Contents
Part 1: Introduction
Part 2: Documentation Requirements in GCP and Federal Regulations
Part 1: Introduction
Proper documentation is critical to the success of a clinical study. Every aspect of the study must be documented in order to obtain useful data and demonstrate compliance with Good Clinical Practice (GCP) guidelines and with all applicable regulations.
正確的文獻(xiàn)記錄對于臨床研究的成功至關(guān)重要。必須記錄研究的每個方面，以獲得有用的數(shù)據(jù)，并證明符合良好臨床實踐（GCP）指南和所有適用法規(guī)。
This module provides an overview of GCP documentation requirements, requirements in federal regulations, and sponsor required documentation.
本模塊概述了GCP文件要求、聯(lián)邦法規(guī)要求以及贊助商要求的文件。
Part 2: Documentation Requirements in GCP and Federal Regulations? ?GCP和聯(lián)邦法規(guī)中的文件要求
Documentation Requirements in Good Clinical Practice Guidelines? ?良好臨床實踐指南中的文件要求
Essential documents for the conduct of a clinical study are defined in ICH GCP 8.1 as follows:
"… those documents that individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced. These documents serve to demonstrate the compliance of the investigator, sponsor, and monitor with the standards of Good Clinical Practice and with all applicable regulatory requirements."
ICH GCP 8.1中定義了進(jìn)行臨床研究的基本文件，如下所示：
“……單獨或集體允許對試驗的進(jìn)行和所產(chǎn)生數(shù)據(jù)的質(zhì)量進(jìn)行評估的文件。這些文件用于證明研究者、贊助者和監(jiān)督者遵守良好臨床實踐標(biāo)準(zhǔn)和所有適用的監(jiān)管要求?！?/p>
Essential documents may be audited or inspected by quality assurance monitors or by regulatory authorities to confirm the validity of the study and the integrity of the data collected.
基本文件可由質(zhì)量保證監(jiān)督員或監(jiān)管機(jī)構(gòu)進(jìn)行審核或檢查，以確認(rèn)研究的有效性和所收集數(shù)據(jù)的完整性。
GCP guidelines list the essential documents (ICH GCP E6 Section 8) that, at a minimum, must be maintained for every clinical study. These documents are to be maintained by the site and the sponsor, and are classified according to the stage of a study at which they are normally created. These documents may be maintained in multiple locations, depending on whether they are stored with regulatory files or as participant documents. The sponsor and the investigator/institution should maintain a record of the location(s) of their respective essential documents, including source documents. Additional documents may be developed and maintained by the sponsor or the sponsor(s) representatives.
GCP指南列出了每項臨床研究必須至少保存的基本文件（ICH GCP E6第8節(jié)）。這些文件由現(xiàn)場和發(fā)起人保存，并根據(jù)通常創(chuàng)建這些文件的研究階段進(jìn)行分類。這些文件可以保存在多個位置，具體取決于它們是與監(jiān)管文件一起存儲還是作為參與者文件存儲。發(fā)起人和研究人員/機(jī)構(gòu)應(yīng)保存其各自基本文件（包括原始文件）的位置記錄。發(fā)起人或發(fā)起人代表可編制和維護(hù)其他文件。
BEFORE
Before a Study Begins
The following essential documents must be created and kept on file at study sites before a study begins:
在研究開始之前，必須在研究地點創(chuàng)建并保存以下基本文件：
Ⅰ、Signed protocol and amendments, if any.
Ⅱ、IRB-approved Informed Consent Form and any other written information that will be given to prospective study participants to enable them to make an informed decision about enrolling in the trial.
Ⅲ、Sample case report forms, either electronic or paper.
Ⅳ、Participant recruitment advertisements, if any.
Ⅴ、Documentation that the Institutional Review Board (IRB) is set up in accordance with GCP and that all necessary IRB approvals have been obtained.
Ⅵ、Decoding procedures for blinded trials to document how, in case of an emergency, identity of blinded investigational product can be revealed without breaking the blind for the remaining subjects' treatment, if applicable.
Ⅶ、Documentation of study personnel's qualifications (e.g., curriculum vitae, professional licenses).
Ⅷ、Documentation of financial agreements and any other arrangements between the parties involved in conducting the study (e.g., investigator(s), institution(s), sponsor, contract research organization).
Ⅸ、Insurance statement, where required, to document that compensation to subject(s) for trial-related injury will be available.
Ⅹ、If the study involves the use of an investigational drug, instructions for handling, dispensing, and tracking the investigational product, as well as shipping records, and a sample of the label to be attached to the investigational product container.
Ⅺ、Investigator's Brochure, when applicable.
Ⅻ、Evidence of notification, approval, or authorization of the protocol and its supporting documentation by regulatory authorities (if required)
XIII、Evidence of approval or certification of facilities that are performing medical or laboratory tests required by the study protocol.
