Why do certain medications work well for some patients but not others? 

Patients’ ages, medical histories, health conditions and other medications can be factors. Yale New Haven’s Pharmacogenomics program is showing just how important genetic differences are. Pharmacogenomics is the study of how inherited differences in enzymes, transporters and other proteins can affect response to medications. 

“Traditionally, medications are dosed based on what works for the average person,” said Rebecca Pulk, PharmD, Yale New Haven Health’s Pharmacogenomics clinical coordinator. “Yet we know that individuals can have very unexpected responses to the same medication.” 

These differences can often be linked to variations encoded in the DNA unique to each patient. One patient who has inherited the ability to process a medication too quickly may never build up enough in the body to benefit from the drug. Another patient may not be able to clear the same drug at all, increasing the risk of side effects unless the dose is lowered. 

Information gathered with a one-time pharmacogenomics test can be applied across a patient’s lifetime to make medications safer and more effective. There are evidence-based guidelines on applying pharmacogenetic information to the dosing for 80 medications. 

Within Yale New Haven Health, pharmacogenomics is being introduced into routine clinical care through a collaboration among Pharmacy, Laboratory Medicine and Information Technology Services. Panel-based testing will be applied to patients who could benefit, and results fully integrated within the medical record. 

“We can test all relevant pharmacogenomic markers with a single test – even markers that are experimental today, yet may affect patient care in the future,” said Wade Schulz, MD, PhD, YNHHS’ medical director of Data Science. “Since we are integrating this genomic information into the electronic medical record, it can be used by all care team members. As our knowledge base grows, we will be able to use additional banked information without having to retest patients.” 

Multiple clinical pilots are under way in YNHHS to build evidence of pharmacogenomic testing’s clinical impact and assess the financial sustainability of adding testing to the standard of care. 

The first pilot focuses on patients 65 and older who experience an acute coronary event and present at hospitals throughout YNHHS. Pharmacogenomic testing of these patients helps ensure that clopidogrel, an antiplatelet agent, is reserved for patients for whom it is safe and effective. 

Other clinical pilots involve patients being evaluated for bone marrow or kidney transplants. Pharmacogenomic information gathered before these procedures allows care teams to customize immunosuppressive therapies, infection prophylaxis and pain control. 

To date, over 90 percent of the nearly 200 patients tested have at least one change that could affect medication therapy across their lifetimes. Over 25 percent had a finding that directly affected the selection and dosing of the medications that triggered testing. The pilots have also identified medication issues beyond those related to the triggering indication. 

“This testing has significant implications for patients, in terms of outcomes and safety,” said Richard Lisitano, YNHH vice president, Administration. “Our hope is that pharmacogenomics will become one of the standard tools we use to determine the best medication and dose for each patient.”