Exposure Matching for Extrapolation of Efficacy in Pediatric Drug Development: Extrapolation of Efficacy in Pediatric Drug Development

During drug development, matching adult systemic exposures of drugs is a common approach for dose selection in pediatric patients when efficacy is partially or fully extrapolated. This is a systematic review of approaches used for matching adult systemic exposures as the basis for dose selection in pediatric trials submitted to the U.S. Food and Drug Administration (FDA) between 1998 and 2012. The trial design of pediatric pharmacokinetic (PK) studies and the pediatric and adult systemic exposure data were obtained from FDA publicly available databases containing reviews of pediatric trials. Exposure matching approaches that were used as the basis for pediatric dose selection were reviewed. The PK data from the adult and pediatric populations were used to quantify exposure agreement between the two patient populations. The main measures were the pediatric PK studies trial design elements and drug systemic exposures (adult and pediatric). There were 31 products (86 trials) with full or partial extrapolation of efficacy with an available PK assessment. Pediatric exposures had a range of mean Cmax and AUC ratios (pediatric/adult) of 0.63-4.19 and 0.36-3.60 respectively. Seven of the 86 trials (8.1%) had a pre-defined acceptance boundary used to match adult exposures. The key PK parameter was consistently predefined for antiviral and anti-infective products. Approaches to match exposure in children and adults varied across products. A consistent approach for systemic exposure matching and evaluating pediatric PK studies is needed to guide future pediatric trials

Expediting Drug Development for Pediatric Inflammatory Bowel Disease A Discussion With Stakeholders

Lack of scientific consensus on efficacy endpoints and outcome assessments presents a hurdle for global drug development in pediatric inflammatory bowel disease (IBD). Multiple stakeholders participated in a meeting November 2015, sponsored by The Pediatric IBD Foundation, which is a 501c3 organization formed by parents of children with IBD whose mission is to improve the lives of children with Crohn disease and ulcerative colitis by supporting innovative research and educational programs (www.pedsibd.org). With representatives of the Food and Drug Administration, European Medicines Agency, pediatric gastroenterologists, and representatives of the pharmaceutical industry, this meeting was organized to harmonize present thinking about various aspects of global drug development in pediatric IBD. The meeting was designed to be interactive, allowing participants from the pharmaceutical industry, regulatory agencies, academia, and clinical practice an opportunity to collaborate in a public forum and to identify potential strategies to expedite drug evaluation in children. Before the meeting, a questionnaire focused on the hurdles hindering approval of medications used to treat children with IBD was sent to all participants and other pediatric gastroenterologists in North America and Europe with expertise in IBD. Responses were reviewed by the steering committee and results presented at the meeting. Following the presentation of the survey, participants were divided into small groups composed of representatives from academia, industry, regulatory agencies, and members of the Pediatric IBD Foundation and assigned the task of working together to find solutions to the hurdles that had been identified. Hurdles hindering approval included pediatric trials start later in the development process; lack of enrollment in pediatric trials; lack of monitoring safety registries that might expedite approval; different priorities among stakeholders. This 1-day meeting discussed how to expedite pediatric drug development in IBD therapy. Hurdles for achieving approvals of pediatric indications for treatments of IBD were identified

Expediting Drug Development for Pediatric Inflammatory Bowel Disease A Discussion With Stakeholders

Lack of scientific consensus on efficacy endpoints and outcome assessments presents a hurdle for global drug development in pediatric inflammatory bowel disease (IBD). Multiple stakeholders participated in a meeting November 2015, sponsored by The Pediatric IBD Foundation, which is a 501c3 organization formed by parents of children with IBD whose mission is to improve the lives of children with Crohn disease and ulcerative colitis by supporting innovative research and educational programs (www.pedsibd.org). With representatives of the Food and Drug Administration, European Medicines Agency, pediatric gastroenterologists, and representatives of the pharmaceutical industry, this meeting was organized to harmonize present thinking about various aspects of global drug development in pediatric IBD. The meeting was designed to be interactive, allowing participants from the pharmaceutical industry, regulatory agencies, academia, and clinical practice an opportunity to collaborate in a public forum and to identify potential strategies to expedite drug evaluation in children. Before the meeting, a questionnaire focused on the hurdles hindering approval of medications used to treat children with IBD was sent to all participants and other pediatric gastroenterologists in North America and Europe with expertise in IBD. Responses were reviewed by the steering committee and results presented at the meeting. Following the presentation of the survey, participants were divided into small groups composed of representatives from academia, industry, regulatory agencies, and members of the Pediatric IBD Foundation and assigned the task of working together to find solutions to the hurdles that had been identified. Hurdles hindering approval included pediatric trials start later in the development process; lack of enrollment in pediatric trials; lack of monitoring safety registries that might expedite approval; different priorities among stakeholders. This 1-day meeting discussed how to expedite pediatric drug development in IBD therapy. Hurdles for achieving approvals of pediatric indications for treatments of IBD were identified