附錄 ADDENDUM
5.0 品質管理
試驗委託者應在試驗過程中所有階 段執行品質管理系統。
試驗委託者應注重確保受試者保護 及試驗結果可信度所必須的試驗活 動。品質管理包括設計有效的臨床試 驗計畫及數據收集與處理之工具及 程序，以及收集對決策至關重要之資 訊。
用於確保及控制試驗品質的方法，應 與試驗的固有風險及所收集資訊的 重要性相均衡。試驗委託者應確保試 驗各面向具有可行性，並應避免非必 要的複雜性、程序及數據收集。試驗 計畫書、個案報告表及其他執行文件 應清晰、簡潔、一致。
品質管理系統應採用如下述，以風險 為基礎之方法。
5.0 Quality Management
The sponsor should implement a system to manage quality throughout all stages of the trial process.
Sponsors should focus on trial activities essential to ensuring human subject protection and the reliability of trial results.
Quality management includes the design of efficient clinical trial protocols and tools and procedures for data collection and processing, as well as the collection of information that is essential to decision making.
The methods used to assure and control the quality of the trial should be proportionate to the risks inherent in the trial and the importance of the information collected.
The sponsor should ensure that all aspects of the trial are operationally feasible and should avoid unnecessary complexity, procedures, and data collection. Protocols, case report forms, and other operational
63
documents should be clear, concise, and consistent.
The quality management system should use a risk-based approach as described below.
5.0.1
關鍵流程及數據之辨識
擬定試驗計畫書時，試驗委託者應辨 識出對受試者保護及試驗結果可信 度的關鍵流程及數據。
5.0.1
Critical Process and Data Identification During protocol development, the sponsor should identify those processes and data that are critical to ensure human subject protection and the reliability of trial results.
5.0.2 風險確認
試驗委託者應對關鍵的試驗流程及 數據確認其風險。系統方面（例如：
標準操作程序、系統電腦化、人力編 制）及臨床試驗方面（例如：試驗設
5.0.2
Risk Identification
The sponsor should identify risks to critical trial processes and data. Risks should be considered at both the system level (e.g., standard operating procedures,
64
計、數據收集、受試者同意程序）之 風險皆應納入考量。
computerized systems, personnel) and clinical trial level (e.g., trial design, data collection, informed consent process)
5.0.3 風險評估
試驗委託者應比對現有的風險管控 措施，針對已確認之風險進行評估，
並考量下列因素：
(一) 發生錯誤的可能性。
(二) 此種錯誤可被偵測出來的程度。
(三) 此種錯誤對受試者保護及試驗結 果可信度之影響。
5.0.3
Risk Evaluation
The sponsor should evaluate the identified risks, against existing risk controls by considering:
(a) The likelihood of errors occurring.
(b) The extent to which such errors would be detectable.
(c) The impact of such errors on human subject protection and reliability of trial results.
5.0.4 風險管制
試驗委託者應決定降低哪些風險或 接受哪些風險。用於降低風險至可接 受範圍之方式，應與風險的重要性成 比例。降低風險的活動可納入試驗設 計及執行、監測計畫、締約者間角色 及職責之協議、遵守標準作業程序之 系統性安全措施，及過程與程序方面 之培訓。
應預先建立品質容忍的限度，將醫學 與統計變異性，以及試驗統計的設計 納入考量，以確認影響受試者安全或 試驗結果可信度的系統性問題。發現 有偏離預定的品質容忍限度時，應進
5.0.4
Risk Control
The sponsor should decide which risks to reduce and/or which risks to accept. The approach used to reduce risk to an acceptable level should be proportionate to the significance of the risk. Risk reduction activities may be incorporated in protocol design and implementation, monitoring plans, agreements between parties defining roles and responsibilities, systematic safeguards to ensure adherence to standard operating procedures, and training in processes and procedures.
Predefined quality tolerance limits should
65
行評估以決定是否需採取行動。 be established, taking into consideration the medical and statistical characteristics of the variables as well as the statistical design of the trial, to identify systematic issues that can impact subject safety or reliability of trial results. Detection of deviations from the predefined quality tolerance limits should trigger an evaluation to determine if action is needed.
