Dane Aaron, Rex John H, Newell Paul, Stallard Nigel
DaneStat Consulting, Cheshire, United Kingdom.
F2G Limited, Manchester, United Kingdom.
Open Forum Infect Dis. 2022 May 27;9(7):ofac266. doi: 10.1093/ofid/ofac266. eCollection 2022 Jul.
In traditional phase 3 trials confirming safety and efficacy of new treatments relative to a comparator, a 1-sided type I error rate of 2.5% is traditionally used and typically leads to minimum sizes of 300-600 subjects per study. However, for rare pathogens, it may be necessary to work with data from as few as 50-100 subjects. For areas with a high unmet need, there is a balance between traditional type I error and power and enabling feasible studies. In such cases, an alternative 1-sided alpha level of 5% or 10% should be considered, and we review herein the implications of such approaches. Resolving this question requires engagement of patients, the medical community, regulatory agencies, and trial sponsors.
在传统的3期试验中，相对于对照药确认新治疗方法的安全性和有效性时，传统上使用单侧I型错误率2.5%，这通常导致每项研究的受试者最小规模为300 - 600名。然而，对于罕见病原体，可能有必要使用少至50 - 100名受试者的数据。对于存在高度未满足需求的领域，在传统的I型错误和检验效能之间以及开展可行的研究之间需要取得平衡。在这种情况下，应考虑替代单侧α水平为5%或10%，我们在此回顾这些方法的影响。解决这个问题需要患者、医学界、监管机构和试验申办者的参与。
