Contents
Part 3: Assessing an Adverse Event
Part 4: Adverse Event Reporting
Part 3: Assessing an Adverse Event 评估不良事件
Every protocol should list specific AEs that are to be addressed at every visit. Generally, this will be a very short list of lab values and clinical signs and symptoms. The protocol should also specify the duration that information on AEs will be collected.
每个协议都应该列出每次访问时要处理的特定的AEs。一般来说，这将是一个非常简短的实验室价值和临床体征和症状的清单。协议还应该指定收集关于AEs的信息的持续时间。
All AEs that occur in any clinical study participant should be assessed for:
在任何临床研究参与者中发生的所有AEs应评估为：
Severity 严重程度
The severity of an AE is not the same as its seriousness. Severity refers to the intensity of a specific event (e.g., mild, moderate, or severe pain). However, the event itself may be of minor medical significance (e.g., a severe toothache). (Click here to see sample definitions of the grades of severity of an AE.)
不良事件的严重程度（severity）与其严重性（seriousness）不同。严重程度是指特定事件的强度（例如，轻度、中度或重度疼痛）。然而，事件本身可能具有轻微的医学意义（例如，严重牙痛）。（单击此处查看不良事件严重程度等级的示例定义）
By contrast, the seriousness of an AE is assessed by the extent to which it poses a threat to the patient’s life or functioning. Thus, an AE may be severe (e.g., severe pain from a toothache) without being serious (threatening the patient’s life or functioning).
相比之下，AE的严重性（seriousness）是通过其对患者生命或功能的威胁程度来评估的。因此，AE可能是严峻的（severe，如牙痛引起的剧烈疼痛），但并不严重（serious，威胁患者的生命或功能）。
Determining the severity of an AE is largely a matter of individual clinical judgment. No universally accepted scale exists for describing or measuring the severity of AEs. The severity of an AE should be determined with input from a qualified physician or licensed medical staff.
AE的严重程度的确定在很大程度上是个人临床判断的问题。没有一个普遍接受的标准来描述或测量AEs的严重程度。AE的严重程度应该由合格的医生或有执照的医务人员输入来确定。
Relatedness 关联性
An AE may or may not be causally related to the study intervention. A causal relationship means that the intervention caused (or is reasonably likely to have caused) the AE. This usually implies a relationship in time between the intervention and the AE (e.g., the AE occurred shortly after the participant received the intervention).
不良事件可能与研究干预有关，也可能与研究干预无关。因果关系是指干预导致（或可能导致）不良事件。这通常意味着干预和不良事件之间的时间关系（例如，不良事件发生在参与者接受干预后不久）。
For all AEs, it is the responsibility of the clinician who examines and evaluates the patient to determine the relatedness of the event to the study intervention. Data managers who have no role in patient clinical assessment must not perform this important task.
对于所有不良事件，检查和评估患者的临床医生有责任确定事件与研究干预的相关性。在患者临床评估中没有角色的数据管理员不得执行此重要任务。
Acceptance that an AE is related to the intervention usually requires a plausible mechanism of action—that is, a believable sequence of events by which the intervention brought about the AE. It may be helpful to seek the opinion of the Study Medical Monitor on this point. It can also be helpful to ask the participant whether he or she thinks the intervention could have brought about the AE. (Click here to see terminology utilized in protocols to assist clinicians in their assessment of the relatedness of an event.)
接受不良事件与干预相关通常需要一个合理的行动机制，即干预导致不良事件的可信事件序列。在这一点上，征求研究医疗监护仪的意见可能会有所帮助。询问参与者是否认为干预可能导致不良事件也很有帮助。（单击此处查看协议中使用的术语，以帮助临床医生评估事件的相关性。）
If an AE is thought to have a causal relationship with the intervention, and the AE raises concern about the safety of the participant, serious consideration must be given to temporarily halting or permanently discontinuing the intervention. Additionally, rechallenging the participant (that is, giving the intervention again to test the causal relationship to see if the AE occurs again) is not often done because of safety concerns. For this reason, it is often impossible to say with certainty that an experimental intervention caused an AE.
如果认为不良事件与干预有因果关系，并且不良事件引起了对参与者安全性的担忧，则必须认真考虑暂时停止或永久停止干预。此外，出于安全考虑，通常不会对参与者进行再质询（即，再次进行干预以测试因果关系，查看不良事件是否再次发生）。出于这个原因，通常不可能肯定地说实验干预导致了AE。
The causal relationship between an intervention and an AE may be tested by discontinuing the intervention and then rechallenging the participant (giving the intervention again) to see if the AE occurs again. However, this is rarely done because of safety concerns. For this reason, it is often impossible to say with certainty that an experimental intervention caused an AE.
