Aiming to reduce adverse drug reactions—which affect some 70,000 children annually in the U.S.—a study at Boston Children's Hospital, in partnership with the Medical College of Wisconsin(MCW) and the Children's Hospital of Wisconsin Research Institute, is using genetic information to predict children's reactions to medications, ultimately enabling clinicians to select a more individualized therapy for the patient.
Boston Children's has offered targeted pharmacogenomic clinical testing at the hospital since August 2012. The new research study, InforMED Kids, currently is enrolling patients seen in the hospital's epilepsy, end-stage renal, inflammatory bowel disease and cardiology programs, whose patients also typically require multiple medications, and may expand to the department of psychiatry.
The researchers plan to enroll 1,000 patients, along with their healthcare providers; to date, more than 220 patients have enrolled. "Ultimately, our goal is to offer this testing to all patients at the hospital," said the study's principal investigator Shannon Manzi, PharmD, of the Boston Children's department of pharmacy.
Blood samples from patients enrolled in InforMED Kids are sent to MCW, an experienced clinical test provider with clinical-grade genetic assays. MCW and the Research Institute offer one of the most comprehensive clinical testing panels for pharmacogenetics. The results are returned to the patient's healthcare provider at Boston Children's, and families are notified and invited to speak with their provider for more information. Families also can request a consult with a genetic counselor.
The study's primary goal is to determine whether individual genetic differences in enzymes involved in the metabolism or action of a drug predict how patients respond to the drug, as indicated by health surveys and information from patients' electronic medical records.
"This project builds on our longstanding experience in clinical pharmacogenetic testing, as well as our ongoing collaborations with other pediatric hospitals for pre-emptive testing,” said Ulrich Broeckel, M.D., professor of pediatrics at MCW. “Based on the data from other hospitals, we are convinced that this test will help physicians in making better drug decisions and provide another example for the power of comprehensive pharmacogenetic testing."
As the study gathers data on the effects of different genetic variants on drug responses, Manzi and colleagues hope to build a repository and database and ultimately develop prescribing guidelines that tailor treatments to patients' genetic makeup. Few such guidelines now exist.
"If we are aware of the genetic information at the time of medication prescribing, we can often substitute another drug, or in other cases reduce the dosage to avoid the adverse reaction," said Manzi, who chaired the Adverse Events Committee at Boston Children's for 10 years.
Nationwide, according to the Institute of Medicine (IOM) report To Err Is Human, an estimated one in 100 hospital patients experienced a preventable adverse drug event, incurring a cost of about $2 billion for hospital inpatients alone. A review of serious adverse drug events reported to the FDA in 2011 estimates that two to four million people suffer serious injuries each year.
As data come back from the study, the patient's electronic medical record will be flagged when genetic test results indicate potential for an adverse drug effect, and physicians and pharmacists will be informed via pop-up alerts. This process already is in place at Boston Children's for a limited number of drug-gene pairs and is now combined with the existing infrastructure at the Research Institute and MCW.
The study data also will be used to encourage health insurance companies to reimburse the cost of pharmacogenomic screening. Whether current insurers will cover it, and to what extent, are still unclear, said Broeckel and Manzi.
A secondary goal of the InforMED Kids study is to learn whether providers, patients and families find the information useful and get feedback on the reports, to improve user satisfaction and ultimately improve the clinical program for all patients.