ICH-GCP 7.1 The Research Protocol（1）

Contents

Part 1: Introduction

Part 2: Contents of the Research Protocol (ICH E3 GCP 6)

Part 1: Introduction

Documents to Ensure Standardization  确保标准化的文件

Standardization — everyone doing the same things in the same way — is critical in a clinical research study and particularly critical for multisite trials. Research that is not conducted in a standardized manner is unethical because it may put research participants at risk while yielding invalid data. (Protection of the safety, rights, and well-being of research participants is discussed in the Introduction, Institutional Review Boards, and Informed Consent module.)

标准化——每个人都以同样的方式做同样的事情——在临床研究中是至关重要的，尤其是在多站点试验中。不以标准化方式进行的研究是不道德的，因为它可能会使研究参与者处于风险之中，同时产生无效数据。（引言、机构审查委员会和知情同意模块中讨论了研究参与者的安全、权利和福利保护）

Several documents are key to ensuring that a research study is conducted in a standardized manner (see the module on Documentation & Record-Keeping for a full list of essential study documents). All research staff that participates in a clinical study must be familiar with, and must strictly adhere to, the procedures described in these documents.

一些文件是确保以标准化方式进行研究的关键（有关基本研究文件的完整列表，请参阅文件和记录保存模块）。所有参与临床研究的研究人员必须熟悉并严格遵守这些文件中描述的程序。

Investigator's Brochure(IB)  研究者手册

The Investigator's Brochure is a document containing nonclinical and clinical data to describe previous experience with the experimental intervention, often a medication.

研究者手册是一份包含非临床和临床数据的文件，用于描述以前的实验干预经验，通常是药物的。

Operations Manual  操作手册

The operations manual “operationalizes” the protocol, providing more detail on the actual procedures needed to perform the research.

操作手册使协议“可操作化”，提供了进行研究所需的实际程序的更多细节。

For example, the protocol might specify that a urine sample is to be collected at each study visit, whereas the operations manual would describe details of the collection, labeling, storage, and shipping of the samples. For another example, the operations manual might state that each study site is to maintain a site contact log containing the names, addresses, and phone numbers of all individuals involved in the study at that site. Additionally, even more detailed information, such as a list of staff responsible for maintaining the contact log and the detailed procedures involved, would be appropriate for an Operations Manual; however, such detail would be inappropriate in the research protocol.

例如，方案可能规定每次研究访视时收集尿液样本，而操作手册将描述样本收集、标记、储存和运输的细节。另一个例子是，操作手册可能会规定，每个研究现场都要维护一个现场联系日志，其中包含该现场参与研究的所有个人的姓名、地址和电话号码。此外，更详细的信息，如负责维护联系日志的工作人员名单和所涉及的详细程序，将适用于操作手册；然而，在研究方案中，这样的细节是不合适的。

Standard Operating Procedures (SOPs)   标准作业程序

Standard operating procedures (SOPs) describe in detail how specific procedures (e.g., taking vital signs, performing urine tests, and assessing adverse events) are to be carried out in the research study. Most SOPs will be identical for all study sites. However, in some cases site-specific variations are needed. For example, if procedures for handling a medical emergency vary slightly from one research site to another, the SOP for these procedures at a specific site will reflect those variations. Additionally, site staff will need to be trained appropriately for the site-specific procedures.

标准操作程序（SOP）详细描述了在研究中如何执行特定程序（例如，采集生命体征、进行尿液测试和评估不良事件）。所有研究地点的大多数SOP都是相同的。然而在某些情况下，需要现场特定的变化。例如，如果处理医疗紧急情况的程序因研究地点而异，则特定地点的这些程序的SOP将反映这些变化。此外，现场工作人员需要接受现场特定程序的适当培训。

Other Study Documents  其他研究文件

This module focuses on the research protocol. Some information may be provided in other documents that accompany the protocol, such as the Investigator's Brochure. Additional site-specific information that may change during the trial (such as the names and addresses of research sites and the sponsor's medical expert information) may be provided in a separate document, such as the operations manual. This is acceptable as long as the protocol contains language that refers to the operations manual for this information.

