- 期刊
Evaluation of the Parallel Line Assay for Assessment of Biosimilar Products Based on Censored Data
平行線檢定於生物相似性藥品之設限資料對等性評估
摘要
生物製劑是以生物為來源所開發的藥品，基本上不同於傳統化學合成的小分子學名藥，而近年來，許多早期生物製劑藥品的專利將到期，許多藥廠紛紛投入生物製劑學名藥的研發，而此類藥品我們一般稱為生物相似性藥品。美國食品藥物管理局（FDA）於2012年2月9日公告了三份關於生物相似性產品發展的草案，其中一份關於科學考量部分，即描述了評估時所用的方法為全面的佐證，並建議以按部就班的方式來進行。另一方面，由於複雜和多變的分子結構，生物製劑藥品製程複雜，所以如何選擇合適的統計分析方法以評估生物相似性藥品與原廠藥品的相似性，對於統計人員與審核主管機構都是一個很大的挑戰。為解決此問題，基於療效指標為設限資料下，以指數分配的條件為基礎，我們嘗試應用對數風險迴歸模式並採用平行線檢定法評估生物製劑相似性藥品與原廠生物製劑是否有差異，執行模擬評估所提出方法之第一型錯誤機率、檢定力和覆蓋率，並以數值例子來介紹所提方法之應用。
並列摘要
The development of biological drug products is therapeutic agents manufactured using of a living system or organisms, which is very different from traditional small molecule drug products. In recent years, patents of many early biological drug products will be expired and this provides the opportunity to manufacture the generic versions of the biological drug products, which are referred to the follow-on biologics or biosimilar products. The US Food and Drug Administration (FDA) released on February 9, 2012, drafts of three new guidance documents about the demonstration of biosimilarity. One of these about scientific considerations, it suggests using a stepwise approach to demonstrate of biosimilarity and assessed by considering the totality of the evidence. On the other hand, the complexity and variability of the molecular structure, complicated manufacturing processes, different statistical analysis methods, and possibility of severe immunogenicity reactions make evaluation of biosimilarity between the biosimilar products and their corresponding innovator product a great challenge for statisticians and regulatory agencies. To resolve this issue, under the exponential distribution, we try to apply log-hazard regression through the parallel line assay to evaluate the extrapolation of the similarity in product characteristics based on the censored endpoints. The simulation studies were conducted to empirically investigate the performance of the size and power. A numerical example is provided to illustrate the suggested procedures.