Skip to main content
Premium Trial:

Request an Annual Quote

Boston Children's, MCW to Assess Broad PGx Testing of Children in New 1,000-Patient Study


Researchers from Boston Children's Hospital, working with the Medical College of Wisconsin and the Children's Hospital of Wisconsin Research Institute, are planning to preemptively test 1,000 children in several different clinical care areas using a broad PGx genotyping approach as part of a study called InforMED Kids

The team hopes the effort will demonstrate the value of such testing in predicting drug response and adverse events in children, and potentially identify new associations between PGx variants and variations in drug response, Shannon Manzi, the study's principal investigator, told PGx Reporter this week.

"The goal of this is that there is not a study out there looking at broad PGx platform preemptive testing in a varied group of patients with different backgrounds and disease states," Manzi said.

"Within each of the different disciplines we are including, physicians have a gene list, a subset of those that are on the platform we are using [and] that they are interested in looking at. But above and beyond that we ... can look at patients across the board and decide whether or not there is influence of genotype on any of their outcomes," she said.

In the study, the Medical College of Wisconsin will analyze patient samples using Affymetrix's DMET-plus array, which gauges 1,936 markers in 231 genes associated with drug metabolism.

Boston Children's is currently recruiting patients for the study from four disease areas — epilepsy, end-stage renal, inflammatory bowel, and cardiology — and plans to also expand to psychiatry by the end of this month, Manzi said.

"DMET is SNP-based so it's not likely we will find a new gene or new variant," Manzi said, "But we [might] find that combinations of different genotypes have an influence."

As part of the study, the group is planning to integrate some genetic testing results into patients' electronic medical records. Boston Children's already has an EMR system into which it has integrated patient data on several drug-genotype pairs. When a physician prescribes a particular drug an alert pops up indicating the relevant genotype information. Manzi said the EMR system currently alerts doctors with regard to 14 drugs whose effectiveness or potential side effects are linked to variants in TPMT, CYP2C9, and VKORC1.

The next gene to be included in the alert system will be CYP2C19, Manzi said, and overall, the group expects the alert system to cover up to 30 drugs by the end of the month.

In the InforMED Kids study, the team will track patients prospectively, but also in some cases they will look at past drug reactions as well.

"In many of these patients, physicians are interested in the study because they had some events during treatment [in the past], so though many patients may go forward and start drugs that are relevant to genes we returned, for others we may be looking at things that happened in the past," she said.

According to Manzi, the study also has the potential to provide cost data that could help convince payors to cover broad PGx testing strategies in pediatric populations.

"Obviously one central thing to demonstrate is cost avoidance," she said. "So, if we do this test on 50 patients how much are we going to save by not admitting that one patient with the adverse reaction to the hospital for three days? It depends on how cheap the test is and how many patients we have to run it on before that one ADR happens."

Apart from InforMED Kids, Manzi said she and her colleagues are also interested in surveying payors on the subject of preemptive PGx testing to gauge their current understanding and opinions.

Additionally, she said, Boston Children's might be able to glean some information about payor positions as it moves forward in offering DMET-based PGx testing clinically. "We'll be able to see as the clinical DMETs come back who pays for them, and why," she said.

According to Manzi, the group has included in the study protocol the potential to move to another analysis platform, which could include sequencing, at some point. "We'll see as we go forward," she said.

MCW has been developing a sequencing-based pharmacogenomics panel on the Ion Torrent PGM since 2012, but currently does not offer sequencing-based PGx testing in the clinical setting.

Overall, the study is intended to take four years, with recruitment of a 1,000-patient cohort by the end of the second year, but Manzi said it looks like recruitment may be completed early.

"We are nearing 300 right now, after three months and two weeks, and as we add new clinical [areas] that increases the numbers we can enroll even more. So, I don’t think it will take the full two years to do," she added.

While the Boston Children's study is the first to evaluate preemptive PGx testing in a diverse pediatric population, several others have adopted similar strategies in the adult setting.

The Mayo Clinic, for example, announced this month that it is conducting a pilot project in collaboration with the Pharmacogenomics Research Network and the Electronic Medical Records and Genomics Network that will integrate sequencing-based pharmacogenomics data into the EMRs of more than 1,000 patients.

Vanderbilt's PREDICT program now reports PGx markers for several drugs, including the antiplatelet drug clopidogrel, the anticoagulant warfarin, the cholesterol-lowering drug simvastatin, and thiopurine drugs for cancer and autoimmune disorders.