Contents

Part 1: Introduction

Part 2: Participant Safety & Adverse Events

Part 1: Introduction

Inherent Complexities of Client Safety and Adverse Events   客户安全和不良事件的内在复杂性

Participant safety is a broad topic that cuts across all aspects of Good Clinical Practice (GCP) as is discussed in the document the ICH Guideline for Industry: Clinical Safety Data Management. Among other issues, ensuring participant safety encompasses protocol design, quality-assurance monitoring, government regulations, and ethical issues. It may also involve the use of clinical judgment, and entail situations/decisions on which no two clinicians may be in complete agreement. As a result, new researchers may feel frustrated when questions arise about participant safety.

参与者安全是一个广泛的话题，它跨越了良好临床实践(GCP)的所有方面，正如ICH行业指南：临床安全数据管理文件中所讨论的那样。在其他问题中，确保参与者的安全包括协议设计、质量保证监测、政府法规和道德问题。它还可能涉及临床判断的使用，并涉及两名临床医生可能不完全一致的情况/决定。因此，当参与者安全问题出现时，新研究人员可能会感到沮丧。

This module focuses on ways of protecting participants’ safety and well-being as well as how adverse events should be recorded and reported for clinical studies.

本单元重点介绍如何保护参与者的安全和福祉，以及如何记录和报告不良事件以供临床研究。

Because of the complexity of the topic, this module cannot cover every participant safety issue that might arise in a clinical trial. Researchers are advised to seek further guidance as needed from the study investigator or other knowledgeable team members. The role of investigators in protecting the safety and well-being of research participants is discussed further in this module.

由于主题的复杂性，本模块不能涵盖临床试验中可能出现的每一个参与者安全问题。建议研究人员根据需要从研究人员或其他知识丰富的团队成员那里寻求进一步的指导。本单元将进一步讨论研究人员在保护研究参与者的安全和福祉方面的作用。

Key Points About the Protection of Participant Safety   参与者安全保护要点

Ⅰ、The obligation to protect the well-being of study participants does not end when a study receives Institutional Review Board (IRB) or Data and Safety Monitoring Board (DSMB) approval, or when a participant signs the informed consent form. The interests of study participants must be safeguarded at all times—and by many entities—throughout a clinical research study.

1、当研究获得机构审查委员会（IRB）或数据和安全监测委员会（DSMB）的批准，或参与者签署知情同意书时，保护研究参与者福祉的义务并不终止。在整个临床研究过程中，研究参与者的利益必须始终受到多个实体的保护。

Ⅱ、Ultimately, no single individual or institution can provide complete protection for trial participants. A systematic plan must be followed for each trial to ensure that everyone involved understands and fulfils his or her responsibilities.

2、最终，没有任何个人或机构能够为试验参与者提供完全的保护。每次试验都必须遵循系统计划，以确保所有相关人员理解并履行其职责。

Ⅲ、Research team members with adequate knowledge of clinical trials, statistics, and the clinical disorder and the Investigational Product being studied must review the study data regularly to ensure that events are properly interpreted and reported.

3、对临床试验、统计、临床疾病和研究药物有充分了解的研究团队成员必须定期审查研究数据，以确保事件得到正确解释和报告。

Ⅳ、Ongoing communication among all study staff is an essential part of ensuring participant safety.

4、所有研究人员之间的持续沟通是确保参与者安全的重要组成部分。

Who is responsible for assuring the safety of study participants?   谁负责确保研究参与者的安全？

Investigator   研究者

In accordance with ICH GCP, the investigator or a sub-investigator that is a qualified physician (or dentist, when appropriate) is responsible for all trial-related medical decisions. The investigator must ensure that adequate medical care is provided to a subject for any adverse events and inform the subject when care is needed for an intercurrent illness that the investigator becomes aware of. (ICH GCP E6(R2), 4.3)

根据 ICH GCP，研究人员或副研究人员是一名合格的医生(或牙医，在适当的情况下)负责所有与试验有关的医疗决定。调查人员必须确保对任何不良事件向受试者提供适当的医疗护理，并告知受试者何时需要对调查人员意识到的并发症进行护理。(ICH GCP E6(R2) ，4.3)

Who is responsible for assuring the safety of participants in studies of investigational new drugs?   谁负责确保研究新药研究参与者的安全？

In studies conducted under the Investigational New Drug (IND) regulations, responsibility for ensuring compliance with FDA regulations on participant safety rests with the sponsor of the IND under which the study is conducted.