该模块侧重于研究协议。一些信息可在方案附带的其他文件中提供，如研究人员手册。试验期间可能发生变化的其他特定于试验地点的信息（如研究地点的名称和地址以及申办方的医学专家信息）可在单独的文件中提供，如操作手册。这是可以接受的，只要协议包含参考操作手册的语言来获取此信息。

Research Protocol  研究协议

The research protocol provides a plan for the essential aspects of the proposed research. (See summarized research protocol contents.) It must be approved by the designated Institutional Review Board (IRB) before the research can begin. Any changes to the protocol must also be approved by the IRB.

研究方案为拟议研究的基本方面提供了计划。（参见概述的研究方案内容）必须在研究开始之前被指定的机构审查委员会（IRB）批准。对议定书的任何更改也必须得到IRB的批准。

Why is the research protocol so important?

The research protocol is one of the main documents that must be approved by the designated Institutional Review Board before any research study can begin.

研究方案是主要文件之一，在任何研究开始之前，必须由指定的机构审查委员会批准。

The Good Clinical Practice (GCP) guidelines of the International Council for Harmonization require a research protocol for any study that involves human participants. In addition, Title 21 Part 312 of the Code of Federal Regulations (21 CFR 312) describes both a research protocol and protocol amendments for studies conducted under an Investigational New Drug application.

国际协调理事会的良好临床实践（GCP）指南要求对涉及人类参与者的任何研究制定研究方案。此外，《联邦法规》（21 CFR 312）第21篇第312部分描述了在试验性新药申请下进行的研究的研究方案和方案修正案。

Part 2: Contents of the Research Protocol (ICH E3 GCP 6)

The research protocol must clearly and succinctly describe the following aspects of the research study:

研究方案必须清楚、简洁地描述研究的以下方面：

Ⅰ、Why the study is being done.

Ⅱ、What will be done in the study.

Ⅲ、Where the study will be done (for multi-site trials, site-specific information may be incorporated into local protocal versions).

Ⅳ、Who is involved in the research study.

Ⅴ、When study interventions will take place.

1、 为什么要进行这项研究；

2、 这项研究将做些什么；

3、 进行研究的地点（对于多地点试验，可将特定地点的信息纳入当地协议版本）；

4、 谁参与了这项研究；

5、 何时进行研究干预。

The protocol should contain enough information to provide a clear and complete, but not overly detailed, description of the study. Further details should appear, as discussed earlier, in other documents such as the operations manual, standard operating procedures, quality assurance plan, training plan, and data management plan.

该方案应包含足够的信息，以提供一个清晰、完整但不过分详细的研究描述。如前所述，进一步的细节应该出现在其他文件中，如操作手册、标准操作程序、质量保证计划、培训计划和数据管理计划。

To ensure that research protocols include the appropriate sections and content, a sponsor may develop a standardized template for investigators to use for each type of study. For example, a research network has developed such templates to assist investigators in preparing research protocol documents for network specific trials. For NIH-funded studies under an Investigational New Drug (IND), there is a protocol template available at the following NIH website.

为确保研究方案包括适当的章节和内容，申办方可为研究人员制定标准化模板，用于每种类型的研究。例如，一个研究网络开发了这样的模板，以帮助研究人员为网络特定试验准备研究方案文件。对于NIH资助的试验新药（IND）研究，在以下NIH网站上提供了方案模板。

The protocol generally covers the following topics (see ICH GCP E6 6).

该协议通常包括以下主题(参见ICH GCP E6 6)。

General Information  一般信息

Ⅰ、Protocol title, identifying number, version number, and date.

Ⅱ、Name and address of the sponsor and monitor (if other than the sponsor).

Ⅲ、Name and title of the person authorized to sign the protocol and the protocol amendments for the sponsor.

Ⅳ、Names and titles of the investigators responsible for conducting the study, and the address and telephone number of the trial sites.

Ⅴ、Name, title, address, and telephone number of the sponsor’s medical expert.

Ⅵ、Name, title, address, and telephone number of the qualified physician who is responsible for all study–related medical decisions.

Ⅶ、qiNames and addresses of all institutions involved in the study (including clinical laboratories and other medical or technical departments).

