台灣新藥臨床試驗計畫審查流程及執行之探討與建議

本研究旨在探討影響台灣新藥臨床試驗計畫審查流程及執行之因素。本研究首先以「文獻回顧」蒐集國內外相關制度現況，再以「個人深度訪談」及「焦點團體訪談法」，透過質性訪談的方式，以自擬的訪談大綱對產業界具有新藥臨床試驗申請或審查流程經驗，或具有執行臨床試驗相關經驗者進行訪談收集資料。希望能對於加速台灣新藥臨床試驗之申請與執行提出政策與審查流程的建議。本研究根據受訪的訪談意見整理摘要說明如下: (一) 新藥臨床試驗申請 1. 審查流程:TFDA雖規範新藥臨床試驗申請審查天數，但多位受訪者表示廠商提出申請時卻無法預知甚麼時間點可以獲得核准，導致難以事先安排後續作業。 2. 補件規定:TFDA雖規範僅有一次補件機會，但有時並非規定的一次補件，所以無法預知是否還有補件或何時會核准。 (二) CIRB/IRB申請 1. 審查流程: Coordinated-IRB (C-IRB)主副審醫院審查機制，雖然表定時間為30天可以完成審核，但因為行政審查不計算在實質審查的時間內，加上副審醫院不一定追認主審醫院的意見，所以最快需要核准時間為1.5-3個月不等。 2. 文件格式要求:即使採取CIRB審查機制，文件格式還是需要配合各家醫院要求準備提供，影響審查效率。 (三) 臨床試驗執行前置作業 1. 臨床試驗合約:無官方統一臨床試驗合約書範本，一旦合約無法達成共識，在簽署速度上比其他國家慢許多，也因此失去全球競爭性收案的案子機會。 2. 其他:欠缺臨床試驗專業人才及無培訓的環境和專業認證，是目前台灣面臨的困境。根據文獻分析以及訪談結果，結論如下: (一) 新藥臨床試驗申請 TFDA的確會在所規範的審查期間內進行回覆，但不表示可以在審查時間結束後就可以知道TFDA同不同意其新藥臨床試驗的申請，而補件以技術文件及臨床相關的缺失居多。 (二) CIRB/IRB申請 CIRB的主審醫院基本上都有於規範的時間內完成審查，但副審醫院卻不受規範。此外，行政文件審查的時間不包含在審查規範的時間內。補件則以受試者同意書的格式及內容的文字敘述被要求修改居多。 (三) 臨床試驗執行前置作業臨床試驗合約的簽署是主要影響臨床試驗收案的時間。一般合約簽署需要2-3個月的時間，有時甚至到半年。本研究建議: (一) 對法規單位(TFDA)之建議 1. 加強TFDA承辦人員教育訓練 2. 強化TFDA與CDE內部溝通與整合 3. 建立電子化系統 (二) 對CIRB/IRB之建議 1. 文件格式統一 2. 加強承辦人員教育訓練 3. IRB權責 (三) 對臨床試驗執行前置作業建議 1. 制定臨床試驗合約範本 2. 專業人才的培養

關鍵字

新藥臨床試驗申請；聯合倫理審查機制；臨床試驗合約；生技產業

並列摘要

The purpose of this study is to identify and discuss the factors that can affect the review process and implementation for Taiwan clinical trial (IND) Applications. “Literature review”, “in-depth review” and “focus group” are used as research methods. Through qualitative research, the researcher interviewed people who have experience of the review process and implementation for Taiwan clinical trial (IND) Applications and collected feedback using the interview questions. Hope to make comprehensive recommendations for speeding up the review process of Taiwan clinical trial implementation. The results based on interviews are summarized as follows: I. Clinical trial application 1. Review process: Although TFDA has announced the review timeline for clinical trial applications, the applicants still can’t foresee when the application can be approved and make it difficult for the applicants to arrange the follow-up work in advance. 2. Amendment requirements: By Regulations, the applicants have one chance to take corrective actions if data insufficient or other matters not in accordance with the Regulations. However, TFDA allows more than one time for amendments, so it is not possible to predict whether there is more to come or when approved. II. CIRB/IRB application 1. Review process: According to Coordinated-IRB (C-IRB) review mechanism, the substantive review should be completed within 30 days; however, the administrative review is not included in this review timeframe. Besides, sub- hospitals may not recognize the review comments provided by main hospitals; therefore, the fastest time for approval is 1.5 to 3 months. 2. Document format requirements: Even though Coordinated-IRB (C-IRB) review mechanism is adopted, the document format still needs to be prepared in line with the requirements of each hospital which affects the efficiency of the review. III. Preparation for clinical trials 1. Clinical trial agreement: There is no official template for clinical trial agreements. Once either party cannot reach consensus, the review process will slow down and the sponsor may loss the opportunity to participate in global trials. 2. Other: The lack of clinical trial professionals, training environment and professional certifications are the current difficult situations we face in Taiwan. Conclusions: I. Clinical trial application TFDA does respond within the stipulated timeframe, but it does not mean that sponsors will know whether the application is approved or not. The amendments are mostly Chemistry, Manufacturing, and Controls (CMC) and clinical related issues. II. CIRB/IRB application The main hospitals basically complete the review within the stipulated timeframe, but the sub hospitals are not regulated. In addition, the administrative review is not included in this review timeframe. The amendments are mostly the format of the subject informed consent form and the description of the content. III. Preparation for clinical trials The time required to sign a clinical trial agreement has a direct impact on the initiation of clinical trials. In general, contract signing takes two to three months and sometimes six months. Suggestions: I. For TFDA 1. Strengthen education and training of project managers 2. Improve and integrate the internal communication between TFDA and CDE and 3. Establish an electronic system II. For CIRB/IRB 1. Document format 2. Strengthen education and training of contact persons 3. Authority and responsibility of IRB III. For preparation for clinical trials 1. Develop official template for clinical trial agreements. 2. Professional development