Description
The first concerted efforts to promote clinical trials in pediatrics came with the Best Pharmaceutical for Children Act (BPCA) in 1997 (renewed as BPCA in 2002) and the Pediatric Research Equity Act (PREA) in 2003. Both BPCA and PREA were permanently reauthorized in 2012. Despite these efforts, the majority of medicines continue to be used in an off-label capacity in children (up to 60% of drugs in children in general and up to 90% of drugs in the neonatal intensive care units (NICUs)). There have been 687 pediatric label changes since the initiation of BPCA and PREA, but up to 42% of trials done under BPCA have failed to support an FDA-approved indication in the pediatric population. It is not clear whether these failures might have been due to investigators not selecting the right drug, not identifying the right patient population, not choosing the right dose, not developing the right trial design, or not identifying the right endpoints for the trials. In addition, many sponsors cite an inability to recruit patients as a reason for not being able to complete pediatric trials. In order to optimize the potential for successful pediatric clinical trials, the scientific community will need to: - leverage basic science research on disease pathophysiology to justify the use of extrapolation from adult data - understand the ontogeny of metabolic pathways to be able to use modeling and simulation to optimize dosing strategies in pediatric patients - develop innovative trial designs, including the development of master protocols, using the experience from past history studying rare diseases - leverage and standardize all sources of information including clinical trials, registries, natural history studies, and electronic health records - develop susceptibility, diagnostic, monitoring, prognostic, predictive, safety, and response biomarkers for use in pediatric trials - develop clinically meaningful short term and long term efficacy and safety endpoints for pediatric trials In 2014, a stakeholder forum was hosted by the American Academy of Pediatrics and funded by an unrestricted grant from the Pharmaceutical Research and Manufacturers of America (PhRMA) where clinicians, academicians, regulators, patient advocates, parents, AAP leaders, and representatives from the pharmaceutical industry and disease-focused networks discussed the importance of establishing a Global Pediatric Clinical Trials Network. No one entity will be able to address all the needs in the pediatric clinical trial space. Bringing together the stakeholders in a network that provides best practices, innovative approaches, and streamlined conduct of regulatory quality clinical trials will increase the efficiency of pediatric studies. A Global Pediatric Clinical Trials Network would be able to support trials for rare diseases where recruitment has been difficult. It would provide education and training with respect to standardized approaches and provide the administrative tools to support stakeholders. A Global Pediatric Clinical Trial Network would ensure quality and efficiency in pediatric therapeutic development, thus increasing the likelihood of successful pediatric trials resulting in labeled products for use in pediatric patients. Following the 2014 stakeholder forum, the Critical Path Institute launched the Pediatric Trials Consortium which was "committed to enabling the creation of a sustainable solution that assures the timely and efficient evaluation of innovative drugs, biologics and devices for children by delivering the regulatory-quality data needed for product labeling." The goals of this program are to support the development of the scientific infrastructure needed to plan and execute pediatric clinical trials through collaboration with stakeholders from academia, industry, parent/patient advocacy groups, and government agencies. This should be based on the findings of the Pediatric Trials Consortium. The Global Pediatric Trial Network should be a resource for pediatric product development with sustainable global infrastructure to plan, start up, conduct, and close out pediatric studies. There should be an emphasis on operational efficiency and network sustainability with early, systematic, and integrative approaches to pediatric studies. The Global Pediatric Trial Network should optimize pediatric study design, protocols, best practices, and training and engagement of stakeholders. It should provide expert advice to investigators, streamline and improve processes and systems to enhance trial quality and reduce administrative burdens. Ultimately, it should coordinate and manage a global network of pre-qualified trial ready sites that will provide pediatric clinical research through investigations and studies to support treatment of pediatric patients. The Global Pediatric Trial Network will provide assistance to academic and industry based institutions in the conduct of research in pediatric diseases. The Food and Drug Administration (FDA), Office of the Commissioner (OC) expects that the applicant for the award of the Cooperative Agreement will have developed or have plans to develop a Global Pediatric Trial Network to facilitate efficient pediatric clinical trials with a high likelihood of success. The applicant should model these efforts based on the Pediatric Trials Consortium Advisory Report. The applicant should demonstrate the development of or plans for feasibility assessment reports, educational program delivery, and streamlined processes and efficient systems that improve the quality, efficiency, and timeliness of pediatric clinical trials. Efforts should include the development of a site selection tool, core infrastructure and a dedicated pediatric research staff. Independent advisory work with stakeholder engagement, a network system to share information, a centralized approach to IRB review, and a core set of performance metrics to measure value creation for stakeholders should be documented. The applicant should demonstrate knowledge of regulatory standards and innovative clinical research. The Global Pediatric Trial Network should be able to provide independent advice based on input from inclusive and comprehensive stakeholder engagement including academia, industry, patient/parent advocacy groups and government agencies.