干预和不良事件之间的因果关系可以通过中止干预，然后重新激发参与者（再次进行干预）来测试，以查看不良事件是否再次发生。然而，出于安全考虑，很少这样做。出于这个原因，通常不可能肯定地说实验干预导致了AE。
When an AE is labeled “associated with the use of the intervention,” therefore, this means there is a reasonable possibility that the AE may have been caused by the intervention and is meant to convey in general that there are facts (evidence) or arguments to suggest a causal relationship.
因此，当不良事件（AE）被标记为“与干预措施的使用相关”时，这意味着不良事件（AE）有合理的可能性可能是由干预措施引起的，并通常意味着总体上传达有事实（证据）或论据表明存在因果关系。
Early in the development of a drug or other intervention, when little is known of its safety profile, it is especially important to maintain a high level of suspicion for AEs and to report all AEs that may in any way be causally related to an experimental drug or intervention.
在药物或其他干预措施开发的早期，当对其安全性知之甚少时，特别重要的是保持对不良事件的高度怀疑，并报告所有可能以任何方式与实验药物或干预措施因果相关的不良事件。
Any AE reported by a participant should be followed up at each subsequent study visit until the AE has resolved. It is important to document both the duration (e.g., minutes, hours, days) and severity of an AE. An AE that persists from one study visit to the next should be documented as one event. For AEs that are sustained past the study duration, follow-up may occur until resolution or for a reasonable period of time defined by the protocol.
参与者报告的任何不良事件应在随后的每次研究访视中进行随访，直到不良事件得到解决。记录不良事件的持续时间（如分钟、小时、天）和严重程度非常重要。从一次研究访视持续到下一次研究访视的不良事件应记录为一个事件。对于持续超过研究持续时间的不良事件，可进行随访，直至解决或在方案规定的合理时间内。
The initial report of an AE is usually made by the participant; however, an AE may also be reported by a family member, friend, nurse or other caregiver, or someone else. For example, a family member or friend may call to report that a participant has been hospitalized. Or another participant may report hearing from a third party that a participant is seriously ill.
不良事件的初始报告通常由参与者进行；然而，AE也可能由家庭成员、朋友、护士或其他护理者或其他人报告。例如，家庭成员或朋友可能会打电话报告参与者已住院。或者，另一名参与者可能会报告从第三方获悉参与者患有重病。
Regardless of who reports an AE, the event should always be documented in the participant’s source documents including progress notes. When an AE is reported by a third party, the Research Assistant should make every effort to contact the participant directly to verify the report. In some cases, a report of an AE may turn out to be false. As more information about the event is gathered and assessed, the Research Assistant must ensure that source documents and reports are updated with accurate information about the AE.
无论谁报告不良事件，都应将事件记录在参与者的原始文件中，包括进度说明。当第三方报告不良事件时，研究助理应尽一切努力直接联系参与者以验证报告。在某些情况下，不良事件的报告可能是虚假的。随着收集和评估更多关于事件的信息，研究助理必须确保源文件和报告更新了关于不良事件的准确信息。
Part 4: Adverse Event Reporting 不良事件报告
AE reporting is an essential part of participant safety protection during a clinical study. Determining whether an incident is a reportable AE—and if so, what should be reported about it, to whom, and when—depends on many factors, including:
Ⅰ、Previous experience and knowledge of the drug or intervention,
Ⅱ、The disease being treated, and
Ⅲ、Regulatory requirements.
不良事件报告是临床研究期间参与者安全保护的重要组成部分。确定事件是否为可报告的不良事件，如果是，应报告什么，向谁报告，何时报告取决于许多因素，包括：
1、以前的药物或干预经验和知识，
2、正在治疗的疾病，以及
3、监管要求。
In addition to the factors listed above, investigators must consider incident reporting requirements for NIH- funded studies, including reportable AEs and unanticipated problems (UPs). All NIH-funded studies are required to comply with 45 CFR 46 for safety event reporting. For OHRP’s current guidance on UPs involving participant safety risks, follow the link here.
