生物相似性藥品之設限資料對等性評估的研究

Abstract

生物製劑的市場近年來逐漸增加，但是所需的開發成本仍然很高，所以在生物製劑的專利到期以後，許多藥廠紛紛投入生物相似性藥品的研發。不同於一般的化學分子學名藥，生物製劑具有製程專一的特性，所以評估生物相似性藥品必須與化學分子學名藥有所不同。現行法規中，生物相似性藥品需依個案，適度的減免臨床試驗，才能被核准上市，成本並不小於開發新的生物製劑，無法降低成本，達到造福病患之目的。 當療效指標為設限資料時，本篇論文以對數風險率回歸檢定法評估生物製劑相似性藥品與原廠生物製劑是否為相似，以評估是否需要執行完整臨床試驗，模擬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方法之應用。

In recent years, biologics market of biological drug increases rapidly, but the development costs are also very high. Therefore, after the patent of biological products expires, many pharmaceutical companies have invested in the development of biosimilar products. But, biological products, with process specificity, are different from traditional small molecule drug products. Therefore the methods for assessment of biosimilar products are also different from that of chemical generic products. Current regulations indicate that the clinical trials for assessment can be waived on a case-by-case basis, but a pharmacovigilance is necessary. However, if the requirement for clinical trials cannot be waived, the development cost of biosimilar products will be the same as that of the innovators. It cannot achieve the goal of cost reduction, and deny of access of biological drug products to needed patients. In this thesis, we propose to apply the parallel-line assay to test whether the approval of the biosimilar products should require clinical trials. We developed the statistical testing procedure to evaluate the equivalence between the biosimilar drug product and innovator’s biological procedure when the primary endpoint is a censored variable which follows an exponential distribution. The results of size and power from the simulation studies are presented. A numerical example is used to illustrate the application of the proposed method.