future prescriptions.

Scenario B: a poor or ultrarapid metabolizer. The patient's report recommends a dose change or an alternative medication. If the prescriber follows a guideline-based recommendation, the patient is more likely to avoid side effects or treatment failure. If the prescriber decides not to follow it, for example because of other clinical factors, documenting the reasoning and monitoring the patient closely is good practice. If an adverse reaction occurs that the genetic result could have helped prevent, the decision not to consider the result may be questioned.

How can Pillcheck help prescribers?

Pillcheck combines a PGx test performed in CAP- and COLA-accredited clinical genetic laboratories in Canada with a medication review by a clinical pharmacist trained in pharmacogenetics. Recommendations follow CPIC guidelines and Health Canada and FDA drug labels. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. Pillcheck does not report HLA genes, so HLA testing, such as HLA-B*15:02 before carbamazepine, should be ordered through a clinical laboratory when recommended. Prescribers can find free educational resources and contact our team on our healthcare provider page.

Summary

• Pharmacogenetic information appears in a growing number of drug labels, from required testing (for example, abacavir and siponimod) to dosing information (for example, clopidogrel and warfarin).
• The legal literature describes risks both from not considering available genetic information and from misinterpreting results.
• Reliable tests, guideline-based recommendations, documentation and pharmacist support help prescribers use PGx results safely.
• PGx testing can help reduce adverse drug reactions when used correctly.
• This article is general information, not legal advice.

Frequently asked questions

Do I have to follow every recommendation in a PGx report?

No. Recommendations support clinical judgment. Consider them together with the patient's full clinical picture, and document your reasoning if you choose a different approach.

Which drugs require a genetic test before prescribing?

Only a few labels require testing, such as abacavir (HLA-B*57:01) and siponimod (CYP2C9). Many more labels recommend testing for some patients or include dosing information based on genes. The FDA's Table of Pharmacogenetic Associations and CPIC guidelines are good starting points.

Where can I get advice about liability?

Physicians in Canada can contact the Canadian Medical Protective Association (CMPA) for advice about their specific situation.

Can a pharmacist help interpret results?

Yes. Every Pillcheck includes a review by a pharmacist trained in pharmacogenetics, who provides written recommendations for the prescriber.

References

1. US Food and Drug Administration. Table of Pharmacogenetic Associations.
2. Marchant GE, Lindor RA. Personalized medicine and genetic malpractice. Genet Med. 2013;15(12):921-922.
3. Canadian Medical Protective Association. Genetic testing: New options, new obligations. 2013.
4. Bousman CA, Mukerjee G, Men X, Dorfman R, Müller DJ, Thomas RE. Encountering Pharmacogenetic Test Results in the Psychiatric Clinic. Can J Psychiatry. 2022;67(2):95-100.
5. Haga SB, Allen LaPointe NM, Moaddeb J. Challenges to integrating pharmacogenetic testing into medication therapy management. J Manag Care Spec Pharm. 2015;21(4):346-352.
6. Mills R, Voora D, Peyser B, Haga SB. Delivering pharmacogenetic testing in a primary care setting. Pharmgenomics Pers Med. 2013;6:105-112.
7. Swen JJ, van der Wouden CH, Manson LE, et al. A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study. Lancet. 2023;401(10374):347-356.
8. Scholz v. Kaiser Foundation Hospital, RG12614636, Alameda County Superior Court (filed January 30, 2012).
9. Sharpe NF, Carter RF. Genetic Testing: Care, Consent, and Liability. Hoboken, NJ: Wiley-Liss; 2006.