除了上面列出的因素之外，调查人员还必须考虑NIH资助的研究的事件报告要求，包括可报告的AES和未预料到的问题（UPS）。所有NIH资助的研究都必须符合45 CFR 46的安全事件报告要求。有关OHRP当前对涉及参与者安全风险的UPs的指导，请点击此处链接。
Not all AEs require reporting, as they might not directly impact participant risk or present significant new findings. Inundating the study IRB with individual, unanalyzed UPs is an uninformative process, and UPs that don’t impact participant risk can be covered during the IRB’s continuing review. Requirements for the reporting of AEs are defined in each protocol.
并非所有不良事件都需要报告，因为它们可能不会直接影响参与者风险或呈现重要的新发现。将未经分析的个人UPs淹没在研究IRB中是一个不具信息性的过程，在IRB的持续审查中可以涵盖不影响参与者风险的UPs。每个协议中都规定了不良事件报告的要求。
The investigator and research team must consider these factors when writing the sections of the protocol and the operations manual that discuss adverse event reporting. The investigators and the study sponsor jointly determine the extent and type of AE data that will be collected for a specific trial.
在讨论不良事件报告的协议和操作手册时，调查人员和研究团队必须考虑这些因素。研究者和研究发起人共同确定将为特定试验收集的不良事件数据的范围和类型。
They may decide that minor complaints of daily living will not be considered AEs. An event such as the worsening of symptoms of a current illness could be captured in the patient’s progress notes or on a case report form.
他们可能会决定，对日常生活的轻微投诉不会被视为AEs。诸如当前疾病症状恶化之类的事件可以在患者的病程记录或病例报告表格中记录下来。
ICH GCP requirements for AE reporting
The investigator must report all Serious Adverse Events to the sponsor immediately. The immediate reports should be followed promptly by detailed, written reports.
调查员必须立即向赞助商报告所有严重的不良事件，由详细的书面报告应及时遵循直接报告。
In the event of a death, the investigator should supply the sponsor and the IRB with any additional requested information.
在发生死亡的情况下，调查人员应向主办方和IRB提供任何额外的要求信息。
In addition, the investigator must comply with the applicable regulatory requirements as well as protocol specific requirements related to the reporting of safety issues. In some instances, the local laws or network requirements may request more stringent reporting of emergent or safety events.
此外，研究人员必须遵守适用的监管要求以及与安全问题报告相关的特定方案要求。在某些情况下，当地法律或网络要求可能要求对紧急或安全事件进行更严格的报告。
FDA Requirements
For IND studies FDA guidelines (21 CFR 312.32) require expedited reporting by the sponsor of all AEs that are associated with the use of the drug, serious, unexpected and reasonably related to the investigational product.
对于IND研究，FDA指南（21 CFR 312.32）要求赞助商加速报告与药物使用相关的所有不良事件，包括严重、意外和与试验药物合理相关的不良事件。
Ⅰ、Related and unexpected fatal or life–threatening AEs (severity grade 4 or 5) that are associated with the use of the drug must be reported to FDA by telephone or fax no later than 7 calendar days after the sponsor first learns of the event. This initial report must be followed within 8 additional calendar days by a written safety report that is as complete as possible.
1、与药物使用相关的、意外的致命或危及生命的不良事件（严重程度为4级或5级），必须在申办方首次获悉事件后7个日历日内通过电话或传真向FDA报告。该初始报告必须在8个额外日历日内提交一份尽可能完整的书面安全报告。
Ⅱ、FDA must be notified of serious, related and unexpected AEs associated with the use of the drug that are not fatal or life-threatening in a written safety report no later than 15 calendar days after the sponsor first learns of the event.
2、申办方首次获悉事件后15个日历日内，必须在书面安全报告中告知FDA与药物使用相关的严重、相关和意外不良事件，这些不良事件不会致命或危及生命。
Ⅲ、The sponsor should report pertinent follow-up information for previously submitted reports to the FDA as soon as it is available, including for AEs that were not initially deemed reportable if the follow-up information causes a change in assessment.
3、申办方应尽快向FDA报告之前提交的报告的相关后续信息，包括如果后续信息导致评估发生变化，最初认为不可报告的不良事件。
Aggregate analyses of adverse events observed from a clinical trial, or from other studies outside the sponsor’s scope, that detail new information regarding the investigational product (i.e. new side effects, or increasing frequency of side effects) should be reported to the FDA. Significant non-clinical findings are also reportable if they’re suggestive of increased risk for human studies. The FDA also accepts voluntary reporting for marketed drugs in studies exempt from FDA reporting requirements with their MedWatch system.