在根据研究新药（IND）法规进行的研究中，确保符合FDA参与者安全法规的责任在于进行研究的IND的赞助商。

The investigator is responsible for:

"protecting the rights, safety, and welfare of study participants under the investigator’s care."

“在研究者的护理下保护研究参与者的权利、安全和福利。”

The U.S. Food and Drug Administration (FDA) requires the investigator to:

"promptly report to the IRB (Institutional Review Board) all unanticipated problems involving risk to human subjects or others"

美国食品和药物管理局（FDA）要求研究人员：

“及时向IRB（机构审查委员会）报告所有涉及人体受试者或其他人风险的意外问题”

and to report to both the sponsor and the IRB:

"any serious adverse event, whether or not considered drug related and must include an assessment of whether there is a reasonable possibility that the drug caused the event" .

并向保证人及内部评核局报告:

“任何严重的不良反应事件，不论是否与药物有关，都必须包括评估药物是否有合理的可能性导致这一事件”。

Click to view Clinical Trial Network（CTN） related content

点击查看临床试验网络(CTN)相关内容

Responsibilities of Role Players in CTN   角色扮演者在 CTN 中的职责

Role of the Lead Investigator   首席调查员的作用

For each CTN protocol, the Lead Investigator (LI) is responsible for the accurate documentation, investigation, and follow-up of all safety reports. In addition, the LI must ensure that each Institutional Review Board (IRB) involved in the study is fully informed of safety issues that may arise from the protocol.

对于每个CTN方案，首席研究员（LI）负责准确记录、调查和跟进所有安全报告。此外，LI必须确保参与研究的每个机构审查委员会（IRB）充分了解方案可能产生的安全问题。

Role of the Site Principal Investigator   现场主要调查人员的作用

In CTN studies, the Node Principal Investigator (PI) is responsible for assuring the safety of study participants at research sites within his or her Node. This includes responsibility for assuring the proper monitoring of study progress and the evaluation and reporting of adverse events at the Node.

在CTN研究中，节点现场研究者（PI）负责确保其节点内研究地点的研究参与者的安全。这包括确保适当监测研究进展以及评估和报告节点不良事件的责任。

For any given protocol, the Node PI may delegate any of these tasks to other appropriately qualified persons, such as the Protocol Principal Investigator (below), affiliated with his or her Node. Such delegation of authority should be formally designated in a delegation of responsibilities log.

对于任何给定的协议，节点PI可以将这些任务中的任何一项委派给其他适当的合格人员，例如与其节点关联的协议主要研究者（下文）。此类授权应在责任授权日志中正式指定。

Role of the Protocol Site Principal Investigator   协议现场主要调查者的作用

In CTN studies, the Protocol Principal Investigator (PI) is charged with assuring the safety of study participants at the research sites within the Node for which he or she is responsible.

在CTN研究中，方案主要研究者（PI）负责确保其负责节点内研究现场的研究参与者的安全。

The Site PI is also expected to be knowledgeable about the policies of all local IRBs concerning the reporting of adverse events and to adhere to these policies.

方案主要研究者还应了解所有地方内部审计机构有关不良事件报告的政策，并遵守这些政策。

Role of the Study Medical Monitor   研究医学监测人的作用

In CTN studies, the Study Medical Monitor is appointed by the Lead Investigator and is responsible for reviewing reports of adverse events (AEs) and serious adverse events (SAEs) that are submitted by study sites. He or she must ensure that participants receive good clinical care and that safety concerns are identified quickly and addressed appropriately. The Study Medical Monitor must:

在CTN研究中，研究医学监测人由首席研究员指定，负责审查研究地点提交的不良事件(AEs)和严重不良事件(SAEs)报告。他或她必须确保参与者得到良好的临床护理，并迅速确定和适当解决安全问题。研究医疗监护必须:

Ⅰ、Review each AE/SAE and consider whether it may be related to study participation.

Ⅱ、Determine if the safety event meets reportability criteria as per federal regulations.

