Dosing is a critical aspect of drug development in pediatrics that has led to trial failures and the inability to label the drug for pediatric use by the US Food and Drug Administration. Developing a structured approach for pediatric dose selection requires knowledge of the current approaches and their success or failure. This study describes the current experience with pediatric dosing methods from 2012 to 2020 and had 2 primary objectives: (1) to identify how the initial pediatric dose was selected and (2) to identify the pivotal dosing strategy used to identify the initially selected dose for safety and efficacy for pediatric clinical trials. Through September 2020, a total of 275 pediatric drug development programs were characterized for initial and pivotal dosing strategies. The success rate for labeling for pediatric use was 76.4%. The most common initial dosing strategy was previous experience with the product, followed by allometric scaling and exposure matching with adults. The most common pivotal dosing strategy was titration to target response in 33% of programs, with the second and third most common being pharmacokinetic/pharmacodynamic studies (30%) and exposure matching (20%), respectively. Additionally, about one‐half of pediatric programs incorporated model‐informed drug development. The emergence of titration to target response may signal a shift toward precision medicine in pediatric patients. Future work in pediatric drug dose selection should move toward the development of a structured pediatric dose selection approach.

Pediatric safety evaluations are an essential part of a pediatric drug development program. Communication of the results of these safety evaluations is primarily accomplished by labeling of the drug either during the initial pediatric drug development program, or during the postmarketing period after drug approval for pediatric patients. During drug development, the dose–adverse drug event (ADE) relationship is an important part of the evaluation, but a consideration for pediatric ADEs that are unrelated to drug dosage must be maintained. Examples of dose‐related and non–dose‐related ADEs are presented. The failure to label a product for pediatric use has been safety related for a number of development programs. The US Food and Drug Administration's Pediatric Advisory Committee is a primary source of the pediatric postmarketing safety review and has been associated with a number of labeling changes through its ongoing review process. Pediatric drug safety remains a critical part of the assessment of dose‐effect relationship in the pediatric patient population during the drug development and postmarketing surveillance process.