NEW YORK – Children's Mercy Kansas City has developed and launched its own 13-gene pharmacogenomic panel that it runs in-house, citing easier integration into clinical workflows and a desire to cut down on wait times.
The Missouri-based pediatric hospital system has been conducting PGx testing for years to guide prescribing decisions, primarily within its GOLDILOKs Clinic, where pediatricians and pharmacists meet with patients and families with complex medication needs, such as those who have experienced adverse reactions to medications or who aren't responding to standard treatment. Providers consider various factors, including PGx, to pinpoint the "just right" medication and dose.
PGx describes how mutations in certain genes can affect patients' ability to metabolize medications, information that can help physicians decide which drugs to prescribe. Genetics-guided prescribing ideally identifies drugs patients may want to steer clear of based on the risk of potential side effects and efficacy concerns, without the patient needing to try it out and experience those issues firsthand.
For the decade that Children's Mercy has been running the GOLDILOKs Clinic, PGx testing has been conducted by external labs, until this fall.
Providers at Children's Mercy realized they could gain efficiencies by bringing PGx testing in-house: creating their own genetic testing panel with variants of interest for its patient population, running the tests in the hospital system's own molecular genetics lab to have better control over turnaround time, and integrating genetic results directly into the electronic health record (EHR) system.
The test Children's Mercy launched internally, dubbed Kiddose PGx, "is a targeted genotyping test that we custom-designed," explained Laura Ramsey, co-lead of the Kiddose PGx program and section chief for individualized therapeutics in Children's Mercy's division of clinical pharmacology. Children's Mercy has said it is the first pediatric hospital in Missouri to offer in-house pharmacogenomic testing.
The Kiddose PGx test examines 79 variants across 13 genes, with implications for dozens of drugs used to treat cancer and heart disease and to prevent organ rejection, and the team is in the process of adding about 10 more variants, as well. Ramsey said that covers all of the PGx variants recommended by the Association for Molecular Pathology and most of those in guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC), an internationally recognized guidelines body.
When a provider orders the Kiddose PGx test, Children's Mercy sends a test kit to the patient's home. Patients use materials in the kit to collect a cheek swab sample and return it to the molecular genetics lab for analysis. That analysis is conducted using Thermo Fisher Scientific's QuantStudio PCR system.
Test results are documented in the hospital system's EHR, including data on a patient's genetic variants, the associated metabolizer status, and what medications might be affected, based on information from CPIC, the Dutch Pharmacogenetics Working Group, and the US Food and Drug Administration.
That's an upgrade from the previous process, in which external labs would return PGx results through their own portal, which providers would copy and paste into a patient note. PGx results "would be buried in a note somewhere," Ramsey said, but now, they "live in the results table in the electronic medical record like any other lab [results]."
All in all, the turnaround time for the Kiddose PGx test is 10 days on average, compared to 24 days when Children's Mercy was sending tests to external labs.
Insurance coverage for the test varies. Without insurance, the out-of-pocket cost for the test is $395.
In the future, the team at Children's Mercy intends to implement clinical decision-support tools within the EHR, such as alerts that notify clinicians when their patients have PGx variants that impact their responses to prescribed drugs, Ramsey said. Children's Mercy plans to install a new EHR from Epic Systems in 2026 and implement those tools after that.
Ramsey noted Children's Mercy has a long history of conducting PGx research. The well-known PGx database Pharmacogene Variation Consortium, known as PharmVar, for example, is housed at the Children's Mercy Research Institute. Ramsey herself has contributed to the CPIC guidelines for selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), two classes of drugs used to treat depression, and is on a CPIC guideline committee that's currently doing an evidence review on antipsychotic medications.
Since its launch in late September, the Kiddose PGx test has been ordered about 80 times, according to Children's Mercy.
The first provider to order the Kiddose PGx test was Stephani Stancil, a clinician scientist in the divisions of adolescent and young adult medicine and clinical pharmacology and toxicology at Children's Mercy. In this case, the patient had tried a medication that hadn't worked and was seeking guidance on what next steps to take.
"We ordered this test to gain more insight into that patient and inform that next prescribing choice," she said. Stancil studies personalized medicine for adolescent mental health conditions, and much of the care she provides focuses on mental health, too, including anxiety and depression.
Diagnoses of these conditions have increased among children and young adults in recent years.
The prevalence of depression increased by about 60 percent from 2017 to 2021, while anxiety increased 35 percent, according to a population study published this fall.
Many of the patients referred to the GOLDILOKs Clinic have a neuropsychiatric disease or family history, so this has been a large proportion of patients for whom PGx testing was ordered at Children's Mercy, Ramsey said. It can be challenging to identify the best medications to treat patients with these conditions, and patients often have to try multiple drugs, doses, or combinations of treatments before symptoms subside in what's commonly referred to as "trial-and-error" prescribing.
For anxiety and depression, "it's a bit of a flip of a coin" what medication a patient will respond best to, Stancil said. "Ideally, we can use as much information about that individual patient as possible to make a more informed choice," including their genetics, she said.
For example, certain variants in the CYP2C19 gene that make patients poor metabolizers of AbbVie's Lexapro (escitalopram), a commonly prescribed SSRI and antidepressant, may also increase their likelihood of experiencing side effects. In guidelines published last year, CPIC said there is strong evidence to consider an alternative drug not predominantly metabolized by the CYP2C19 enzyme for these patients or start these patients on a lower dose of the drug with a slower titration schedule.
In situations where there are PGx guidelines to inform prescribing decisions, Stancil said testing is something she'll often recommend to patients and families at the outset, even before they've failed an initial medication. Eventually, she'd like to see healthcare organizations move toward preemptive PGx testing, so that results are already available when prescribing.
"Pharmacogenetic testing is one tool that we have that can make my prescribing decision a bit more informed," Stancil said.