Quantitative Medicine, Critical Path Institute, Tucson, Arizona, USA.
College of Chemical and Biological Engineering, Drexel University, Philadelphia, Pennsylvania, USA.
J Clin Pharmacol. 2021 Jun;61 Suppl 1:S36-S51. doi: 10.1002/jcph.1830.
Precision dosing is progressing beyond the conceptual and proof-of-concept stages toward implementation. As the availability of dosing algorithms, tools, and platforms increases, so do the investment in technology services and actual implementation of clinical services offering these solutions to patients. Nowhere is this needed more than in pediatric populations, which are still reliant on adult drug development and bridging strategies to support dosing, often in the absence of actual dose-finding studies in the target pediatric population. Still, there is more work to be done to ensure that proper governance of these services is maintained, and that sustainability of these early implementations is guided by new science as it evolves and meaningful outcome data to confirm that such services deliver on both clinical and economic return on investment. In addition, the field should ensure that all approaches beyond a therapeutic drug monitoring-driven, pharmacokinetic-centric approach should be considered as the tools and services evolve, especially when pediatric-specific pharmacokinetic/pharmacodyamic and pharmacogenetic data are available and shown to be useful to guide dosing. This review evaluates current pediatric precision dosing efforts, highlighting their utility, longevity, and sustainability and assesses the current process for implementing such approaches examining current barriers that stand in the way of broader implementation and the stakeholders that must engage to ensure its ultimate success.
精准剂量给药正从概念和概念验证阶段发展到实施阶段。随着给药算法、工具和平台的可用性的增加,对技术服务的投资以及为患者提供这些解决方案的临床服务的实际实施也在增加。在儿科人群中,这一点更为必要,因为他们仍然依赖于成人药物开发和桥接策略来支持剂量,而在目标儿科人群中通常缺乏实际的剂量发现研究。尽管如此,仍有更多工作要做,以确保对这些服务进行适当的管理,并确保这些早期实施的可持续性,因为随着新科学的发展和有意义的结果数据的出现,这些科学可以证实这些服务在临床和投资回报方面都有成效。此外,随着工具和服务的不断发展,该领域应确保考虑到所有超越治疗药物监测驱动、以药代动力学为中心的方法,尤其是当有针对儿科的药代动力学/药效学和药物遗传学数据可用并显示其对指导剂量有用时。这篇综述评估了当前的儿科精准剂量给药工作,强调了它们的实用性、持久性和可持续性,并评估了实施这些方法的当前流程,检查了目前阻碍更广泛实施的障碍以及必须参与的利益相关者,以确保其最终成功。