The United Stated Food and Drug Administration (FDA) implemented its version of the International Council for Harmonization’s (ICH) addendum on pediatric clinical trials and drug development, RAPS reports.¹ FDA added a considerable amount of new information to the policy principles originally established in 2000.
The new guidance, ICH E11(R1) Addendum: Clinical Investigation of Medicinal Products in the Pediatric Population, does not alter the scope of the original guidance set forth in 2000. However, pediatric drug development has evolved since the original guidance, and the new guidance reflects current regulatory perspectives on new scientific and technical advances.
Several key topics within the E11(R1) Addendum received new recommendations from FDA, including ethical considerations, age subgroups, pediatric formulations, and drug development research.
Ethical considerations
Regarding children’s participation in clinical trials, the guidance reads: “A fundamental principle in pediatric drug development requires that children should not be enrolled in a clinical study unless necessary to achieve an important pediatric public health need.”²
Regarding assent, the guidance reads: “The general principles of ethical considerations for parental (legal guardian) consent/permission and child assent are outlined in ICH E11 (2000) section II.F.3 (2.6.2) and continue to apply… [However,] over the course of a clinical study, it may be necessary to reassess the assent of a child in recognition of the child’s evolving maturity and competency.”²
Chronological age
FDA states that researchers should provide a rationale for the selection of the pediatric population involved in clinical studies, and that chronological age alone may not serve as an adequate categorical determinant to define developmental subgroups. FDA recommends that “physiological development and maturity of organs, pathophysiology of disease or condition, and the pharmacology of the investigational product are factors to be considered in determining the subgroups.” Furthermore, FDA cautions that “the arbitrary division of pediatric subgroups by chronological age for some conditions may have no scientific basis and could unnecessarily delay development of medicines for children by limiting the population for study.”²
Pediatric formulations
Regarding pediatric drug formulations, the guidance reads: “Additional considerations for pediatric formulations to optimize efficacy and reduce the risk for medication and dosing errors should include age-appropriate dosage forms, ease of preparations and instructions for use for caregivers, acceptability (e.g. palatability, tablet size), choice and amount of excipients, delivery systems, and appropriate packaging.”² FDA provides more detailed recommendations for four categories: Dosage and Administration, Excipients, Palatability and Acceptability, and Neonates.
Optimizing pediatric drug development
In this section of the guidance, FDA provides specific recommendations on the use of existing knowledge, extrapolation, modelling, and simulation in pediatric drug development.
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²https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm530012.pdf