Therapeutic Development in Polyarticular Course Juvenile Idiopathic Arthritis: Extrapolation, Dose Selection, and Clinical Trial Design.

OBJECTIVE: Stakeholders met to address persistent challenges facing the development of therapeutics for polyarticular juvenile idiopathic arthritis (pJIA), which result in fewer approved therapies for children with pJIA than adults with rheumatoid arthritis (RA) and long lag times from adult RA approval to pediatric labeling. Ensuring that new medications are authorized in a timely manner to meet the needs of JIA patients worldwide is critically important to multiple stakeholders. METHODS: The Food and Drug Administration in collaboration with the University of Maryland Center for Regulatory Science and Innovation held a public workshop entitled "Accelerating Drug Development for pJIA" on October 2, 2019, to address challenges surrounding access to new medications for children and adolescents with pJIA. Regulatory, academic, and industry stakeholders, as well as patient representatives, participated in the workshop, which consisted of 4 sessions, including panel discussions. RESULTS: The workshop facilitated broad public discussion of challenges facing the development of pJIA therapeutics, highlighting areas of need and outlining opportunities to expedite development, while underscoring the necessity of close collaboration between all stakeholders, including patients and families. CONCLUSION: This report summarizes key aspects of the workshop, including the appropriate application of innovative approaches to the development of pJIA therapeutics, including extrapolation, to address current challenges and provide timely access to newer safe and effective treatments. Long-term safety assessment is of pressing concern to stakeholders and cannot be fully extrapolated from adult studies but requires consistent postmarketing long-term follow-up.

The Importance of Clinical Research in Pregnant Women to Inform Prescription Drug Labeling.

Pregnant women have historically been an understudied population and have been excluded from clinical trials. Recent efforts by stakeholders have raised awareness of the importance of clinical research in pregnant women to inform prescribing decisions. The Food and Drug Administration continues working to improve the format and content of prescription drug labeling for pregnant and lactating women, as demonstrated with the Pregnancy and Lactation Labeling Rule (PLLR), effective in 2015. The pregnancy labeling subsection now includes a subheading dedicated to the inclusion of pharmacokinetic (PK) data that inform the need for dose adjustments during pregnancy and the postpartum period. In addition, the PLLR also requires prescription drug labeling to be updated when important pregnancy information becomes available. Although PLLR improved the presentation of pregnancy-related information in labeling, there is a need to increase the quality and quantity of human data on the use of prescription drugs during pregnancy. PK studies in pregnant women should be incorporated into drug development programs and prioritized to obtain important information about safe and appropriate doses of a drug when used during pregnancy. In addition, opportunistic PK studies, postapproval pregnancy safety studies, ex vivo studies, and in silico modeling can be leveraged to better inform the risks and benefits of using a drug during pregnancy to inform study design and to further understand various mechanisms impacting pharmacokinetic/pharmacodynamic of drugs during pregnancy. It is important to address the significant existing data gaps and better inform the safety and dosing of prescription drugs for pregnant women.

Leveraging Big Data in Pediatric Development Programs: Proceedings From the 2016 American College of Clinical Pharmacology Annual Meeting Symposium.

This article discusses the use of big data in pediatric drug development. The article covers key topics discussed at the ACCP annual meeting symposium in 2016 including the extent to which big data or real-world data can inform clinical trial design and substitute for efficacy and safety data typically obtained in clinical trials. The current states of use, opportunities, and challenges with the use of big data in future pediatric drug development are discussed.