Ⅲ、Propose changes in the protocol or consent form, if warranted by the severity or frequency of adverse events.

1、回顾每个AE/SAE，并考虑其是否与参与研究有关。

2、根据联邦法规确定安全事件是否符合可报告性标准。

3、根据不良事件的严重程度或频率提出方案或同意书的变更建议。

Role of the NIDA Study Medical Officer   NIDA 研究医务官员的作用

In CTN studies, the NIDA Study Medical Officer has overall responsibility for evaluating, monitoring, and reporting on the safety of participants.

在CTN研究中，NIDA研究医生全面负责评估、监测和报告参与者的安全性。

Ongoing Informed Consent   持续知情同意

As discussed in the Informed Consent module, informed consent is a process as well as a legally required document. Throughout any study, researchers must continue to keep study participants informed about any new information with regard to the safety of the product and, in particular, about any new developments or findings that may affect participants’ willingness to remain in the study.

如知情同意模块中所述，知情同意是一个过程，也是法律要求的文件。在整个研究过程中，研究人员必须继续让研究参与者了解有关产品安全性的任何新信息，特别是可能影响参与者继续参与研究意愿的任何新发展或发现。

Researchers must:

Ⅰ、Inform participants, in a language that they understand, about emerging developments in the study, related studies utilizing the same Investigational Product(s), or pertinent pre-clinical studies that are significant to participant safety.

Ⅱ、Offer participants the opportunity to ask questions about the information they have been given.

Ⅲ、Ensure that participants understand they may withdraw from the study at any time and cannot be penalized for doing so.

Ⅳ、Be satisfied that each participant understands what he or she has been told and is making a voluntary, informed decision to remain in the study.

研究人员必须:

1、用他们能够理解的语言告知参与者研究的新进展，使用相同研究产品的相关研究，或对参与者安全具有重要意义的相关临床前研究。

2、为参与者提供机会，就他们获得的信息提出问题。

3、确保参与者了解他们可以随时退出研究，并且不会因此而受到惩罚。

4、每个参与者都理解他或她被告知的内容，并做出自愿的、知情的决定继续参与研究，请对此感到满意。

Part 2: Participant Safety & Adverse Events   参与者安全与不良事件

What is an adverse event?

The Good Clinical Practice (GCP) guidelines of the International Council for Harmonization (ICH) define an adverse event (AE) as: “any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment” (ICH GCP, E6(R2) 1.2).

国际协调理事会（ICH）的良好临床实践（GCP）指南将不良事件（AE）定义为：“服用药品的患者或临床研究对象发生的任何不良医疗事件，且不一定与该治疗有因果关系”（ICH GCP，E6（R2）1.2).

The term adverse event is defined in the U.S. Code of Federal Regulations (CFR) Title 21 Section 312.32(a) as follows: "any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related."

“不良事件”一词在《美国联邦法规》（CFR）第21篇第312.32（a）节中定义如下：“与人类使用药物相关的任何不良医疗事件，无论是否与药物相关。”

An AE may be “any unfavorable or unintended" sign, symptom, or disease that occurs in a person who has taken a medication. The occurrence does not need to be related to the drug treatment.

不良事件可能是在服用药物的人身上发生的“任何不利或意外”的迹象、症状或疾病。这种发生不需要与药物治疗有关。

An adverse event (AE) may be:

Ⅰ、A physical event (e.g., a rash).

Ⅱ、A psychological event (e.g., depressed mood).

Ⅲ、A laboratory event (e.g., elevated blood sugar).

Ⅳ、An increase in the severity or frequency of a pre-existing symptom or condition (e.g., increased pain in a painful tooth)

不良事件（AE）可能是：

1、身体事件（如皮疹）。

2、心理事件（如抑郁情绪）。

3、实验室事件（如血糖升高）。

4、先前存在的症状或状况的严重程度或频率增加（例如，疼痛牙齿疼痛加剧）

An adverse event may also be referred to as an “adverse experience.”

不良事件也可称为“不良经历”

Click here for examples of situations involving the use of a drug in humans in which an AE may occur.

Click here for examples of events that should or should not be reported as AEs.

