论文标题
小儿药物开发中安全数据库的范围：评估的类型，分析精度和通过靶向效应外推的途径
Extent of Safety Database in Pediatric Drug Development: Types of Assessment, Analytical Precision, and Pathway for Extrapolation through On-Target Effects
论文作者
论文摘要
小儿患者应获得适当评估的安全性和功效的药物。鉴于经过修订的标签的目标，小儿临床开发计划的适当性和由此产生的安全数据库必须为有利的福利风险评估提供预期使用药用产品的评估。虽然可以使用成人推断来支持儿童药物的功效，但可能不愿在安全评估中使用相同的方法，从而通过降低样本量来消除试验效率的潜在提高。为了解决这种不愿，我们探讨了小儿试验中的安全审查，包括影响这些数据的因素，特定类型的安全评估以及可以实现的特定不良事件（AE）事件速率估计的精确度。此外，我们讨论了可以为使用靶向效果的安全性外推的基准提供基准的评估。最后，我们探讨了一种使用贝叶斯方法作为最合适的方法来理解精度的统一方法，以描述/确定概率术语中的风险，以估算特定AE的事件率。
Pediatric patients should have access to medicines that have been appropriately evaluated for safety and efficacy. Given this goal of revised labelling, the adequacy of the pediatric clinical development plan and resulting safety database must inform a favorable benefit-risk assessment for the intended use of the medicinal product. While extrapolation from adults can be used to support efficacy of drugs in children, there may be a reluctance to use the same approach in safety assessments, wiping out potential gains in trial efficiency through a reduction of sample size. To address this reluctance, we explore safety review in pediatric trials, including factors affecting these data, specific types of safety assessments, and precision on the estimation of event rates for specific adverse events (AEs) that can be achieved. In addition, we discuss the assessments which can provide a benchmark for the use of extrapolation of safety that focuses on on-target effects. Finally, we explore a unified approach for understanding precision using Bayesian approaches as the most appropriate methodology to describe/ascertain risk in probabilistic terms for the estimate of the event rate of specific AEs.