Ⅷ、Addresses and telephone numbers of all clinical laboratories and/or institutions involved in the trial.

1、协议标题、识别号、版本号和日期。

2、发起人和监督员的姓名和地址（如果不是发起人）。

3、被发起人授权签署协议和协议修正案的人员的姓名和职务。

4、负责进行研究的研究人员的姓名和职务，以及试验地点的地址和电话号码。

5、发起人医学专家的姓名、职务、地址和电话号码。

6、负责所有研究相关医疗决策的合格医师的姓名、职务、地址和电话号码。

7、参与研究的所有机构（包括临床实验室和其他医疗或技术部门）的姓名和地址。

8、参与试验的所有临床实验室和/或机构的地址和电话号码。

Background Information  背景资料

Ⅰ、A description of the issue the study is addressing as well as its public health significance.

Ⅱ、Findings from clinical or nonclinical studies that may be significant to the proposed study.

Ⅲ、Summary of the known potential risks and benefits to human participants.

Ⅳ、A statement that the trial will be conducted in compliance with the protocol, GCP, and the applicable regulatory requirement(s).

Ⅴ、Description of the study population.

Ⅵ、References to relevant literature and data (this will often be compiled in a separate section in the protocol).

Ⅶ、If the study involves the use of an investigational product or therapy:

   i、Name and description of the investigational product or therapy.

   ii、Description of and justification for the route of administration, dosage, dosage regimen, and treatment period(s).

1、对研究所涉及的问题及其公共卫生意义的描述。

2、临床或非临床研究的发现，可能对拟定研究有重要意义。

3、人类参与者已知潜在风险和利益的总结。

4、说明试验将按照方案、GCP和适用监管要求进行的声明。

5、研究人群的描述。

6、相关文献和数据的参考资料（通常在方案的单独章节中进行汇编）。

7、如果研究涉及使用试验产品或治疗：

（1）试验产品或治疗的名称和说明。

（2）给药途径、剂量、给药方案和治疗周期的说明和理由。

Study Objectives and Purposes  研究目标及目的

A detailed description of the major (primary) and minor (secondary and exploratory) objectives and the purpose of the trial.

主要（重要）和次要（次要和探索性）目标以及试验目的的详细说明。

Study Design  研究设计

The scientific integrity of the study and the credibility of the data obtained from the study largely depend on the study design. This section of the protocol should describe:

研究的科学完整性和研究数据的可信度在很大程度上取决于研究设计。议定书的这一部分应说明:

Ⅰ、Primary and secondary endpoints to be measured and how they will be measured.

Ⅱ、Study type (e.g., double-blind), with a schematic diagram of the study design, procedures, and stages.

Ⅲ、Measures that will be taken to avoid or minimize bias (e.g. randomization, blinding).

Ⅳ、Dosage and dosage regimen, dosage form, packaging, and labeling of investigational products.

Ⅴ、Expected duration of participant participation, sequence and duration of all study periods, including follow–up.

Ⅵ、"Stopping rules" or "discontinuation criteria" for individual participants, parts of the study, and the entire study.

Ⅶ、Accountability procedures for the investigational product, including the placebo and comparator.

Ⅷ、Maintenance of study treatment randomization codes and procedures for breaking codes.

Ⅸ、Identification of any data to be recorded directly on the CRFs and considered to be source data.

1、待测量的主要终点和次要终点，以及如何测量。

2、研究类型（如双盲），包括研究设计、程序和阶段的示意图。

3、为避免或最小化偏差而采取的措施（如随机化、盲法）。

4、研究药物的剂量和给药方案、剂型、包装和标签。

5、参与者参与的预期持续时间、所有研究阶段的顺序和持续时间，包括随访。

6、个体参与者、部分研究和整个研究的“停止规则”或“中止标准”。

7、试验产品的责任程序，包括安慰剂和对照品。

8、研究治疗随机化代码的维护和破译代码的程序。

9、识别直接记录在CRF上并被视为源数据的任何数据。

Selection and Withdrawal of Participants  参与者的选择和撤回

Ⅰ、Criteria for inclusion and exclusion of participants.

