Contains Nonbinding Recommendations
Draft — Not for Implementation 包含不具约束力的建议 草案 — 不用于实施
1. Study?Design?for?Multiple?Batch?Analyses??
1. 多批次分析的研究设计?
Analyses of batch effects on clinical endpoints (i.e., batch effect analyses) should be considered when drug product batches exhibit variations (e.g., a variation in chemical composition), potentially affecting clinical outcomes. These are additional analyses beyond the standard primary efficacy analyses usually performed. Standard analyses involve comparing a control group to a treatment group composed of subjects pooled across different batches. The batches that are chosen should be representative of the marketing batches and should not be too homogenous. The goal of these analyses is to quantify potential heterogeneity in clinical outcomes for subjects who receive different batches in the study. This is in principle similar to other types of subgroup analyses. 32
在药品批次显示出变异（例如化学组成变异），可能影响临床结果的情况下，应考虑对临床终点的批次效果分析（即批次效果分析）。除了通常开展的标准的主要疗效分析之外，有其它的分析。标准分析涉及对照组与不同批次汇总的受试者所组成的治疗组的比较。选择的批次应该代表上市销售批次，不应过于同质。这些分析的目的是量化在研究中接受不同批次的患者的临床结果中可能的异质性。在原理上类似于其它类型的亚组分析。32
If batch effect analyses are warranted, the sponsor should design clinical studies to facilitate these analyses, pre-specify in the protocols how these analyses will be carried out, discuss with the appropriate OND review division the pre-planned models for these analyses, and present the results of these analyses in the clinical study report. Batch effect analyses are usually exploratory, with no formal requirement of control of the Type I error rate. The remainder of this section provides more details on our recommendations for clinical study design, as well as modeling and presentation of clinical study results, to accommo