Background Guidelines for off-label prescribing are emerging.^1–6 However, these guidelines do not provide practical guidance to assess the risk benefit balance and select the right paediatric dose We, therefore, aimed to develop a practical framework to guide paediatric healthcare professionals to assess the risks and benefits of off-label use.

Methods We have reviewed available literature on the suggested criteria for appropriate off-label use and evaluated these criteria for relevance in paediatrics. For guidance on dose-selection we searched for regulatory guidance on paediatric drug development. Next, the literature was searched for strategies that can be applied to assess the risks and benefits of off-label use. Based on literature findings a framework was proposed to provide practical guidance to physicians for off-label prescribing. Finally, the framework was applied to a case.

Results The following conditions for appropriate off-label use were identified based on available literature: 1. Medical need for off-label use. 2. Off-label use is based on ‘high quality evidence’. As ‘high quality evidence’ in paediatrics is often lacking-, we propose to replace the need for high quality evidence by a positive risk-benefit assessment based on available evidence. 3. Parents and patients are informed. This is not feasible for every single drug prescribed off-label, we propose a graded approach 4. The outcomes of off-label use are followed up.

The PROACT-URL framework⁷ for decision-making as well as the FDA paediatric decision tree⁸ seem helpful tools to guide decisions in real-life practice.

Conclusion We identified important aspects and tools to develop a framework (ARBOP-P) to guide healthcare professionals on how to systematically assess and balance the benefits and risks for off-label use, including dose selection, to ultimately optimize efficacy and safety of paediatric off-label prescribing.

References

1. Frattarelli DA, Galinkin JL, Green TP, et al. Off-label use of drugs in children. Pediatrics 2014;133:563–7Online.

2. Dooms M, Killick J. Off-label use of medicines: The need for good practice guidelines. Int J Risk Saf Med. 2017;29:17–23Online.

3. Gazarian M, Kelly M, McPhee JR, Graudins LV, Ward RL, Campbell TJ. Off-label use of medicines: consensus recommendations for evaluating appropriateness. Med J Aust 2006;185:544–8Online.

4. Largent EA, Miller FG, Pearson SD. Going off-label without venturing off-course: evidence and ethical off-label prescribing. Arch Intern Med 2009;169:1745–7Online.

5. Ansani N, Sirio C, Smitherman T, et al. Designing a strategy to promote safe, innovative off-label use of medications. Am J Med Qual 2006;21:255–61Online.

6. Weda M, Hoebert J, Vervloet M, et al. Study on the off-label use of medicinal products in the European Union.: www.ec.europa.com 2017.

7. Hammond J, Keeney R, Raiffa H. Smart Choices:A practical guide to making better decisions. Boston, MA.: Harvard Business School Press.; 2002.

8. Dunne J, Rodriguez WJ, Murphy MD, et al. Extrapolation of adult data and other data in pediatric drug-development programs. Pediatrics. 2011;128:e1242–9 Online.

Disclosure(s) Nothing to disclose