单击此处查看可能发生AE的人类药物使用情况示例。

单击此处查看应报告或不应报告为不良事件的事件示例。（PS：原文件中链接失效）

What is an adverse event in a behavioral study?   什么是行为研究中的不良事件?

As defined in the previous section, an AE is commonly understood to be an event that occurs during treatment with a drug or device. However, the definition can also be applied to any “untoward occurrence” that occurs in any clinical trial, including behavioral studies.

如前一节所定义，AE通常被理解为在药物或设备治疗期间发生的事件。然而，该定义也适用于任何临床试验中发生的任何“不良事件”，包括行为研究。

For trials that are not regulated by the FDA, the Investigators and protocol teams may define the term adverse event to reflect what is clinically and scientifically relevant to their study.

对于不受FDA监管的试验，研究人员和方案团队可以定义不良事件一词，以反映与他们的研究在临床和科学上的相关性。

Thus, for a behavioral trial that does not involve treatment with a drug, an AE may be defined as:

“Any unfavorable, unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome, or disease that occurs during the study, having been absent at baseline, or—if present at baseline—appears to worsen.” (Interim Guidelines for NIH Intramural Principal Investigators and for NIH Institutional Review Boards on Reporting Adverse Events)

因此，对于不涉及药物治疗的行为试验，AE可定义为：

“在研究期间发生的任何不利的、非预期的诊断、症状、体征(包括实验室异常发现)、综合征或疾病，在基线时未出现，或如果在基线时出现，则会出现恶化。”(NIH内部首席研究员和NIH机构审查委员会不良事件报告临时指南)

In certain studies, including some behavioral studies, it may be important to capture the occurrence of nonmedical events such as arrest, imprisonment, and violence to others, which may be contributing factors to an AE or may indicate that an AE has occurred. As an example of the latter, a participant’s increased drug abuse—an AE—could result in an arrest.

在某些研究中，包括一些行为研究，捕捉非医学事件的发生可能是重要的，如逮捕、监禁和对他人的暴力，这些事件可能是AE的促进因素或可能表明AE已经发生。作为后者的一个例子，一个参与者增加的药物滥用(AE)可能导致逮捕。

Investigators may elect to capture nonmedical events that may be behavioral (e.g., violence) or social (e.g., arrest, imprisonment) on the AE Case Report Form (CRF), or such events may be captured elsewhere.

调查人员可选择在不良事件病例报告表（CRF）上记录可能是行为（如暴力）或社会（如逮捕、监禁）的非医疗事件，或在其他地方记录此类事件。

What is an adverse drug reaction?   什么是药物不良反应？

The terms adverse event and adverse drug reaction are easily confused, but they have distinctly different meanings. As discussed in earlier sections, an adverse event (AE) is any “untoward occurrence” in a patient or clinical study participant that need not be related to treatment.

不良事件(adverse event)和药物不良反应(adverse drug reaction)这两个术语容易混淆，但含义却截然不同。正如前面所讨论的，不良事件(AE)是指患者或临床研究参与者发生的任何“不愉快的事件”，且与治疗无关。

By contrast, an adverse drug reaction (ADR) implies an adverse event that results from a medicine or treatment (i.e., there is a degree of relatedness between the adverse reaction and the treatment).

相反，药物不良反应(ADR)是指药物或治疗引起的不良事件(即不良反应与治疗之间存在一定程度的相关性)。

FDA regulations define an ADR as

“an undesirable effect, reasonably associated with the use of a drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence” (21 CFR 201.57(c)).

FDA法规将ADR定义为

“与药物使用合理相关的不良作用，可能作为药物药理作用的一部分发生，或其发生可能不可预测”（21 CFR 201.57（c））。

Remember: Although every ADR is also an AE, only some AEs will also be ADRs. Therefore, it is very important to collect clear and complete information about every AE.

记住：虽然每一个ADR也是一个AE，但只有一些AE会成为ADR。因此，收集清楚完整的每一个AE信息是非常重要的。

What is a serious adverse event?   什么是严重不良事件？

An AE is considered serious if it poses a threat to the patient’s life or functioning. The FDA defines a serious adverse event (SAE) as any untoward medical occurrence that:

Ⅰ、Results in death, or

Ⅱ、Is life-threatening (places the patient at risk of death), or

Ⅲ、Requires hospitalization or prolongs an existing hospitalization, or

Ⅳ、Causes persistent or significant disability or incapacity, or

Ⅴ、Is a birth defect, or

Ⅵ、Requires medical intervention to prevent one of the above outcomes (e.g., an asthma attack that requires intensive treatment in an emergency room, a seizure that does not result in hospitalization but requires medical treatment).