Ⅱ、Procedures for withdrawal of participants (participant or investigator-initiated):

   i、When and how to withdraw participants from the study/investigational product treatment.

   ii、Type and timing of data to be collected for participants who withdraw from the study.

   iii、Whether and how participants are to be replaced.

   iv、Follow–up for participants withdrawn from trial treatment.

1、纳入和排除参与者的标准。

2、参与者退出程序（参与者或研究者发起）：

（1）何时以及如何让参与者退出研究/试验药物治疗。

（2）为退出研究的参与者收集数据的类型和时间。

（3）是否以及如何更换参与者。

（4）退出试验治疗的参与者的随访。

Treatment of Participants  参与者的治疗

Ⅰ、Pharmacological treatment:

   i、Names of all products to be administered.

   ii、Doses.

   iii、Dosing schedules.

   iv、Method(s) of administration (i.e., oral, intramuscular).

   v、Other medications or treatments permitted (including rescue medication) and not permitted before and/or during the study.

1、药理治疗：

（1）所有待管理产品的名称。

（2）剂量。

（3）给药方案。

（4）给药方法（即口服、肌肉注射）。

（5）在研究之前和/或研究期间允许和不允许的其他药物或治疗（包括救援药物）。

Ⅱ、Other interventions (i.e., chiropractic, physical therapy, social therapy, behavioral therapy, counseling):

   i、Name of intervention (i.e., Motivational Interviewing, Cognitive Behavioral Therapy).

   ii、Frequency of sessions.

   iii、Duration of each session.

   iv、Method of each intervention (i.e. individual, group).

   v、Treatment adherence.

2、其他干预措施（即脊骨疗法、物理疗法、社会疗法、行为疗法、咨询）：

（1）干预的名称（即动机式访谈、认知行为疗法）。

（2）会议频率。

（3）每次会议的会期。

（4）每次干预的方法（即个人、小组）。

（5）治疗依从性。

Ⅲ、All interventions:

   i、Period(s) of intervention, including follow–up periods for participants in each group.

   ii、Procedures for monitoring participant compliance.

   iii、Identification of who will administer an intervention.

3、所有干预措施：

（1）干预期，包括每组参与者的随访期。

（2）监控参与者合规性的程序。

（3）确定谁将实施干预。

Assessment of Efficacy  疗效评估/有效性评估

This section describes the methods that will be used to determine the success of the treatment, including:

Ⅰ、Criteria for determining the treatment’s effectiveness.

Ⅱ、Methods and timing for assessing, recording, and analyzing the effectiveness criteria.

本节描述了用于确定治疗成功与否的方法，包括：

Ⅰ、确定治疗效果的标准。

Ⅱ、评估、记录和分析有效性标准的方法和时间。

Assessment of Safety  安全评估/安全性评估

This section describes how the study will be monitored and how adverse events will be dealt with. (See Participant Safety and Adverse Events module.)

Ⅰ、Specification of safety criteria.

Ⅱ、Methods and timing for assessing, recording, and analyzing the safety criteria.

Ⅲ、Procedures for obtaining reports of adverse events and illnesses experienced by participants during the study period and for recording and reporting these events, including expedited reporting procedures.

Ⅳ、Type and duration of follow–up of participants who experience adverse events.

本节描述了如何监测研究以及如何处理不良事件。（参见参与者安全和不良事件模块。）

1、安全标准规范。

2、评估、记录和分析安全标准的方法和时间。

3、获取研究期间参与者经历的不良事件和疾病报告以及记录和报告这些事件的程序，包括快速报告程序。

4、经历不良事件的参与者的随访类型和持续时间。

Statistics  数据统计

This section describes the strategy for analyzing the data collected during the study, including:

Ⅰ、Statistical methods to be employed, including the timing of any planned interim analyses.

Ⅱ、Total number of participants to be enrolled. (In multi–center studies, the minimum and maximum number of participants to be enrolled at each study site should be specified.)

Ⅲ、Reason for the choice of sample size, including reflections on (or calculations of) the power of the study and clinical justification.

Ⅳ、Level of significance to be used.

Ⅴ、Criteria for termination of the study.

Ⅵ、Procedure for accounting for missing, unused, and false data.