从临床试验或赞助商范围外的其他研究观察到的不良事件的汇总分析，详细的研究产品的新信息(即新的副作用，或增加的副作用频率)应报告给FDA。重要的非临床发现如果提示人类研究风险增加，也可以报告。在MedWatch系统中，FDA也接受在不受FDA报告要求的研究中销售的药品的自愿报告。
Under these guidelines, expedited reporting to the FDA is generally not necessary for AEs that are:
Ⅰ、Serious but expected.
Ⅱ、Serious but not related to the study drug, whether expected or not (e.g., a patient who dies of a cancer that was present prior to entry into a study of an antidepressant).
Ⅲ、Non-serious, whether expected or not.
根据这些指南，以下不良事件通常不需要向FDA快速报告：
1、严重但预料之中。
2、严重但与研究药物无关，无论预期与否（例如，患者在进入抗抑郁剂研究之前死于癌症）。
3、不严重，无论是否预期。
For studies of investigational new drugs, FDA requires the sponsor to notify all participating investigators in a written safety report of any serious and unexpected AE that is associated with the use of the study drug. The sponsor may add additional requirements to this notification. Consider how NIDA fufills this obligation. NIDA has directed Lead Investigators to distribute such reports within 24 hours of learning of an AE that:
对于研究新药的研究，FDA要求申办方在书面安全报告中通知所有参与研究的研究人员与使用研究药物相关的任何严重和意外不良事件。发起人可在本通知中添加其他要求。想想奈达是如何履行这个义务的。NIDA已指示首席调查人员在获悉不良事件后24小时内分发此类报告，其中：
Ⅰ、Is considered serious, related and unexpected, or
Ⅱ、Requires revision of the protocol or the informed consent form, or
Ⅲ、Requires termination of the study or suspension of enrolment.
1、被认为是严重的、相关的和意外的，或
2、需要修改方案或知情同意书，或
3、要求终止学习或暂停入学。
If a serious related and unexpected AE represents an increased risk to study participants, investigators must inform participants of this increased risk as soon as possible.
如果严重相关和意外的不良事件对研究参与者来说意味着风险增加，研究者必须尽快通知参与者这一增加的风险。
Click to view Clinical Trial Network（CTN） related content
点击查看临床试验网络（CTN）相关内容
CTN Requirements
ICH GCP guidelines (E6) state that all serious adverse events (SAEs) should be reported immediately to the sponsor. An exception is made for SAEs that are identified in the protocol or other document (e.g., Investigator's Brochure as not requiring immediate reporting).
ICH GCP指南（E6）规定，所有严重不良事件（SAE）应立即报告给申办方。方案或其他文件中确定的严重不良事件除外（例如，研究人员手册不要求立即报告）。
For CTN studies (whether conducted under an Investigational New Drug application or not), any AE that meets FDA’s criteria for a serious adverse event (SAE) must be reported within 24 hours to the NIDA Study Medical Officer and all parties specified in the protocol. The FDA’s definition of an SAE is to be used unless the protocol specifically limits or expands the FDA definition.
对于CTN研究（无论是否在研究性新药申请下进行），任何符合FDA严重不良事件（SAE）标准的不良事件必须在24小时内报告给NIDA研究医生和方案中规定的所有各方。除非协议明确限制或扩展了FDA对SAE的定义，否则应使用FDA对SAE的定义。
Following the initial report of the SAE by phone, fax, or e-mail all efforts will be made to gather additional information available on the SAE. Once received, this information will be sent to NIDA within the time frame specified in the research study protocol.
在通过电话、传真或电子邮件提交SAE初始报告后，将尽一切努力收集SAE上可用的其他信息。一旦收到，该信息将在研究方案规定的时间范围内发送给NIDA。
For studies conducted under an IND, it is then NIDA’s responsibility (as sponsor of most investigational new drug studies conducted within the CTN) to send an IND (Investigational New Drug) Safety Report to the FDA within the required timeframe.
对于根据IND进行的研究，NIDA有责任（作为在CTN内进行的大多数研究性新药研究的赞助者）在规定时间内向FDA发送IND（研究性新药）安全性报告。
SAEs that are exempt from expedited reporting must be documented and reported in a timely fashion (e.g., monthly, quarterly) in accordance with local IRB requirements. For all CTN studies, any serious adverse event (SAE) must be reported to NIDA within 24 hours after CTN protocol staff learn of the event. This deadline applies:
豁免快速报告的SAE必须按照当地IRB要求及时记录和报告（如每月、每季度）。对于所有CTN研究，任何严重不良事件（SAE）必须在CTN方案工作人员获悉事件后24小时内报告给NIDA。此截止日期适用于：
Ⅰ、Whether or not the investigator considers the SAE to be related to the study intervention.
