Benefit-Risk Assessment of Off-Label Drug Use in Children: The Bravo Framework

Van Der Zanden TM, Mooij MG, Vet NJ, Neubert A, Rascher W, Lagler FB, Male C, Grytli H, Halvorsen T, De Hoog M, De Wildt SN (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Clinical Pharmacology & Therapeutics American Society for Clinical Pharmacology and Therapeutics

DOI: 10.1002/cpt.2336

Abstract

A drug is granted a license for use after a thorough assessment of risks and benefits based on high-quality scientific proof of its efficacy and safety. 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-benefit balance in children, or implying insufficient information to establish the risk-benefit 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-label use (BRAvO) decision framework. This pragmatic framework offers a structured assessment of benefits and risks of off-label drug use, including a clinical pharmacological based approach to age-appropriate dose selection. As proof of concept and to illustrate the practical use, we have applied the framework to assess benefits and risks of off-label use of ondansetron for gastroenteritis-induced nausea and vomiting. The framework could also guide decisions on off-label use in other special populations (e.g., pregnant women, elderly, obese, or critically ill patients) where off-label drug use is frequent, thereby contributing to effective and safe pharmacotherapy.

Authors with CRIS profile

Antje Neubert Department of Paediatrics and Adolescent Medicine Wolfgang Rascher Department of Paediatrics and Adolescent Medicine

Involved external institutions

Erasmus University Medical Center (MC) NL Netherlands (NL) Leiden University NL Netherlands (NL) St. Antonius Ziekenhuis NL Netherlands (NL) Paracelsus Medizinische Privatuniversität AT Austria (AT) Medizinische Universität Wien AT Austria (AT) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet NO Norway (NO) Haukeland University Hospital / Haukeland universitetssykehus NO Norway (NO) Radboud University Nijmegen NL Netherlands (NL)

How to cite

APA:

Van Der Zanden, T.M., Mooij, M.G., Vet, N.J., Neubert, A., Rascher, W., Lagler, F.B.,... De Wildt, S.N. (2021). Benefit-Risk Assessment of Off-Label Drug Use in Children: The Bravo Framework. Clinical Pharmacology & Therapeutics. https://dx.doi.org/10.1002/cpt.2336

MLA:

Van Der Zanden, Tjitske M., et al. "Benefit-Risk Assessment of Off-Label Drug Use in Children: The Bravo Framework." Clinical Pharmacology & Therapeutics (2021).

BibTeX: Download