Untying the Gordian Knot

Abstract

In Response: We appreciate the thoughtful comments by Drs. Su, Zuppa, and Adamson (1) in response to our editorial, “Pediatric Research and Scholarship : Another Gordian Knot?” (2). We discussed the difficulties in pediatric pharmaceutical research and in developing data to support pediatric drug labels. We do not suggest that investigator-initiated studies cannot meet the Food and Drug Administration's (FDA) definition for adequate and well-controlled studies. However, most pediatric studies involve small numbers of patients in investigator-initiated trials that do not meet the FDA's definition for adequate and well controlled studies. Adequately trained investigators can and do perform these studies, but usually under the sponsorship of a pharmaceutical company. The Pediatric Pharmacology Research Unit is a very valuable resource allowing implementation of pediatric research trials. The accompanying letter highlights this valuable resource. As the correspondents state, they were unable to engage the previous pharmaceutical sponsor to initiate pediatric studies of dexmedetomidine. As related to one of the authors (JRT, personal communication), the sponsor claimed that they were unable to initiate pediatric trials until the FDA was satisfied with an adult trial with more than 24 h infusion of dexmedetomidine. That study is underway and was not required for the initial approval of the drug. Regardless of the etiology, progress with pediatric studies and labeling has been delayed. Following publication of data which might support a labeling change, it should be acknowledged that only the sponsor can request labeling changes, or special consideration for labeling changes can be considered at the initiative of the FDA. We are delighted to hear of the success of the correspondents in their preparation of the current trials by having contacted the FDA and used an Investigational New Drug application to support the current studies. This route should be considered for any new pharmaceutical that investigators believe will have significant impact in pediatric care but does not have the support of the sponsor. We are pleased to have had initial communications with the manufacturer of dexmedetomidine, Hospira, Inc., in initiating sponsor-funded pediatric trials. A Gordian Knot may not easily be untied, but one historical anecdote states that Alexander the Great “cut through it with a sword.” As Dr. Su and colleagues suggest, maybe the solution is not so complex if interested parties decide it is a priority. We appreciate the opportunity to focus attention on the easily disregarded needs of children's health in anesthesia and other fields of medicine. Joseph R. Tobin, MD Wake Forest University School of Medicine Winston Salem, NC Steven L. Shafer, MD Stanford University Stanford, CA Peter J. Davis, MD University of Pittsburgh School of Medicine Pittsburgh, PA [email protected]