Until 2016, a ratio of means (ROM) non-inferiority (NI) test was recommended in FDA product-specific guidances (PSGs) to evaluate adhesion performance for prospective generic transdermal delivery systems (TDS). However, the ROM NI test had low power for well-adhering TDS, which were becoming increasingly prevalent. Mathematical proof and simulation revealed that the low power wasn’t because the non-normality of adhesion data violated the normality assumption of parametric methods; it was because the ROM NI test was coupled with an adhesion scale where scores approached 0 as adhesion got better. In June 2016, FDA published a draft general guidance on TDS adhesion and recommended a new statistical approach, replacing the ROM NI test with a difference-of-means (DOM) NI test, using the same scale and primary endpoint (mean adhesion scores). An analysis of 40 TDS adhesion studies submitted in ANDAs after the publication of the 2016 draft guidance suggests that, consistent with simulation results, the new statistical approach markedly improves the low power, and thereby reduces the sample size required by the old approach for moderately to well-adhering TDS, while retaining comparable power for poorly adhering TDS. The new statistical approach thus enhances the potential approvability and patient access to well-adhering generic TDS.

直到2016年，在FDA产品特定指南（PSG）中建议使用均数（ROM）非劣效（NI）测试来评估预期的通用透皮给药系统（TDS）的粘附性能。但是，ROM NI测试对TDS的良好粘附力很低，而TDS越来越流行。数学证明和仿真表明，低功耗不是因为粘附数据的非正态性违反了参数方法的正态性假设；而是因为粘附力数据的非正态性违反了参数方法的正态性假设。这是因为ROM NI测试与附着力量表相结合，随着附着力的提高，评分接近0。FDA在2016年6月发布了有关TDS粘附性的一般指南草案，并建议了一种新的统计方法，即使用相同的量表和主要终点（平均粘附性评分）将ROM NI测试替换为均值差（DOM）NI测试。 。对2016年指南草案发布后在ANDA中提交的40项TDS粘附性研究的分析表明，与模拟结果一致，新的统计方法显着改善了低功效，从而将旧方法所需的样本量减少了适度至TDS附着力好，而TDS附着力却保持可比。因此，新的统计方法增强了潜在的可批准性，并提高了患者获得良好遵循的通用TDS的机会。同时保留与TDS附着力不佳的性能相当的性能。因此，新的统计方法增强了潜在的可批准性，并提高了患者获得良好遵循的通用TDS的机会。同时保留与TDS附着力不佳的性能相当的性能。因此，新的统计方法增强了潜在的可批准性，并提高了患者获得良好遵循的通用TDS的机会。