Nordbrock E
Marion Merrell Dow Inc., Kansas City, Missouri 64134-0627.
J Biopharm Stat. 1992;2(1):91-113. doi: 10.1080/10543409208835033.
Studies are routinely conducted during development of a new drug to investigate the effect of strength, package, batch, storage condition, and storage time on stability of the dosage form. A typical study will have three batches, several strengths, several packages, and several storage conditions. Thus, if every batch by strength by package combination is tested for every storage condition, i.e., if a complete factorial design is used, a substantial expense is involved. To reduce expense, a matrix design is commonly used; e.g., only the smallest and largest bottles are tested. Fractional factorial-type designs for stability studies are proposed, and the statistical powers of various designs are compared.
在新药研发过程中，通常会开展研究以考察规格、包装、批次、储存条件及储存时间对剂型稳定性的影响。一项典型的研究将涉及三批产品、几种规格、几种包装以及几种储存条件。因此，如果针对每种储存条件对每个批次与规格及包装的组合进行测试，即如果采用完全析因设计，将会产生高昂的费用。为降低成本，通常采用矩阵设计；例如，仅对最小和最大的瓶子进行测试。本文提出了用于稳定性研究的部分析因类型设计，并比较了各种设计的统计效能。
