LAUSR

The lack of proper pediatric labeling of medications results in many tragedies, such as Emily, a delightful 6-year-old girl who failed the treatment with imiquimod 5% cream (1). It is very important to legislate to promote the research and development of pediatric drugs. The rules for promoting drug development for children could date back to 1977— The General Considerations for the Clinical Evaluation of Drugs in Infants and Children (Figure 1). To improve the labeling of medications for children, the US Food and Drug Administration (FDA) and Congress promulgated Pediatric Rule in 1994. In 1997, a 6-month extension to existing marketing exclusivity, as known as pediatric exclusivity, which could translate into an about $500 million additional revenue for each drug, was first promulgated in the section 111 of the FDA Modernization Act (FDAMA) if pharmaceutical companies finished the study of medications in pediatric populations (2,3). In 2002, the Best Pharmaceuticals for Children Act (BPCA) was enacted by the US FDA. Followed by its companion legislation acts, the Pediatric Research Equity Act (PREA) in 2003. Both Acts were made permanent in 2012 (Figure 1). The BPCA and the PREA have facilitated the clinical studies in children. Clinical trials conducted under BPCA mainly focused on pediatric-specific or rare diseases. Drug company perform BPCA clinical trials is completely voluntary. But a reward known as Pediatric Exclusivity will be granted by the US FDA with an additional 6 months of marketing exclusivity if the pediatric clinical trials are completed. The BPCA and the PERA have increased labeling of drugs in children. Results from Avant et al. indicated that from September 2007 to September 2016, there were 292 BPCA pediatric therapeutic trials resulted in 107 pediatric labeling changes and 57% pediatric labeling changes had a new or expanded age group (4). New pediatric information has been added into labeling of more than 650 products as a result of BPCA and PREA (4). Based on data from US FDA pediatric exclusivity statistics, till October 1, 2019, there were 1,084 Proposed Pediatric Study Requests (PPSRs) received and 561 Written Requests issued under pediatric exclusivity (Table 1) (5). In the European Union (EU), the Pediatric Regulation came into force in 2007, has promoted the development of pediatric drugs in the EU (Figure 1) (6,7). Anti-infective, gastrointestinal, psychiatry, neurology and cardiovascular are five most commonly studied therapeutic categories (4). However, the US was the most common host country with an 87% of all documented clinical trials sites by country, followed by Canada, the United Kingdom, Russia, South Africa, France and 66 other countries (4). Timeline of key laws, regulations and guidelines to improve pediatric clinical trials are shown in Figure 1. There is still a lack of Acts like BPCA and PREA in China.