Off-label Use of Medications in Pediatric Patients; Pediatric Formulation InnovationGREAT II MeetingOctober 21-22, 2013Anne Zajicek, MD, PharmDChief, Obstetric and Pediatric Pharmacology and Therapeutics Branch

DisclosureI have no conflicts to disclose.2

OutlineBest Pharmaceuticals for Children Act (BPCA)Off-label Use of MedicationsStudy Design and Pediatric EndpointsFormulations3

Best Pharmaceuticals for Children Act (BPCA)Role of the National Institutes of HealthPrioritize drugs/therapeutic areas, Sponsor pediatric clinical trialsSubmit data to FDA for labeling change4

Prioritization: Areas of Focus2005: hypertension2006: infectious diseases2007: formulations2008: biodefense 2009: adolescents, OTC treatments for cough and cold, atypical antipsychotics2010: gastroenterology, endocrinology, neurology2011: hematology, pulmonary, renal, formulations5

Gaps/problemsAcademic vs regulatory framework, goalsLack of validated outcome measuresNeed for validated biomarkers6

Validating Endpoints for Neonates with “Hypotension”Questions:How is BP measured in the NICU?Have these methods been standardized or validated in this population?What is a normal neonatal BP at a given gestational or postnatal age?What is the definition of hypotension? Value – systolic/diastolic/mean BP“Perfusion”ShockOliguria or anuriaWhat is the clinical endpoint in the treatment of hypotension?How is this endpoint measured?7

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Medication Adherence and Health Care Utilization in Pediatric Chronic Illness: A Systematic Review McGrady ME and Hommel SA. Pediatrics 2013; doi: 10.1542/peds.2013-1451CONCLUSIONS: Medication non-adherence is related to increased health care use in children and adolescents who have a chronic medical condition and should be addressed in clinical care. Future studies should include randomized controlled trials examining the impact of adherence promotion efforts on health care use and costs. 9

Isotretinoin 10 mg10

Hydroxyurea 500 mg 11

Pediatric formulations 201312

Pediatric FormulationsNeed for swallowabilityPalatability- taste and textureRight dosage increment13

ProblemsInaccurate dosingLack of stabilityBad tasteAdherence problemsLack of standardization in extemporaneous compoundingEnvironmental safety from home compounding14

NICHD-FDA Formulations PlatformIn 2009, the National Institutes of Health (NIH) and the FDA entered into an Inter-Agency Agreement (IAA) entitled Pediatric Formulations Platform using NIH BPCA funds to fund FDA chemists’ assessment of pediatric product formulations and produce an open-source, publicly available approach to pediatric oral formulations manufacturing.www.bpca.nichd.nih.gov15

Funding Opportunity AnnouncementsDevelopment of Appropriate Pediatric Formulations and Pediatric Drug Delivery Systems (PAR 11-301-305)R01, R03, R21SBIR, STTR16

Funding Opportunity Announcementshttps://www.nichd.nih.gov/about/org/der/branches/opptb/Pages/overview.aspx Translation Research in Pediatric and Obstetric Pharmacology Biomarkers: Bridging Pediatric and Adult TherapeuticsDevelopmental PharmacologyMechanisms of Adverse Drug Reactions in Children17

Challenge Questions1. Lack of validated outcome measures in children are an impediment to drug development.TrueFalse2. Lack of easy to swallow, palatable formulations is a problem only for children.TrueFalse18

Contact InformationAnne Zajicek, MD, PharmD301-435-6865zajiceka@mail.nih.gov 19