如果AE对患者的生命或功能构成威胁，则视为严重AE。FDA将严重不良事件（SAE）定义为以下任何不良医疗事件：

1、导致死亡，或

2、危及生命（使患者面临死亡风险），或

3、需要住院或延长现有住院时间，或

4、导致持续或严重残疾或无行为能力，或

5、是出生缺陷，或

6、需要医疗干预以防止上述结果之一（例如，需要在急诊室进行强化治疗的哮喘发作，不需要住院但需要医疗的癫痫发作）。

An AE needs to meet only one of the above criteria to be considered serious. A change in vital signs, diagnostic tests (e.g., an electrocardiogram), or laboratory test results may be an SAE if the change is of sufficient magnitude to meet one of the above criteria.

不良事件只需满足上述标准中的一项即可被视为严重。如果生命体征、诊断测试（如心电图）或实验室测试结果的变化幅度足以满足上述标准之一，则可能是SAE。

An adverse event is judged “serious” on the basis of the threat it poses to a patient’s life or functioning. For example, a patient could be diagnosed with pneumonia in his or her doctor’s office and given antibiotics to take at home. The pneumonia is an AE, but not an SAE. 

However, if the patient is hospitalized for the pneumonia, that is considered an SAE. (The SAE is pneumonia resulting in hospitalization.)

根据不良事件对患者生命或功能造成的威胁，判断不良事件为“严重”。例如，患者可能在医生的办公室被诊断为肺炎，并在家服用抗生素。肺炎是AE，但不是SAE。

但是，如果患者因肺炎住院，则视为SAE。（SAE是导致住院的肺炎。）

It is also imperative to clarify between severe and serious. While the intensity of an event may be severe, it may not meet the criteria for serious (e.g. Severe Migraine). Severity is discussed in this module.

还必须澄清 "severe" 与 "serious" 之间的区别。虽然事件的强度可能很严重（severe），但可能不符合严重（serious，如严重偏头痛）的标准。严重性将在本模块中讨论。

Elective surgery (i.e. surgery that is planned prior to entry into the study) is not a Serious Adverse Event. For example, removal of bunions on feet, nose reconstruction, planned hysterectomy, etc.

选择性手术（即进入研究前计划的手术）不是严重的不良事件。例如，去除足部的囊泡、重建鼻子、计划子宫切除术等。

What is a serious adverse event in a behavioral study?   行为研究中的严重不良事件是什么？

The definition of an SAE in the previous section is commonly understood to relate to clinical studies of drug treatments. However, the definition can be applied to any kind of clinical study, including behavioral studies.

前一节中SAE的定义通常被理解为与药物治疗的临床研究相关。然而，该定义可以应用于任何类型的临床研究，包括行为研究。

The Investigator of a study may, for the purposes of the study, limit or expand the FDA criteria for an SAE to reflect the specific risks of the study intervention and the characteristics of the study population.

为了研究的目的，研究人员可以限制或扩大FDA SAE标准，以反映研究干预的具体风险和研究人群的特征。

The Investigator may describe in the research protocol other AEs that in that particular study are to be considered serious, although the AE may not meet the FDA criteria. For example, all suicide attempts may be considered SAEs in a specific research protocol, whether or not they require hospitalization or place the patient at immediate risk of death. On the other hand, certain occurrences that would be considered SAEs under the standard definition, such as hospitalizations for normal childbirth or voluntary admissions for detoxification, may be explicitly defined not to be reportable as AEs and/or SAEs, if the Investigator so chooses. Any such modifications to the definition of an SAE must be approved during the protocol review process and by the appropriate IRBs.

