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Department of Pediatrics; Division of Clinical Pharmacology and Therapeutics; Department of Anesthesia and Critical Care Medicine; Division of Critical Care Medicine; The Children's Hospital of Philadelphia (Su, Zuppa) Department of Pediatrics; Division of Clinical Pharmacology and Therapeutics; Philadelphia, PA; su{at}email.chop.edu (Adamson)
To the Editor:
In their editorial that accompanied four articles on dexmedetomidine use in children, Drs. Tobin, Shafer, and Davis (1) assessed the broad impact of the pharmaceutical industry's lack of interest in conducting appropriate drug development studies for children. Yet the solution to "untying the Gordian knot" extends beyond the Food and Drug Administration (FDA) and industry. A critical factor largely absent from the discussion is training clinical investigators to meet the needs of pediatric drug development. We take issue with the contention that investigator-initiated studies cannot meet "... the FDA's definition for adequate and well controlled studies, ..." because adequately trained investigators can certainly undertake such studies when given adequate support.
Our recent experience with dexmedetomidine shows how this can be done. From October 2003 to December 2005, we repeatedly attempted to engage various members of Abbott Pharmaceuticals to initiate appropriate pediatric studies. These efforts failed. However, we garnered limited support from the National Institute of Child Health and Human Development's Pediatric Pharmacology Research Unit (PPRU), allowing us to implement a pediatric, drug development plan for dexmedetomidine. The PPRU comprises 13 academic sites that develop and perform clinical pharmacologic research in the pediatric population, often in collaboration with industry partners. The network includes experts in quantitative drug analysis, pharmacokinetic/pharmacodynamic (PK/PD) modeling, pediatric clinical trial design, and a wide range of pediatric subspecialties. Our initial trial is a PK/PD study of dexmedetomidine administered as a continuous infusion in infants after open-heart surgery. This dose-escalation study evaluates both the PK profile in this population and concentration-response relationships with respect to hemodynamic variables, tracheal extubation readiness, quality of sedation, and overall safety. The trial is nearly complete, and has produced a preliminary model of dexmedetomidine PK in infants. This model will enable us to design the next stage of investigations. As described in the accompanying editorial (2), our investigator-initiated study is being performed under an Investigational New Drug application, and our interaction with the FDA has been productive.
There is a paucity of funding and an insufficient number of programs available to train experts in pediatric drug development. Although there are more than 250 children's hospitals in the United States, only a few train pediatric subspecialists in clinical pharmacology. Future efforts to assure appropriate design of clinical pharmacologic studies in children must include a comprehensive effort to train young investigators. These investigators are desperately needed in academia, industry, and the FDA. The solution to this Gordian knot is perhaps not that complex. Society, academia, government, and industry must simply decide that it is important enough to untie.
REFERENCES
This article has been cited by other articles:
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  J. R. Tobin, S. L. Shafer, and P. J. Davis Untying the Gordian Knot Anesth. Analg., April 1, 2007; 104(4): 993 - 994. [Full Text] [PDF]
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