5.0.5 風險溝通
試驗委託者應記錄品質管理之活動。
試驗委託者應與參與其中或受此類 活動影響之人員，就品質管理活動進 行溝通，以促進臨床試驗執行期間之 風險審查及持續改進。
5.0.5
Risk Communication
The sponsor should document quality management activities. The sponsor should communicate quality management activities to those who are involved in or affected by such activities, to facilitate risk review and continual improvement during clinical trial execution.
5.0.6 風險審查
試驗委託者應定期審查風險管控措 施，將新興知識及經驗納入考量後，
評估其所實施之品質管理活動是否 仍具有效及相關性。
5.0.6
Risk Review
The sponsor should periodically review risk control measures to ascertain whether the implemented quality management activities remain effective and relevant, taking into account emerging knowledge and experience.
5.0.7 風險報告
試驗委託者應在臨床試驗報告中，描
5.0.7
Risk Reporting
The sponsor should describe the quality
66
述試驗中所實施之品質管理方法，並 總結重要偏離預定品質容忍限度之 情形及所採取之補救措施（參閱 ICH E3 9.6「數據之品質保證」）。
management approach implemented in the trial and summarize important deviations from the predefined quality tolerance limits and remedial actions taken in the clinical study report (ICH E3, Section 9.6 Data Quality Assurance).
5.1 品質保證及品質管制 5.1 Quality Assurance and Quality Control
5.1.1
試驗委託者應依照書面標準作業程 序實施及維護品質保證及品質管制 系統，以確保試驗執行及數據的產 生，紀錄，及報告均遵從試驗計畫書、
GCP 及相關法規要求。
5.1.1
The sponsor is responsible for implementing and maintaining quality assurance and quality control systems with written SOPs to ensure that trials are conducted and data are generated, documented (recorded), and reported in compliance with the protocol, GCP, and the applicable regulatory requirement(s).
5.1.2
試驗委託者應負責確認所有參與試 驗相關單位的同意，確保所有試驗相 關場所、原始資料/文件及報告，可由 試驗委託者直接進行監測和稽核，並 可接受國內外主管機關查核。（參閱 1.21）。
5.1.2
The sponsor is responsible for securing agreement from all involved parties to ensure direct access (see 1.21) to all trial related sites, source data/documents, and reports for the purpose of monitoring and auditing by the sponsor, and inspection by domestic and foreign regulatory authorities.
5.1.3
數據處理的每一步驟應採取品質管 制，以確保所有數據之可信度及其處 理的正確性。
5.1.3
Quality control should be applied to each stage of data handling to ensure that all data are reliable and have been processed
67
correctly.
5.1.4
試驗委託者與試驗主持人\機構和\或 任何其他參與此臨床試驗之人員所 訂之協議應以書面紀錄，作為試驗計 畫書之一部分或為獨立之協議。
5.1.4
Agreements, made by the sponsor with the investigator/institution and any other parties involved with the clinical trial, should be in writing, as part of the protocol or in a separate agreement.
5.2 受託研究機構 5.2 Contract Research Organization (CRO)
5.2.1
試驗委託者可移轉部份或全部與試 驗相關的責任與功能予受託研究機 構，但關於維護試驗數據的品質與完 整性之最終責任仍在試驗委託者。受 託研究機構應執行試驗品質保證與 品質管制。
5.2.1
A sponsor may transfer any or all of the sponsor's trial-related duties and functions to a CRO, but the ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor. The CRO should implement quality assurance and quality control.
5.2.2
試驗委託者應以書面委託方式，將與 試驗相關的責任與功能委託受託研 究機構辦理。
附錄
試驗委託者應對其受託執行與試驗 相關的責任與功能進行監督，包括受 託研究機構再委託第三方履行與試 驗相關之責任及功能。
5.2.2
Any trial-related duty and function that is transferred to and assumed by a CRO should be specified in writing.
ADDENDUM
The sponsor should ensure oversight of any trial-related duties and functions carried out on its behalf, including trial-related duties and functions that are subcontracted to another party by the sponsor's contracted CRO(s).
5.2.3 5.2.3
68
未移轉給受託研究機構的試驗責任 與功能，仍屬於試驗委託者。
Any trial-related duties and functions not specifically transferred to and assumed by a CRO are retained by the sponsor.
5.2.4
本指引有關試驗委託者的規章，亦適 用於承擔試驗委託者有關試驗責任 與功能的受託研究機構。
5.2.4
All references to a sponsor in this guideline also apply to a CRO to the extent that a CRO has assumed the trial related duties and functions of a sponsor.