Ⅶ、Procedures for reporting deviations from the statistical plan (any deviations from the statistical plan should be described and justified in the protocol and/or in the final report, as appropriate).

Ⅷ、Selection of participants to be included in analyses (e.g. all randomized participants, all dosed or treated participants, all eligible participants, all evaluable participants, per a stated definition of “evaluable”).

本节描述了分析研究期间收集的数据的策略，包括：

1、拟采用的统计方法，包括任何计划中期分析的时间安排。

2、报名参加人数。（在多中心研究中，应指定每个研究地点登记的最小和最大参与者人数）

3、选择样本量的原因，包括对研究力量的思考（或计算）和临床证明。

4、使用的重要性级别。

5、终止研究的标准。

6、缺失、未使用和虚假数据的会计处理程序。

7、报告与统计计划偏差的程序（与统计计划的任何偏差应在方案和/或最终报告（视情况而定）中予以说明和证明）。

8、选择要包括在分析中的参与者（例如，所有随机参与者、所有给药或治疗参与者、所有合格参与者、所有可评估参与者，根据“可评估”的规定定义）。

Direct Access to Source Data or Documents  直接访问源数据或文档

The sponsor should ensure that the protocol or other written agreement specifies that study investigators or institutions will permit study–related monitoring, audits, IRB review, and regulatory inspections by providing direct access to source data or documents.

申办方应确保方案或其他书面协议规定，研究调查人员或机构将通过提供直接访问源数据或文件的方式，允许研究相关的监测、审计、IRB审查和监管检查。

Quality Control and Quality Assurance  质量控制和质量保证

A detailed quality assurance plan describing the set standards and controls that are in place to confirm that the execution of each step follows the agreed–upon plan is usually submitted as a separate document. The protocol should, however, provide a general description of the quality assurance methods. (See Quality Assurance module.)

一份详细的质量保证计划，描述了设定的标准和控制，以确保每一步的执行都符合商定的计划，通常作为单独的文件提交。然而，方案应该提供质量保证方法的一般描述。(参见质量保证模块。)

Ethics  道德准则

This section should describe ethical considerations relating to the study and measures taken to protect human participants and maintain confidentiality of study data. (See Informed Consent, Institutional Review Boards, and Confidentiality modules.)

本节应说明与研究相关的伦理考虑因素，以及为保护人类参与者和维护研究数据保密性而采取的措施。（参见知情同意书、机构审查委员会和保密模块。）

Data Management  数据管理

A detailed data management plan describing the way study data will be gathered, documented, submitted, verified, and archived is usually submitted as a separate document. The protocol should, however, provide a general description of the data management activities associated with the protocol.

详细的数据管理计划描述了研究数据的收集、记录、提交、验证和归档方式，通常作为单独的文件提交。然而，协议应提供与协议相关的数据管理活动的一般描述。

The data management plan describes the procedures that will ensure data integrity throughout the study and at all study sites, including:

Ⅰ、A description of the data system design and development.

Ⅱ、Data collection methods and activities.

Ⅲ、Methods of data entry and editing.

Ⅳ、Procedures for data monitoring (including query resolution), reporting, and transfer.

Ⅴ、Data recipients and procedures for data dissemination.

数据管理计划描述了在整个研究中和所有研究网站中确保数据完整性的程序，包括：

1、数据系统的设计和开发说明。

2、数据收集方法和活动。

3、数据录入和编辑方法。

4、数据监控（包括查询解析）、报告和传输程序。

5、数据接收人和数据发布程序。

Financing and Insurance  融资和保险

This section describes how the study will be financed and insured. In some research networks, these issues are addressed in a separate agreement and need not be included in the protocol.

本节描述了如何为研究提供资金和保险。在一些研究网络中，这些问题在单独的协议中解决，不需要包含在协议中。

Publication Policy  出版政策

This section describes the policies and procedures relating to publication of findings from the study. In some research networks, policies and guidelines are established for researchers for the publications planning process. For example, it is a common requirement for the publication on primary outcome data to precede other publications on the study findings. Researchers should be familiar with and adhere to institutional and sponsor policies and requirements for publications.