Ⅱ、Regardless of the severity or outcome of the SAE.
Ⅲ、For SAEs that occur in both drug studies and behavioral studies.
Ⅳ、For studies conducted under the Investigational New Drug regulations and those that are not.
Ⅴ、For all SAEs that occur during a study, including those that occur during a post–treatment observation period as defined by the study protocol.
1、研究者是否认为SAE与研究干预有关。
2、无论SAE的严重程度或结果如何。
3、药物研究和行为研究中出现的严重不良事件。
4、根据研究性新药法规进行的研究和未进行的研究。
5、研究期间发生的所有严重不良事件，包括研究方案规定的治疗后观察期内发生的严重不良事件。
The National Institutes of Health (NIH) has issued guidance to NIH-supported investigators on reporting to IRBs about AEs that occur in multi-center clinical trials. Investigators must know the policies of the local IRB, adhere to them, and keep a copy of them in the study file. Investigators are also responsible for accurately documenting, investigating, and following up all possible study-related adverse events.
美国国立卫生研究院（NIH）已经向NIH支持的研究人员发布了关于向IRBs报告多中心临床试验中发生的不良事件的指南。调查人员必须了解当地IRB的政策，遵守这些政策，并将其副本保存在研究文件中。研究人员还负责准确记录、调查和跟踪所有可能的研究相关不良事件。
Site PIs should follow the policies of their Institutional Review Board on timeframes for reporting AEs. Additionally, investigators must ensure that NIDA is informed of any actions taken by the IRB as a result of its continuing review of participant safety.
现场PI应遵循其机构审查委员会关于报告不良事件时间框架的政策。此外，调查人员必须确保NIDA了解IRB在持续审查参与者安全性后采取的任何行动。
Adverse Event Reporting in CTN Studies CTN研究中的不良事件报告
Multiple parties need to be notified of AEs that occur in CTN studies. This can lead to confusion.
需要向CTN研究中发生的AES通知多方。这可能导致混淆。
Study investigators must report AEs to:
Ⅰ、The study sponsor (NIDA for most CTN trials).
Ⅱ、Relevant IRBs.
研究调查人员必须将不良事件报告给：
1、研究发起人（大多数CTN试验的NIDA）。
2、相关内部评级机构。
If NIDA is the study sponsor, and the study is conducted under an IND, NIDA must inform FDA and any other relevant regulatory agencies of findings that could adversely affect participant safety, affect the conduct of the trial, or alter IRB approval to continue the trial.
如果NIDA是研究发起人，并且该研究是在IND下进行的，NIDA必须告知FDA和任何其他相关的调查结果，可能会对参与者安全产生不利影响，影响审判的行为，或改变IRB批准继续审判。
The research protocol may, if appropriate, establish additional reporting requirements based on the severity of an AE. For example, the protocol and consent forms could state that trial-related hospitalizations will be reported to the participant’s treating physician.
如果合适，研究方案可根据不良事件的严重程度制定额外的报告要求。例如，协议和同意书可以规定，与试验相关的住院情况将报告给参与者的治疗医生。
In CTN trials, any AE that occurs between the times a participant signs the informed consent form and the time he or she leaves the study after the final follow-up visit must be captured and recorded, unless the protocol states differently. The investigators and NIDA (as the study sponsor) may jointly determine an alternative period (e.g., beginning with the first trial-related procedure or the first time a participant takes the study drug) during which AEs must be reported.
在CTN试验中，除非方案另有规定，否则必须捕获并记录参与者签署知情同意书与最终随访后离开研究之间发生的任何不良事件。研究者和NIDA（作为研究发起人）可共同确定一个替代期（例如，从第一次试验相关程序开始或参与者首次服用研究药物开始），在此期间必须报告不良事件.
How quickly an AE must be reported and to whom depends, in part, on the nature of the event. Reporting requirements encompass both routine reporting and expedited (rapid) reporting.
