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Getting the right dose regimen for children and adolescents is important but poses great scientific, practical, and ethical challenges. At the same time, the availability of data in adults is a huge advantage and needs to be used optimally when designing studies in children and analyzing pediatric data. Furthermore, the processes of maturation and growth are always key when selecting doses for children. All the above make study adaptations and model-informed approaches imperative for dose exposure-response characterization and dose selection in children. This article summarizes the experience gained in the European Medicines Agency on this topic and proposes some general guiding principles for defining objectives, study designs, and methodology tools for pediatric dose selection., (© 2021, The American College of Clinical Pharmacology.)

Accounting for subject nonadherence and eliminating inappropriate subjects in clinical trials are critical elements of a successful study. Nonadherence can increase variance, lower study power, and reduce the magnitude of treatment effects. Inappropriate subjects (including those who do not have the illness under study, fail to report exclusionary conditions, falsely report medication adherence, or participate in concurrent trials) confound safety and efficacy signals. This paper, a product of the International Society for CNS Clinical Trial Methodology (ISCTM) Working Group on Nonadherence in Clinical Trials, explores and models nonadherence in clinical trials and puts forth specific recommendations to identify and mitigate its negative effects. These include statistical analyses of nonadherence data, novel protocol design, and the use of biomarkers, subject registries, and/or medication adherence technologies., (© 2016, The American College of Clinical Pharmacology.)

Registration of innovative biologics in Emerging Markets (EMs) poses many opportunities and challenges. The BRIC-MT countries (Brazil, Russia, India, China, Mexico, and Turkey) that are the fastest growing markets and regulators in these countries have imposed certain requirements, including the need for local clinical studies, for registration of biologics. The regulatory landscape in these countries is rapidly evolving, which necessitates an up-to-date understanding of such requirements. There is growing evidence which suggests that race, after accounting for body weight differences, may not influence the pharmacokinetics of biologics to the same extent that it does for small molecules. Thus, the requirements for clinical pharmacology trials in EMs are driven mainly by regulatory needs set forth by local Ministry of Health. In addition to the clinical Phase I to III studies done in the global program that supports registration in large geographies, countries such as China require local single and multiple dose Phase I studies. Participating in global studies with clinical sites within their country may be sufficient for some markets, while other regulators may be satisfied with a Certificate of Pharmaceutical Product. This paper discusses the current requirements for registration of innovative biologics in key EMs., (© 2015, The American College of Clinical Pharmacology.)