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Drug development for pediatric neurogenic bladder dysfunction: Dosing, endpoints, and study design
Author(s) -
Momper Jeremiah D.,
Karesh Alyson,
Green Dionna J.,
Hirsch Mark,
Khurana Mona,
Lee Jinoo,
Kim MyongJin,
Mulugeta Yeruk,
Sachs Hari C.,
Yao Lynne,
Burckart Gilbert J.
Publication year - 2014
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.345
Subject(s) - medicine , clinical trial , drug development , dosing , drug , clinical study design , intensive care medicine , pharmacokinetics , clinical endpoint , etiology , disease , pharmacology
Pediatric drug development is challenging when a product is studied for a pediatric disease that has a different underlying etiology and pathophysiology compared to the adult disease. Neurogenic bladder dysfunction (NBD) is such a therapeutic area with multiple unsuccessful development programs. The objective of this study was to critically evaluate clinical trial design elements that may have contributed to unsuccessful drug development programs for pediatric NBD. Trial design elements of drugs tested for pediatric NBD were identified from trials submitted to the U.S. Food and Drug Administration. Data were extracted from publically available FDA reviews and labeling and included trial design, primary endpoints, enrollment eligibilities, and pharmacokinetic data. A total of four products were identified. Although all four programs potentially provided clinically useful information, only one drug (oxybutynin) demonstrated efficacy in children with NBD. The lack of demonstrable efficacy for the remainder of the products illustrates that future trials should give careful attention to testing a range of doses, using objectively measured, clinically meaningful endpoints, and selecting clinical trial designs that are both interpretable and feasible. Compiling the drug development experience with pediatric NBD will facilitate an improved approach for future drug development for this, and perhaps other, therapeutic areas.