不良事件的报告速度和报告对象部分取决于事件的性质。报告要求包括常规报告和加快（快速）报告。
For studies conducted under an IND, FDA regulations require investigators to “promptly” report to the study sponsor any AE that is reasonably likely to have been caused by the study drug. If the AE is “alarming”, the investigator must report it immediately. The sponsor, in turn, is responsible for expedited (rapid) reporting to the FDA of certain serious adverse events (SAEs) that are both reasonably related and unexpected. All other AEs must be reported to the FDA in protocol amendments or in annual reports (21 CFR 312.32).
对于根据IND进行的研究，FDA法规要求研究人员“及时”向研究发起人报告任何合理可能由研究药物引起的不良反应。如果不良事件“令人担忧”，研究人员必须立即报告。赞助商则负责向FDA加快（快速）报告某些合理相关和意外的严重不良事件（SAE）。所有其他不良事件必须在方案修正案或年度报告（21 CFR 312.32）中报告给FDA。
Adverse Event Reporting in CTN Behavioral Studies CTN行为研究中的不良事件报告
For NIH-funded studies that do not involve the use of investigational new drugs, requirements for AE reporting vary depending on the nature of the study. Federal regulations (45 CFR Part 46, Subpart A) require written procedures and policies for ensuring that “unanticipated problems” involving risks to participants are reported to the IRB, appropriate institutional officials, and the relevant department or agency head.
对于NIH资助的不涉及使用试验新药的研究，AE报告的要求因研究的性质而异。联邦法规（45 CFR第46部分A子部分）要求书面程序和政策，以确保向IRB、相关机构官员和相关部门或机构负责人报告涉及参与者风险的“意外问题”。
Most AEs that occur in CTN behavioral studies are found to be unrelated to the study treatments received. For this reason, unlike FDA requirements for drug trials, non-serious AEs are sometimes not tracked in CTN studies. The Lead Investigator should specify in the protocol of a behavioral study which untoward occurrences should be captured and reported as adverse events, and which should not. Furthermore, the protocol should specify the types of events that will or will not qualify as SAEs and be reported as such.
CTN行为研究中出现的大多数不良事件与接受的研究治疗无关。因此，与FDA对药物试验的要求不同，CTN研究中有时不跟踪非严重不良事件。首席研究者应在行为研究方案中明确哪些不良事件应记录并报告为不良事件，哪些不应记录为不良事件。此外，协议应规定将或将不符合SAE的事件类型，并作为SAE报告。
For NIH-funded studies in which investigational drugs or devices are used, i.e. studies conducted under IND or IDE, investigators must comply with both NIH and FDA requirements for the reporting of AEs.
对于使用研究药物或设备的NIH资助研究，即在IND或IDE下进行的研究，研究人员必须遵守NIH和FDA关于不良事件报告的要求。
Additionally, OHRP provides the definition of unanticipated problems that affect the safety risks to study participants and others. As NIH-funded studies are regulated by 45 CFR 46, OHRP provides the criteria for determining unanticipated problems and the review and reporting of these incidents and AEs (follow this link for guidance).
此外，OHRP为研究参与者和其他人提供了影响安全风险的意外问题的定义。由于NIH资助的研究受45 CFR 46的监管，OHRP提供了确定意外问题的标准，以及这些事件和不良事件的审查和报告（遵循此链接获得指导）
Expedited Reporting of Adverse Events 不良事件的快速报告
Participants in clinical studies may experience AEs which, if they are thought to be probably or possibly caused by an experimental intervention, might be significant enough to lead to important changes in the way a drug or other intervention is developed or used (e.g., changes in dose, treatment population, required monitoring, consent forms). This is particularly true for AEs that, in their most severe forms, threaten life or function.
临床研究参与者可能会出现不良事件，如果认为这些不良事件可能是或可能是由实验性干预引起的，则其严重程度可能足以导致药物或其他干预措施的开发或使用方式发生重大变化（例如，剂量、治疗人群、所需监测、同意书的变化）。这对于AEs尤其如此，因为AEs以最严重的形式威胁生命或功能。
Such AEs must be reported promptly to investigators, sponsors, regulators, and IRBs. This is referred to as expedited or rapid reporting. The purpose of expedited reporting is to ensure that the appropriate parties are quickly made aware of important new information about the potential adverse effects of a drug or other experimental intervention.
此类不良事件必须立即报告给调查人员、发起人、监管机构和IRB。这称为快速或快速报告。快速报告的目的是确保有关各方迅速了解有关药物或其他实验干预的潜在不良影响的重要新信息。
