Technical University of Braunschweig, Institute of Pharmaceutical Chemistry, Beethovenstrasse 55, 38106 Braunschweig, Germany.
J Pharm Biomed Anal. 2010 Dec 15;53(5):1124-9. doi: 10.1016/j.jpba.2010.04.034. Epub 2010 May 4.
A method development process is commonly finalized by a method transfer from the developing to the routine laboratory. Statistical tests are performed in order to survey if a transfer succeeded or failed. However, using the classic two-sample t-test can lead to misjudgments and unsatisfying transfer results due to its test characteristics. Therefore the International Society of Pharmaceutical Engineering (ISPE) employed a fixed method transfer design using equivalence tests in their Guide for Technology Transfer. Although it was well received by analytical laboratories worldwide this fixed design can easily bring about high beta-errors (rejection of successful transfers) or high workload (many analysts employed during transfer) if sigma(AN) (error due to different analysts) exceeds 0.6%. Hence this work introduces an extended concept which will help to circumvent this disadvantage by providing guidance to select a personalized and more appropriate experimental design. First of all it demonstrates that former t-test related acceptance criteria can be scaled by a factor of 1.15, which allows for a broader tolerance without a loss of decision certainty. Furthermore a decision guidance to choose the proper number of analysts or series at given percentage acceptance limits (%AL) is presented.
方法开发过程通常通过从开发实验室到常规实验室的方法转移来完成。为了调查转移是否成功或失败，通常会进行统计测试。然而，由于经典的两样本 t 检验的测试特征，使用它可能会导致错误判断和不满意的转移结果。因此，国际制药工程学会（ISPE）在其技术转移指南中采用了使用等效性检验的固定方法转移设计。尽管这种固定设计在全球范围内得到了分析实验室的广泛认可，但如果 sigma(AN)（由于不同分析人员造成的误差）超过 0.6%，则很容易导致高β错误（成功转移被拒绝）或高工作量（转移期间需要雇用许多分析人员）。因此，这项工作引入了一个扩展的概念，通过提供指导来选择个性化和更合适的实验设计，有助于规避这一缺点。首先，它表明可以通过 1.15 的因子对以前与 t 检验相关的接受标准进行缩放，这在不降低决策确定性的情况下允许更宽的容差。此外，还提出了一个决策指导，以在给定的百分比接受限（%AL）下选择适当数量的分析人员或系列。