研究者可在研究方案中描述该特定研究中被视为严重的其他不良事件，尽管不良事件可能不符合FDA标准。例如，在特定的研究方案中，所有自杀未遂都可能被视为严重急性呼吸窘迫综合征，无论是否需要住院治疗或使患者面临直接死亡风险。另一方面，根据标准定义被视为严重不良事件的某些事件，如因正常分娩住院或自愿戒毒，如果研究者选择，可明确定义为不可报告为不良事件和/或严重不良事件。对SAE定义的任何此类修改必须在方案审查过程中获得批准，并由适当的IRB批准。

What is an unexpected adverse event?   什么是意外不良事件？

For clinical studies that involve the use of marketed drugs (as opposed to investigational new drugs), FDA defines an unexpected AE as:

Ⅰ、An AE that is not listed in the drug’s current labeling, or

Ⅱ、An AE that is more severe or more specific than indicated in the labeling.

对于涉及使用上市药物（与研究新药相反）的临床研究，FDA将意外不良事件（AE）定义为：

Ⅰ、药物当前标签中未列出的不良事件，或

Ⅱ、比标签上注明的更严重或更具体的不良事件。

For clinical studies in which investigational new drugs are used, the FDA defines an unexpected AE as:

Ⅰ、An AE that is not consistent with the information about the drug’s risks that appears in the relevant source document(s) (e.g., protocol, Investigator's Brochure, and consent documents), or

Ⅱ、An AE that is not consistent with the risk information, or

Ⅲ、An AE that has occurred within the class of drugs, but not specifically with the Investigational Product.

对于使用研究新药的临床研究，FDA将意外不良事件定义为：

1、与相关源文件（如方案、研究人员手册和同意书文件）中出现的药物风险信息不一致的不良事件，或

2、与风险信息不一致的不良事件，或

3、在药物类别内发生的不良事件，但不是针对试验药物。

What is an unexpected adverse event in a behavioral study?    行为研究中的意外不良事件是什么？

In studies conducted under the Investigational New Drug regulations, the known risks and expected benefits of an investigational new drug are described in the Investigator's Brochure.

在根据研究新药法规进行的研究中，研究者手册中描述了研究新药的已知风险和预期收益。

However, an Investigator’s Brochure is often not prepared for behavioral studies. For this reason, researchers who conduct behavioral studies are expected to describe in the research protocol any adverse events that might be expected to occur in the study population as a result of the experimental behavioral intervention. They must also briefly describe these events in the consent documents.

然而，研究人员的手册通常不用于行为研究。因此，进行行为研究的研究人员应在研究方案中描述由于实验性行为干预可能在研究人群中发生的任何不良事件。他们还必须在同意文件中简要描述这些事件。

In a behavioral study, therefore, an unexpected adverse event would be an AE that is not mentioned in the protocol or consent documents or an AE that has not been seen before. Aditionally, unexpected AEs in a behavioral study can be considered as unanticipated problems (discussed further below) and are thereby regulated under 45 CFR46.

因此，在行为研究中，意外不良事件可能是方案或同意书文件中未提及的不良事件，或者是以前从未见过的不良事件。传统上，行为研究中意外的不良事件可被视为意外问题（下文将进一步讨论），因此受45 CFR46的监管。

What is an unanticipated problem?   什么是未预料到的问题？

The Office of Human Research Protections (OHRP) defines unanticipated problems involving risks to study participants and others as an event that meets all of the following criteria:

人类研究保护办公室（OHRP）将涉及研究参与者和其他人风险的意外问题定义为符合以下所有标准的事件：

Ⅰ、unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied;

1、由于（a）方案相关文件中描述的研究程序（如IRB批准的研究方案和知情同意文件）而导致的意外（性质、严重程度或频率）；及(b)方案相关文件中所研究对象的特征；

Ⅱ、related or possibly related to participation in the research (in this guidance document, possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and

2、与参与研究相关或可能相关（在本指导文件中，可能相关指事件、经验或结果有合理的可能性是由参与研究的程序引起的）；和

Suspected unanticipated problems must be promptly reported to the IRB, who will make the subsequent determination to report it to the proper regulatory authority.

必须立即将怀疑的意外问题报告给IRB，IRB将做出后续决定，将其报告给适当的监管机构。

Although unanticipated problems are found but not defined in 45 CFR 46, all NIH funded studies are required to comply with 45 CFR 46. For OHRP’s current guidance on unanticipated problems, follow the link here.

