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Many drugs that are relevant to children are not licensed for use in this population implying that a thorough assessment of risks and benefits in the pediatric population has not been made at all, implying a negative risk\u2010benefit balance in children, or implying insufficient information to establish the risk\u2010benefit balance. Use of drugs without positive assessment of risks and benefits exposes children to potential lack of efficacy, unknown toxicity, and harm. To aid guideline committees and individual prescribers, we here present a tutorial of the Benefit and Risk Assessment for Off\u2010label use (BRAvO) decision framework. This pragmatic framework offers a structured assessment of benefits and risks of off\u2010label drug use, including a clinical pharmacological based approach to age\u2010appropriate dose selection. As proof of concept and to illustrate the practical use, we have applied the framework to assess benefits and risks of off\u2010label use of ondansetron for gastroenteritis\u2010induced nausea and vomiting. 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