Because of a paucity of pediatric clinical drug trials, up to 80% of pediatric drug use is considered unapproved or """"""""off-label"""""""". Clinicians are forced to extrapolate findings from adult studies and prescribe medications to children on a trial and error basis without age-specific research on dosing, safety, or efficacy. Increasing representation of pediatric patients in clinical trials is a high priority area for the National Institute of Child Halth and Human Development (NICHD), which oversees activities under the Best Pharmaceuticals for Children Act (BPCA) and recently established the Pediatric Trials Network (PTN) to support clinical trials conducted under the BPCA. Though the lack of high quality evidence to support pediatric drug therapy has been previously recognized, there has not until now been an adequate data source for comprehensive surveillance of the pediatric trial portfolio. This proposal uses a unique develops methods to, for the first time, take stock of the entire pediatric research portfolio, assessing the relevance and alignment of research with actual disease burden as well as quality and validity of trials. We propose to use this registry to analyze pediatric drug trials in three specific aims: 1) To determine how closely the pediatric research portfolio corresponds to actual pediatric disease burden;2) To determine the prevalence of pediatric patients in drug trials and trial characteristics associated with the study of pediatric patients;and 3) To measure quality indicators of pediatric trial design and reporting as compared to adult trials. We hypothesize that the focus of pediatric drug research corresponds poorly to high priority areas defined by actual global pediatric disease burden. Further, we hypothesize that the design and reporting of pediatric trials are less methodologically rigorous than adult-based trials. Because the body of clinical trials is constantly evolving, this work provides not only a snapshot of current pediatric drug trials, but also a framework and toolkit for surveillance of the evidence base going forward. Metrics developed under these aims will be made publicly available through a prototype of a web-based front application to that automatically displays the current status of pediatric clinical trials.

Public Health Relevance

This proposal addresses the lack of high-quality clinical trials available to support the evidence-based use of medications in pediatric populations. Off-label drug use is prevalent among critically ill, hospitalized patients as well as millions of children treated for minor illnesses in the ambulatory setting. Without high-quality clinical data, children given untested medications may suffer harm or may forgo potentially effective treatments. Defining the current state of pediatric drug research in terms of its relevance and quality will allow directed measures to improve the pediatric evidence-base around pharmacotherapy.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (SEIR)
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Zajicek, Anne
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Children's Hospital Boston
United States
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Pica, Natalie; Bourgeois, Florence (2016) Discontinuation and Nonpublication of Randomized Clinical Trials Conducted in Children. Pediatrics 138:
Hwang, Thomas J; Bourgeois, Florence T (2014) New regulatory paradigms for innovative drugs to treat pediatric diseases. JAMA Pediatr 168:879-80
Bourgeois, Florence T; Monuteaux, Michael C; Stack, Anne M et al. (2014) Variation in emergency department admission rates in US children's hospitals. Pediatrics 134:539-45
Hwang, Thomas J; Kesselheim, Aaron S; Bourgeois, Florence T (2014) Postmarketing trials and pediatric device approvals. Pediatrics 133:e1197-202
Pfiffner, Pascal B; Oh, JiWon; Miller, Timothy A et al. (2014) as a data source for semi-automated point-of-care trial eligibility screening. PLoS One 9:e111055
Bourgeois, Florence T; Olson, Karen L; Ioannidis, John P A et al. (2014) Association between pediatric clinical trials and global burden of disease. Pediatrics 133:78-87
Mandl, Kenneth D; Kohane, Isaac S; McFadden, Douglas et al. (2014) Scalable Collaborative Infrastructure for a Learning Healthcare System (SCILHS): architecture. J Am Med Inform Assoc 21:615-20
Bourgeois, Florence T; Kim, Jeong Min; Mandl, Kenneth D (2014) Premarket safety and efficacy studies for ADHD medications in children. PLoS One 9:e102249
Dunn, Adam G; Bourgeois, Florence T; Coiera, Enrico (2013) Industry influence in evidence production. J Epidemiol Community Health 67:537-8
Murthy, Srinivas; Mandl, Kenneth D; Bourgeois, Florence (2013) Analysis of pediatric clinical drug trials for neuropsychiatric conditions. Pediatrics 131:1125-31

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