尽管在45 CFR 46中发现了未预料到的问题，但未对其进行定义，但所有NIH资助的研究都必须符合45 CFR 46的要求。有关OHRP当前对意外问题的指导，请点击此处链接。

Interactive: Participant Safety & Adverse Events   参与者安全和不良事件

A new research coordinator has started working on a clinical study comparing the effectiveness of two marketed drugs to treat facial acne. There are 37 participants enrolled at the research site. She is tasked with entering all safety events for these participants into the electronic Case Report Form.

一位新的研究协调员开始进行一项临床研究，比较两种上市药物治疗面部痤疮的效果。研究现场共有37名参与者。她负责将这些参与者的所有安全事件输入电子病例报告表。

Users are instructed as follows:

Below is a list of seven safety events that study participants experienced. The research coordinator has to crosscheck her understanding of each safety event with the safety monitor to ensure that the data she enters is accurate. Evaluate each safety event and choose whether it is an Adverse Event by choosing AE or a Serious Adverse Event by choosing SAE. After assessing each event, you will be given feedback on your response.

以下是研究参与者经历的七个安全事件列表。研究协调员必须与安全监视器交叉检查她对每个安全事件的理解，以确保她输入的数据准确无误。评估每个安全事件，并通过选择AE来选择是不良事件还是通过选择SAE来选择严重不良事件。在评估每个事件后，将向您提供反馈。

Scenario 1

Severe cramps in arms and legs. Is this an AE or SAE?

手臂和腿部严重抽筋。这是AE还是SAE？

Scenario 2：Nausea and vomiting at day 7 of dosing. Is this an AE or SAE? 

给药第7天出现恶心和呕吐。这是AE还是SAE？

Scenario 3：Severe bronchospasms that resulted in ER visit for intervention. Is this an AE or SAE?

严重的支气管痉挛导致急诊介入治疗。这是AE还是SAE？

Scenario 4：Tinnitus (ringing in ears) after taking an anti-histamine. Is this an AE or SAE?

服用抗组胺药后出现耳鸣（耳鸣）。这是AE还是SAE？

Scenario 5：An intercurrent infection resulting in death. Is this an AE or SAE?

并发感染导致死亡。这是 AE 还是 SAE？

Scenario 6：Broke right arm while riding a bike. Is this an AE or SAE?

骑自行车时摔断了右臂。这是AE还是SAE？

Scenario 7：Emergency hysterectomy during the study. Is this an AE or SAE?

研究期间紧急子宫切除术。这是AE还是SAE？

Feedback 1: Is this an AE or SAE? This is an AE-Adverse Event – this is an untoward event experienced by the participant.

反馈1：这是AE还是SAE？这是不良事件-这是参与者经历的不良事件。

Feedback 2: Is this an AE or SAE? This is an AE-Adverse Event – this is an untoward event experienced by the participant.

反馈2：这是AE还是SAE？这是不良事件-这是参与者经历的不良事件。

Feedback 3: Is this an AE or SAE? This is a SAE-Serious Adverse Event – it meets the criteria of important medical event.

反馈3：这是AE还是SAE？这是SAE严重不良事件–符合重要医疗事件的标准。

Feedback 4: Is this an AE or SAE? This is an AE-Adverse Event – this is an untoward event experienced by the participant.

反馈4：这是AE还是SAE？这是不良事件-这是参与者经历的不良事件。

Feedback 5: Is this an AE or SAE? This is a SAE-Serious Adverse Event – In this case, the diagnosis will be infection and Death is the outcome.

反馈5：这是AE还是SAE？这是SAE严重不良事件–在这种情况下，诊断为感染，结果为死亡。

Feedback 6: Is this an AE or SAE? This is an AE-Adverse Event – This is an untoward event experienced by the participant irrespective of its relation to the investigational product.

反馈6：这是AE还是SAE？这是一个不良事件-这是参与者经历的一个不良事件，与试验药物无关。

Feedback 7: Is this an AE or SAE? This is a SAE-Serious Adverse Event – This is emergency surgery and not planned.

反馈7：这是 AE 还是 SAE？这是一个SAE 严重的不良事件-这是紧急手术，而不是计划。