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首页> 外文期刊>Journal of Pharmacy and Pharmaceutical Sciences >Sample Sizes for Designing Bioequivalence Studies for Highly Variable Drugs
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Sample Sizes for Designing Bioequivalence Studies for Highly Variable Drugs

机译：用于设计高度可变药物的生物等效性研究的样本尺寸

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Purpose. To provide tables of sample sizes which are required, by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), for the design of bioequivalence (BE) studies involving highly variable drugs. To elucidate the complicated features of the relationship between sample size and within-subject variation. Methods. 3- and 4-period studies were simulated with various sample sizes. They were evaluated, at various variations and various true ratios of the two geometric means (GMR), by the approaches of scaled average BE and by average BE with expanding limits. The sample sizes required for yielding 80% and 90% statistical powers were determined. Results. Because of the complicated regulatory expectations, the features of the required sample sizes are also complicated. When the true GMR = 1.0 then, without additional constraints, the sample size is independent of the intrasubject variation. When the true GMR is increased or decreased from 1.0 then the required sample sizes rise at above but close to 30% variation. An additional regulatory constraint on the point estimate of GMR and a cap on the use of expanding limits further increase the required sample size at high variations. Fewer subjects are required by the FDA than by the EMA procedures. Conclusions. The methods proposed by EMA and FDA lower the required sample sizes in comparison with unscaled average BE. However, each additional regulatory requirement (applying the mixed procedure, imposing a constraint on the point estimate of GMR, and using a cap on the application of expanding limits) raises the required number of subjects. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on on the issue’s contents page.
机译：目的。提供欧洲药物局（EMA）和美国食品和药物管理局（FDA）所必需的样品尺寸表，用于设计生物等效性（BE）研究，涉及高度可变药物。为了阐明样品大小与对象内变化之间的关系的复杂特征。方法。用各种样品尺寸模拟3-和4个期的研究。在各种几何手段（GMR）的各种变型和各种真实比率下，评估它们的各种变化，通过缩放平均值的方法和平均是扩展限制的方法。确定产生80％和90％统计功率所需的样品尺寸。结果。由于监管期望复杂，所需样本尺寸的特征也很复杂。当真正的GMR = 1.0然后，没有额外的约束时，样本大小与intrAsbject变化无关。当真正的GMR增加或从1.0增加或减少时，所需的样本尺寸在上方上升，但接近30％的变化。关于GMR的点估计的额外监管限制和在使用扩张限度的盖帽进一步增加了高变化的所需样品尺寸。 FDA需要更少的科目而不是通过EMA程序。结论。 EMA和FDA提出的方法与未划平的平均值相比降低所需的样品尺寸。但是，每个额外的监管要求（应用混合程序，对GMR的点估计产生限制，并在申请扩大限制时使用盖子）提高了所需的受试者数量。本文对发布后审查开放。注册读者（参见“对于读者”）可以通过单击“问题的内容”页面进行评论。

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