Implementation of PPI Medication PGX Testing

The long-term objective of this research is to implement pharmacogenomic (PGX) testing of
approved gene-drug pairs to maximize the efficacy and minimize adverse events for drugs that
are used to treat childhood disease. Personalized medicine, that is, the use of the patient's
own genetic information to predict the right dose of the right drug, has been a goal of
medicine's since the publication of the human genome and HAPMAP projects. However, the
adoption of PGX testing has been slow owing to several barriers and challenges. Recently
President Obama announced the precision medicine initiative, which includes PGX testing, and
has earmarked $ 1 b to implement it. The precision medicine initiative is expected to move
personalized medicine forward so that most patients including pediatric patients will
benefit. The Nemours Children's Health System is uniquely positioned to lead the effort to
personalize medicine among pediatric patients. The goal of the proposed 1-year pilot project
is to implement PGX testing in the Nemours children's health system. The experience,
knowledge and skills gained in this pilot project will position Nemours to help lead
precision medicine initiatives including PGX testing among pediatric populations. To
implement PGX testing in Nemours we propose to begin testing the cyp2c19 - proton pump
inhibitor gene-drug pair in the division of gastroenterology, Nemours children's hospital. A
total of 120 children 2-17 yo who have been diagnosed with gastroesophageal reflux disease
(GERD) or other stomach acid mediated conditions for which a PPI is prescribed will be
recruited into the study by pediatric gastroenterologists (aim 1a). Drs. Franciosi and Lima
will educate staff in the division of PGX testing and of the study. GI pediatricians are not
required to participate in PGX testing. After obtaining consent, the study coordinator will
obtain and bar code samples of saliva from the patient. Samples will be genotyped by Spartan
Rx, a point-of-care genotyping platform, which are housed (2 of them) in the division of
pathology. Loss-of-function alleles (*2, *3) and the gain-of-function allele (*17) are
identified in < 60 minutes. The result of genotyping will be checked by dr. Badizadegan and
entered into the patient's EMR. Clinical Decision Support (CDS) tools will advise Drs.
Badizadegan and Franciosi of the patient's metabolic phenotype based on cyp2c19 genotype. Dr.
Franciosi (or other GI pediatricians) will decide the dose of PPI to use based CDS tools
carrying algorithms for conventional dosing and for genotype-guided dosing of PPIs. The
electronic prescription for the PPI with genotype-guided dosing will be called in. PPI
efficacy and safety for each study participant will be monitored weekly (aim 1B) by
collecting and recording scores on validated GERD and adverse reaction questionnaires.
Efficacy and safety scores will be communicated by each participant (or caregiver) using
mobile devices (iPhone; computer) and recorded using redcap. Dr. Blake will supervise this
phase of the study. Outcome metrics for aim 1A include: % of patients agreeing to volunteer
for the study; % of patients reporting efficacy and toxicity data; % of providers agreeing to
participate in study; and % of participants agreeing to future use of DNA. Outcome metrics
for aim B will be judgments by Dr. Franciosi and his staff regarding success based on scores
from GERD and adverse event questionnaires.

Inclusion Criteria:

- Children diagnosed with Gastroesophageal Reflux Disease (GERD) or a stomach acid
mediated condition for which a PPI is prescribed.

- Currently taking or will be prescribed Proton Pump Inhibitor (PPI) medication

- Parents/legal guardians and or child must also have access to the internet and a valid
email address to complete weekly required forms.

Exclusion Criteria:

- Children who have had peptic ulcer surgery;

- with a history of PKU

- with a history of previous adverse effects from PPI treatment or a sensitivity to
aspartame (NutraSweet, Equal);

- who are non-adherent including inability or unwillingness of the legal guardian to
provide consent of unwillingness of the child to provide assent;

- who are unable to take study medications;

- who are unable to communicate via telephone or other device;

- who do not have access to a computer with internet access