5.3 醫療專業
試驗委託者應任用合適合格，並能對 試驗相關醫療問題提供意見的醫療 人員。若有必要，亦可指派外部顧問 擔任上述工作。
5.3 Medical Expertise
The sponsor should designate appropriately qualified medical personnel who will be readily available to advise on trial related medical questions or problems. If necessary, outside consultant(s) may be appointed for this purpose.
5.4 試驗設計 5.4 Trial Design
5.4.1
於所有試驗階段期間，試驗委託者應 採用合適且合格之人員（例如：生物 統計學家，臨床藥理人員及醫師）從 事試驗計畫書與個案報告及規畫分 析，和分析及準備期中與最後臨床試 驗報告。
5.4.1
The sponsor should utilize qualified individuals (e.g. biostatisticians, clinical pharmacologists, and physicians) as appropriate, throughout all stages of the trial process, from designing the protocol and CRFs and planning the analyses to analyzing and preparing interim and final clinical trial reports.
5.4.2
其他相關的基準：試驗計畫書及其變 更（參閱第 6 章）、ICH「藥品臨床 試驗報告之格式及內容」及其他與試
5.4.2
For further guidance: Clinical Trial Protocol and Protocol Amendment(s) (see 6.), the ICH Guideline for Structure and Content of
69
驗設計、試驗計畫書及執行相關之 ICH 指導文件。
Clinical Study Reports, and other appropriate ICH guidance on trial design, protocol and conduct.
5.5 試驗管理、數據處理及紀錄保存 5.5 Trial Management, Data Handling, and Record Keeping
5.5.1
試驗委託者應任用合適合格之人員，
監督所有試驗 的執行，處理與驗證 試驗數據，進行統計分析，及準備試 驗報告。
5.5.1
The sponsor should utilize appropriately qualified individuals to supervise the overall conduct of the trial, to handle the data, to verify the data, to conduct the statistical analyses, and to prepare the trial reports.
5.5.2
試驗委託者得設置獨立數據監測委 員會，以評估臨床試驗之進展，包括 定期評估安全性數據及重要療效指 標，及建議試驗委託者是否繼續、修 正或終止試驗。獨立數據監測委員會 應建立書面標準作業程序，並保存所 有會議之書面紀錄。
5.5.2
The sponsor may consider establishing an independent data-monitoring committee (IDMC) to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial. The IDMC should have written operating procedures and maintain written records of all its meetings.
5.5.3
當試驗使用電子資料處理系統或遠 端電子資料處理系統時，試驗委託者 應：
(一) 確保並記錄電子資料處理系統符 合試驗委託者對資料完整性、精
5.5.3
When using electronic trial data handling and/or remote electronic trial data systems, the sponsor should:
(a) Ensure and document that the electronic data processing system(s) conforms to
70
the sponsor's established requirements for completeness, accuracy, reliability, and consistent intended performance (i.e. validation).
ADDENDUM
The sponsor should base their approach to validation of such systems on a risk assessment that takes into consideration the intended use of the system and the potential of the system to affect human subject protection and reliability of trial results.
(b) Maintains SOPs for using these systems.
ADDENDUM
The SOPs should cover system setup, installation, and use. The SOPs should describe system validation and functionality testing, data collection and handling, system maintenance, system security measures, change control, data backup, recovery, contingency planning, and decommissioning. The responsibilities of the sponsor, investigator, and other parties with respect to the use of these computerized systems should be clear, and the users should be provided with training in their use.
(c) Ensure that the systems are designed to
71
附錄
(八) 確保數據的完整性，包括對數據
的描述背景、內容及結構。其對電腦 化系統進行變更時尤為重要，例如軟 體升級或資料遷移時。
permit data changes in such a way that the data changes are documented and that there is no deletion of entered data (i.e. maintain an audit trail, data trail, edit trail).
(d) Maintain a security system that prevents unauthorized access to the data.
(e) Maintain a list of the individuals who are authorized to make data changes (see 4.1.5 and 4.9.3).
(f) Maintain adequate backup of the data.
(g) Safeguard the blinding, if any (e.g.
maintain the blinding during data entry and processing).
ADDENDUM
(h) Ensure the integrity of the data including
(h) Ensure the integrity of the data including