The globalization of pediatric clinical trials.

OBJECTIVE: To examine the characteristics of pediatric trials conducted under US legislation and to compare results with data from 2002 to 2007. METHODS: We reviewed all pediatric trials provided to the US Food and Drug Administration in submissions that were approved between September 28, 2007 and December 21, 2010. We extracted data for each trial including age range, therapeutic indication, design, duration, and patient and center enrollment by location. RESULTS: Overall 346 studies on 113 drugs and biologicals enrolled 55 819 pediatric patients. The United States participated in 86% of the studies, providing 71% of the centers and 74% of the patients. Corresponding percentages for non-US countries were 43%, 29%, and 26% respectively. Developing or transition countries participated in 22% of the studies, providing 12% of the centers and 10% of the patients; our earlier analysis found corresponding percentages of 38%, 12%, and 23%. The most common therapeutic areas studied in the latter countries were infectious, neurologic, and pulmonary diseases. Seventy-eight vaccine studies enrolled 147 692 patients. The United States participated in 40% of the studies, providing 39% of the centers and 22% of the patients. Corresponding percentages for non-US countries were 74%, 61%, and 78% respectively. Developing or transition countries participated in 27% of the studies, providing 15% of the centers and 52% of the patients. CONCLUSIONS: The United States remains an important location for pediatric trials. Developing country involvement in pediatric drug development is not increasing, although these countries participate significantly in vaccine trials.

Extrapolation of adult data and other data in pediatric drug-development programs.

OBJECTIVES: In 1994, the US Food and Drug Administration (FDA) proposed an approach, based on extrapolation of efficacy findings from adults to the pediatric population, to maximize the use of adult data and other data when designing pediatric drug-development programs. We examined the experience of the FDA in using extrapolation to evaluate how and when it was used and any changes in scientific assumptions over time. METHODS: We reviewed 370 pediatric studies submitted to the FDA between 1998 and 2008 in response to 159 written requests (166 products) issued under the Pediatric Exclusivity Provision. We identified cases in which efficacy was extrapolated from adult data or other data, we categorized the type of pediatric data required to support extrapolation, and we determined whether the data resulted in new pediatric labeling. RESULTS: Extrapolation of efficacy from adult data occurred for 82.5% of the drug products (137 of 166). Extrapolation was defined as complete for 14.5% of the products (24 of 166) and partial for 68% of them (113 of 166). Approaches to extrapolation changed over time for 19% of the therapeutic indications studied (13 of 67). When extrapolation was used, 61% of the drug products (84 of 137) obtained a new pediatric indication or extension into a new age group; this number decreased to 34% (10 of 29) when there was no extrapolation. CONCLUSIONS: Extrapolating efficacy from adult data or other data to the pediatric population can streamline pediatric drug development and help to increase the number of approvals for pediatric use.

The European Regulation on medicines for paediatric use.

The European Regulation on medicines for paediatric use entered into force on 26 January 2007. It marks a radical change in the European Union in terms of encouraging the development of medicines for paediatric age groups and improving the availability of information on the use of medicines in children. How will the new Paediatric Regulation achieve this? For the first time, companies will be required to study medicines in the paediatric population and develop age-appropriate formulations. As a reward or incentive for conducting these studies, companies will be entitled to extensions of patent protection and market exclusivity. The Regulation establishes a European paediatric clinical trials network and a paediatric study programme for off-patent medicines, the latter to be funded through the Community Framework Programmes. A Paediatric Committee, based at the European Medicines Agency, will be responsible for agreeing the paediatric investigation plan (PIP) with companies. This will describe the clinical trials and other measures necessary to investigate a particular medicine in the paediatric population. A European paediatric clinical trials database, partly accessible to the public, will hold the details and the results of all paediatric trials conducted in line with these PIPs. All medicines authorised for a paediatric use will be identified by a new symbol on the package label. After 5 years, there will be a stocktake with a view to making changes to the Regulation if necessary.