XIV、Normal value(s)/ range(s) for medical, laboratory, and/or technical procedures and tests included in the protocol.
XV、Reports of site initiation visits and qualification visits by quality assurance monitors.
1、簽署的協(xié)議和修正案（如有）。
2、IRB批準(zhǔn)的知情同意書以及將提供給潛在研究參與者的任何其他書面信息，以使他們能夠就參加試驗做出知情決定。
3、案例報告表樣本，電子版或紙質(zhì)版。
4、參與者招聘廣告（如有）。
5、證明機(jī)構(gòu)審查委員會（IRB）是根據(jù)GCP成立的，且已獲得所有必要的IRB批準(zhǔn)的文件。
6、盲法試驗的解碼程序，以記錄在緊急情況下，盲法試驗產(chǎn)品的身份如何在不打破盲法的情況下被披露，以供剩余受試者治療（如適用）。
7、研究人員資格證明文件（如簡歷、專業(yè)執(zhí)照）。
8、參與研究的各方（如研究人員、機(jī)構(gòu)、贊助人、合同研究機(jī)構(gòu)）之間的財務(wù)協(xié)議和任何其他安排的文件。
9、保險聲明，如有需要，記錄受試者因試驗相關(guān)傷害而獲得的賠償。
10、如果研究涉及試驗藥物的使用，則應(yīng)提供處理、配藥和跟蹤試驗藥物的說明，以及裝運(yùn)記錄，以及貼在試驗藥物容器上的標(biāo)簽樣本.
11、研究人員手冊（如適用）
12、監(jiān)管機(jī)構(gòu)通知、批準(zhǔn)或授權(quán)協(xié)議及其支持文件的證據(jù)（如需要）
13、 進(jìn)行研究方案要求的醫(yī)療或?qū)嶒炇以囼灥?b>設(shè)施的批準(zhǔn)或認(rèn)證證據(jù)。
14、 協(xié)議中包括的醫(yī)療、實驗室和/或技術(shù)程序和測試的正常值/范圍。
15、 質(zhì)量保證監(jiān)督員的現(xiàn)場啟動訪問和資格訪問報告。
IN PROGRESS
While a Study is in Progress? ?正在進(jìn)行的研究
The following are essential documents that should be added to the file while a study is in progress:
以下是在進(jìn)行研究時應(yīng)添加到文件中的基本文件：
Ⅰ、Amendments to the Protocol and changes to the case report forms (CRFs), recruitment materials, Informed Consent Form, and Investigator's Brochure.
Ⅱ、Documentation of approval of amendments by the Institutional Review Board (IRB) and regulatory authorities (if required).
Ⅲ、Copies of all reports, including interim and annual reports, sent to the IRB and other regulatory authorities.
Ⅳ、Informed consent forms signed by study participants.
Ⅴ、Signed, dated, and completed CRFs and documentation of any CRF corrections with the signature sheet.
Ⅵ、Documentation of investigational products and trial-related materials shipment.
Ⅶ、Relevant communications, such as letters and meeting notes, that document agreements or discussions about issues including protocol violations, adverse events, the conduct and administration of the study, and all safety information notifications and communications.
Ⅷ、Relevant communications other than site visits, such as letters and meeting notes.
Ⅸ、Reports of interim visits by quality assurance monitors.
Ⅹ、Curriculum vitae for new investigators and sub-investigators.
Ⅻ、Participant screening log, enrollment log, and identification code list.
XIII、Documentation that investigational drugs, if used in the study, have been handled and accounted for as required in the protocol.
XIV、Records of location and identification of retained tissue samples, if any.
XV、Staff signature log, documenting signatures and initials of all persons authorized to make entries and/or corrections to CRFs.
XVI、Updates to CVs, license etc.
