Steyn H S, Koeleman H A, Gouws E, Ritschel W A
Statistical Consultation Service, Potchefstroom University for Christian Higher Education, South Africa.
Int J Clin Pharmacol Ther Toxicol. 1991 Apr;29(4):156-60.
Since most bioavailability studies are usually done with only a limited number of volunteers (usually 10-30), the statistical properties of the calculated bioavailability parameters are not well defined. The established statistical methods to test bioequivalence are usually based on either the assumption of normality or a symmetrical distribution. However, the decision of which method to apply, depends primarily on the distributional assumption of the data. In this study, an approach is followed where the small data base of a limited number of volunteers is expanded by adding pseudo-volunteers by "bootstrap" simulations. From such a larger data base it is easier to determine the statistical distributional properties of bioavailability parameters, which in its turn leads to the identification of an appropriate statistical method. With more certainty on which statistical method to apply, the original data can be used more effectively in testing for bioequivalence. In this paper, comparisons are made between the distributions of bioavailability parameters of an actual 60-volunteer study and those of two simulated data sets. Each such data set contained a random sample of 10 volunteers each (from the 60 volunteers), together with 50 pseudo-volunteers. These 50 volunteers were simulated from the random sample of 10 real volunteers. Good correspondences were obtained when comparing these two data sets with the original data, which indicated the validity to use this approach in bioavailability studies where a small number of volunteers had been used. This method proved useful to define the distributional properties for a relative small number of parameter-values available.
由于大多数生物利用度研究通常仅在有限数量的志愿者（通常为10 - 30名）身上进行，因此计算得出的生物利用度参数的统计特性并不明确。用于测试生物等效性的既定统计方法通常基于正态性假设或对称分布假设。然而，应用哪种方法的决策主要取决于数据的分布假设。在本研究中，采用了一种方法，即通过“自助法”模拟添加虚拟志愿者来扩展有限数量志愿者的小数据库。从这样一个更大的数据库中更容易确定生物利用度参数的统计分布特性，进而有助于确定合适的统计方法。在更确定应用哪种统计方法的情况下，原始数据可以更有效地用于生物等效性测试。在本文中，对一项实际的60名志愿者研究的生物利用度参数分布与两个模拟数据集的分布进行了比较。每个这样的数据集包含10名志愿者的随机样本（从60名志愿者中选取）以及50名虚拟志愿者。这50名志愿者是从10名真实志愿者的随机样本中模拟出来的。将这两个数据集与原始数据进行比较时获得了良好的对应关系，这表明在使用少量志愿者的生物利用度研究中使用这种方法是有效的。该方法被证明对于定义相对少量可用参数值的分布特性很有用。
