Bird Sheila M, Bailey Rosemary A, Grieve Andrew P, Senn Stephen
MRC Biostatistics Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
School of Mathematics and Statistics, University of St Andrews, St Andrews, UK.
Pharm Stat. 2017 Mar;16(2):100-106. doi: 10.1002/pst.1801. Epub 2017 Feb 16.
By setting the regulatory-approved protocol for a suite of first-in-human studies on BIA 10-2474 against the subsequent French investigations, we highlight 6 key design and statistical issues, which reinforce recommendations by a Royal Statistical Society Working Party, which were made in the aftermath of cytokine release storm in 6 healthy volunteers in the United Kingdom in 2006. The 6 issues are dose determination, availability of pharmacokinetic results, dosing interval, stopping rules, appraisal by safety committee, and clear algorithm required if combining approvals for single and multiple ascending dose studies.
通过将针对BIA 10-2474的一系列首次人体研究的监管批准方案与随后的法国调查进行对比，我们突出了6个关键的设计和统计问题，这些问题强化了皇家统计学会工作小组的建议，该建议是在2006年英国6名健康志愿者发生细胞因子释放风暴之后提出的。这6个问题是剂量确定、药代动力学结果的可用性、给药间隔、停止规则、安全委员会的评估，以及如果合并单次和多次递增剂量研究的批准所需的明确算法。