1、對方案的修訂以及對病例報告表（CRF）、招募材料、知情同意書和研究人員手冊的更改。
2、機(jī)構(gòu)審查委員會（IRB）和監(jiān)管機(jī)構(gòu)（如需要）批準(zhǔn)修訂的文件。
3、發(fā)送給IRB和其他監(jiān)管機(jī)構(gòu)的所有報告（包括中期報告和年度報告）的副本。
4、研究參與者簽署的知情同意書。
5、簽署、注明日期并填寫完整的CRF以及任何CRF更正的文件以及簽名表。
6、研究產(chǎn)品和試驗相關(guān)材料的裝運(yùn)文件。
7、相關(guān)通信，如信函和會議記錄，記錄有關(guān)問題的協(xié)議或討論，包括違反方案、不良事件、研究的進(jìn)行和管理，以及所有安全信息通知和通信。
8、現(xiàn)場考察以外的相關(guān)溝通，如信函、會議紀(jì)要等。
9、質(zhì)量保證監(jiān)督員的臨時訪問報告。
10、新調(diào)查員和副調(diào)查員的簡歷。
11、原始文件。
12、參與者篩選日志、報名日志、身份代碼清單。
13、 證明試驗藥物（如果在研究中使用）已按照方案要求進(jìn)行處理和說明的文件。
14、 保留組織樣本的位置和標(biāo)識記錄（如有）。
15、員工簽名日志，記錄所有被授權(quán)錄入和/或修改crf的人員的簽名和首字母。
16、更新簡歷、許可證等。
AFTER
After a Study is Completed or Terminated? ?研究完成或終止后
The following are essential documents that should be added to the file after a study is completed or terminated:
以下是研究完成或終止后應(yīng)添加到文件中的基本文件：
Ⅰ、Documentation that investigational drugs, if used, were handled, accounted for, and returned or destroyed as required in the protocol.
Ⅱ、List of all participants enrolled in the study at the site (completed subject identification code list).
Ⅲ、Reports of closeout visits by quality assurance monitors.
Ⅳ、Final reports to Institutional Review Boards and regulatory authorities.
Ⅴ、Clinical study report, which documents the study’s results, if applicable.
1、研究藥物（如使用）按照方案要求進(jìn)行處理、說明、退回或銷毀的文件。
2、現(xiàn)場登記參加研究的所有參與者名單（填寫完整的受試者識別碼清單）。
3、質(zhì)量保證監(jiān)督員的收尾訪問報告。
4、向機(jī)構(gòu)審查委員會和監(jiān)管機(jī)構(gòu)提交的最終報告。
5、臨床研究報告，記錄研究結(jié)果（如適用）。
Documentation Requirements in Federal Regulations? ?聯(lián)邦法規(guī)中的文件要求
21 CFR 312.62 requires investigators to:
21 CFR 312.62要求調(diào)查人員：
Ⅰ、Maintain adequate records of the disposition of investigational drugs.
Ⅱ、Maintain adequate case histories for all participants in studies that involve the use of investigational products.
Ⅲ、Retain records for 2 years after the date a marketing application is approved for the drug for the indication for which is it has been investigated by the U.S. Food and Drug Administration (FDA) or for 2 years after the study is discontinued and the FDA is notified.
Ⅳ、Records of all NIH–sponsored studies must be maintained for at least 3 years after the study ends per NIH policy and for a longer time if required by regulations or local institutional policies. This requirement applies to all research projects, including studies of investigational drugs, behavioral studies, and survey–based studies.
1、保持試驗藥物處置的充分記錄。
2、為所有參與使用試驗藥物的研究的參與者保留充分的病例記錄。
3、在美國食品和藥物管理局（FDA）對該藥物的適應(yīng)癥進(jìn)行調(diào)查后，在批準(zhǔn)該藥物的上市申請之日起2年內(nèi)保留記錄，或在該研究終止并通知FDA后保留記錄2年。
4、根據(jù)NIH政策，所有NIH贊助研究的記錄必須在研究結(jié)束后至少保存3年，如果法規(guī)或當(dāng)?shù)貦C(jī)構(gòu)政策要求，則必須保存更長的時間。該要求適用于所有研究項目，包括試驗藥物研究、行為研究和基于調(diào)查的研究。
Click to view Clinical Trial Network（CTN） related content
點擊查看臨床試驗網(wǎng)絡(luò)（CTN）相關(guān)內(nèi)容
Records of all CTN–sponsored studies must be maintained for at least 3 years after the study ends per NIH policy and for a longer time if required by regulations or local institutional policies. This requirement applies to all research projects, including studies of investigational drugs, behavioral studies, and survey–based studies.
根據(jù)NIH政策，所有CTN贊助研究的記錄必須在研究結(jié)束后至少保存3年，如果法規(guī)或當(dāng)?shù)貦C(jī)構(gòu)政策要求，則必須保存更長的時間。該要求適用于所有研究項目，包括試驗藥物研究、行為研究和基于調(diào)查的研究。
Of note, most facilities where CTN research is conducted are covered entities that must comply with the HIPAA Privacy Rule. Covered entities are required to account for disclosures (must retain documentation) 6 years from the date of creation on which the accounting is requested. (Reference the Clinical Research and the HIPAA Privacy Rule.)
值得注意的是，大多數(shù)進(jìn)行CTN研究的設(shè)施都是必須遵守HIPAA隱私規(guī)則的覆蓋實體。被覆蓋的實體被要求從被要求進(jìn)行會計核算的創(chuàng)立之日起6年內(nèi)進(jìn)行披露(必須保留文件)。(參考臨床研究和HIPAA隱私規(guī)則)