本节描述了与发布研究结果相关的政策和程序。在一些研究网络中，为研究人员制定了出版物规划过程的政策和指南。例如，关于主要结果数据的出版物通常要求先于关于研究结果的其他出版物。研究人员应熟悉并遵守机构和赞助商的政策和出版物要求。

In accordance with the Food and Drug Administration Amendments Act (42 CFR Part 11), trial results will also be published on a public website, ClinicalTrials.gov. This website will not identify participants, but will provide a resource for clinical trial participants, and those seeking clinical trial involvement, to inform themselves.

根据《食品和药物管理局修正法案》（42 CFR第11部分），试验结果也将在公共网站ClinicalTrials.gov上公布。该网站不会识别参与者，但将为临床试验参与者和寻求参与临床试验的人提供一个信息来源。

Supplements  补充

This section supplies any additional information that may be required, depending on the nature of the research. For example, the informed consent template, the therapy manual, a patient information handbook, etc., may be included as attachments.

本节根据研究性质提供可能需要的任何其他信息。例如，可以包括知情同意书模板、治疗手册、患者信息手册等作为附件。

Interactive: Developing the Research Protocol  交互式：制定研究方案

Users are instructed as follows:   用户须遵守以下指示:

Of the 10 items listed below, which sections are relevant to the development of the research protocol document for a trial investigating the effectiveness of motivational counselling sessions in reducing Body Mass Index (BMI) in individuals with a BMI of 30 or more? After choosing your response, consider the feedback.

在下面列出的10个项目中，哪些部分与研究方案文件的制定有关，该文件用于调查动机咨询课程在降低体重指数（BMI）为30或以上的个体的体重指数（BMI）方面的有效性？选择你的反应后，考虑反馈。

SECTION Ⅰ: Assessment of Efficacy

SECTION Ⅱ: Assessment of Safety

SECTION Ⅲ: Background

SECTION Ⅳ: Drug Accountability

SECTION Ⅴ: Investigational Product and Dosage

SECTION Ⅵ: Quality Assurance and Monitoring

SECTION Ⅶ: Statistical Analysis

SECTION Ⅷ: Study Intervention

SECTION Ⅸ: Study Objectives and Design

SECTION Ⅹ: Study Population and Eligibility Criteria

Feedback 1 : Is this section necessary for this research protocol: Yes or No? The correct response is Yes.

Feedback 2: Is this section necessary for this research protocol: Yes or No? The correct response is Yes.

Feedback 3: Is this section necessary for this research protocol: Yes or No? The correct response is Yes.

Feedback 4: Is this section necessary for this research protocol: Yes or No? Investigational product (drug or device) is not used in this study. Therefore, Investigational Product and Drug Accountability sections should not be included in the research protocol document. The correct response is No.

Feedback 5: Is this section necessary for this research protocol: Yes or No? Investigational product (drug or device) is not used in this study. Therefore, Investigational Product and Dosage and Drug Accountability sections should not be included in the research protocol document. The correct response is No.

Feedback 6: Is this section necessary for this research protocol: Yes or No? The correct response is Yes.

Feedback 7: Is this section necessary for this research protocol: Yes or No? The correct response is Yes.

Feedback 8: Is this section necessary for this research protocol: Yes or No? The correct response is Yes.

Feedback 9: Is this section necessary for this research protocol: Yes or No? The correct response is Yes.

Feedback 10: Is this section necessary for this research protocol: Yes or No? The correct response is Yes.

第一部分:疗效评估。反馈:是。

第二部分: 安全评估。反馈: 是。

第三部分：背景资料。反馈：是。

第四部分：药品责任。反馈：否，本研究不使用试验产品(药物或装置)。因此，调查产品和药物责任部分不应包含在研究方案文件中。

第五部分：试验药物和剂量。反馈：否，本研究不使用试验产品(药物或装置)。因此，研究方案文件中不应包括试验药物、剂量和药物责任部分。

第六部分：质量保证和监测。反馈：是。

第七部分：统计分析。反馈：是。

第八部分：研究干预。反馈：是。

第九部分：研究目标和设计。反馈：是。

第十部分：研究人群和资格标准。反馈：是。